Page last updated: 2024-12-05

midazolam

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Description

Midazolam: A short-acting hypnotic-sedative drug with anxiolytic and amnestic properties. It is used in dentistry, cardiac surgery, endoscopic procedures, as preanesthetic medication, and as an adjunct to local anesthesia. The short duration and cardiorespiratory stability makes it useful in poor-risk, elderly, and cardiac patients. It is water-soluble at pH less than 4 and lipid-soluble at physiological pH. [Medical Subject Headings (MeSH), National Library of Medicine, extracted Dec-2023]

midazolam : An imidazobenzodiazepine that is 4H-imidazo[1,5-a][1,4]benzodiazepine which is substituted by a methyl, 2-fluorophenyl and chloro groups at positions 1, 6 and 8, respectively. [Chemical Entities of Biological Interest (ChEBI), Hastings J, Owen G, Dekker A, Ennis M, Kale N, Muthukrishnan V, Turner S, Swainston N, Mendes P, Steinbeck C. (2016). ChEBI in 2016: Improved services and an expanding collection of metabolites. Nucleic Acids Res]

Cross-References

ID SourceID
PubMed CID4192
CHEMBL ID655
CHEBI ID6931
SCHEMBL ID35061
MeSH IDM0013843

Synonyms (87)

Synonym
BIDD:GT0647
AKOS015842580
4h-imidazo[1,5-a][1,4]benzodiazepine, 8-chloro-6-(2-fluorophenyl)-1-methyl-
8-chloro-6-(o-fluorophenyl)-1-methyl-4h-imidazo[1,5-a][1,4]-benzodiazepine
usl-261
buccolam
versed
8-chloro-6-(2-fluorophenyl)-1-methyl-4h-imidazo[1,5-a][1,4]benzodiazepine
dea no. 2884
8-chloro-6-(o-fluorophenyl)-1-methyl-4h-imidazo(1,5-a)(1,4)benzodiazepine
brn 0625572
einecs 261-774-5
4h-imidazo(1,5-a)(1,4)benzodiazepine, 8-chloro-6-(2-fluorophenyl)-1-methyl-
hsdb 6751
8-chlor-6-(2-fluorphenyl)-1-methyl-4h-imidazo(1,5-a)(1,4)benzodiazepin
midazolamum [inn-latin]
dormicum
midazolam hydrochloride, solid
bdbm21363
ro 21-3981
12-chloro-9-(2-fluorophenyl)-3-methyl-2,4,8-triazatricyclo[8.4.0.0^{2,6}]tetradeca-1(10),3,5,8,11,13-hexaene
chembl655 ,
midazolam
59467-70-8
C07524
DB00683
midazolam (jan/usp/inn)
4h-imidazo[1,5-a][1,4]benzodiazepine, 8-chloro-6-(2-fluoro-phenyl)-1-methyl-, (z)-2-butenedioate
D00550
nayzilam (tn)
dormicum (tn)
buccolam (tn)
NCGC00168254-01
chebi:6931 ,
usl261
midazolam civ
A832332
08j ,
midazolam base
midazolamum
unii-r60l0sm5bc
midazolam [usp:inn:ban:jan]
r60l0sm5bc ,
midazolam [usp monograph]
8-chloro-6-(2-fluorophenyl)-1-methyl-4h-imidazo(1,5-a)(1,4)benzodiazepine
nayzilam
midazolam [inn]
4h-imidazo(1,5-a)(1,4)benzodiazepine, 8-chloro-6-(2-fluorophenyl)-1-methyl
midazolam [mart.]
midazolam [mi]
midazolam [vandf]
midazolam [jan]
midazolam [who-dd]
midazolam [orange book]
midazolam [ep monograph]
midazolam civ [usp-rs]
usl261 (nasal spray formulation)
12-chloro-9-(2-fluorophenyl)-3-methyl-2,4,8-triazatricyclo[8.4.0.0^{2,6}]tetradeca-1(14),3,5,8,10,12-hexaene
gtpl3342
HY-B0676
SCHEMBL35061
mezolam
flormidal (salt/mix)
versed (salt/mix)
hypnovel (salt/mix)
dormonid (salt/mix)
DTXSID5023320 ,
midazolam hydrochloride, united states pharmacopeia (usp) reference standard
midazolam 1.0 mg/ml in methanol
midazolam 0.1 mg/ml in methanol
BCP21296
Q423071
medazolam
59467-70-8 (free)
midazolam in 0.9% sodium chloride
n05cd08
midazolamum (inn-latin)
midazolam (usp:inn:ban:jan)
midazolam (usp monograph)
midazolam civ (usp-rs)
midazolam injection, 10 mg
midazolam (mart.)
midazolam (ep monograph)
midazolamum (latin)
dtxcid503320
midazolam in 0.8% sodium chloride
midazolam, 1mg/ml in methanol

Research Excerpts

Overview

Midazolam is a neurological drug with diverse functions, including sedation, hypnosis, decreased anxiety, anterograde amnesia, brain-mediated muscle relaxation, and anticonvulsant activity. It is a benzodiazepine used for sedation in patients hospitalized in the intensive care unit (ICU) for coronavirus disease 2019.

ExcerptReferenceRelevance
"Midazolam is a benzodiazepine commonly utilized in anesthesia and intensive care."( Midazolam suppresses ischemia/reperfusion-induced cardiomyocyte apoptosis by inhibiting the JNK/p38 MAPK signaling pathway.
Cai, D; Zhou, W, 2022
)
2.89
"Midazolam is a benzodiazepine sedative used in NICUs. "( Reducing Benzodiazepine Exposure by Instituting a Guideline for Dexmedetomidine Usage in the NICU.
Hansen, A; Labrecque, M; Leeman, K; Moline, M; Morton, SU, 2021
)
2.06
"Midazolam is a neurological drug with diverse functions, including sedation, hypnosis, decreased anxiety, anterograde amnesia, brain-mediated muscle relaxation, and anticonvulsant activity. "( Effects of Midazolam on the Development of Adult Leydig Cells From Stem Cells
Chen, D; Chen, H; Guan, X; Huang, F; Huang, L; Ji, M; Lin, H; Shao, J; Tian, J; Wang, J; Wen, X; Xie, J; Ye, L; Zhao, X, 2021
)
2.45
"Midazolam is a sedative agent commonly used in this manner."( Comparison of Dexmedetomidine and Midazolam in Conscious Sedation During Dental Implant Surgery: A Randomized Clinical Trial.
Delilbasi, C; Guldiken, IN; Gurler, G,
)
1.13
"Midazolam is an anesthetic widely used for anxiolysis and sedation; however, to date, a possible role for midazolam in diabetic kidney disease remains unknown. "( Midazolam Ameliorates Hyperglycemia-Induced Glomerular Endothelial Dysfunction by Inhibiting Transglutaminase 2 in Diabetes.
Cho, S; Ha, KS; Hong, SH; Jeon, HY; Kim, EB; Kim, M; Lee, YJ; Sayyed, ND; Seo, JA, 2022
)
3.61
"Midazolam is a novel sedative acting on the benzodiazepine receptor, which is recently reported to exert a neuroprotective effect by inhibiting inflammation."( Midazolam Ameliorates Impairment of the Blood-Brain Barrier (BBB) Against LPS.
Bai, H; He, K; Kang, P; Yu, X; Zhang, W; Zheng, J; Zheng, X, 2022
)
2.89
"Midazolam is a benzodiazepine used for sedation, however, can cause respiratory depression and increases morbidity in patients. "( Midazolam reduction with pre-operative melatonin in abdominal hysterectomy: double-blind randomized clinical trial.
Ángeles-Castellanos, M; Castelán-Martínez, OD; Mora-Magaña, I; Rosas-Luna, LE; Ubaldo-Reyes, LM, 2022
)
3.61
"Midazolam is a benzodiazepine frequently used for sedation in patients hospitalized in the intensive care unit (ICU) for coronavirus disease 2019 (COVID-19). "( Impact of Inflammation on Midazolam Metabolism in Severe COVID-19 Patients.
Bellouard, R; Canet, E; Dailly, É; Deslandes, G; Gaultier, A; Gregoire, M; Le Carpentier, EC; Martin, M; Masson, D, 2022
)
2.46
"Midazolam is a widely used short-acting benzodiazepine. "( Midazolam impacts acetyl-And butyrylcholinesterase genes: An epigenetic explanation for postoperative delirium?
Adamzik, M; Bazzi, M; Bazzi, Z; Bergmann, L; Holtkamp, C; Koos, B; Nowak, H; Orlowski, J; Rahmel, T; Rump, K; Thon, P; Unterberg, M, 2022
)
3.61
"Midazolam is a classic sedative drug. "( Can Remimazolam Be a New Sedative Option for Outpatients Undergoing Ambulatory Oral and Maxillofacial Surgery?
Guo, Z; Liu, Y; Wang, L; Wang, X; Yang, X, 2023
)
2.35
"Midazolam is a benzodiazepine commonly administered intravenously during surgical procedures because it reacts rapidly, causes anterograde amnesia, and has few side effects."( Effects of Chronic Oral Administration of Midazolam on Memory and Circadian Rhythms in Rats.
Kalinina, AI; Murphy, HM; Wideman, CH, 2023
)
1.9
"Midazolam is a hypnotic-sedative drug with pleiotropic properties."( Midazolam alleviates cellular senescence in SH-SY5Y neuronal cells in Alzheimer's disease.
Chen, Y; Luan, H; Wang, P; Wu, Y, 2023
)
3.07
"Midazolam is an excellent anxiolytic, whereas dexmedetomidine is superior in the postoperative period and for sedation during diagnostic imaging.A total intravenous technique with propofol is often considered to be the standard for the prevention of emergence agitation; but alternatives do exist, such as a co-medication with dexmedetomidine or opioids."( A new view on old problems in paediatric anaesthesia: premedication, postoperative agitation and dosing.
Jöhr, M, 2023
)
1.63
"Midazolam hydrochloride is a widely accepted benzodiazepine for premedication in pediatric patients. "( Efficacy and safety of oral versus intranasal midazolam as premedication in children: a systematic review and meta-analysis.
Chen, S; Lang, B; Wu, L; Zhang, W, 2023
)
2.61
"Midazolam rectal gel is a novel rectal formulation that may be a promising and potential alternative to oral administration for pediatric sedation. "( Safety, Pharmacokinetics, and Pharmacodynamics of Midazolam Gel After Rectal Administration in Healthy Chinese Subjects.
Chen, J; Ding, S; Li, Y; Shao, F; Sun, X; Wang, L; Xie, L; Zhao, Y; Zheng, A; Zhou, C; Zhou, S; Zhu, B; Zhu, J, 2023
)
2.61
"Midazolam is a first-line drug for the treatment of status epilepticus, both by buccal and intravenous administration. "( Midazolam Pharmacokinetics in Obese and Non-obese Children and Adolescents.
Burhenne, J; Christensen, HR; Dalhoff, K; Gade, C; Holm, JC; Holst, H; Johansen, MØ; Lund, TM; Mikus, G; Sonne, J; Sverrisdóttir, E, 2020
)
3.44
"Midazolam is a short-acting benzodiazepine approved for sedation and anesthesia induction. "( Off-label use of midazolam in older inpatients: analysis of prescribing practices in a French hospital (MIDnight study).
Gourdon, M; Herr, M; Le Dastumer, B; Michelon, H; Pons-Peyneau, C; Teillet, L, 2020
)
2.34
"Midazolam is a benzodiazepine derivative commonly used in intensive care units to control sedation. "( Long-term stability of ready-to-use 1-mg/mL midazolam solution.
Barthélémy, C; Décaudin, B; Feutry, F; Genay, S; Gilliot, S; Masse, M; Odou, P, 2020
)
2.26
"Midazolam is an anesthetic agent commonly used for anesthesia and sedation in surgery. "( Anti-metastatic effect of midazolam on melanoma B16F10 cells in the lungs of diabetic mice.
Ha, KS; Han, ET; Hong, SH; Jeon, HY; Kim, M; Kim, YM; Lee, YJ; Park, WS; Seo, JA, 2020
)
2.3
"Midazolam is an established probe drug to assess cytochrome P450 3A activity (phenotyping). "( Absolute Bioavailability of Microdosed Midazolam After Buccal Administration Is Dependent on Buccal Exposure Time.
Blank, A; Burhenne, J; Grass, J; Haefeli, WE; Mikus, G; Rose, P, 2021
)
2.33
"Midazolam is a short acting sedative with small number of adverse effects. "( Midazolam and its effect on vital signs and behavior in children under conscious sedation in dentistry.
Broukal, Z; Drapalova, K; Duskova, J; Duskova, M; Lunackova, J; Starka, L; Vasakova, J; Zuzankova, L, 2020
)
3.44
"Midazolam is a benzodiazepine commonly used in procedural sedation and general anaesthesia. "( A prospective observational cohort pilot study of the association between midazolam use and delirium in elderly endoscopy patients.
Chapman, G; Fernando, J; Hayman, M; Lee, D; Petersen, F; Tomkins, K; Wu, M, 2021
)
2.29
"Midazolam (MDZ) is a commonly used sedative drug and serves as a marker substrate for the CYP3A4 activity assessment."( Homotropic Cooperativity of Midazolam Metabolism by Cytochrome P450 3A4: Insight from Computational Studies.
Chen, Y; Li, J; Li, W; Tang, Y; Tu, Y, 2021
)
1.64
"Midazolam is a short-acting benzodiazepine with central nervous system depressing action, commonly used for conscious sedation for various procedures and for its pharmacologic properties.In literature, severe adverse reactions to this drug are described, but only in few cases positive allergological tests were demonstrated.The authors collected herein five clinical cases of different allergic reactions to midazolam demonstrated by positive skin tests."( Allergic reactions to midazolam: A case series from an Italian allergy unit.
Aruanno, A; Buonomo, A; Nucera, E; Parrinello, G; Rizzi, A, 2021
)
2.38
"Midazolam (MDZ) is a short-acting benzodiazepine with rapid onset of action, which is metabolized by CYP3A isoenzymes to two hydroxylated metabolites, 1'-hydroxymidazolam and 4-hydroxymidazolam. "( UPLC-MS/MS analysis of the Michaelis-Menten kinetics of CYP3A-mediated midazolam 1'- and 4-hydroxylation in rat brain microsomes.
DuBois, B; Mehvar, R; Venkatapura Chandrashekar, D, 2021
)
2.3
"Midazolam is a sedative used by patients with mechanical ventilation. "( Midazolam prevents motor neuronal death from oxidative stress attack mediated by JNK-ERK pathway.
Li, GZ; Peng, CB; Tao, HL; Wang, DD; Zhou, C, 2018
)
3.37
"Midazolam is a well-accepted anxiolytic in this setting."( A comparison of midazolam and zolpidem as oral premedication in children, a prospective randomized double-blinded clinical trial.
Andrews, G; Applegate, RL; Austin, B; Cano, S; Hanna, AH; Leiter, P; Ramsingh, D; Sullivan-Lewis, W; Wallace, D, 2018
)
1.55
"Midazolam (MDZ) is a benzodiazepine drug that is clinically used during surgical procedures and for the treatment of insomnia, with a potential ability to treat stroke."( Neuroprotective effects of midazolam on focal cerebral ischemia in rats through anti‑apoptotic mechanisms.
Chen, Z; Dai, M; Kang, F; Meng, Y; Wang, X; Yu, H, 2019
)
1.53
"Midazolam is a suitable alternative to guaifenesin when co-infused with ketamine and medetomidine for anaesthesia in young horses undergoing noninvasive procedures. "( Total intravenous anaesthesia with ketamine, medetomidine and guaifenesin compared with ketamine, medetomidine and midazolam in young horses anaesthetised for computerised tomography.
Cunneen, A; Farry, T; Goodwin, W; Kidd, L; McEwen, M; Perkins, N; Pratt, S; Rainger, J; Truchetti, G, 2019
)
2.17
"As midazolam is an established marker substance for cytochrome P450 3A activity, this single-arm prospective trial was designed to obtain a 4-h pharmacokinetic profile of midazolam after oral administration of a 10-µg dose from each enrolled patient. "( Alteration of drug-metabolizing enzyme activity in palliative care patients: Microdosed assessment of cytochrome P450 3A.
Bardenheuer, H; Burhenne, J; Geist, M; Mikus, G, 2019
)
1.14
"Midazolam proved to be a safe drug."( Higher mortality rate is associated with advanced age and periodic lateralized epileptiform discharges in patients with refractory status epilepticus.
Garzon, E; Liberalesso, PB; Sakamoto, AC; Yacubian, EM, 2013
)
1.11
"Midazolam (MDZ) is a benzodiazepine commonly administered in preanesthesia of children by oral or by sublingual routes. "( Benefits of methylated cyclodextrins in the development of midazolam pharmaceutical formulations.
Cailleu, D; Djedaïni-Pilard, F; Dubaele, JM; Marçon, F; Mathiron, D; Pilard, S, 2013
)
2.08
"Midazolam is a benzodiazepine derivative drug that has powerful anxiolytic, amnestic, hypnotic, and sedative properties. "( Midazolam provides cytoprotective effect during corticosterone-induced damages in rat astrocytes by stimulating steroidogenesis.
An, LN; Chen, HX; Guo, WZ; Li, YF; Ma, YQ; Mi, WD; Miao, YL; Pan, NL; Wang, XY; Zhang, H; Zhao, N, 2013
)
3.28
"Midazolam is a commonly used premedication in children but, because of its undesirable effects such as postoperative behavior changes and cognitive impairment, it is not an ideal premedicant."( Comparison of sublingual midazolam and dexmedetomidine for premedication in children.
Pant, D; Sethi, N; Sood, J, 2014
)
1.43
"Midazolam is a widely used anesthetic of the benzodiazepine class that has shown cytotoxicity and apoptosisinducing activity in neuronal cells and lymphocytes. "( Midazolam induces cellular apoptosis in human cancer cells and inhibits tumor growth in xenograft mice.
Bae, YS; Kang, JH; Kim, HM; Lee, CW; Mishra, SK; Oh, SH; Ryu, JS, 2013
)
3.28
"Midazolam is a widely used sedative agent during colonoscopy, with cognitive toxicity. "( Evident cognitive impairments in seemingly recovered patients after midazolam-based light sedation during diagnostic endoscopy.
Hsu, YH; Hua, MS; Lin, CP; Lin, FS; Sun, WZ; Yang, CC, 2015
)
2.1
"Midazolam is a short-acting benzodiazepine central nervous system depressant available as an injection, tablet, or oral syrup. "( Stability of midazolam in syrspend SF and syrspend SF cherry.
Geiger, CM; Sorenson, B; Whaley, PA,
)
1.94
"Midazolam is a frequently used sedative for this indication, although it has never been investigated how therapeutic hypothermia and asphyxia influence midazolam metabolism in neonates.9 asphyxiated newborns were treated with whole body hypothermia of 32-34°C for 72 h and all of them received continuous midazolam infusion for sedation."( Disposition of midazolam in asphyxiated neonates receiving therapeutic hypothermia--a pilot study.
Junghaenel, S; Mueller, C; Roth, B; Weiss, V; Welzing, L; Wiesen, MH, 2013
)
1.46
"Midazolam is a benzodiazepine commonly used for conscious sedation in dentistry.This paper reports a state of unconsciousness in a 14-year-old girl after administration of midazolam sedation for dental treatment, which was not reversible with flumazenil.The patient remained in an Intensive Care Unit for two days, unresponsive to any stimulus. "( An unusual response to intravenous sedation: a case report.
Lourenço-Matharu, L; Raval, P, 2014
)
1.85
"Midazolam is a short-acting benzodiazepine that has clearly demonstrated to be an effective option for the acute management of epileptic seizures. "( The safety and tolerability of intranasal midazolam in epilepsy.
Mula, M, 2014
)
2.11
"Midazolam is a short-acting benzodiazepine that is widely used in anesthesia. "( Inhibition of cardiac Kv1.5 potassium current by the anesthetic midazolam: mode of action.
Fischer, F; Katus, HA; Scherer, D; Scholz, EP; Seyler, C; Thomas, D; Vonderlin, N; Zitron, E, 2014
)
2.08
"Midazolam is a short-acting benzodiazepine that is in wide clinical use as an anxiolytic, sedative, hypnotic, and anticonvulsant. "( Anesthetic drug midazolam inhibits cardiac human ether-à-go-go-related gene channels: mode of action.
Fischer, F; Katus, HA; Scherer, D; Scholz, EP; Seyler, C; Thomas, D; Vonderlin, N; Zitron, E, 2015
)
2.21
"Midazolam is a benzodiazepine anticonvulsant with rapid onset and short duration of action. "( Antiseizure Activity of Midazolam in Mice Lacking δ-Subunit Extrasynaptic GABA(A) Receptors.
Clossen, BL; Reddy, DS; Reddy, SD; Younus, I, 2015
)
2.17
"Midazolam is a benzodiazepine hypnotic with a rapid onset and short duration of action."( Midazolam as an anticonvulsant antidote for organophosphate intoxication--A pharmacotherapeutic appraisal.
Reddy, DS; Reddy, SD, 2015
)
2.58
"Midazolam is a positive allosteric modulator of synaptic γ-aminobutyric acid (GABA)A receptors in the brain."( Midazolam as an anticonvulsant antidote for organophosphate intoxication--A pharmacotherapeutic appraisal.
Reddy, DS; Reddy, SD, 2015
)
2.58
"Midazolam is a sedative-hypnotic agent with amnestic and anticonvulsant properties that can be administrated to mammals through various routes, such as intravenous, intramuscular, oral, intrathecal, rectal, and buccal. "( Locomotor differences in Mongolian gerbils with the effects of midazolam administration in the form of eye drops.
Akkaya, A; Apuhan, T; Ayaz, E; Bayir, H; Demirhan, A; Erdurmus, M; Kocoglu, H; Tekelioglu, UY, 2014
)
2.08
"Midazolam is a short-acting water-soluble benzodiazepine with a rapid onset of action and short half-life."( A randomised, double-blind controlled trial of intranasal midazolam for the palliation of dyspnoea in patients with life-limiting disease.
Allan, S; Flatley, C; Gibbons, K; Hardy, J; Pinkerton, E; Randall, C, 2016
)
1.4
"Midazolam is an anxiolytic, and thought to be effective for the management of this sort of transient hypertension."( Effect of a low dose of midazolam on high blood pressure in dental patients: a randomised, double-blind, placebo-controlled, two-centre study.
Higuchi, H; Honda, Y; Ishii-Maruhama, M; Maeda, S; Miyawaki, T; Tomoyasu, Y; Watanabe, Y; Yabuki-Kawase, A; Yamane-Hirano, A, 2016
)
1.46
"Midazolam is an anesthetic agent commonly used during clinical and surgical procedures, which has been shown to exert ROS‑suppressing and apoptosis‑modulating pharmacological activities in various cellular systems. "( Midazolam anesthesia protects neuronal cells from oxidative stress-induced death via activation of the JNK-ERK pathway.
Guo, F; Liu, JS; Liu, JY; Wang, Y; Wu, HL, 2017
)
3.34
"Midazolam is a benzodiazepine agonist that affects the acquisition, retention, and retrieval of malaise-induced conditioned taste aversion (CTA) in rats. "( Midazolam impairs the retrieval of conditioned taste aversion via opioidergic transmission in mice.
Shimura, T; Yasoshima, Y, 2017
)
3.34
"Midazolam is a commonly used marker substrate for the in vivo assessment of CYP3A activity. "( An ultra-sensitive LC-MS/MS method to determine midazolam levels in human plasma: development, validation and application to a clinical study.
Chen, M; Fraier, D; Kang, L; Lin, ZJ; Lu, W; Lu, Y; Ottaviani, G; Wang, W; Zhao, H, 2017
)
2.15
"Midazolam is a short-acting benzodiazepine that is used increasingly in neonatal intensive care units (NICUs)."( Intravenous midazolam infusion for sedation of infants in the neonatal intensive care unit.
Ng, E; Ohlsson, A; Taddio, A, 2017
)
1.56
"Midazolam is a frequently used benzodiazepine in anaesthesiology and intensive care."( Changes in biomechanical parameters during heart perfusion and after midazolam pre-medication--experimental pilot study.
Bartosik, T; Bartosikova, L; Frana, P; Necas, J; Pavlik, M, 2008
)
2.02
"Midazolam (MDZ) is a benzodiazepine used as a CYP3A4 probe in clinical and in vitro studies. "( In vitro and in vivo glucuronidation of midazolam in humans.
Ezzeddine, K; Hyland, R; Jones, B; Kempshall, S; Logan, YR; Osborne, T; Payne, A, 2009
)
2.06
"Midazolam is a benzodiazepine with hypnotic action widely used as pre-anesthetic medication in pediatric anesthesia. "( Oral midazolam as pre-anesthetic medication in children and teenagers with cerebral palsy. A comparative study on the variations of the bispectral index.
Arci, EC; da Costa, VV; Saraiva, RA; Torres, RV,
)
2.09
"1. Midazolam is a common fast-acting GABA(A) receptor agonist. "( Administration of midazolam in infancy does not affect learning and memory of adult mice.
Deng, XM; Liu, Y; Liu, ZQ; Xiong, YC; Xu, B; Xu, H; Zhang, WS, 2009
)
1.31
"Midazolam (MDZ) is a substrate for both CYP3A4 and CYP3A5."( Association of genotypes of the CYP3A cluster with midazolam disposition in vivo.
Gorski, CJ; Hall, SD; Jin, Y; Kim, S; Li, L; Marunde, RL; Miao, J; Quinney, S; Radovich, M, 2009
)
1.33
"Midazolam is a commonly used sedative and anaesthetic adjuvant and the agent is known to decrease core temperature by core-to-periphery redistribution of heat. "( Forced-air warming effectively prevents midazolam-induced core hypothermia in volunteers.
Imai, Y; Ishiyama, T; Iwashita, H; Matsukawa, T; Okuyama, K; Sato, H; Yamakage, M, 2009
)
2.06
"Midazolam (MDZ) is a commonly used benzodiazepine in clinical practice. "( Validation of a new HPLC method for determination of midazolam and its metabolites: application to determine its pharmacokinetics in human and measure hepatic CYP3A activity in rabbits.
Attia, A; Elbarbry, F; Shoker, A, 2009
)
2.05
"Midazolam is a benzodiazepine derivative with an anxiolytic, sedative, amnestic and hypnotic action. "( Transrectal ultrasound-guided prostatic biopsy: midazolam, the ideal analgesic.
Bhandari, Y; Gaitonde, S; Kharbanda, S; Mankeshwar, R; Patil, M; Shrimali, P; Srinivas, V, 2009
)
2.05
"Midazolam is an efficient treatment for RSE in children. "( [Use of midazolam for refractory status epilepticus in children].
Auvin, S; Botte, A; Dorkenoo, A; Lamblin, MD; Lampin, ME; Leclerc, F,
)
2.01
"Midazolam is an ultra short acting benzodiazepine derivative and a specific probe for phenotyping cytochrome P450 (P450) 3A4/5 activity. "( Development and validation of a rapid and sensitive assay for simultaneous quantification of midazolam, 1'-hydroxymidazolam, and 4-hydroxymidazolam by liquid chromatography coupled to tandem mass-spectrometry.
Akhlaghi, F; Chitnis, SD; Dostalek, M; Ionita, IA; Macwan, JS, 2010
)
2.02
"Midazolam is a potent anticonvulsant and is rapidly absorbed from the rectal, nasal, and buccal mucosa."( Efficacy and usability of buccal midazolam in controlling acute prolonged convulsive seizures in children.
Ashrafi, MR; Bavarian, B; Karimi, P; Khosroshahi, N; Kompani, F; Malamiri, RA; Mirzaei, M; Zarch, AV, 2010
)
1.36
"Midazolam appears to be a better option in the treatment of recurrent seizures or statural convulsivus than diazepam."( [A control study on the treatment of acute seizures with midazolam and diazepam in children].
Tang, RH; Zhou, JB, 2010
)
1.33
"Midazolam is a benzodiazepine with hypnotic action most often used as pre-anesthetic medication and its drug interactions in patients with CP are unknown."( Effect of isolated anticonvulsant drug use and associated to midazolam as pre-anesthetic medication on the Bispectral Index (BIS) in patients with cerebral palsy.
da Costa, VV; de Oliveira, SB; Saraiva, RA; Torres, RV,
)
1.09
"Oral midazolam is a safe and effective method of sedation although some children were agitated and distressed either during or after treatment. "( Oral sedation for dental treatment in young children in a hospital setting.
Lourenço-Matharu, L; Roberts, GJ, 2010
)
0.87
"Midazolam is an efficacious short-acting benzodiazepine with an excellent safety record."( The use of oral midazolam for perioperative anxiolysis of healthy patients undergoing Mohs surgery: conclusions from randomized controlled and prospective studies.
Hoverson Schott, A; Killian, JM; Otley, CC; Phillips, PK; Ravitskiy, L; Roenigk, RK; Weaver, AL, 2011
)
1.44
"Midazolam is a short-acting benzodiazepine that is widely used as an i.v. "( Role of neurosteroids in the anticonvulsant activity of midazolam.
Dhir, A; Rogawski, MA, 2012
)
2.07
"Midazolam is a rapid-onset, short-acting benzodiazepine which is used safely to reduce pain in children."( Sedation with intranasal midazolam of Angolan children undergoing invasive procedures.
Barbi, E; Capobianco, I; Felipe, D; Kawanda, L; Malundo, L; Munkela, N; Not, T; Rodrigues, V; Starc, M; Zanon, D, 2012
)
1.4
"Midazolam is a short-acting benzodiazepine that is increasingly used in neonatal intensive care units (NICU)."( Intravenous midazolam infusion for sedation of infants in the neonatal intensive care unit.
Ng, E; Ohlsson, A; Taddio, A, 2012
)
1.48
"Midazolam is a licensed medication, but the buccal formulation is currently used off-licence."( Significant hypotension following buccal midazolam administration.
Kensche, M; Sander, JW; Sisodiya, SM, 2010
)
1.35
"Midazolam is a benzodiazepine widely used in intensive care unit, as a sedative, anxiety-relieving, and amnesic drug. "( [Sedation induced by midazolam in intensive care: pharmacologic and pharmacokinetic aspects].
Bastien, O; Bolon, M; Boulieu, R; Flamens, C; Paulus, S, 2002
)
2.08
"Oral midazolam appears to be a safe and acceptable form of sedation for 10-16-year-old paediatric dental patients."( A randomised, controlled, crossover trial of oral midazolam and nitrous oxide for paediatric dental sedation.
Girdler, NM; Welbury, RR; Wilson, KE, 2002
)
1.02
"Midazolam is a broadly used drug that can enhance tolerance to transesophageal echocardiography (TEE) in patients with cardiac conditions. "( Central-nervous side effects of midazolam during transesophageal echocardiography.
Bartel, T; Eggebrecht, H; Erbel, R; Philipp, T; Wenzel, RR, 2002
)
2.04
"Midazolam is a useful drug used preoperatively because it can produce anxiolysis and sedation. "( [Effects of midazolam premedication on induction doses of propofol and hemodynamic changes during tumor patient induction].
Lin, WQ; Tan, HY; Wang, J; Xu, MX; Zeng, WA, 2002
)
2.14
"Midazolam is a central nervous system depressant and can produce cognitive impairment."( Flumazenil reduces midazolam-induced cognitive impairment without altering pharmacokinetics.
Bertino, JS; Jones, CL; Morrison, AL; Nafziger, AN; Rocci, ML; Rogers, JF, 2002
)
1.36
"Midazolam is a short acting benzodiazepine that has been increasingly used in the NICU."( Intravenous midazolam infusion for sedation of infants in the neonatal intensive care unit.
Ng, E; Ohlsson, A; Taddio, A, 2003
)
1.42
"Midazolam is an effective and safe drug to control RGCSE, and may represent a substantial improvement over current therapeutic approaches such as pentobarbital anesthesia."( Continuous infusion of midazolam in the treatment of refractory generalized convulsive status epilepticus.
Müngen, B; Ulvi, H; Yigiter, R; Yoldas, T, 2002
)
1.35
"Midazolam is a relatively new anticonvulsive agent in the benzodiazepine group. "( Buccal midazolam for treatment of prolonged seizures in children.
Dogrul, M; Kutlu, NO; Soylu, H; Yakinci, C, 2003
)
2.22
"Midazolam is a commonly used anaesthetic agent and is metabolised by the 3A4 isoform of the cytochrome P450 enzyme system. "( The effects of concurrent atorvastatin therapy on the pharmacokinetics of intravenous midazolam.
Harte, S; Mc Donnell, CG; O'Driscoll, J; O'Loughlin, C; Shorten, GD; Van Pelt, FD; Van Pelt, FN, 2003
)
1.98
"Midazolam is a mixed-type agonist of PBRs."( Effects of midazolam on equine innate immune response: a flow cytometric study.
Massoco, C; Palermo-Neto, J, 2003
)
1.43
"Midazolam is an effective and safe drug to be used in a first-line or second-line therapy for status epilepticus and clusters of seizures in children."( [Eight-year study on the treatment with intravenous midazolam for status epilepticus and clusters of seizures in children].
Minagawa, K; Watanabe, T, 2003
)
1.29
"Midazolam is a widely accepted probe for phenotyping cytochrome P4503A. "( Determination of picogram levels of midazolam, and 1- and 4-hydroxymidazolam in human plasma by gas chromatography-negative chemical ionization-mass spectrometry.
Baumann, P; Bouchoux, G; Eap, CB; Powell Golay, K, 2004
)
2.04
"Midazolam is a benzodiazepine which produces a dense anterograde amnesia, while permitting relatively well-preserved short-term memory, semantic retrieval, and other higher cognitive functions. "( Metamemory without the memory: are people aware of midazolam-induced amnesia?
Berrigan, M; Hirshman, E; Hsu, J; Merritt, P, 2005
)
2.02
"Midazolam is a widely used sedative and anaesthetic induction agent."( Midazolam attenuates adenosine diphosphate-induced P-selectin expression and platelet-leucocyte aggregation.
Hong, GJ; Hsu, PC; Huang, GS; Li, CY; Lin, TC; Shih, CM; Tsai, CS, 2004
)
2.49
"i.m. midazolam is an effective agent for controlling acute convulsions in children especially in children with febrile convulsions. "( Intramuscular midazolam vs intravenous diazepam for acute seizures.
Deshmukh, CT; Shah, I, 2005
)
1.2
"Midazolam is a short-acting benzodiazepine commonly used for conscious sedation for a variety of procedures. "( [Facial edema and pruritus after intravenous injection of midazolam].
Kudoh, I; Ohmura, A; Uchimura, A; Yogo, H, 2006
)
2.02
"Midazolam is a drug that creates temporary anterograde amnesia. "( Drug-induced amnesia hurts recognition, but only for memories that can be unitized.
Kaufer, A; Oates, JM; Quinlan, JJ; Reder, LM; Sauer, J; Thornton, ER, 2006
)
1.78
"Oral midazolam was found to be a useful drug for the management of young children with behaviour problems. "( Effectiveness of oral midazolam for paediatric dental care: a retrospective study in two specialist centres.
Day, PF; Hibbert, SA; Paterson, SA; Power, AM, 2006
)
1.16
"Midazolam is a commonly used sedative in critically ill, mechanically ventilated patients in intensive care unit (ICU) settings worldwide. "( Clinical pharmacokinetic monitoring of midazolam in critically ill patients.
Ensom, MH; Spina, SP, 2007
)
2.05
"Midazolam is a potent benzodiazepine derivative with sedative, hypnotic, anticonvulsant, muscle-relaxant, and anxiolytic activities. "( Characterization of 1'-hydroxymidazolam glucuronidation in human liver microsomes.
Bush, D; Doss, GA; Franklin, RB; Vincent, S; Xu, S; Zhu, B, 2008
)
2.08
"Midazolam is a common probe used to predict CYP3A activity, but multiple blood samples are necessary to determine midazolam's area under the concentration-time curve (AUC). "( Limitations of using a single postdose midazolam concentration to predict CYP3A-mediated drug interactions.
Alfaro, RM; Busse, KH; Davey, RT; Formentini, E; Penzak, SR; Robertson, SM, 2008
)
2.06
"Midazolam is an i.v."( [Comparative study of the effect of midazolam and hypnomidate on the cardiovascular system].
List, WF; Ponhold, H, 1983
)
1.26
"Midazolam may prove to be a particularly useful hypnotic for shiftworkers whose rest periods tend to be shorter than in those who have a regular nocturnal sleep pattern."( Midazolam: sleep and performance studies in middle age.
Nicholson, AN; Stone, BM, 1983
)
2.43
"Midazolam appears to be a useful short-acting hypnotic having almost no residual effects the following morning."( Pharmacokinetics and the sedative effect of midazolam.
Allonen, H; Kanto, J, 1983
)
1.25
"Midazolam is a water soluble benzodiazepine of interest to the anaesthetist for use as a premedicant and for induction of anaesthesia. "( Effects of midazolam on directly stimulated muscle biopsies from control and malignant hyperthermia positive patients.
Fletcher, JE; Hilf, M; Rosenberg, H, 1984
)
2.1
"Midazolam is a short-acting water-soluble benzodiazepine (at pH less than 4), a member of a new class of imidazobenzodiazepine derivatives. "( Midazolam. A review of its pharmacological properties and therapeutic use.
Brogden, RN; Dundee, JW; Halliday, NJ; Harper, KW, 1984
)
3.15
"Midazolam proved to be a satisfactory agent for premedication compared with papaveretum and hyoscine, producing a similar degree of sedation and anxiolysis, but causing significantly more anterograde amnesia."( Intramuscular midazolam. A comparison of midazolam with papaveretum and hyoscine for intramuscular premedication.
Dixon, J; McAteer, EJ; Whitwam, JG, 1984
)
1.35
"Midazolam is a new imidazobenzodiazepine. "( Midazolam, a new more potent benzodiazepine, compared with diazepam: a randomized, double-blind study of preendoscopic sedatives.
Brozinsky, S; Cole, SG; Isenberg, JI, 1983
)
3.15
"Midazolam is a water-soluble benzodiazepine whose quick onset after intravenous injection, short duration of action, absence of venous irritation, and mild cardiovascular and respiratory effects suggest its use for induction of anesthesia. "( Comparative renal effects of midazolam and thiopental in humans.
Bonventre, JV; Cote, ME; Daniels, AL; Lebowitz, PW, 1983
)
2
"Oral midazolam is a new anxiolytic drug which can be used as an alternative to existing premedicant drugs, but, in children, it should still be combined with an anticholinergic agent."( Midazolam versus atropine plus pethidine as premedication in children.
Himberg, JJ; Iisalo, E; Kangas, L; Kanto, J; Sjövall, S, 1984
)
2.17
"Midazolam proved to be a good alternative to thiopentone, the longer induction time being compensated by a lower incidence and duration of apnoea."( Midazolam as induction agent prior to inhalational anaesthesia: a comparison with thiopentone.
Lee, PF; Nilsson, A; Revenäs, B, 1984
)
2.43
"Midazolam is an acceptable alternative to diazepam for upper gastrointestinal endoscopy."( Midazolam for upper gastrointestinal endoscopy.
Brophy, TO; Dundee, JW; Hunter, EK; Kawar, P; McLaughlin, J; Porter, KG, 1984
)
2.43
"Midazolam is an efficacious, safe premedicant in relatively healthy patients."( Premedication with intramuscular midazolam: a prospective randomized double-blind controlled study.
Reves, JG; Vinik, HR; Wright, D, 1982
)
1.27
"Midazolam appears to be a valuable alternative to conventional induction agents without adverse effects on the cardiovascular system."( Haemodynamic responses to induction of anaesthesia using midazolam in cardiac surgical patients.
Hess, W; Schulte-Sasse, U; Tarnow, J, 1982
)
1.23
"Midazolam seems to be a good alternative for induction of balanced anaesthesia."( Midazolam, a new intravenous induction agent for anaesthesia.
Brock-Utne, JG; Holloway, AM; Pavy, TJ; Sommerville, TE, 1982
)
2.43
"Midazolam is a new alternative agent for induction in combination anaesthesia."( Midazolam compared with thiopentone as an induction agent.
Kanto, J; Pakkanen, A, 1982
)
2.43
"Midazolam is a benzodiazepine that is more potent than diazepam as a sedative, muscle relaxant and in its influence on electroencephalographic measures."( New anticonvulsant drugs. Focus on flunarizine, fosphenytoin, midazolam and stiripentol.
Bebin, M; Bleck, TP, 1994
)
1.25
"Midazolam (MDZ) is a recently developed short-elimination half-life benzodiazepine."( [Use of intravenous midazolam in status epilepticus in children].
Daoud, P; Desguerre, I; Lemerle, J; Moutard, ML; Rodriguez, D, 1995
)
1.34
"Midazolam is a short-acting benzodiazepine routinely used in intensive-care medicine. "( Prolonged sedation due to accumulation of conjugated metabolites of midazolam.
Bauer, TM; Ha, HR; Haberthür, C; Haefeli, WE; Hunkeler, W; Ritz, R; Scollo-Lavizzari, G; Sleight, AJ, 1995
)
1.97
"Midazolam is a commonly used sedative and anesthetic adjuvant whose thermoregulatory effects are unknown."( Midazolam minimally impairs thermoregulatory control.
Annadata, R; Bjorksten, AR; Christensen, R; Dechert, M; Kurz, A; Sessler, DI, 1995
)
2.46
"Midazolam is a relatively short-acting water-soluble benzodiazepine that provides anxiolysis and anterograde amnesia and can be given orally with few adverse effects. "( Premedication with oral midazolam for voiding cystourethrography in children: safety and efficacy.
Elder, JS; Longenecker, R, 1995
)
2.04
"Midazolam is a short-acting water soluble benzodiazepine that has been used with an increasing frequency in the last years. "( Midazolam for treatment of refractory neonatal seizures. A case report.
Gherpelli, JL; Luccas, FJ; Roitman, I; Troster, EJ, 1994
)
3.17
"Oral midazolam (0.3 mg/kg) is a safe and effective treatment for reducing anxiety during the suturing of lacerations in children less than 10 years of age. "( A randomized, controlled trial of oral midazolam and buffered lidocaine for suturing lacerations in children (the SLIC Trial).
Fatovich, DM; Jacobs, IG, 1995
)
1.07
"Midazolam is an effective benzodiazepine with a rapid onset and short duration of action, properties that could permit its use in outpatient areas or in short but stressful situations."( Midazolam in patients receiving anticancer chemotherapy and antiemetics.
Baltzer, L; Clark, RA; Gralla, RJ; Kris, MG; Pisters, KM; Potanovich, LM; Tyson, LB, 1993
)
2.45
"Midazolam is a new short-acting benzodiazepine which is more potent than diazepam. "( An evaluation of oral and nasal midazolam for pediatric dental sedation.
Hartgraves, PM; Primosch, RE,
)
1.86
"Midazolam is a short-acting, water-soluble benzodiazepine used for induction and maintenance of general anesthesia and as an adjunct to regional anesthesia. "( Midazolam-induced athetoid movements of the lower extremities during epidural anesthesia reversed by physostigmine.
Roberts, JT; Vorsanger, GJ,
)
3.02
"Midazolam is a water-soluble benzodiazepine proven to be efficacious in sedation, hypnosis, and induction and maintenance of anesthesia. "( Intravenous versus intramuscular midazolam in treatment of chemically induced generalized seizures in swine.
Bradford, SM; Orebaugh, SL, 1994
)
2.01
"Midazolam is a water-soluble benzodiazepine imide that has been used in recent years to manage status epilepticus (SE). "( [Treatment of status epilepticus with midazolam: report of four cases].
Aguilera Olivares, L; Galdames Poblete, D; Silva-Rosas, C, 1994
)
2
"Midazolam is an effective and safe drug to control refractory seizures in children with status epilepticus."( Midazolam in the treatment of status epilepticus in children.
Baltodano, A; Pérez, V; Rivera, R; Segnini, M, 1993
)
3.17
"Midazolam is a more recent benzodiazepine used for sedation during endoscopic procedures, including sphincter of Oddi (SO) manometry. "( Effect of midazolam on sphincter of Oddi motility.
Arlebäck, A; Rolny, P, 1993
)
2.13
"Midazolam is a suitable drug for long-term sedation in patients with tetanus."( Midazolam for prolonged intravenous sedation in patients with tetanus.
Fahr, J; Gyasi, HK; Kurian, E; Mathew, M, 1993
)
2.45
"Midazolam is a short-acting benzodiazepine that is metabolized by CYP3A enzymes. "( Rifampin drastically reduces plasma concentrations and effects of oral midazolam.
Backman, JT; Neuvonen, PJ; Olkkola, KT, 1996
)
1.97
"Midazolam is a short-acting benzodiazepine which is used as an oral hypnotic agent in several countries. "( Concentrations and effects of oral midazolam are greatly reduced in patients treated with carbamazepine or phenytoin.
Backman, JT; Laaksovirta, H; Neuvonen, PJ; Ojala, M; Olkkola, KT, 1996
)
2.01
"Midazolam is a benzodiazepin derivate with express sedative and hypnotic qualities, powerful amnesia, a short half-life time and few secondary effects."( Midazolam intravenous conscious sedation in oral surgery. A retrospective study of 372 cases.
Runes, J; Ström, C, 1996
)
2.46
"Midazolam proved to be an effective sedative and anxiolytic drug with no remarkable effects on vigilance and cooperation during induction of anaesthesia."( [Premedication with midazolam in adults with special reference to anxiety treatment].
Röse, VW, 1996
)
1.34
"Midazolam is a short-acting benzodiazepine hypnotic extensively metabolized by CYP3A4 enzyme. "( Effect of route of administration of fluconazole on the interaction between fluconazole and midazolam.
Ahonen, J; Neuvonen, PJ; Olkkola, KT, 1997
)
1.96
"IM midazolam is an effective anticonvulsant for children with motor seizures. "( A prospective, randomized study comparing intramuscular midazolam with intravenous diazepam for the treatment of seizures in children.
Altieri, MA; Chamberlain, JM; Futterman, C; Ochsenschlager, DW; Waisman, Y; Young, GM, 1997
)
1.16
"Midazolam is a safe and effective oral premedicant for children."( A comparison of midazolam with trimeprazine as an oral premedicant for children.
Black, A; Grange, C; Mitchell, V; Train, J, 1997
)
1.36
"Midazolam is a familiar agent commonly used in the emergency department to provide sedation prior to procedures such as laceration repair and reduction of dislocations. "( Midazolam: a review of therapeutic uses and toxicity.
Clark, RF; Nordt, SP,
)
3.02
"Midazolam was found to be a safe and viable alternative to muscle relaxants, allowing endotracheal intubation and ventilation, in addition to other invasive procedures, to be carried out with minimal distress to the patient."( The use of midazolam in trauma resuscitation.
Deo, S; Knottenbelt, JD, 1994
)
1.4
"Midazolam is a recently developed water-soluble benzodiazepine that shares anxiolytic, muscle relaxant, hypnotic and anticonvulsant actions with other members of this class. "( Midazolam in treatment of various types of seizures in children.
Durmaz, Y; Karabiber, H; Müngen, B; Sahin, S; Yakinci, C, 1997
)
3.18
"Oral midazolam is an effective and safe premedication for children undergoing upper endoscopy and should be used in all anxious children and in patients previously judged to be difficult to sedate."( Placebo-controlled trial assessing the use of oral midazolam as a premedication to conscious sedation for pediatric endoscopy.
Liacouras, CA; Mascarenhas, M; Poon, C; Wenner, WJ, 1998
)
1.07
"Midazolam is a parenteral benzodiazepine with sedative, amnesic, anxiolytic, muscle relaxant and anticonvulsant properties. "( Clinical pharmacology of midazolam in infants and children.
Blumer, JL, 1998
)
2.05
"Midazolam is a commonly used benzodiazepine that is ideal for conscious sedation during a variety of procedures. "( Reversal of midazolam-induced laryngospasm with flumazenil.
Davis, DP; Hamilton, RS; Webster, TH, 1998
)
2.12
"Midazolam is a benzodiazepine with short elimination half-life, used as induction or continuous agent for general anesthesia. "( Development of midazolam sublingual tablets: in vitro study.
Barthelemy, C; Odou, P; Robert, H,
)
1.93
"Midazolam is a water-soluble benzodiazepine with a fast onset of action, a short half-life, and inactive metabolites that has been very effective in terminating seizures refractory to diazepam, lorazepam, phenytoin, and phenobarbital in pediatric patients."( Use of midazolam for refractory status epilepticus in pediatric patients.
Pellock, JM, 1998
)
1.48
"Midazolam is a short-acting agent used for preoperative and conscious sedation. "( The effect of flumazenil on patient recovery and discharge following ambulatory surgery.
Fryzel, S; Gerbasi, F; Hourrigan, J; Masserant, J; Motz, J; Nagelhout, J; Wakefield, F; Wigton, T; Zaglaniczny, KL, 1999
)
1.75
"Midazolam appears to be a good choice for initial treatment of refractory generalized convulsive status epilepticus in children, but the attribution of differences in efficacy and mortality solely to drug effect is not possible based on the published literature."( Efficacy and mortality in treatment of refractory generalized convulsive status epilepticus in children: a meta-analysis.
Gartside, PS; Gilbert, DL; Glauser, TA, 1999
)
1.02
"Oral midazolam is a safe and effective premedication before flexible sigmoidoscopy in patients who require or prefer sedation."( A double-blind placebo controlled trial of oral midazolam as premedication before flexible sigmoidoscopy.
Chen, ST; Clarkston, WK; Cuddy, PG; Dierenfeldt, WT; Jonnalagadda, SS; Kuganeswaran, E; Pandya, PK; Quiason, SG; Smith, OJ, 1999
)
1.01
"Midazolam is a short acting benzodiazepine that has been increasingly used in the NICU."( Intravenous midazolam infusion for sedation of infants in the neonatal intensive care unit.
Ng, E; Ohlsson, A; Taddio, A, 2000
)
1.41
"Midazolam is a water-soluble benzodiazepine. "( Physostigmine reversal of midazolam-induced electroencephalographic changes in healthy subjects.
Ebert, U; Kirch, W; Oertel, R, 2000
)
2.05
"Midazolam is a water-soluble benzodiazepine, and has recently emerged as a safe and effective treatment option after ordinary antiepileptic therapy in the management of status epilepticus. "( Midazolam as a first-line agent for status epilepticus in children.
Abe, T; Oda, Y; Yamazaki, S; Yoshikawa, H, 2000
)
3.19
"Oral midazolam is a short-acting benzodiazepine that can ameliorate procedure-related anxiety."( Anxiolysis with oral midazolam in pediatric patients undergoing dermatologic surgical procedures.
Nguyen, TH; Otley, CC; Phillips, PK, 2001
)
1.08
"Oral midazolam is an effective anxiolytic agent in pediatric patients undergoing dermatologic surgical procedures."( Anxiolysis with oral midazolam in pediatric patients undergoing dermatologic surgical procedures.
Nguyen, TH; Otley, CC; Phillips, PK, 2001
)
1.14
"Oral midazolam is a frequently used sedative in pediatric dentistry. "( Oral midazolam-grapefruit juice drug interaction.
Goho, C,
)
1.16
"Midazolam appears to be a safe and effective drug when given in the appropriate doses."( Conscious sedation in paediatric dentistry: current philosophies and techniques.
Alcaino, EA, 2000
)
1.03
"Midazolam is a short-acting benzodiazepine with rapid onset, short duration of action and minimal side effects. "( Conscious sedation by oral administration of midazolam in paediatric dental treatment.
Bäckman, B; Erlandsson, AL; Stecksén-Blicks, C; Stenström, A, 2001
)
2.01
"Midazolam is a water-soluble benzodiazepine with low toxicity. "( Use of intravenous midazolam for sedation in children undergoing ward procedures.
I Chan, LY; Tan, CL, 1992
)
2.05
"Midazolam is a relatively safe and effective sedative for accurate lower esophageal sphincter pressure measurement and esophageal manometry when a mild sedative such as choral hydrate does not work."( Midazolam as a sedative in esophageal manometry: a study of the effect on esophageal motility.
Fung, KP; Ho, CO; Math, MV; Yap, KM, 1992
)
2.45
"Midazolam is a water soluble benzodiazepine, with a short elimination half-life in adults and children. "( Pharmacokinetics of midazolam during continuous infusion in critically ill neonates.
Beaufils, F; Burtin, P; Daoud, P; Jacqz-Aigrain, E; Maherzi, S, 1992
)
2.05
"Midazolam is an effective swine sedative that is associated with stable cardiac function."( Sedative and cardiovascular effects of midazolam in swine.
Smith, AC; Spinale, FG; Swindle, MM; Zellner, JL, 1991
)
1.27
"Midazolam is a new imidazobenzodiazepine derivative that is two to three times as potent as diazepam, is water-soluble, has a rapid onset and short duration of action, and produces a profound amnestic effect. "( Midazolam use in the emergency department.
Glasgow, C; Linkenheimer, R; Ramoska, EA,
)
3.02
"Midazolam (MDZ, Versed) is a water-soluble, rapid-onset, short-duration benzodiazepine that has not been studied widely in children."( Midazolam for conscious sedation during pediatric oncology procedures: safety and recovery parameters.
Berde, CB; Blanding, PJ; Foley, ME; Sievers, TD; Yee, JD, 1991
)
2.45
"Midazolam is a short-acting 1,4-imidazole benzodiazepine with sedative-hypnotic, anxiolytic, and amnestic properties. "( Urinary screening for midazolam and its major metabolites with the Abbott ADx and TDx analyzers and the EMIT d.a.u. benzodiazepine assay with confirmation by GC/MS.
Bryan, W; Fraser, AD; Isner, AF,
)
1.89
"Midazolam is a widely used drug which has anxiolytic, sedative-hypnotic, muscle relaxing, anticonvulsant action and strong anterograde amnesic effect. "( [Minidose midazolam anesthesia].
Aoyagi, M; Itoh, K; Sumida, M, 1991
)
2.13
"Midazolam is a short-acting benzodiazepine with anxiolytic, hypnotic, and antegrade amnestic effects."( The effect of oral midazolam on anxiety of preschool children during laceration repair.
Bonadio, WA; Glaeser, PW; Hennes, HM; Losek, JD; Smith, DS; Wagner, V; Walsh-Kelly, CM, 1990
)
1.33
"Midazolam is a water soluble benzodiazepine, with a short elimination half-life in adults and children. "( Pharmacokinetics of midazolam in critically ill neonates.
Jacqz-Aigrain, E; Robieux, I; Wood, C, 1990
)
2.05
"Midazolam is a new ultra short-acting benzodiazepine whose physical dependence properties have not been well characterized. "( Tolerance and physical dependence to a short-acting benzodiazepine, midazolam.
Boisse, NR; Guarino, JJ; Quaglietta, N; Samoriski, GM, 1990
)
1.96
"Midazolam is a short-acting benzodiazepine with a short half life (1.5-2.5 h) due to intense biotransformation by liver monooxygenases. "( [Drug interactions of midazolam].
Dayer, P; Gascon, MP; Waldvogel, F, 1989
)
2.03
"Midazolam is a water soluble benzodiazepine with potent sedative and amnestic properties. "( Midazolam in upper gastrointestinal endoscopy: a single-blind dose-finding study.
Goldenberg, E; Hershfield, N; MacCannell, K; Price, L; Shaffer, E; Sutherland, LR, 1989
)
3.16
"Midazolam is a short-acting benzodiazepine with anxiolytic, sedative-hypnotic and marked amnestic properties. "( [Clinical pharmacology of midazolam].
Klotz, U, 1989
)
2.02
"Midazolam hydrochloride is an ultra-short acting benzodiazepine recently approved by the Food and Drug Administration for anesthesia induction and preoperative sedation. "( Precipitation of benzodiazepine withdrawal following sudden discontinuation of midazolam.
Finley, PR; Nolan, PE, 1989
)
1.95
"Midazolam appeared to be a more effective premedicant than diazepam, analgesics or placebo."( Midazolam for intramuscular premedication: dose-effect relationships compared to diazepam, fentanyl and fentanyl-droperidol in a placebo controlled study.
Camu, F; Claeys, MA; Van de Velde, A, 1986
)
2.44
"Midazolam is a water-soluble benzodiazepine with rapid onset and short half-life."( Premedication with midazolam in out-patient general anaesthesia. A comparison with morphine-scopolamine and placebo.
Breivik, H; Raeder, JC, 1987
)
1.32
"Midazolam appears to be a suitable alternative to thiopental for the induction and maintenance of anesthesia for elective cesarean section."( A randomized comparison between midazolam and thiopental for elective cesarean section anesthesia. I. Mothers.
Bach, V; Carl, P; Crawford, ME; Mikkelsen, BO; Ravlo, O; Werner, M, 1989
)
1.28
"Midazolam is a new parenteral benzodiazepine premedication for endoscopy. "( Diazepam versus midazolam (versed) in outpatient colonoscopy: a double-blind randomized study.
Aldoroty, RA; Knight, RJ; Lewis, BS; Shlien, RD; Wayne, JD,
)
1.92
"Midazolam is a suitable alternative to diazepam as part of an intravenous induction regimen in patients with ischaemic heart disease."( Haemodynamic changes during induction of anaesthesia with midazolam and diazepam (Valium) in patients undergoing coronary artery bypass surgery.
Carson, IW; Clarke, RS; Dundee, JW; Kawar, P; Lyons, SM, 1985
)
1.23
"Midazolam is an imidazobenzodiazepine with unique properties when compared with other benzodiazepines. "( Midazolam: pharmacology and uses.
Fragen, RJ; Greenblatt, DJ; Reves, JG; Vinik, HR, 1985
)
3.15
"Midazolam is a short-acting sedative-anxiolytic agent with a rapid onset of action especially useful for patients operated on under local anesthesia."( The usefulness of radioreceptor assay and gas liquid chromatography in pharmacokinetic studies on midazolam.
Aaltonen, L; Himberg, JJ; Kanto, J; Vuori, A, 1985
)
1.21
"Midazolam is a 1,4-benzodiazepine derivative with a unique chemical structure: depending on environmental pH, the drug can produce highly water-soluble salts (pH less than 4) or exist in lipophilic diazepine ring-closed form (pH greater than 4). "( Midazolam: the first water-soluble benzodiazepine. Pharmacology, pharmacokinetics and efficacy in insomnia and anesthesia.
Kanto, JH,
)
3.02
"Midazolam is a water-soluble benzodiazepine used for anesthetic induction. "( Effects of midazolam (a benzodiazepine) on cerebral perfusion and oxygenation in dogs.
Chang, CL; Chen, HI; Yeh, FC, 1988
)
2.11
"Midazolam is a relatively new benzodiazepine that is widely used in both medicine and dentistry. "( Midazolam: review of a versatile agent for use in dentistry.
Giovannitti, JA,
)
3.02
"Midazolam is a good premedicant for general or regional anesthesia."( Use of midazolam hydrochloride in anesthesia.
Khanderia, U; Pandit, SK, 1987
)
1.45
"Midazolam is a very useful drug in outpatient aesthetic surgery. "( Midazolam (Versed) in ambulatory surgery.
Baker, TJ; Gordon, HL, 1988
)
3.16
"Midazolam is a new water-soluble benzodiazepine with a much shorter pharmacologic half-life than diazepam. "( Recovery following sedation with midazolam or diazepam alone or in combination with fentanyl for outpatient surgery.
Anderson, JA; Ochs, MW; Tucker, MR; White, RP,
)
1.86
"Midazolam is a new, water-soluble benzodiazepine that has been reported to produce a greater degree of amnesia than does diazepam. "( A comparison of amnesia in outpatients sedated with midazolam or diazepam alone or in combination with fentanyl during oral surgery.
Ochs, MW; Tucker, MR; White, RP, 1986
)
1.96
"Midazolam appeared to be a more effective sedative agent than diazepam for short-term administration during mechanical ventilation."( The use of midazolam and diazepam for sedation following aorto-coronary bypass surgery.
Demeyere, R; Ferdinande, P; Lauwers, P; Schetz, M; Van Damme, K; Verwaest, C, 1987
)
1.38
"Midazolam is a recently introduced benzodiazepine with a half life of 1-4 hours. "( A comparison of midazolam and diazepam for sedation during locoregional anesthesia.
Donadoni, R; Herregods, L; Mortier, E; Rolly, G, 1987
)
2.06
"Midazolam is seen to be an effective agent in the emergency treatment of seizures."( Midazolam: an effective intravenous agent for seizure control.
Galvin, GM; Jelinek, GA, 1987
)
2.44
"Midazolam is a water soluble 1,4 benzodiazepine which is suitable for intramuscular administration. "( A pharmacodynamic evaluation of midazolam as an antiepileptic compound.
Jawad, S; Oxley, J; Richens, A; Wilson, J, 1986
)
2

Effects

Midazolam has a rapid onset of action following intravenous, intramuscular, oral, nasal, and rectal administration. It has a significantly shorter time to onset of sedation and a more rapid time to arousal than diazepam or lorazepam.

Midazolam has no side-effects but also has the advantages of sedation and amnesia. It has been reported to be effective for preventing PONV in adults undergoing middle ear surgery and children undergoing strabismus surgery or tonsillectomy.

ExcerptReferenceRelevance
"Midazolam has a good anterograde amnesia-inducing effect, can prevent and reduce the occurrence of intraoperative awareness."( ED50 for intravenous midazolam-induced amnesia and its duration in surgical patients.
Gao, C; Wang, Y; Wu, AS; Yan, J; Yue, Y, 2021
)
1.66
"Midazolam has a neuroprotective effect in some neuropathological conditions."( Midazolam contributes to neuroprotection against hypoxia/reoxygenation-induced brain injury in neonatal rats via regulation of EAAT2.
Dong, Y; Liu, H; Ma, C; Shan, Y; Sun, S; Tang, Z; Yang, F; Zhang, Y, 2020
)
2.72
"Midazolam has a clinically active metabolite, 1-hydroxymidazolam."( Differential depression of neuronal network activity by midazolam and its main metabolite 1-hydroxymidazolam in cultured neocortical slices.
Antkowiak, B; Balk, M; Drexler, B; Hentschke, H; Rudolph, U, 2017
)
1.42
"Midazolam has a relaxing effect on airway muscles."( Midazolam Premedication Facilitates Mask Ventilation During Induction of General Anesthesia: A Randomized Clinical Trial.
Bae, SI; Han, SH; Hwang, JW; Kim, BY; Kim, JH; Min, BH; Park, JW; Park, SJ, 2019
)
2.68
"Midazolam has a significantly shorter time to onset of sedation and a more rapid time to arousal than lorazepam or haloperidol. "( A prospective, double-blind, randomized trial of midazolam versus haloperidol versus lorazepam in the chemical restraint of violent and severely agitated patients.
Dresden, GM; Levitt, MA; Nobay, F; Simon, BC, 2004
)
2.02
"Midazolam has a higher clearance and shorter half-life than other benzodiazepines, and prolonged sedation is achieved with continuous infusion."( Clinical pharmacokinetic monitoring of midazolam in critically ill patients.
Ensom, MH; Spina, SP, 2007
)
1.33
"Midazolam has a similar pharmacologic potency and broad therapeutic range as diazepam."( Pharmacology of midazolam.
Burkard, WP; Cook, L; Cumin, R; Da Prada, M; Davidson, A; Gerold, M; Haefely, W; Keller, HH; Möhler, H; Müller, RK; Pieri, L; Pieri, M; Polc, P; Schaffner, R; Scherschlicht, R; Sepinwall, J, 1981
)
1.33
"Midazolam has a considerable advantage over diazepam being water soluble and injectable safely without dilution."( Midazolam in paediatric anaesthesia.
Cole, WH, 1982
)
2.43
"Midazolam has a half-life of about two hours and can be applied simultaneously with oxytocin by motor driven syringe."( [Intranatal Administration of midazolam (author's transl)].
Gitsch, E; Philipp, K; Schönbauer, M, 1982
)
1.27
"Midazolam has a slow onset of action, while thiamylal causes pain on injection and circulatory changes. "( [Induction of anesthesia with midazolam and thiamylal].
Hirasaki, A; Ishii, S; Nishiyama, T; Odaka, Y; Ono, T; Seto, K, 1994
)
2.02
"Midazolam has a rapid onset of action following intravenous, intramuscular, oral, nasal, and rectal administration."( Midazolam: a review of therapeutic uses and toxicity.
Clark, RF; Nordt, SP,
)
2.3
"Midazolam has a spasmolytic effect on constricted airways but this bronchodilatation was not reversed by flumazenil."( Midazolam reverses histamine-induced bronchoconstriction in dogs.
Hashimoto, Y; Hirota, K; Ishihara, H; Kudo, T; Matsuki, A; Ohtomo, N, 1997
)
3.18
"Midazolam has a faster onset and shorter duration of action than other benzodiazepines such as diazepam and lorazepam."( Clinical pharmacology of midazolam in infants and children.
Blumer, JL, 1998
)
1.32
"As midazolam has a long elimination half-life as that of diazepam, prolongation of its effects has to be considered when a large dose or continuous infusion is employed."( [Usefulness of midazolam in a modified NLA--study on plasma concentrations].
Iwado, S; Kosaka, F; Morita, K; Nishiyama, T; Taga, N; Ueno, T; Yaida, Y, 1989
)
1.14
"Midazolam also has a relatively rapid onset of action and high metabolic clearance when compared with other benzodiazepines."( Midazolam: pharmacology and uses.
Fragen, RJ; Greenblatt, DJ; Reves, JG; Vinik, HR, 1985
)
2.43
"Midazolam has a good anterograde amnesia-inducing effect, can prevent and reduce the occurrence of intraoperative awareness."( ED50 for intravenous midazolam-induced amnesia and its duration in surgical patients.
Gao, C; Wang, Y; Wu, AS; Yan, J; Yue, Y, 2021
)
1.66
"Midazolam has dose-dependent effects on SLC differentiation. "( Effects of Midazolam on the Development of Adult Leydig Cells From Stem Cells
Chen, D; Chen, H; Guan, X; Huang, F; Huang, L; Ji, M; Lin, H; Shao, J; Tian, J; Wang, J; Wen, X; Xie, J; Ye, L; Zhao, X, 2021
)
2.45
"Midazolam has the potential to affect adult Leydig cell (ALC) development at concentrations comparable with the blood serum levels in human patients. "( Effects of Midazolam on the Development of Adult Leydig Cells From Stem Cells
Chen, D; Chen, H; Guan, X; Huang, F; Huang, L; Ji, M; Lin, H; Shao, J; Tian, J; Wang, J; Wen, X; Xie, J; Ye, L; Zhao, X, 2021
)
2.45
"Midazolam has for many years been a standard premedication for children."( Clonidine Versus Midazolam Premedication and Postoperative Negative Behavioral Changes in Younger Children: A Randomized Controlled Trial.
Haney, M; Hedlund, L; Hult, AC; Johansson, G; Winsö, O; Zickerman, C, 2022
)
1.78
"Midazolam has been found to be safe for the heart in sedoanalgesia."( The impact of midazolam used in cataract surgery sedation on frontal QRS-T angle.
Gokalp, G; Ozbeyaz, NB, 2022
)
1.8
"Midazolam has become the preferred benzodiazepine in pre- and in-hospital settings, both in children and adults. "( Trends and Differences in Status Epilepticus Treatment of Children and Adults Over 10 Years: A Comparative Study of Medical Records (2012-2021) from a University Hospital in Germany.
Czabanka, M; Kieslich, M; Merker, M; Purwien, L; Ronellenfitsch, MW; Rosenow, F; Schubert-Bast, S; Strzelczyk, A; Willems, LM, 2023
)
2.35
"Oral midazolam has been shown to be safe in various procedures."( Safety of Premedication with Oral Midazolam before Rhinoplasty as Indicated by Intraoperative Levels of Blood Oxygen Saturation.
Frand, J; Harel, M; Leibou, L; Shalom, A, 2019
)
1.25
"Midazolam has a neuroprotective effect in some neuropathological conditions."( Midazolam contributes to neuroprotection against hypoxia/reoxygenation-induced brain injury in neonatal rats via regulation of EAAT2.
Dong, Y; Liu, H; Ma, C; Shan, Y; Sun, S; Tang, Z; Yang, F; Zhang, Y, 2020
)
2.72
"Midazolam has a clinically active metabolite, 1-hydroxymidazolam."( Differential depression of neuronal network activity by midazolam and its main metabolite 1-hydroxymidazolam in cultured neocortical slices.
Antkowiak, B; Balk, M; Drexler, B; Hentschke, H; Rudolph, U, 2017
)
1.42
"Midazolam has some potential in pain control of patients undergoing knee arthroscopy. "( The effect of midazolam on pain control after knee arthroscopy: a systematic review and meta-analysis.
Chen, X; He, Z; Mou, X; Zhu, Y, 2017
)
2.26
"Midazolam has a relaxing effect on airway muscles."( Midazolam Premedication Facilitates Mask Ventilation During Induction of General Anesthesia: A Randomized Clinical Trial.
Bae, SI; Han, SH; Hwang, JW; Kim, BY; Kim, JH; Min, BH; Park, JW; Park, SJ, 2019
)
2.68
"Midazolam has been found to exacerbate or unmask limb motor dysfunction in patients with brain tumors. "( Midazolam Sedation Induces Upper Limb Coordination Deficits That Are Reversed by Flumazenil in Patients with Eloquent Area Gliomas.
Gelb, AW; Han, R; Hui, X; Lin, N; Zhang, K, 2019
)
3.4
"Midazolam has been widely studied for preventing emergence agitation. "( Comparison of the effects of 0.03 and 0.05 mg/kg midazolam with placebo on prevention of emergence agitation in children having strabismus surgery.
Cho, EJ; Cho, JE; Lee, HW; Yoon, SZ, 2014
)
2.1
"When midazolam has failed to control RSE, the evidence points to barbiturate anesthesia as the next frequently used option."( Continuous infusion, general anesthesia and other intensive care treatment for uncontrolled status epilepticus.
Tasker, RC; Vitali, SH, 2014
)
0.86
"Midazolam has protective effects on the proliferation and apoptosis of astrocytes via JAK2/STAT3 signal pathway in vitro. "( Midazolam inhibits the apoptosis of astrocytes induced by oxygen glucose deprivation via targeting JAK2-STAT3 signaling pathway.
Gu, J; Li, Q; Li, X; Liu, L; Tu, Y; Wang, G; You, Q; Zheng, L, 2015
)
3.3
"Midazolam has been shown to inhibit ion channels, including calcium and potassium channels."( Anesthetic drug midazolam inhibits cardiac human ether-à-go-go-related gene channels: mode of action.
Fischer, F; Katus, HA; Scherer, D; Scholz, EP; Seyler, C; Thomas, D; Vonderlin, N; Zitron, E, 2015
)
1.48
"Midazolam has been found to have beneficial effects on anxiety in children in the preoperative setting. "( A randomized trial examining preoperative sedative medication and postoperative sleep in children.
Fortier, MA; Jenkins, B; Kain, ZN; Min, CB; Stevenson, RS, 2016
)
1.88
"Oral midazolam has been the most commonly used premedication for pediatric patient but the use of midazolam may be associated with paradoxical reactions in children."( Premedication with melatonin vs midazolam in anxious children.
Baygin, O; Bodur, H; Isik, B, 2008
)
1.08
"Midazolam not only has no side-effects but also has the advantages of sedation and amnesia."( Comparative study of postoperative analgesia and sedation after upper abdominal surgery with thoracic epidural administration of bupivacaine with/without midazolam.
Kamdar, BM; Kaushal, V; Shroff, PP, 2009
)
1.27
"Midazolam has only sedative properties. "( Intravenous dexmedetomidine, but not midazolam, prolongs bupivacaine spinal anesthesia.
Gurbet, A; Kaya, FN; Mogol, EB; Ozcan, B; Turker, G; Yavascaoglu, B; Yildirim, A, 2010
)
2.08
"Midazolam has analgesic effects mediated by gamma aminobutyric acid-A receptors. "( Quality of lidocaine analgesia with and without midazolam for intravenous regional anesthesia.
Aly, A; Farouk, S, 2010
)
2.06
"Midazolam has no effect on endothelium-dependent relaxation, whereas propofol suppresses endothelium-dependent relaxation."( The different effects of midazolam and propofol sedation on dynamic cerebral autoregulation.
Aoki, K; Gokan, D; Hirose, N; Iwasaki, K; Kato, J; Ogawa, S; Ogawa, Y, 2010
)
1.39
"Midazolam has been reported to be effective for preventing PONV in adults undergoing middle ear surgery and children undergoing strabismus surgery or tonsillectomy."( A prospective, randomized, double-blind, placebo-controlled study to assess the antiemetic effects of midazolam on postoperative nausea and vomiting in women undergoing laparoscopic gynecologic surgery.
Fujii, Y; Itakura, M, 2010
)
1.3
"Midazolam has neurotoxic properties when administered neuraxially in vivo. "( Midazolam activates the intrinsic pathway of apoptosis independent of benzodiazepine and death receptor signaling.
Bauer, I; Braun, S; Gaza, N; Hermanns, H; Hollmann, MW; Kremer, D; Küry, P; Stevens, MF; Werdehausen, R,
)
3.02
"Midazolam has been reported to modulate IL-6 response."( Combination of midazolam and a cyclooxygenase-2 inhibitor inhibits lipopolysaccharide-induced interleukin-6 production in human peripheral blood mononuclear cells.
Arai, Y; Higuchi, H; Kohjitani, A; Maeda, S; Miyawaki, T; Shimada, M; Tomoyasu, Y, 2012
)
1.45
"Midazolam and propofol have been examined with the aim of reducing emergence agitation after sevoflurane anaesthesia."( Prophylactic use of midazolam or propofol at the end of surgery may reduce the incidence of emergence agitation after sevoflurane anaesthesia.
Kim, YH; Lim, HJ; Yoon, SM; Yoon, SZ, 2011
)
1.41
"Midazolam, which has spinally mediated analgesic potency, was epidurally administered in dogs, and serum and cerebrospinal fluid concentrations were measured. "( Serum and cerebrospinal fluid concentrations of midazolam after epidural administration in dogs.
Hanaoka, K; Nishiyama, T; Tamai, H, 2003
)
2.02
"Midazolam has a significantly shorter time to onset of sedation and a more rapid time to arousal than lorazepam or haloperidol. "( A prospective, double-blind, randomized trial of midazolam versus haloperidol versus lorazepam in the chemical restraint of violent and severely agitated patients.
Dresden, GM; Levitt, MA; Nobay, F; Simon, BC, 2004
)
2.02
"Midazolam has proved to be very successful in reducing anxiety and stress pre-, peri-, and postoperatively with no significant effect on the vital signs of a healthy patient. "( Midazolam in the reduction of surgical stress: a randomized clinical trial.
Hopper, C; Jerjes, W; Jerjes, WK; Kattan, M; Kumar, S; Leeson, R; Swinson, B; Wood, PJ, 2005
)
3.21
"Midazolam has antinociceptive effects when administered intrathecally, while its effects associated with systemic administration remain controversial. "( Analgesic effects of systemic midazolam: comparison with intrathecal administration.
Nishiyama, T, 2006
)
2.07
"Midazolam has a higher clearance and shorter half-life than other benzodiazepines, and prolonged sedation is achieved with continuous infusion."( Clinical pharmacokinetic monitoring of midazolam in critically ill patients.
Ensom, MH; Spina, SP, 2007
)
1.33
"Midazolam has hypnotic and sedative activities, which may be mediated by different neuronal structures. "( The time-dependent effects of midazolam on regional cerebral glucose metabolism in rats.
Dam, M; Freo, U; Ori, C, 2008
)
2.08
"Midazolam has a similar pharmacologic potency and broad therapeutic range as diazepam."( Pharmacology of midazolam.
Burkard, WP; Cook, L; Cumin, R; Da Prada, M; Davidson, A; Gerold, M; Haefely, W; Keller, HH; Möhler, H; Müller, RK; Pieri, L; Pieri, M; Polc, P; Schaffner, R; Scherschlicht, R; Sepinwall, J, 1981
)
1.33
"Midazolam has the lowest residual fraction of all known benzodiazepines and thus, administered in the appropriate dosage, also has the shortest duration of activity."( Pharmacokinetic and clinical considerations in the choice of a hypnotic.
Amrein, R; Eckert, M; Haefeli, H; Leishman, B, 1983
)
0.99
"Midazolam has a considerable advantage over diazepam being water soluble and injectable safely without dilution."( Midazolam in paediatric anaesthesia.
Cole, WH, 1982
)
2.43
"Midazolam has a half-life of about two hours and can be applied simultaneously with oxytocin by motor driven syringe."( [Intranatal Administration of midazolam (author's transl)].
Gitsch, E; Philipp, K; Schönbauer, M, 1982
)
1.27
"Midazolam has no effect on the release of stored Ca2+."( Effects of midazolam on intracellular Ca2+ and tension in airway smooth muscles.
Kai, T; Kanaide, H; Kobayashi, S; Nishimura, J; Takahashi, S; Yoshimura, H, 1995
)
1.4
"Midazolam has been demonstrated to preserve the response of cerebral blood flow to CO2. "( Response of pial vessel diameter and regional cerebral blood flow to CO2 during midazolam administration in cats.
Furuya, H; Kumano, H; Nagahata, T; Okuda, T; Sakaki, T; Yomosa, H, 1994
)
1.96
"Midazolam has a slow onset of action, while thiamylal causes pain on injection and circulatory changes. "( [Induction of anesthesia with midazolam and thiamylal].
Hirasaki, A; Ishii, S; Nishiyama, T; Odaka, Y; Ono, T; Seto, K, 1994
)
2.02
"Midazolam sedation has been shown to diminish recall of one to four cards shown prior to induction of general anesthesia in pediatric patients. "( Midazolam enhances anterograde but not retrograde amnesia in pediatric patients.
Beaton, C; Berger, BJ; Hartung, J; McClain, J; Twersky, RS, 1993
)
3.17
"Midazolam and propofol have been investigated as potential partners for those two indications."( Co-induction of anaesthesia: the rationale.
Allen, SR; Amrein, R; Hetzel, W, 1995
)
1.01
"Midazolam has GABAergic effects in children that may modify propofol-induced involuntary movements, yet delay recovery. "( Midazolam premedication delays recovery after propofol without modifying involuntary movements.
Bevan, JC; Macnab, AJ; Marsland, C; Ries, CR; Veall, GR, 1997
)
3.18
"Midazolam has a rapid onset of action following intravenous, intramuscular, oral, nasal, and rectal administration."( Midazolam: a review of therapeutic uses and toxicity.
Clark, RF; Nordt, SP,
)
2.3
"Midazolam has been used clinically as a sedative and as an anaesthetic induction agent. "( Midazolam reverses histamine-induced bronchoconstriction in dogs.
Hashimoto, Y; Hirota, K; Ishihara, H; Kudo, T; Matsuki, A; Ohtomo, N, 1997
)
3.18
"Midazolam has a spasmolytic effect on constricted airways but this bronchodilatation was not reversed by flumazenil."( Midazolam reverses histamine-induced bronchoconstriction in dogs.
Hashimoto, Y; Hirota, K; Ishihara, H; Kudo, T; Matsuki, A; Ohtomo, N, 1997
)
3.18
"Midazolam has been associated with shorter recovery room stays and less vomiting in children who undergo outpatient surgery."( Intravenous conscious sedation with midazolam in paediatric patients.
Rosen, DA; Rosen, KR,
)
1.13
"Midazolam has been shown to have an analgesic effect by single shot epidural administration. "( Midazolam improves postoperative epidural analgesia with continuous infusion of local anaesthetics.
Hanaoka, K; Nishiyama, T; Yokoyama, T, 1998
)
3.19
"Midazolam has a faster onset and shorter duration of action than other benzodiazepines such as diazepam and lorazepam."( Clinical pharmacology of midazolam in infants and children.
Blumer, JL, 1998
)
1.32
"Midazolam has good anxiolytic qualities and is a well established premedication agent before anaesthesia or short surgical procedures. "( Midazolam pharmacokinetics following intravenous and buccal administration.
Alincic, S; Schwagmeier, R; Striebel, HW, 1998
)
3.19
"Midazolam has been reported to cause hypotension or to depress sympathetic activity following intravenous injection. "( Inhibition by midazolam of the adrenergic function in the isolated canine mesenteric vein.
Hagiwara, T; Kiyose, M; Kobayashi, Y; Kumasaka, S; Muldoon, SM; Okabe, E, 1998
)
2.1
"Midazolam has been reported to have a spinally mediated analgesic effect. "( Continuous epidural administration of midazolam and bupivacaine for postoperative analgesia.
Hanaoka, K; Matsukawa, T; Nishiyama, T, 1999
)
2.02
"Midazolam has the shortest t1/2 of the commonly used BZs, generates few active metabolites, and is water soluble at physiologic pH."( Benzodiazepines in the intensive care unit.
Prielipp, RC; Young, CC, 2001
)
1.03
"Midazolam has shown in this follow-up to be an effective and safe drug for premedication of infants in the stressed dental situation."( Rectal administration of midazolam for conscious sedation of uncooperative children in need of dental treatment.
Lindh-Strömberg, U, 2001
)
1.34
"Midazolam has several advantages over diazepam as a sedative agent in electrophysiologic studies, but its electrophysiologic effects in humans are unknown. "( Lack of effect of midazolam on inducibility of arrhythmias at electrophysiologic study.
Davis, L; Ho, DS; McGuire, MA; Richards, DA; Ross, DL; Uther, JB; Yip, AS, 1992
)
2.06
"Midazolam has no adverse effect on in vitro development of two-cell-to-blastocyst-stage embryos nor on in vivo fertilization and cell division at concentrations approximating and exceeding those that ova are exposed to during clinical anesthesia."( Fertilization and mouse embryo development in the presence of midazolam.
Leavitt, MG; Swanson, RJ, 1992
)
1.25
"Midazolam has limited influence on the cardiac toxic effects of amitriptyline."( Flumazenil in mixed benzodiazepine/tricyclic antidepressant overdose: a placebo-controlled study in the dog.
Askenasi, R; Leduc, D; Lheureux, P; Vranckx, M, 1992
)
1
"Midazolam has shown better results in all the parameters evaluated (memory scale, pharmacokinetics and pharmacodynamics values) and in controlling sedation."( [Diazepam versus midazolam for "wakeful sedation" in oral surgery].
Arcioni, R; Marci, MC; Sanfilippo, M; Varrassi, G; Vilardi, V,
)
1.19
"Midazolam has been extensively used for a variety of outpatient procedures, but there has been no documentation of its safety in emergency department patients."( Midazolam use in the emergency department.
Borron, SW; Chudnofsky, CR; Dronen, SC; Wright, MB; Wright, SW, 1990
)
2.44
"Midazolam has not yet been investigated for its possible properties as a histamine releaser. "( [The plasma histamine level during anesthesia induction using midazolam].
Asskali, F; Behne, M; Janshon, G; Lischke, V, 1989
)
1.96
"Midazolam (M) has been successfully used in oral and rectal premedication of children of one to six years of age. "( [Midazolam for premedication of infants. A comparison of the effect between oral and rectal administration].
Bremerich, D; Nordmeyer, U; Tolksdorf, W, 1989
)
2.63
"As midazolam has a long elimination half-life as that of diazepam, prolongation of its effects has to be considered when a large dose or continuous infusion is employed."( [Usefulness of midazolam in a modified NLA--study on plasma concentrations].
Iwado, S; Kosaka, F; Morita, K; Nishiyama, T; Taga, N; Ueno, T; Yaida, Y, 1989
)
1.14
"Midazolam also has a relatively rapid onset of action and high metabolic clearance when compared with other benzodiazepines."( Midazolam: pharmacology and uses.
Fragen, RJ; Greenblatt, DJ; Reves, JG; Vinik, HR, 1985
)
2.43
"Midazolam (0.15 mg/kg) has been compared with diazepam (0.2 mg/kg) for sedation during locoregional anesthesia in 60 premedicated patients."( A comparison of midazolam and diazepam for sedation during locoregional anesthesia.
Donadoni, R; Herregods, L; Mortier, E; Rolly, G, 1987
)
1.34
"Midazolam has been studied as an induction agent compared to thiopentone in forty patients. "( A comparative study of midazolam and thiopentone for induction of anesthesia for short operations.
Badran, I, 1987
)
2.03

Actions

Midazolam produced lower SaO(2) values during colonoscopy compared with placebo or control groups (p < 0.001) 57% had falls in oxygen saturation of greater than 2.5% compared with only 35% given an equivalent dose of diazepam. An increase in elimination half-life and the apparent volume of distribution was positively correlated to an increase of body-weight.

ExcerptReferenceRelevance
"Midazolam is known to cause anterograde amnesia; however, the possibility of retrograde amnesia has also been raised."( Immediate retrograde amnesia induced by midazolam: A prospective, non-randomised cohort study.
Do, SH; Hwang, JW; Koung Yi, I; Lim, D; Na, HS; Nam, SW; Sohn, HM, 2021
)
1.61
"The midazolam MR was lower in treatment-naïve patients with CHC than in health volunteers with a mean effect ratio of 0.63 [90 % confidence interval (CI) 0.56-0.72]. "( Influence of chronic hepatitis C infection on cytochrome P450 3A4 activity using midazolam as an in vivo probe substrate.
Blotner, S; Brennan, BJ; Morcos, PN; Moreira, SA; Shulman, NS; Smith, PF, 2013
)
1.17
"Midazolam-S-ketamine promotes effective chemical restraint for quick and minimally invasive procedures and dexmedetomidine-S-ketamine promotes effective chemical restraint for prolonged and more invasive procedures."( COMPARISON BETWEEN DEXMEDETOMIDINE-S-KETAMINE AND MIDAZOLAM-S-KETAMINE IN IMMOBILIZATION OF ONCILLA (LEOPARDUS TIGRINUS).
Cortopassi, SR; das Candeias, IZ; de Mattos, E; de Moura, CA; Dias Neto, Rd; Lima, CF; Pedron, BG; Teixeira, RH, 2016
)
1.41
"Midazolam doses were lower in P than in C group (0.04 (0.02-0.07) and 0.06 (0.03-0.08) mg/kg/h respectively, p =0.005)."( [Protocol based sedation versus conventional treatment in critically ill patients on mechanical ventilation].
Asenjo B, R; Aspée L, P; Castro O, J; Lanas M, A; Pino P, S; Prat R, D; Rivas V, S; Tobar A, E, 2008
)
1.07
"Midazolam at a lower dose (10 mg/kg) had no significant effects."( Effects of midazolam on brain injury after transient focal cerebral ischemia in rats*.
Cottrell, JE; Kass, IS; Lei, B; Popp, S, 2009
)
1.46
"Midazolam may suppress conditioned fear after an aversive event by disrupting the memory trace formed during conditioning, by altering the emotional part of the aversive event, or by the combination of both effects. "( Mechanisms of action of midazolam on expression of contextual fear in rats.
Fouquet, N; Launoy, A; Oberling, P; Pain, L, 2002
)
2.06
"Midazolam can also cause paradoxical reactions, including increased agitation, poor co-operation and aggressive or violent behaviour, which has been successfully managed with flumazenil."( Toxicity of intravenous anaesthetics.
Short, TG; Young, Y, 2003
)
1.04
"Midazolam appears to cause significantly less sedation and cognitive impairment in red haired subjects."( Midazolam causes less sedation in volunteers with red hair.
Chua, MV; Doufas, AG; Tsueda, K, 2004
)
3.21
"With midazolam, however, the increase was comparable to that of the control group."( Flumazenil mimics whereas midazolam abolishes ischemic preconditioning in a rabbit heart model of ischemia-reperfusion.
Berenshtein, E; Chevion, M; Drenger, B; Gozal, Y; Raphael, J; Rivo, J, 2006
)
1.09
"Midazolam produced lower SaO2 values during gastroscopy compared with lidocaine, placebo or control groups (P<0.001)."( Sedation, topical pharyngeal anesthesia and cardiorespiratory safety during gastroscopy.
Hartikainen, J; Heikkinen, M; Julkunen, R; Laitinen, T; Mattila, M; Ristikankare, M; Wang, SX,
)
0.85
"Midazolam appeared to produce light sedation which required powerful premedication (i.m."( Effect of different kinds of premedication on the induction properties of midazolam.
Kanto, J; Sjövall, S; Vuori, A, 1982
)
1.22
"Midazolam was found to increase CVR (P < 0.01) and further depress CBF (P < 0.01), and to antagonize the ketamine-induced increase in CMRO2 (P < 0.05)."( Low-dose midazolam antagonizes cerebral metabolic stimulation by ketamine in the pig.
Akeson, J; Björkman, S; Messeter, K; Rośen, I, 1993
)
1.42
"Midazolam was found to increase treatment visit success rates in the present study."( Oral midazolam in pediatric dentistry.
Naqvi, A, 1996
)
1.53
"Midazolam can produce antinociceptive effects when used via intrathecal or epidural routes. "( Histological changes following epidural injection of midazolam in the neonatal rabbit.
Bozkurt, P; Kaya, G; Okar, I; Tunali, Y, 1997
)
1.99
"Midazolam may inhibit morphine tolerance and dependence by reversing some of the changes induced in met-enkephalin levels in brain by morphine in morphine tolerant and dependent animals."( Met-enkephalin alteration in the rat during chronic injection of morphine and/or midazolam.
Rattan, AK; Tejwani, GA, 1997
)
1.24
"Midazolam can produce useful amnesia in many patients and the memory loss can be high for both artificial and procedural stimuli. "( Memory and midazolam conscious sedation.
Coulthard, P; Nadin, G,
)
1.96
"Midazolam is known to cause a dose-dependent increase and decrease in the contractile force of the myocardium. "( Midazolams cardiac depressant effects and their lack of reversal by flumazenil in isolated rabbit hearts.
Aran, G; Guven, H; Kalkan, S; Ozturk, T; Tuncok, Y, 1999
)
3.19
"Midazolam produced lower SaO(2) values during colonoscopy compared with placebo or control groups (p < 0.001, repeated measures analysis of variance). "( Conscious sedation and cardiorespiratory safety during colonoscopy.
Hartikainen, J; Heikkinen, M; Janatuinen, E; Julkunen, R; Laitinen, T; Mattila, M; Ristikankare, M; Wang, SX, 2000
)
1.75
"Midazolam level was lower than that of sedation level."( [Epidural administration of midazolam with saline or bupivacaine for postoperative pain].
Hirasaki, A; Kobayashi, O; Mikane, T; Nishiyama, T; Odaka, Y; Seto, K, 1991
)
1.3
"Midazolam appeared to produce slightly greater hypoxaemia with 57% having falls in oxygen saturation of greater than 2.5% compared with only 35% given an equivalent dose of diazepam."( A comparison of diazepam and midazolam as endoscopy premedication assessing changes in ventilation and oxygen saturation.
Bell, GD; Coady, T; Lee, J; Logan, RF; Morden, A, 1988
)
1.29
"For midazolam, an increase in the elimination half-life and the apparent volume of distribution was positively correlated to an increase of body-weight."( Pharmacokinetics of midazolam and alfentanil in outpatient general anesthesia. A study with concomitant thiopentone, flumazenil or placebo administration.
Hole, A; Nilsen, OG; Raeder, JC, 1988
)
1.08
"Midazolam was found to produce the greatest degree of amnesia and sedation at the time of anaesthetic induction and triazolam was found to have the greatest degree of residual sedation at the time of discharge, four hours postoperatively."( Placebo controlled comparison of midazolam, triazolam and diazepam as oral premedicants for outpatient anaesthesia.
Forrest, P; Galletly, DC; Yee, P, 1987
)
1.28

Treatment

Midazolam treatment significantly downregulated Adora2b or Per2 mRNA in the hippocampus of C57BL/6J mice, and hippocampal PER2 protein expression or T-maze alternation was significantly reduced. MidazolAm pretreatment did not affect heroin-induced brain hypoxia but potentiated the initial hypothermia induced by heroin.

ExcerptReferenceRelevance
"Midazolam-treated rats had significant neuronal degeneration in limbic structures, mainly at one month postexposure, followed by neuronal loss in the basolateral amygdala and the CA1 hippocampal area."( Delayed tezampanel and caramiphen treatment but not midazolam protects against long-term neuropathology after soman exposure.
Apland, JP; Aroniadou-Anderjaska, V; Braga, MF; Figueiredo, TH; Rossetti, K, 2023
)
1.88
"Midazolam treated C57BL/6J mice were analyzed for Adora2b hippocampal mRNA expression levels, and spontaneous T-maze alternation was determined in Adora2b-/- mice. "( A Role for the Adenosine ADORA2B Receptor in Midazolam Induced Cognitive Dysfunction.
Eckle, T; Gile, J; Oyama, Y; Shuff, S, 2020
)
2.26
"Midazolam treatment significantly downregulated Adora2b or Per2 mRNA in the hippocampus of C57BL/6J mice, and hippocampal PER2 protein expression or T-maze alternation was significantly reduced in Adora2b-/- mice. "( A Role for the Adenosine ADORA2B Receptor in Midazolam Induced Cognitive Dysfunction.
Eckle, T; Gile, J; Oyama, Y; Shuff, S, 2020
)
2.26
"midazolam as first-line treatment for seizures."( Midazolam as a first-line treatment for neonatal seizures: Retrospective study.
Dao, K; Diezi, M; Giannoni, E; Lebon, S; Roulet-Perez, E, 2018
)
2.64
"Midazolam treatment could alleviate the neuronal death and promote the neuronal maturation in hippocampal neurons in vitro."( Midazolam prevents sevoflurane-induced death in hippocampal neurons.
Cui, C; Long, R; Ma, J; Yu, D; Zhu, Y, 2019
)
2.68
"Midazolam pretreatment did not affect heroin-induced brain hypoxia but potentiated the initial hypothermia induced by heroin."( Interactions of benzodiazepines with heroin: Respiratory depression, temperature effects, and behavior.
Afzal, A; Kiyatkin, EA, 2019
)
1.24
"In midazolam (10 mg/kg) treated rats, clonic seizures were observed 25 min after drug administration and the number of rats exhibiting clonic seizures was highest within 40 min."( Comparison between the effect of propofol and midazolam on picrotoxin-induced convulsions in rat.
Abdel Razzak, RL; Alzoubi, KH; Hasan, ZA, 2014
)
1.17
"Midazolam-treated patients were intubated only when necessary, whereas barbiturate coma therapy patients were routinely intubated."( Midazolam fails to prevent neurological damage in children with convulsive refractory febrile status epilepticus.
Fujita, K; Maruyama, A; Nagase, H; Nakagawa, T; Nishiyama, M; Saji, Y, 2014
)
2.57
"Midazolam treatment decreased GM1 expression in the detergent-resistant membrane microdomains of neurons, and these effects were regulated by the gamma-aminobutyric acid-A receptor."( Midazolam inhibits the formation of amyloid fibrils and GM1 ganglioside-rich microdomains in presynaptic membranes through the gamma-aminobutyric acid A receptor.
Arima, H; Hirate, H; Kusama, N; Sobue, K; Sugiura, T; Suzuki, K; Yamamoto, N, 2015
)
2.58
"Midazolam treatment resulted on average in a statistically significant reduction of the BIS values (-4.5, 95% CI -7.0 to -2.0), whereas morphine and haloperidol did not."( Bispectral Index Monitoring in Terminally Ill Patients: A Validation Study.
Baar, FP; Blussé van Oud-Alblas, HJ; Ista, E; Masman, AD; Tibboel, D; van Dijk, M; van Rosmalen, J, 2016
)
1.16
"No midazolam and diazepam treatment related adverse events were observed."( [A control study on the treatment of acute seizures with midazolam and diazepam in children].
Tang, RH; Zhou, JB, 2010
)
1.12
"Midazolam-treated DCs impaired the induction of contact-hypersensitivity response."( Midazolam suppresses maturation of murine dendritic cells and priming of lipopolysaccharide-induced t helper 1-type immune response.
Fujino, Y; Mashimo, T; Ohashi, Y; Ohta, N; Takayama, C, 2011
)
2.53
"Mean midazolam pretreatment dose was 0.09 ± 0.02 mg/kg and did not correlate with measured opening pressure."( Pretreatment with midazolam blunts the rise in intracranial pressure associated with ketamine sedation for lumbar puncture in children.
Berkenbosch, JW; Michalczyk, K; Sullivan, JE, 2013
)
1.18
"Midazolam-pretreatment inhibited the increase of Fos protein expression, not cyclic AMP content, in rat spinal cord during morphine withdrawal."( Pretreatment with midazolam suppresses morphine withdrawal response in mice and rats.
Cao, JL; Ding, HL; Duan, SM; Zeng, YM; Zhang, LC, 2002
)
1.37
"midazolam treatment (0.09 mg/kg) has a pain-reducing effect after third molar surgery, thus improving postoperative pain management."( Sedation with midazolam leads to reduced pain after dental surgery.
Ong, CK; Seymour, RA; Tan, JM, 2004
)
1.41
"The midazolam-treated patients had a numerically lower mean pain score (1.5 +/- 0.4 vs 4.0 +/- 0.7) (mean +/- SEM) (P = 0.07) and significantly lower mean memory score (4.8 +/- 0.7 vs 9.9 +/- 0.1) (P < 0.01) than the untreated patients."( Midazolam sedation for percutaneous liver biopsy.
Alexander, JA; Smith, BJ, 1993
)
2.21
"Midazolam and placebo treatments were randomized and blinded to the investigators."( Thiamylal-sparing effect of midazolam for canine endotracheal intubation. A clinical study of 118 dogs.
Benson, GJ; Greene, SA; Hartsfield, SM,
)
1.15
"Midazolam-treated patients used significantly larger amounts of drug for similar levels of sedation and anxiolysis (14.4 +/- 1.2 mg/8 hrs vs."( Lorazepam and midazolam in the intensive care unit: a randomized, prospective, multicenter study of hemodynamics, oxygen transport, efficacy, and cost.
Boysen, PG; Cernaianu, AC; Cilley, JH; DelRossi, AJ; Flum, DR; Grosso, MA; Ross, SE; Vassilidze, TV, 1996
)
1.38
"Midazolam pretreatment produced transient decreases in blood pressure and the bispectral index."( The bispectral index during induction of anesthesia with midazolam and propofol.
Albrecht, RF; Hoffman, WE; Zsigmond, E, 1996
)
1.26
"Midazolam-saline-treated animals showed a significant increase in beta-endorphin levels only in the medulla, and a decrease in its levels in hippocampus, striatum, and adrenals."( Effect of chronic treatment with morphine, midazolam, and both together on beta-endorphin levels in the rat.
Rattan, AK; Tejwani, GA, 1996
)
1.28
"Midazolam treatment (0.1-1.0 mg/kg) had no effect on the reinforcing impact of an appetitive CS."( Symmetrical effects of amphetamine and alpha-flupenthixol on conditioned punishment and conditioned reinforcement: contrasts with midazolam.
Everitt, BJ; Killcross, AS; Robins, TW, 1997
)
1.22
"The midazolam treated animals showed a significant decrease in dynorphin(1-13) levels in the cortex, cerebellum, cervical region of spinal cord, heart and adrenals, and a significant increase in the hypothalamus, striatum and lumbar region of the spinal cord."( Effect of chronic treatment with morphine, midazolam and both together on dynorphin(1-13) levels in the rat.
Rattan, AK; Tejwani, GA, 1997
)
1.04
"Midazolam treated animals showed a significant decrease in met-enkephalin levels in the pituitary (63%), cortex (39%), medulla (58%), kidneys (36%), heart (36%) and adrenals (43%), and a significant increase in met-enkephalin levels in the striatum (54%) and pons (51%)."( Met-enkephalin alteration in the rat during chronic injection of morphine and/or midazolam.
Rattan, AK; Tejwani, GA, 1997
)
1.24
"Midazolam is a valuable treatment option for refractory status epilepticus, especially in pediatric patients."( Use of midazolam for refractory status epilepticus in pediatric patients.
Pellock, JM, 1998
)
1.48
"In midazolam pre-treated rats the maximum EEG effect was reduced by 51 +/- 23 microV from the original value of 109 +/-15 microV in vehicle treated group."( Mechanism-based modeling of functional adaptation upon chronic treatment with midazolam.
Cleton, A; Danhof, M; Ghijsen, W; Odman, J; Van der Graaf, PH; Voskuyl, R, 2000
)
1.05
"Midazolam pretreatment was associated with a significant reduction in propofol dose requirement in both younger and older patients."( Effect of midazolam pretreatment on induction dose requirements of propofol in combination with fentanyl in younger and older adults.
Bhaskaran, NC; Claydon, P; Cressey, DM; Reilly, CS, 2001
)
1.43
"Midazolam-treated patients were more cooperative with a mask induction of anesthesia compared with non-midazolam-treated children (83% vs 56%)."( Oral midazolam in children: effect of time and adjunctive therapy.
Watcha, MF; Weldon, BC; White, PF, 1992
)
1.52
"Midazolam treatment resulted in significantly greater reductions in self-ratings of bodily symptoms of anxiety, shaking and trembling compared with the control (local anaesthetic) group."( Amnesia for dental procedures and mood change following treatment with nitrous oxide or midazolam.
Easton, P; File, SE; Skelly, AM, 1991
)
1.22
"Midazolam-treated rabbits showed significant changes in both BBB and light microscopy studies."( Ketamine and midazolam neurotoxicity in the rabbit.
Cozian, A; Lepage, JY; Malinovsky, JM; Mussini, JM; Pinaud, M; Souron, R, 1991
)
1.37
"In midazolam treated group, no arrhythmias were observed at the time of intubation."( [Midazolam for rapid sequence induction].
Goto, I; Hirasaki, A; Nishiyama, T; Odaka, Y; Seto, K, 1990
)
1.7
"Pretreatment with midazolam reversed H/R-induced apoptosis and downregulation of EAAT2 mRNA and protein expression in the hippocampus."( Midazolam contributes to neuroprotection against hypoxia/reoxygenation-induced brain injury in neonatal rats via regulation of EAAT2.
Dong, Y; Liu, H; Ma, C; Shan, Y; Sun, S; Tang, Z; Yang, F; Zhang, Y, 2020
)
2.32
"Rats treated with midazolam, nitrous oxide, and isoflurane exhibited a significant increase in rapid eye movement sleep three weeks later when compared with control rats, regardless of whether they were treated for 2 h (174.0 ± 7.2 min in anesthetized, 108.6 ± 5.3 in controls, P < 0.0001) or 6 h (151.6 ± 9.9 min in anesthetized, 108.8 ± 7.1 in controls, P = 0.002)."( Disruption of Rapid Eye Movement Sleep Homeostasis in Adolescent Rats after Neonatal Anesthesia.
Atluri, N; Beenhakker, MP; Goodkin, HP; Keller, C; Lunardi, N; Salvati, KA; Sica, R; Zuo, Z, 2019
)
0.85
"Treatment with midazolam, nitrous oxide, and isoflurane on postnatal day 7 increases rapid eye movement sleep three weeks later in rats."( Disruption of Rapid Eye Movement Sleep Homeostasis in Adolescent Rats after Neonatal Anesthesia.
Atluri, N; Beenhakker, MP; Goodkin, HP; Keller, C; Lunardi, N; Salvati, KA; Sica, R; Zuo, Z, 2019
)
0.87
"The treatments of midazolam inhibited cell viability to 85%-16% respectively (p < 0.05). "( Midazolam suppresses osteogenic differentiation of human bone marrow-derived mesenchymal stem cells.
Chen, RF; Kuang, LT; Shao, H; Xiu, HH; Xu, KQ; Zhang, T, 2014
)
2.18
"Treatment with midazolam is advisable for headaches in patients with MELAS, in the event that L-arginine therapy is unsuccessful."( [Effectiveness of midazolam for L-arginine-resistant headaches during stroke-like episodes in MELAS: a case report].
Hasegawa, Y; Hoshiyama, M; Tsujikawa, K; Yanagi, T; Yasui, K; Yokoi, S, 2014
)
1.08
"Pretreatment with midazolam 6 h prior to TMZ incubation reduced cytotoxic effects (IC25 1005 ± 197 μM; IC50 1676 ± 557 μM; P < 0.05) compared to incubation with TMZ alone (IC25 449 ± 304 μM; IC50 925 ± 196 μM) and reduced the antiproliferative effect of TMZ (1000 μM) by 43.9 % (P < 0.05)."( Pretreatment but not subsequent coincubation with midazolam reduces the cytotoxicity of temozolomide in neuroblastoma cells.
Bauer, I; Braun, S; Pannen, B; Werdehausen, R, 2015
)
0.99
"Pretreatment with midazolam reduces the cytotoxic and antiproliferative effects of TMZ without interfering with G2/M cell cycle arrest."( Pretreatment but not subsequent coincubation with midazolam reduces the cytotoxicity of temozolomide in neuroblastoma cells.
Bauer, I; Braun, S; Pannen, B; Werdehausen, R, 2015
)
0.99
"Treated with midazolam, DCs also secreted less interleukin-12 p40."( Midazolam suppresses maturation of murine dendritic cells and priming of lipopolysaccharide-induced t helper 1-type immune response.
Fujino, Y; Mashimo, T; Ohashi, Y; Ohta, N; Takayama, C, 2011
)
2.16
"Mice treated with midazolam had significantly lower serum IL-1β (p=0.002), TNF-α (p=0.002), IL-6 (p=0.016), IL-10 (p=0.009), and TGF-β (p=0.004) than saline-treated mice, with little impact on serum chemokine levels."( The burn wound inflammatory response is influenced by midazolam.
Babcock, GF; Dugan, A; Hernandez, L; Schwemberger, S; Yadav, E, 2012
)
0.95
"Pretreatment with midazolam lowered the number and incidence of naloxone-precipitated withdrawal jumping and prevented loss in body weight in chronic morphine-dependent mice (P<0.01)."( Pretreatment with midazolam suppresses morphine withdrawal response in mice and rats.
Cao, JL; Ding, HL; Duan, SM; Zeng, YM; Zhang, LC, 2002
)
0.97
"Pretreatment with midazolam prevented the facilitatory effects of those treatments."( Interaction between midazolam-induced anterograde amnesia and memory enhancement by treatments given immediately after training on an inhibitory avoidance task in rats.
Barichello, T; de-Paris, F; Kapczinski, F; Quevedo, J; Roesler, R; Vianna, MR, 2002
)
0.96
"Treatment with midazolam (1 mg/kg i.m.) 10 min after the onset of EGSA abolished EGSA within 389+/-181 s."( Nasal midazolam as a novel anticonvulsive treatment against organophosphate-induced seizure activity in the guinea pig.
Alkalai, D; Amitai, G; Brandeis, R; Cohen, G; Eshel, G; Gilat, E; Goldman, M; Lahat, E; Levy, A; Rabinovitz, I, 2003
)
1.14
"Pre-treatment with midazolam maleate, however, completely prevented the effects of the NO donor."( Benzodiazepine receptor and serotonin 2A receptor modulate the aversive-like effects of nitric oxide in the dorsolateral periaqueductal gray of rats.
Guimarães, FS; Moreira, FA, 2004
)
0.64
"Pretreatment with midazolam (MDZ), a positive modulator of GABAA sites, prevented the facilitating influence on fear memory of both stress and GABAA receptor blockade in the BLA."( Previous stress facilitates fear memory, attenuates GABAergic inhibition, and increases synaptic plasticity in the rat basolateral amygdala.
Carrer, HF; Isoardi, NA; Molina, VA; Rodríguez Manzanares, PA, 2005
)
0.65
"Pre-treatment with midazolam diminishes increased expression of cerebral endothelial intercellular adhesion molecule-1 and P-selectin expression following hypoxia-reoxygenation."( The effect of midazolam on cerebral endothelial (P-selectin and ICAM-1) adhesion molecule expression during hypoxia-reperfusion injury in vitro.
Ghori, K; Harmon, D; Lan, W; Seigne, P; Shorten, GD; Walsh, F, 2008
)
1.04
"In untreated rats, midazolam (100 microM) or verapamil (30 or 100 microM) added in the intestinal perfusate (single perfusion) decreased the exsorption clearance and biliary clearance of Rho123 by approximately 30 to 50%."( Pharmacokinetic interaction of cytochrome P450 3A-related compounds with rhodamine 123, a P-glycoprotein substrate, in rats pretreated with dexamethasone.
Murakami, T; Nagai, J; Nasu, R; Sanemasa, M; Takano, M; Yumoto, R, 2001
)
0.63
"Pretreatment with midazolam seemed to protect the patient from this undesirable reaction."( [Low-dose midazolam. Effect on the induction doses of fentanyl and on hemodynamics in the coronary patient].
Brasey, AM; Burgener, MH; Morel, D; Neidhart, P, 1988
)
1

Toxicity

Ongoing monitoring of this particular adverse event will be required with a sustained patient safety message to health services to maintain awareness of the issue and reduction in the number of midazolam-related errors.

ExcerptReferenceRelevance
"Isoflurane is a useful agent for prolonged sedation of ventilated patients and does not have any adverse effect on the cardiorespiratory system or on hepatic, renal or adrenal function."( Isoflurane for prolonged sedation in the intensive care unit; efficacy and safety.
Spencer, EM; Willatts, SM, 1992
)
0.28
" However, neurotoxicity studies are required before these agents can be considered safe for clinical use."( Ketamine and midazolam neurotoxicity in the rabbit.
Cozian, A; Lepage, JY; Malinovsky, JM; Mussini, JM; Pinaud, M; Souron, R, 1991
)
0.65
"Sedoanalgesia is a technique developed to provide safe and satisfactory operating conditions for a wide range of patients independent of age and overall level of fitness (although its use in children remains to be established)."( Sedoanalgesia in urology: a safe, cost-effective alternative to general anaesthesia. A review of 1020 cases.
Anson, KM; Birch, BR; Miller, RA, 1990
)
0.28
" No marked adverse reactions were found in any area for any group."( Clinical safety of flurazepam and midazolam during 14-day use in chronic insomniacs.
Hauri, P; Kripke, D; Roehrs, T; Sateia, MJ, 1990
)
0.56
" Basic principles of safe intravenous sedation and colonoscopy were followed strictly."( Office colonoscopy--a safe procedure in selected patients.
Christensen, JB; Christensen, MA; Perry, RE; Thorson, AG, 1989
)
0.28
" Twenty minutes later 2 X LD50 of paraoxon was injected sc and the incidence of seizures and death were recorded for 24 hr."( Comparative effects of diazepam and midazolam on paraoxon toxicity in rats.
Domino, EF; Krutak-Krol, H, 1985
)
0.54
"05 mg/kg to provide a safe outpatient intravenous sedative technique."( Nalbuphine combined with midazolam for outpatient sedation. An assessment of safety in volunteers.
Cole, PV; Sury, MR, 1988
)
0.58
"The LD50 in the rat and the mouse is about 1600 mg/kg (oral administration) and 75 mg/kg (rat) and 50 mg/kg (mouse) on intravenous administration."( Safety aspects of midazolam.
Schläppi, B, 1983
)
0.6
"To determine which of atracurium or vecuronium is associated with fewer adverse cardiovascular and pulmonary events in high-risk patients, the authors administered these drugs to patients with known asthma."( Atracurium versus vecuronium in asthmatic patients. A blinded, randomized comparison of adverse events.
Caldwell, JE; Fisher, DM; Lau, M, 1995
)
0.29
"1 mg/kg vecuronium over 5-10 s, and a blinded observer recorded cardiovascular, pulmonary, and cutaneous signs of adverse reactions for 6 min."( Atracurium versus vecuronium in asthmatic patients. A blinded, randomized comparison of adverse events.
Caldwell, JE; Fisher, DM; Lau, M, 1995
)
0.29
" The incidence of noncardiovascular adverse events (increase in peak airway pressure > 5 cmH2O, tidal volume decrease > 10%, rashes, and wheezing) did not differ between atracurium (17%) and vecuronium (7%)."( Atracurium versus vecuronium in asthmatic patients. A blinded, randomized comparison of adverse events.
Caldwell, JE; Fisher, DM; Lau, M, 1995
)
0.29
"The authors conclude that, in patients with asthma, adverse cardiovascular events are more common with atracurium than with vecuronium."( Atracurium versus vecuronium in asthmatic patients. A blinded, randomized comparison of adverse events.
Caldwell, JE; Fisher, DM; Lau, M, 1995
)
0.29
"Midazolam is a relatively short-acting water-soluble benzodiazepine that provides anxiolysis and anterograde amnesia and can be given orally with few adverse effects."( Premedication with oral midazolam for voiding cystourethrography in children: safety and efficacy.
Elder, JS; Longenecker, R, 1995
)
2.04
"In children who have been or are likely to be excessively frightened during cystourethrography or nuclear cystography, midazolam usually provides satisfactory amnesia and anxiolysis with few side effects or adverse impact on voiding dynamics."( Premedication with oral midazolam for voiding cystourethrography in children: safety and efficacy.
Elder, JS; Longenecker, R, 1995
)
0.81
" The overall incidence of adverse effects to midazolam in the patients studied was 17%."( A prospective study of the adverse effects of midazolam on withdrawal in critically ill children.
Billingham, I; Choonara, I; Gill, A; Hughes, J; Leach, HJ; Nunn, AJ; Ratcliffe, J; Thornington, R, 1994
)
0.81
" Effectiveness of the sedation, recovery time, and adverse events associated with the sedative regimen were documented."( Efficacy and safety of intravenous midazolam and ketamine as sedation for therapeutic and diagnostic procedures in children.
Giugliano, D; Mahan, RA; Parker, MM; Parker, RI, 1997
)
0.57
" This side effect resolved spontaneously after 5 to 10 minutes in one patient and was effectively treated with diphenhydramine hydrochloride in the other."( Efficacy and safety of intravenous midazolam and ketamine as sedation for therapeutic and diagnostic procedures in children.
Giugliano, D; Mahan, RA; Parker, MM; Parker, RI, 1997
)
0.57
"This sedative regimen of intravenous midazolam and ketamine was found to be safe and effective."( Efficacy and safety of intravenous midazolam and ketamine as sedation for therapeutic and diagnostic procedures in children.
Giugliano, D; Mahan, RA; Parker, MM; Parker, RI, 1997
)
0.85
" Hiccups, cough, nausea, and vomiting are the most commonly reported adverse effects."( Midazolam: a review of therapeutic uses and toxicity.
Clark, RF; Nordt, SP,
)
1.57
" There were no serious adverse effects related to the study drug, and minor adverse effects were similar for the 2 groups."( Safety and efficacy of flumazenil in reversing conscious sedation in the emergency department. Emergency Medicine Conscious Sedation Study Group.
Chudnofsky, CR, 1997
)
0.3
"Flumazenil is safe and efficacious in reversing midazolam-induced sedation in ED patients given a combination of fentanyl and midazolam to facilitate the performance of a short, painful procedure."( Safety and efficacy of flumazenil in reversing conscious sedation in the emergency department. Emergency Medicine Conscious Sedation Study Group.
Chudnofsky, CR, 1997
)
0.55
" Thirty-seven of 107 patients (35%) experienced a total of 56 adverse events, most of which were considered to be unrelated to flumazenil administration."( Safety and efficacy of flumazenil in the reversal of benzodiazepine-induced conscious sedation. The Flumazenil Pediatric Study Group.
Albers, G; Burkhart, K; Hoffman, J; Kelley, M; Liebelt, E; Massarella, J; McCubbin, MM; Shannon, M, 1997
)
0.3
"Flumazenil promptly and effectively reverses the central nervous system depressant effects of midazolam in children undergoing conscious sedation, with no significant adverse effects."( Safety and efficacy of flumazenil in the reversal of benzodiazepine-induced conscious sedation. The Flumazenil Pediatric Study Group.
Albers, G; Burkhart, K; Hoffman, J; Kelley, M; Liebelt, E; Massarella, J; McCubbin, MM; Shannon, M, 1997
)
0.52
" The incidence of adverse events during the sedation period was also similar."( Propofol versus midazolam: safety and efficacy for sedating the severe trauma patient.
Alted-Lopez, E; Ambros-Checa, A; Caballero-Cubedo, RE; Cantalapiedra-Santiago, JA; Perez-Vela, JL; Sanchez-Izquierdo-Riera, JA, 1998
)
0.65
"Cardiopulmonary adverse effects are commonly observed in patients undergoing colonoscopy with sedation."( Complications and adverse effects of colonoscopy with selective sedation.
Bernhard, G; Eckardt, AJ; Eckardt, VF; Kanzler, G; Schmitt, T, 1999
)
0.3
" Additional adverse effects occurring during or after the procedure were noted in the patients' protocol."( Complications and adverse effects of colonoscopy with selective sedation.
Bernhard, G; Eckardt, AJ; Eckardt, VF; Kanzler, G; Schmitt, T, 1999
)
0.3
" Adverse effects occurred in 59 patients (2."( Complications and adverse effects of colonoscopy with selective sedation.
Bernhard, G; Eckardt, AJ; Eckardt, VF; Kanzler, G; Schmitt, T, 1999
)
0.3
" If selective sedation is used, cardiopulmonary adverse effects occur in approximately 2% of all patients, most of whom require no medical intervention."( Complications and adverse effects of colonoscopy with selective sedation.
Bernhard, G; Eckardt, AJ; Eckardt, VF; Kanzler, G; Schmitt, T, 1999
)
0.3
"Intravenous sedation with propofol for ERCP is (1) more effective than sedation with midazolam, (2) safe under adequate patient monitoring, and (3) associated with a faster postprocedure recovery."( Efficacy and safety of intravenous propofol sedation during routine ERCP: a prospective, controlled study.
Caspary, WF; Kokabpick, S; Lembcke, B; Seifert, H; Wehrmann, T, 1999
)
0.53
"To determine the adverse event and complication rate for the use of procedural sedation and analgesia for painful procedures and diagnostic imaging studies performed in a pediatric emergency department."( Adverse events of procedural sedation and analgesia in a pediatric emergency department.
Krauss, B; Peña, BM, 1999
)
0.3
" Adverse events and complications were recorded."( Adverse events of procedural sedation and analgesia in a pediatric emergency department.
Krauss, B; Peña, BM, 1999
)
0.3
"3%) experienced adverse events, which included oxygen desaturation less than 90% requiring intervention (10 patients) [supplemental oxygen (9), bag-mask ventilation (1)], paradoxical reactions (7), emesis (3), paradoxical reaction and oxygen desaturation requiring supplemental oxygen (2), apnea requiring bag-mask ventilation (1), laryngospasm requiring bag-mask ventilation (1), bradycardia (1), stridor and emesis (1) and oxygen desaturation requiring bag-mask ventilation with subsequent emesis (1)."( Adverse events of procedural sedation and analgesia in a pediatric emergency department.
Krauss, B; Peña, BM, 1999
)
0.3
"Although sedation-related adverse events in children in the hospital setting have been extensively reported, limited data are available regarding adverse events after discharge home."( Prolonged recovery and delayed side effects of sedation for diagnostic imaging studies in children.
Malviya, S; Prochaska, G; Tait, AR; Voepel-Lewis, T, 2000
)
0.31
" Demographics, sedative(s) administered, and adverse events including hypoxemia (decrease in SpO(2) by >/=10% of baseline) and sedation events such as inadequate, failed, or excessive sedation, were documented on the institutional quality assurance tool."( Prolonged recovery and delayed side effects of sedation for diagnostic imaging studies in children.
Malviya, S; Prochaska, G; Tait, AR; Voepel-Lewis, T, 2000
)
0.31
" However, colonoscopy proved to be a safe procedure both with and without sedation."( Conscious sedation and cardiorespiratory safety during colonoscopy.
Hartikainen, J; Heikkinen, M; Janatuinen, E; Julkunen, R; Laitinen, T; Mattila, M; Ristikankare, M; Wang, SX, 2000
)
0.31
"Propofol's new preparation is safe when used in severely traumatized patients."( Midazolam and 2% propofol in long-term sedation of traumatized critically ill patients: efficacy and safety comparison.
Alted Lopez, E; Peinado Rodriguez, J; Sa Borges, M; Sanchez-Izquierdo Riera, JA; Sandiumenge Camps, A; Toral Vazquez, D, 2000
)
1.75
" Pharmacological strategies used in outpatient dental settings must be both safe and effective."( Comparing efficacy and safety of four intravenous sedation regimens in dental outpatients.
Beirne, OR; Dionne, RA; Gonty, A; Moore, PA; Yagiela, JA; Zuniga, J, 2001
)
0.31
"These data provide evidence that the drugs and doses evaluated resulted in therapeutic benefit to dental outpatients, with minimal incidence of potentially serious adverse effects."( Comparing efficacy and safety of four intravenous sedation regimens in dental outpatients.
Beirne, OR; Dionne, RA; Gonty, A; Moore, PA; Yagiela, JA; Zuniga, J, 2001
)
0.31
"To identify rates of adverse events associated with the use of conscious sedation in interventional radiology."( Safety of conscious sedation in interventional radiology.
Arepally, A; Kirkwood, S; Oechsle, D; Savader, SJ,
)
0.13
" Adverse events were categorized as respiratory, sedative, or major adverse events."( Safety of conscious sedation in interventional radiology.
Arepally, A; Kirkwood, S; Oechsle, D; Savader, SJ,
)
0.13
"The frequency of adverse events is low with the use of conscious sedation during interventional procedures."( Safety of conscious sedation in interventional radiology.
Arepally, A; Kirkwood, S; Oechsle, D; Savader, SJ,
)
0.13
"To determine the safety and efficacy of midazolam premedication to minimize the subjective adverse effects of adenosine."( Randomized controlled trial of midazolam premedication to reduce the subjective adverse effects of adenosine.
Hourigan, C; Jacobs, I; Lockney, A; Rogers, I; Safih, S, 2001
)
0.86
" Side-effect recall was judged by a questionnaire at 1 h and 24 h postadenosine administration."( Randomized controlled trial of midazolam premedication to reduce the subjective adverse effects of adenosine.
Hourigan, C; Jacobs, I; Lockney, A; Rogers, I; Safih, S, 2001
)
0.6
" There were no adverse outcomes in any of the patients studied."( Randomized controlled trial of midazolam premedication to reduce the subjective adverse effects of adenosine.
Hourigan, C; Jacobs, I; Lockney, A; Rogers, I; Safih, S, 2001
)
0.6
"Co-administration of midazolam can safely reduce the recall of the unpleasant adverse effects of adenosine."( Randomized controlled trial of midazolam premedication to reduce the subjective adverse effects of adenosine.
Hourigan, C; Jacobs, I; Lockney, A; Rogers, I; Safih, S, 2001
)
0.92
"Intranasal midazolam administered using an atomizer is as safe (as assessed by physiologic parameters) and effective (as assessed by behavior ratings) as oral chloral hydrate/promethazine for conscious sedation of pediatric dental patients."( Comparing the safety, efficacy and recovery of intranasal midazolam vs. oral chloral hydrate and promethazine.
Briskie, DM; Dallman, JA; Ignelzi, MA,
)
0.77
"To determine the incidence of adverse events related to an endoscopy sedation regimen that included propofol, delivered by general practitioner (GP) sedationists."( Sedation for endoscopy: the safe use of propofol by general practitioner sedationists.
Chiragakis, L; Clarke, AC; Hillman, LC; Kaye, GL, 2002
)
0.31
"Audit of reports of sedation-related adverse events in patients undergoing endoscopy."( Sedation for endoscopy: the safe use of propofol by general practitioner sedationists.
Chiragakis, L; Clarke, AC; Hillman, LC; Kaye, GL, 2002
)
0.31
" There were 185 sedation-related adverse events (6."( Sedation for endoscopy: the safe use of propofol by general practitioner sedationists.
Chiragakis, L; Clarke, AC; Hillman, LC; Kaye, GL, 2002
)
0.31
"The GP sedationists encountered a low incidence of adverse events, which they managed effectively."( Sedation for endoscopy: the safe use of propofol by general practitioner sedationists.
Chiragakis, L; Clarke, AC; Hillman, LC; Kaye, GL, 2002
)
0.31
" We suggest that intravenous ketorolac combined with midazolam is a safe and effective anesthetic regiment for ESWL, particularly on ambulatory basis."( Effects of intravenous ketorolac and fentanyl combined with midazolam on analgesia and side effects during extracorporeal shock wave lithotripsy.
Cherng, CH; Ho, ST; Wong, CS; Yang, CP, 2002
)
0.81
" However, anecdotal reports suggest that their use in infants may be associated with serious adverse effects (AEs)."( Safety of benzodiazepines in newborns.
Klinger, G; Ng, E; Shah, V; Taddio, A,
)
0.13
" Ten (16%) of the infants had 14 documented adverse events: seizures (n = 6), hypotension (n = 5), and respiratory depression (n = 3)."( Safety of benzodiazepines in newborns.
Klinger, G; Ng, E; Shah, V; Taddio, A,
)
0.13
" Adverse reactions to midazolam have been described previously."( Central-nervous side effects of midazolam during transesophageal echocardiography.
Bartel, T; Eggebrecht, H; Erbel, R; Philipp, T; Wenzel, RR, 2002
)
0.91
"7%) clinically significant adverse effects to midazolam occurred."( Central-nervous side effects of midazolam during transesophageal echocardiography.
Bartel, T; Eggebrecht, H; Erbel, R; Philipp, T; Wenzel, RR, 2002
)
0.86
" The administration of the benzodiazepine antagonist flumazenil can reverse the adverse effects to midazolam successfully."( Central-nervous side effects of midazolam during transesophageal echocardiography.
Bartel, T; Eggebrecht, H; Erbel, R; Philipp, T; Wenzel, RR, 2002
)
0.81
" It is also safe and effective at the dosage studied in children undergoing MRI."( Efficacy and safety of rectal thiopental, intramuscular cocktail and rectal midazolam for sedation in children undergoing neuroimaging.
Alp, H; Altinkaynak, S; Güler, I; Orbak, Z, 2002
)
0.54
"This first randomized controlled multicenter trial on the use of xenon as an inhalational anesthetic confirms, in a large group of patients, that xenon in oxygen provides effective and safe anesthesia, with the advantage of a more rapid recovery when compared with anesthesia using isoflurane-nitrous oxide."( Multicenter randomized comparison of the efficacy and safety of xenon and isoflurane in patients undergoing elective surgery.
Del Turco, M; Erdmann, W; Giunta, F; Hammerle, AF; Nagele, P; Reyle-Hahn, M; Rossaint, R; Scherpereel, P; Scholz, J; Schulte Am Esch, J; Tenbrinck, R; Vallet, B, 2003
)
0.32
"Conscious intravenous sedation is a safe alternative method to general anaesthesia."( Continuous intravenous versus bolus parenteral midazolam: a safe technique for conscious sedation in plastic surgery.
Arscott, G; Bayat, A, 2003
)
0.58
" Because concern about delayed adverse effects commonly delays discharge after sedation, we attempted to establish the timing of adverse effects in our cohort of procedural sedations."( When is a patient safe for discharge after procedural sedation? The timing of adverse effect events in 1367 pediatric procedural sedations.
Azer, MM; Newman, DH; Pitetti, RD; Singh, S, 2003
)
0.32
" We determined the timing of serious (eg, hypoxia, stridor, hypotension) and other adverse effects from final medication administration and calculated adverse effect risk ratios in relation to sedation characteristics."( When is a patient safe for discharge after procedural sedation? The timing of adverse effect events in 1367 pediatric procedural sedations.
Azer, MM; Newman, DH; Pitetti, RD; Singh, S, 2003
)
0.32
"7%) adverse effects, of which 159 (11."( When is a patient safe for discharge after procedural sedation? The timing of adverse effect events in 1367 pediatric procedural sedations.
Azer, MM; Newman, DH; Pitetti, RD; Singh, S, 2003
)
0.32
"Adverse effects were common; however, serious adverse effects rarely occurred after 25 minutes from the final medication administration."( When is a patient safe for discharge after procedural sedation? The timing of adverse effect events in 1367 pediatric procedural sedations.
Azer, MM; Newman, DH; Pitetti, RD; Singh, S, 2003
)
0.32
" We characterize the fasting status of patients receiving procedural sedation and analgesia in a pediatric ED and assess the relationship between fasting status and adverse events."( Preprocedural fasting state and adverse events in children undergoing procedural sedation and analgesia in a pediatric emergency department.
Agrawal, D; Gupta, R; Krauss, B; Manzi, SF, 2003
)
0.32
" Preprocedural fasting state and adverse events were recorded."( Preprocedural fasting state and adverse events in children undergoing procedural sedation and analgesia in a pediatric emergency department.
Agrawal, D; Gupta, R; Krauss, B; Manzi, SF, 2003
)
0.32
" Seventy-seven adverse events occurred in 68 (6."( Preprocedural fasting state and adverse events in children undergoing procedural sedation and analgesia in a pediatric emergency department.
Agrawal, D; Gupta, R; Krauss, B; Manzi, SF, 2003
)
0.32
" There was no association between preprocedural fasting state and adverse events."( Preprocedural fasting state and adverse events in children undergoing procedural sedation and analgesia in a pediatric emergency department.
Agrawal, D; Gupta, R; Krauss, B; Manzi, SF, 2003
)
0.32
"We conclude that stepwise sedation is effective and safe in haemodialysis patients and leads to a complete amnesia for the procedure."( Stepwise sedation is safe and effective for the insertion of central venous catheters.
Bosch, FH; Schiltmans, SK, 2004
)
0.32
"The combination of midazolam and ketamine appears to provide safe and effective sedation for pediatric patients undergoing endoscopy."( Safety and effectiveness of ketamine as a sedative agent for pediatric GI endoscopy.
Dietrich, CL; Gilger, MA; Spearman, G; Spearman, RS; Wilsey, MJ; Zayat, MN, 2004
)
0.65
" In clinical practice, intrathecal midazolam (2 mg) did not increase adverse neurological symptoms compared with conventional therapies."( Intrathecal midazolam I: a cohort study investigating safety.
Goodchild, CS; Lai, C; Nadeson, R; Tucker, AP, 2004
)
0.98
" Analgesia-based sedation with remifentanil was very effective, well tolerated and had a similar adverse event and haemodynamic profile to those of hypnotic-based regimens when used in critically ill neuro-intensive care unit patients for up to 5 days."( Safety and efficacy of analgesia-based sedation with remifentanil versus standard hypnotic-based regimens in intensive care unit patients with brain injuries: a randomised, controlled trial [ISRCTN50308308].
Karabinis, A; Kirkham, AJ; Komnos, A; Mandragos, K; Soukup, J; Speelberg, B; Stergiopoulos, S, 2004
)
0.32
" The BIS offers an objective, safe and reliable measure of sedation, without disturbing either patient or operator."( Bispectral index monitoring for conscious sedation in intervention: better, safer, faster.
Bell, JK; England, RE; Laasch, HU; Martin, DF; Morris, JA; Wilbraham, L, 2004
)
0.32
"To compare the frequency and severity of adverse events associated with parenteral drugs commonly used for procedural sedation and analgesia (PSA) in a pediatric emergency department."( Adverse events associated with procedural sedation and analgesia in a pediatric emergency department: a comparison of common parenteral drugs.
Bajaj, L; Bothner, JP; Roback, MG; Wathen, JE, 2005
)
0.33
" A total of 458 adverse events were observed in 426 patients (17%)."( Adverse events associated with procedural sedation and analgesia in a pediatric emergency department: a comparison of common parenteral drugs.
Bajaj, L; Bothner, JP; Roback, MG; Wathen, JE, 2005
)
0.33
"Drug types used in pediatric PSA are associated with different adverse event profiles."( Adverse events associated with procedural sedation and analgesia in a pediatric emergency department: a comparison of common parenteral drugs.
Bajaj, L; Bothner, JP; Roback, MG; Wathen, JE, 2005
)
0.33
"The aim of the study was to evaluate adverse events related to the use of anesthesia and anesthetic procedures associated with interventional radiology."( Adverse effects of anesthesia in interventional radiology.
Derbent, A; Memiş, A; Oran, I; Parildar, M; Uyar, M; Yurtseven, T, 2005
)
0.33
"Interventional radiological procedures seem to be safe from an anesthesiologist's point of view."( Adverse effects of anesthesia in interventional radiology.
Derbent, A; Memiş, A; Oran, I; Parildar, M; Uyar, M; Yurtseven, T, 2005
)
0.33
"Continuous flow 50% nitrous oxide and oral midazolam are comparably safe and effective in reducing anxiety and distress during VCU in children older than 3 years."( Sedation during voiding cystourethrography: comparison of the efficacy and safety of using oral midazolam and continuous flow nitrous oxide.
Augarten, A; Ben-Shlush, A; Jacobson, JM; Keidan, I; Mor, Y; Weinberg, M; Zaslansky, R, 2005
)
0.81
" There were a total of 70 patients who had 77 adverse events."( Safety of intravenous sedation administered by the operating oral surgeon: the first 7 years of office practice.
Rodgers, SF, 2005
)
0.33
"The administration of intravenous sedation by the operating surgeon for outpatient oral surgery procedures is safe and results in a low incidence of adverse events."( Safety of intravenous sedation administered by the operating oral surgeon: the first 7 years of office practice.
Rodgers, SF, 2005
)
0.33
"5 million adverse drug reaction (ADR) reports for 8620 drugs/biologics that are listed for 1191 Coding Symbols for Thesaurus of Adverse Reaction (COSTAR) terms of adverse effects."( Assessment of the health effects of chemicals in humans: II. Construction of an adverse effects database for QSAR modeling.
Benz, RD; Contrera, JF; Kruhlak, NL; Matthews, EJ; Weaver, JL, 2004
)
0.32
" Although commonly accepted as a safe drug, midazolam produced adverse effects which could make early as well late treatment outcome worse."( [Midazolam--how safe is it in sedation of newborn?].
Gulczyńska, E, 2005
)
1.5
" Procedural sedation and analgesia (PSA) is the safe and effective control of pain, anxiety and motion so as to allow a necessary procedure to be performed and to provide an appropriate degree of memory loss or decreased awareness."( Safe and efficacious use of procedural sedation and analgesia by non-anesthesiologists in a pediatric hematology-oncology unit.
Advani, SH; Ambulkar, I; Borker, A; Gopal, R, 2006
)
0.33
" Adverse events occurred in 15 (27%) episodes and included transient drop in oxygen saturation, vomiting, dizziness and disinhibition with crying spells."( Safe and efficacious use of procedural sedation and analgesia by non-anesthesiologists in a pediatric hematology-oncology unit.
Advani, SH; Ambulkar, I; Borker, A; Gopal, R, 2006
)
0.33
"Procedural sedation and analgesia using midazolam and ketamine is a safe and efficient method of limiting anxiety and procedure related pain and can be successfully administered by non-anaesthesiologists."( Safe and efficacious use of procedural sedation and analgesia by non-anesthesiologists in a pediatric hematology-oncology unit.
Advani, SH; Ambulkar, I; Borker, A; Gopal, R, 2006
)
0.6
" The adverse events associated with this moderate sedation were assessed."( Safety and effectiveness of moderate sedation for radiologic non-vascular intervention.
Kim, TH,
)
0.13
"Moderate sedation allows performance of safe and effective radiologic non-vascular intervention, and it is also easy for an interventional radiologist to use."( Safety and effectiveness of moderate sedation for radiologic non-vascular intervention.
Kim, TH,
)
0.13
"It has been proposed that objective cognitive testing provides additional information to that collected via adverse event (AE) recordings."( Cognitive testing in early phase clinical trials: outcome according to adverse event profile in a Phase I study.
Collie, A; Darekar, MA; Huggins, JP; Maruff, P; Snyder, PJ, 2006
)
0.33
" However, gastroscopy proved to be a safe procedure both with and without sedation."( Sedation, topical pharyngeal anesthesia and cardiorespiratory safety during gastroscopy.
Hartikainen, J; Heikkinen, M; Julkunen, R; Laitinen, T; Mattila, M; Ristikankare, M; Wang, SX,
)
0.13
" The adverse event (AE) rate was 18% and included apnea (10%), inadequate sedation (3%), bradycardia (2%), desaturation (1%), hypotension (1%) and bag-valve-mask use (1%)."( Emergency department procedural sedation and analgesia: A Canadian Community Effectiveness and Safety Study (ACCESS).
Mensour, M; Michaud, J; Pineau, R; Sahai, V, 2006
)
0.33
"Procedural sedation was safe and effective in our environment."( Emergency department procedural sedation and analgesia: A Canadian Community Effectiveness and Safety Study (ACCESS).
Mensour, M; Michaud, J; Pineau, R; Sahai, V, 2006
)
0.33
" The recorded information included demographic, medication, and adverse event data."( Safety of intravenous midazolam and fentanyl for pediatric GI endoscopy: prospective study of 1578 endoscopies.
Cook-Sather, SD; Farace, L; Garofolo, M; Lachewitz, G; Liacouras, CA; Lombardi, S; Mamula, P; Markowitz, JE; Morgan, V; Neiswender, K; Nieberle, M; Puma, A; Sargent-Harkins, L; Trautwein, A; Wood, S; Zimmerman, A, 2007
)
0.65
"Description of adverse events relating to intravenous sedation."( Safety of intravenous midazolam and fentanyl for pediatric GI endoscopy: prospective study of 1578 endoscopies.
Cook-Sather, SD; Farace, L; Garofolo, M; Lachewitz, G; Liacouras, CA; Lombardi, S; Mamula, P; Markowitz, JE; Morgan, V; Neiswender, K; Nieberle, M; Puma, A; Sargent-Harkins, L; Trautwein, A; Wood, S; Zimmerman, A, 2007
)
0.65
" Serious adverse events (apnea) were noted in 2 patients (0."( Safety of intravenous midazolam and fentanyl for pediatric GI endoscopy: prospective study of 1578 endoscopies.
Cook-Sather, SD; Farace, L; Garofolo, M; Lachewitz, G; Liacouras, CA; Lombardi, S; Mamula, P; Markowitz, JE; Morgan, V; Neiswender, K; Nieberle, M; Puma, A; Sargent-Harkins, L; Trautwein, A; Wood, S; Zimmerman, A, 2007
)
0.65
"Intravenous sedation with midazolam and fentanyl is safe for pediatric GI endoscopy."( Safety of intravenous midazolam and fentanyl for pediatric GI endoscopy: prospective study of 1578 endoscopies.
Cook-Sather, SD; Farace, L; Garofolo, M; Lachewitz, G; Liacouras, CA; Lombardi, S; Mamula, P; Markowitz, JE; Morgan, V; Neiswender, K; Nieberle, M; Puma, A; Sargent-Harkins, L; Trautwein, A; Wood, S; Zimmerman, A, 2007
)
0.95
"This study strongly suggests that CO(2) insufflation is safe and effective during lengthy colonic endoscopic procedures, eg, ESD, with the patient under conscious sedation."( A pilot study to assess the safety and efficacy of carbon dioxide insufflation during colorectal endoscopic submucosal dissection with the patient under conscious sedation.
Emura, F; Ikehara, H; Kikuchi, T; Kozu, T; Mashimo, Y; Matsuda, T; Saito, D; Saito, Y; Uraoka, T, 2007
)
0.34
" At least in the case of colonoscopy, the associated use of midazolam allows the propofol dose to be decreased, thus, theoretically, reducing the drug's adverse effects."( [Safety of propofol administration by the staff of a gastrointestinal endoscopy unit].
Amorós, A; Aparicio, JR; Casellas, JA; Garmendia, M; Martínez, J, 2007
)
0.58
" Study outcome measures evaluated the level of sedation, length of procedure, sedation/recovery time, patient satisfaction, and adverse events."( A prospective safety study of a low-dose propofol sedation protocol for colonoscopy.
Baluyut, A; Scheidler, M; Sipe, BW; Wright, B, 2007
)
0.34
" No serious adverse events occurred."( A prospective safety study of a low-dose propofol sedation protocol for colonoscopy.
Baluyut, A; Scheidler, M; Sipe, BW; Wright, B, 2007
)
0.34
"This protocol for propofol administration is safe and effective for patients undergoing elective colonoscopy."( A prospective safety study of a low-dose propofol sedation protocol for colonoscopy.
Baluyut, A; Scheidler, M; Sipe, BW; Wright, B, 2007
)
0.34
" No adverse events were reported in the Fentanyl group, while in the Midazolam group a decrease in oxygen saturation was noted in 23/60 (35%) patients."( Single use of fentanyl in colonoscopy is safe and effective and significantly shortens recovery time.
Bakaloudis, T; Chatzopoulos, D; Dokas, S; Gavalas, E; Kountouras, J; Lazaraki, G; Metallidis, S; Zavos, C, 2007
)
0.57
"To synthesize the evidence comparing the adverse event (AE) profile and clinical effectiveness of midazolam and propofol for procedural sedation (PS) in adults in the emergency care setting."( Safety and clinical effectiveness of midazolam versus propofol for procedural sedation in the emergency department: a systematic review.
Anis, AH; Hohl, CM; Nosyk, B; Sadatsafavi, M, 2008
)
0.84
" Three emergency medicine journals, the Canadian Adverse Drug Reaction Newsletter, and conference proceedings were hand-searched."( Safety and clinical effectiveness of midazolam versus propofol for procedural sedation in the emergency department: a systematic review.
Anis, AH; Hohl, CM; Nosyk, B; Sadatsafavi, M, 2008
)
0.62
" The aim of this prospective observational audit was to evaluate our practice and report the occurrence of adverse events and behavioral reactions related to the use of ketamine, propofol, and midazolam combinations."( Adverse events and behavioral reactions related to ketamine based anesthesia for anorectal manometry in children.
Dalal, PG; Seth, N; Somerville, N; Taylor, D, 2008
)
0.54
" Intra- and postoperative adverse events, times to spontaneous awakening and discharge from the PACU were noted."( Adverse events and behavioral reactions related to ketamine based anesthesia for anorectal manometry in children.
Dalal, PG; Seth, N; Somerville, N; Taylor, D, 2008
)
0.35
" Secondary outcomes included adverse effects, hemodynamics alterations and recovery time."( To study the effectiveness and safety of ketamine and midazolam procedural sedation in the incision and drainage of abscesses in the adult emergency department.
Seet, CM; Sim, TB, 2008
)
0.59
" This paper proposes that the technique described is safe and effective in providing a good standard of dental care for adults with severe learning disability."( Retrospective audit of the efficacy and safety of the combined intranasal/intravenous midazolam sedation technique for the dental treatment of adults with learning disability.
Forbes, M; Lewis, DA; Manley, MC; Ransford, NJ; Thompson, SA, 2008
)
0.57
" The current practice of conscious sedation is safe and tolerated well by most adults in our population."( Tolerance and safety to colonoscopy with conscious sedation in Malaysian adults.
Goh, KL; Ma, WT; Mahadeva, S; Quek, KF, 2007
)
0.34
"Low-dose propofol sedation was safe and recovery including driving ability was with 60 min."( Safety and driving ability following low-dose propofol sedation.
Horiuchi, A; Ichise, Y; Katsuyama, Y; Nakayama, Y; Ohmori, S; Tanaka, N, 2008
)
0.35
" These included; introduction of a unit sedation policy, exchange of midazolam 10 mg vials to 5 mg repacked syringes, adverse events recording of midazolam use of greater than 5 mg and reversal agents, more stringent patient monitoring procedures and endoscopists education and feedback."( Safer sedation practice may not translate into improvements in endoscopic outcomes.
Azim, W; Bodger, K; Bowering, K; Sarkar, S, 2009
)
0.59
"23) and the adverse events (1."( Safer sedation practice may not translate into improvements in endoscopic outcomes.
Azim, W; Bodger, K; Bowering, K; Sarkar, S, 2009
)
0.35
"To identify clinically significant drug interactions and potentially related adverse drug events associated with the use of midazolam."( Midazolam-related drug interactions: detection of risk situations to the patient safety in a brazilian teaching hospital.
de Freitas, O; Kawano, DF; Pereira, LR; Sankarankutty, AK; Ueta, J, 2009
)
2
" Patients' orders were checked for the presence of clinically significant drug interactions and for the inclusion and discontinuation of potential trigger medications for adverse drug events related to midazolam."( Midazolam-related drug interactions: detection of risk situations to the patient safety in a brazilian teaching hospital.
de Freitas, O; Kawano, DF; Pereira, LR; Sankarankutty, AK; Ueta, J, 2009
)
1.98
" Analysis of inclusion and discontinuation of drugs demonstrated that the first order for opiates preceded the use of flumazenil in 31% of the cases and, except for tramadol, all opiates were discontinued after its administration, highlighting the potential of these drugs to act as triggers for adverse drug events."( Midazolam-related drug interactions: detection of risk situations to the patient safety in a brazilian teaching hospital.
de Freitas, O; Kawano, DF; Pereira, LR; Sankarankutty, AK; Ueta, J, 2009
)
1.8
"Midazolam-related drug interactions are not infrequent and may conduce to serious adverse drug events, including hypotension, respiratory depression, and arrest."( Midazolam-related drug interactions: detection of risk situations to the patient safety in a brazilian teaching hospital.
de Freitas, O; Kawano, DF; Pereira, LR; Sankarankutty, AK; Ueta, J, 2009
)
3.24
" We suggest that the performance of peripheral foot and ankle blocks with monitored intravenous sedation appears to be a safe and useful option for ASA 3 and 4 patients undergoing limb-preservation surgery."( Safety of local anesthesia combined with monitored intravenous sedation for American Society of Anesthesiologists 3 and 4 patients undergoing lower limb-preservation procedures.
Blume, P; Gesquire, M; Kodumudi, G; Mitra, S; Shelley, K; Vadivelu, N; Xia, Y,
)
0.13
"to determine whether a combination of intranasal midazolam (IN) and inhalation sedation with nitrous oxide and oxygen is a safe and practical alternative to DGA."( The safety and efficacy of intranasal midazolam sedation combined with inhalation sedation with nitrous oxide and oxygen in paediatric dental patients as an alternative to general anaesthesia.
Wood, M, 2010
)
0.89
"In selected cases this technique provides a safe and effective alternative to DGA and could reduce the number of patients referred to hospitals for DGA."( The safety and efficacy of intranasal midazolam sedation combined with inhalation sedation with nitrous oxide and oxygen in paediatric dental patients as an alternative to general anaesthesia.
Wood, M, 2010
)
0.63
"Based on our results, the ESDs for EGC performed under sedation using propofol continuous infusion were as safe as those performed using intermittent MDZ injection."( Safe and effective sedation in endoscopic submucosal dissection for early gastric cancer: a randomized comparison between propofol continuous infusion and intermittent midazolam injection.
Gotoda, T; Hirashima, T; Kiriyama, S; Kusano, C; Kuwano, H; Nishimoto, F; Oda, I; Sano, H, 2010
)
0.56
" No serious adverse events were noted during the study."( Human safety and pharmacokinetic study of intramuscular midazolam administered by autoinjector.
Atkinson, AJ; Burback, BL; Corwin, MJ; Hong, SP; Johnson, JD; Reichard, DW, 2010
)
0.61
" Adverse events and patient recall were similar in both groups."( A Phase IIIb, randomized, double-blind, placebo-controlled, multicenter study evaluating the safety and efficacy of dexmedetomidine for sedation during awake fiberoptic intubation.
Bekker, AY; Bergese, SD; Bokesch, PM; Candiotti, KA; Wisemandle, W; Zura, A,
)
0.13
" Overall, midazolam-ketamine provided safe and effective sedation for catheterization and intubation of both healthy and CI pigs."( Effective and safe anesthesia for Yorkshire and Yucatan swine with and without cardiovascular injury and intervention.
Abusakran-Monday, KA; Burkholder, TH; Foltz, CJ; Linkenhoker, JR; Linton, CG; Rosero, AP; Walden, A, 2010
)
0.76
"Retrograde ileoscopy via stoma is a safe and effective procedure for evaluating recurrence of CD of the neoterminal ileum."( Ileoscopy via stoma after diverting ileostomy: a safe and effective tool to evaluate for Crohn's recurrence of neoterminal ileum.
Alkhouri, N; Lopez, R; Mahajan, L; Shen, B; Vadlamudi, N, 2011
)
0.37
"To add to the evidence base for safe and effective paediatric conscious sedation techniques in primary dental care."( The safety and efficacy of using a concentrated intranasal midazolam formulation for paediatric dental sedation.
Wood, M, 2011
)
0.61
"In selected cases intranasal sedation provides a safe and effective alternative for dental GA in short invasive procedures limited to one or two quadrants in children."( The safety and efficacy of using a concentrated intranasal midazolam formulation for paediatric dental sedation.
Wood, M, 2011
)
0.61
"Sevoflurane is an effective and safe alternative to midazolam in ICU patients associated with a moderate increase in costs."( [Efficacy, safety and cost of sedation with sevoflurane in intensive care unit].
Arnal, JM; Bisbal, M; Corno, G; Demory, D; Donati, SY; Durand-Gasselin, J; Granier, I; Passelac, A; Sallée, M, 2011
)
0.62
"To provide data on the epidemiology of adverse events during sedation for endoscopy."( Adverse events during monitored anesthesia care for GI endoscopy: an 8-year experience.
Agostoni, M; Beretta, L; Fanti, L; Gemma, M; Pasculli, N; Testoni, PA, 2011
)
0.37
" Adverse events were defined as occurrences that warranted intervention and were classified as hypotension, desaturation, bradycardia, hypertension, arrhythmia, aspiration, respiratory depression, vomiting, cardiac arrest, respiratory arrest, angina, hypoglycemia, and/or allergic reaction."( Adverse events during monitored anesthesia care for GI endoscopy: an 8-year experience.
Agostoni, M; Beretta, L; Fanti, L; Gemma, M; Pasculli, N; Testoni, PA, 2011
)
0.37
" Adverse events were rare in both the adult (4."( Adverse events during monitored anesthesia care for GI endoscopy: an 8-year experience.
Agostoni, M; Beretta, L; Fanti, L; Gemma, M; Pasculli, N; Testoni, PA, 2011
)
0.37
"Deep sedation during endoscopic procedures is safe in both adults and children."( Adverse events during monitored anesthesia care for GI endoscopy: an 8-year experience.
Agostoni, M; Beretta, L; Fanti, L; Gemma, M; Pasculli, N; Testoni, PA, 2011
)
0.37
"57% of patients having complications (52 patients having 60 adverse events)."( Safety of intravenous sedation administered by the operating oral surgeon: the second 7 years of office practice.
Rodgers, MS; Rodgers, SF, 2011
)
0.37
" Eight patients developed adverse reactions, 3 of which required further evaluation in the emergency department."( Safety of deep sedation in an urban oral and maxillofacial surgery training program.
Braidy, HF; Singh, P; Ziccardi, VB, 2011
)
0.37
" By acting via the GABA(A) receptor, midazolam exerts its toxic effect through the suppression of neuronal Ca(2+)-oscillations, a reduction in synapsin expression and consecutively reduced synaptic integrity."( Toxic effects of midazolam on differentiating neurons in vitro as a consequence of suppressed neuronal Ca2+-oscillations.
Bein, T; Friedrich, O; Graf, BM; Sinner, B; Zausig, Y, 2011
)
0.98
" The rate of adverse events with conscious sedation has not been previously assessed in the interventional spine procedure setting."( Adverse events of conscious sedation in ambulatory spine procedures.
Marín, DR; Schaufele, MK; Simmons, AC; Tate, JL, 2011
)
0.37
"The goal of this study was to determine the rate of adverse events when using conscious sedation in the ambulatory interventional spine setting."( Adverse events of conscious sedation in ambulatory spine procedures.
Marín, DR; Schaufele, MK; Simmons, AC; Tate, JL, 2011
)
0.37
"The rate and type of adverse events were analyzed and compared between those who received conscious sedation with local anesthesia and those who received local anesthesia alone."( Adverse events of conscious sedation in ambulatory spine procedures.
Marín, DR; Schaufele, MK; Simmons, AC; Tate, JL, 2011
)
0.37
" Of these cases, 66 immediate adverse events (5."( Adverse events of conscious sedation in ambulatory spine procedures.
Marín, DR; Schaufele, MK; Simmons, AC; Tate, JL, 2011
)
0.37
"The findings of this study suggest that mild to moderate conscious sedation in interventional spine procedures is associated with low rates of adverse events when established protocols are followed."( Adverse events of conscious sedation in ambulatory spine procedures.
Marín, DR; Schaufele, MK; Simmons, AC; Tate, JL, 2011
)
0.37
"Midazolam + alfentanil and propofol are equally safe for sedation during bronchoscopy."( Propofol safety in bronchoscopy: prospective randomized trial using transcutaneous carbon dioxide tension monitoring.
Carmi, U; Fruchter, O; Kramer, MR; Rosengarten, D; Zemtzov, D, 2011
)
1.81
" The investigators conducted a review of procedural sedation forms for all pediatric and adult patients admitted to this burn center from January 1, 2005, through December 31, 2005, for demographic and clinical data including patient age, gender, body weight, TBSA, dates of burn injury and wound care procedures, length of procedure, pre- and postprocedural pain assessment, procedural sedation/analgesia medications and doses, adverse drug events, and related interventions."( Efficacy and safety of procedural sedation and analgesia for burn wound care.
Andrews, DD; Christ-Libertin, C; Thompson, EM,
)
0.13
"To compare the occurrence of post-discharge adverse events in children having received a high dose of either chloral hydrate (CH) or midazolam (MZ) during outpatient dental treatment."( Post-discharge adverse events following pediatric sedation with high doses of oral medication.
Bendo, CB; Brasileiro, SV; Costa, LR; Costa, PS; Paiva, SM; Viegas, CM, 2012
)
0.58
" During treatment, a single observer recorded intraoperative adverse events."( Post-discharge adverse events following pediatric sedation with high doses of oral medication.
Bendo, CB; Brasileiro, SV; Costa, LR; Costa, PS; Paiva, SM; Viegas, CM, 2012
)
0.38
"The most common intraoperative and post-discharge adverse events were hallucination (3."( Post-discharge adverse events following pediatric sedation with high doses of oral medication.
Bendo, CB; Brasileiro, SV; Costa, LR; Costa, PS; Paiva, SM; Viegas, CM, 2012
)
0.38
"High doses of CH were associated with post-discharge adverse events in children having undergone pediatric dental sedation, whereas high doses of MZ were not associated with these events in pediatric patients."( Post-discharge adverse events following pediatric sedation with high doses of oral medication.
Bendo, CB; Brasileiro, SV; Costa, LR; Costa, PS; Paiva, SM; Viegas, CM, 2012
)
0.38
" Remimazolam was well tolerated in all dose cohorts, and no serious adverse events (AEs) were reported."( A placebo- and midazolam-controlled phase I single ascending-dose study evaluating the safety, pharmacokinetics, and pharmacodynamics of remimazolam (CNS 7056): Part I. Safety, efficacy, and basic pharmacokinetics.
Antonik, LJ; Borkett, KM; Goldwater, DR; Kilpatrick, GJ; Tilbrook, GS, 2012
)
0.73
"The paper concerns the anesthetic aspects of safe conscious sedation and dental treatment of patients with metabolic syndrome."( [The improvement of safe sedation and dental treatment in patients with metabolic syndrome].
Dobrodeev, AS; Rabinovich, SA; Remez, GA, 2011
)
0.37
"Prolonged dexmedetomidine administration in children with heart disease appears to be safe and is associated with decreased opioid and benzodiazepine requirement and decreased inotropic support."( Safety and efficacy of prolonged dexmedetomidine use in critically ill children with heart disease*.
Gossett, JM; Gupta, P; Roth, SJ; Sabati, A; Tesoro, TM; Tobias, JD; Whiteside, W, 2012
)
0.38
"The objectives of this study were to describe the type and frequency of postdischarge adverse events related to sedation for elective diagnostic imaging in children and to determine if any patient or drug characteristics were associated with such adverse events."( Postdischarge adverse events related to sedation for diagnostic imaging in children.
Chen, X; Kaila, R; Kannikeswaran, N, 2012
)
0.38
" We administered a postdischarge adverse event questionnaire to families within 3 to 5 days after sedation to assess adverse events such as behavioral changes, vomiting, recovery time to baseline status, and need for medical follow-up."( Postdischarge adverse events related to sedation for diagnostic imaging in children.
Chen, X; Kaila, R; Kannikeswaran, N, 2012
)
0.38
"4% patients experienced postdischarge adverse events."( Postdischarge adverse events related to sedation for diagnostic imaging in children.
Chen, X; Kaila, R; Kannikeswaran, N, 2012
)
0.38
"Postdischarge adverse events related to sedation for diagnostic imaging are minor, mostly behavioral, but occur in a significant number of patients."( Postdischarge adverse events related to sedation for diagnostic imaging in children.
Chen, X; Kaila, R; Kannikeswaran, N, 2012
)
0.38
"The results of this study suggest that (a) etomidate is much safer than propofol for first-trimester surgical abortions and (b) using a lower dose of etomidate, supplemented with fentanyl and midazolam, is more beneficial than the use of etomidate with or without fentanyl in reducing adverse effects like myoclonus and postoperative nausea and vomiting."( A comparison of anesthetic regimens using etomidate and propofol in patients undergoing first-trimester abortions: double-blind, randomized clinical trial of safety and efficacy.
Chu, S; Deng, F; Wu, J; Wu, Z; Xia, G; Yao, S, 2013
)
0.58
" The purpose of this study was to evaluate the frequency of adverse events during IV conscious sedation provided by credentialed general dentists and periodontists in the United States Air Force (USAF)."( The rate of adverse events during IV conscious sedation.
Chong, CH; Hancock, RH; Hartup, GR; Schwamburger, NT; Vandewalle, KS,
)
0.13
"To assess the effects of lipid on ropivacaine-induced convulsion and LD50 in rats and compare with those of the traditional anticonvulsants midazolam and propofol."( [Effects of pretreatment of lipid, midazolam and propofol on ropivacaine-induced convulsion and LD50 in rats].
Lü, XL; Wan, FH; Zuo, YX, 2012
)
0.86
" Protocol 2: Additional 100 male SD rats were used for the measurements of ropivacaine LD50 with different pretreatments including lipid, midazolam, propofol and saline through the up-and-down method."( [Effects of pretreatment of lipid, midazolam and propofol on ropivacaine-induced convulsion and LD50 in rats].
Lü, XL; Wan, FH; Zuo, YX, 2012
)
0.86
" The LD50 of ropivacaine in group C was 64."( [Effects of pretreatment of lipid, midazolam and propofol on ropivacaine-induced convulsion and LD50 in rats].
Lü, XL; Wan, FH; Zuo, YX, 2012
)
0.66
" None of the patients experienced serious adverse events."( Efficacy and safety of ketamine in refractory status epilepticus in children.
Cecchi, C; Guerrini, R; Ilvento, L; L'Erario, M; Mirabile, L; Pisano, T; Rosati, A, 2012
)
0.38
"In this small, open-label, unblinded series with no concurrent control group, KE appears effective and safe in treating RSE in children."( Efficacy and safety of ketamine in refractory status epilepticus in children.
Cecchi, C; Guerrini, R; Ilvento, L; L'Erario, M; Mirabile, L; Pisano, T; Rosati, A, 2012
)
0.38
"Among the 149 patients included in the safety analysis set, 6 adverse reactions were reported in 6 patients."( [Safety and efficacy of midazolam in children under mechanical ventilation in the intensive care unit].
Lee, T; Miyasaka, K; Sogabe, K; Sou, M, 2012
)
0.69
"No additional safety issues (status of adverse reactions, status of adverse events, status of serious adverse events, etc."( [Safety and efficacy of midazolam in children under mechanical ventilation in the intensive care unit].
Lee, T; Miyasaka, K; Sogabe, K; Sou, M, 2012
)
0.69
"To evaluate the side effects and other adverse outcomes following use of oral midazolam for behaviour management in paediatric dentistry."( Safety of oral midazolam sedation use in paediatric dentistry: a review.
Ashley, PF; Lourenço-Matharu, L; Papineni, A, 2014
)
0.98
" We calculated rates of adverse events according to benzodiazepine use and identified risk factors for complications using univariate and multivariate analyses."( Safety of midazolam for sedation of HIV-positive patients undergoing colonoscopy.
Arpino, P; Backman, ES; Ehrenfeld, JM; Gandhi, RT; Losina, E; Lu, Z; Triant, VA, 2013
)
0.79
"Nitrous oxide is a safe and effective method to achieve analgesia and sedation during minor, but painful procedures."( Nitrous oxide provides safe and effective analgesia for minor paediatric procedures--a systematic review.
Bayat, A; Jacobsson, ML; Pedersen, RS; Steen, NP, 2013
)
0.39
" This technique produced predictable and effective sedation for quality computed tomography imaging studies with minimal artifact and no significant adverse events."( Aerosolized intranasal midazolam for safe and effective sedation for quality computed tomography imaging in infants and children.
de Carvalho, WB; Gilio, AE; Mason, KP; Mekitarian Filho, E; Robinson, F, 2013
)
0.7
"Pleuroscopy is considered a safe procedure with a high diagnostic accuracy but this record is based on studies published by pulmonologists experienced in performing the procedure."( Safety and accuracy of semirigid pleuroscopy performed by pulmonary fellows at a major university hospital: our initial experience.
Bajwa, AA; Cury, JD; Jones, L; Shujaat, A; Usman, F, 2013
)
0.39
" Evaluation criteria were success of dental treatment, cooperation level (modified Venham scale), and occurrence of adverse effects."( Conscious sedation procedures using intravenous midazolam for dental care in patients with different cognitive profiles: a prospective study of effectiveness and safety.
Collado, V; Faulks, D; Hennequin, M; Nicolas, E, 2013
)
0.65
" There were no clinically significant adverse effects."( The safety and efficacy of intranasal dexmedetomidine during electrochemotherapy for facial vascular malformation: a double-blind, randomized clinical trial.
Bai, X; Lu, L; Wang, X; Zhang, Q; Zhang, X, 2013
)
0.39
"Conscious sedation with midazolam for electrical cardioversion of AF appears to be safe and effective because it does not affect adversely the respiratory parameters of pts as demonstrated by the analysis of EtCO2 and IPI index."( Electrical cardioversion of atrial fibrillation: evaluation of sedation safety with midazolam by means of EtCO₂ and IPI algorithm analysis.
Mantovan, R; Sabbatani, P, 2013
)
0.92
"Community-based, face-to-face interviews were carried out with 34 carers to evaluate the effectiveness, adverse effects and convenience of buccal midazolam as a rescue treatment for prolonged seizures."( Carers' express positive views on the acceptability, efficacy and safety of buccal midazolam for paediatric status epilepticus.
Baheerathan, A; Hussain, N; Khan, A; Setty, G, 2014
)
0.83
"Carers felt that buccal midazolam was an effective, safe and more acceptable alternative to rectal diazepam in the management of paediatric status epilepticus."( Carers' express positive views on the acceptability, efficacy and safety of buccal midazolam for paediatric status epilepticus.
Baheerathan, A; Hussain, N; Khan, A; Setty, G, 2014
)
0.93
"Midazolam was effective and safe for pediatric sedation in the dosages studied."( Efficacy and safety of midazolam for sedation in pediatric dentistry: a controlled clinical trial.
Azevedo, ID; Bosco, VL; da Costa, AP; Ferreira, MA; Moritz, RD,
)
1.88
"Administration of flumazenil resulted in a safe shortening of the recovery period and offers the possibility for substantial savings in time, space, and nurse resources."( Significant and safe shortening of the recovery time after flumazenil-reversed midazolam sedation.
de Jong, L; Kos-Foekema, HA; Mathus-Vliegen, EM, 2014
)
0.63
"025 mg kg(-1) as premedication had significantly low anxiety scores, without any adverse effects on the newborns."( Premedication with midazolam prior to caesarean section has no neonatal adverse effects.
Mergan, F; Senel, AC,
)
0.46
"Forefoot surgery under ankle block alone may be safe and effective."( Safety and efficacy of forefoot surgery under ankle block anaesthesia.
Kumar, CS; Pillai, A; Russell, DF, 2014
)
0.4
" We recorded adverse events during the endoscopic procedure and additionally retrieved questionnaires investigating subjective parameters 24 h after the endoscopic procedure."( Safety analysis of endoscopist-directed propofol sedation: a prospective, national multicenter study of 24 441 patients in German outpatient practices.
Beck, S; Friedrich, K; Gotthardt, DN; Heil, FJ; Rex, DK; Scholl, SG; Sieg, A; Stremmel, W, 2014
)
0.4
" Major adverse events occurred in four patients (0."( Safety analysis of endoscopist-directed propofol sedation: a prospective, national multicenter study of 24 441 patients in German outpatient practices.
Beck, S; Friedrich, K; Gotthardt, DN; Heil, FJ; Rex, DK; Scholl, SG; Sieg, A; Stremmel, W, 2014
)
0.4
"Four years after the implementation of a German S3-Guideline for endoscopic sedation, we demonstrated that EDP is a safe procedure."( Safety analysis of endoscopist-directed propofol sedation: a prospective, national multicenter study of 24 441 patients in German outpatient practices.
Beck, S; Friedrich, K; Gotthardt, DN; Heil, FJ; Rex, DK; Scholl, SG; Sieg, A; Stremmel, W, 2014
)
0.4
"The aim of this study is to assess the prevalence of sedation-related adverse events and the independent predictors of sedation requirements in RYGB patients."( Conscious sedation for upper endoscopy in the gastric bypass patient: prevalence of cardiopulmonary adverse events and predictors of sedation requirement.
Abu Dayyeh, BK; Jirapinyo, P; Thompson, CC, 2014
)
0.4
" Primary outcomes are sedation-related adverse events and predictors of sedation requirement."( Conscious sedation for upper endoscopy in the gastric bypass patient: prevalence of cardiopulmonary adverse events and predictors of sedation requirement.
Abu Dayyeh, BK; Jirapinyo, P; Thompson, CC, 2014
)
0.4
" The non-cardiopulmonary adverse events were procedure-specific and unrelated to sedation."( Conscious sedation for upper endoscopy in the gastric bypass patient: prevalence of cardiopulmonary adverse events and predictors of sedation requirement.
Abu Dayyeh, BK; Jirapinyo, P; Thompson, CC, 2014
)
0.4
"The midazolam dosing protocol examined in this study was safe and effective."( Prospective analysis of efficacy and safety of an individualized-midazolam-dosing protocol for sedation during prolonged bronchoscopy.
Hasegawa, Y; Hashimoto, I; Hashimoto, N; Imai, N; Imaizumi, K; Ito, S; Kondo, M; Ogawa, T; Sato, M; Shimokata, T; Shindo, Y; Uozu, S, 2014
)
1.2
"Both forms of midazolam, IM and IV, are effective and safe for paediatric sedation in ED."( Intramuscular compared to intravenous midazolam for paediatric sedation: A study on cardiopulmonary safety and effectiveness.
Ghane, MR; Javadzadeh, HR; Mahmoudi, S; Najafian, B; Saburi, A,
)
0.76
" We aim to determine whether the administration of propofol infusion is safe by comparing it to intravenous midazolam/meperidine in patients undergoing DBE."( The safety of propofol infusion compared to midazolam and meperidine intravenous bolus for patients undergoing double balloon enteroscopy.
Angsuwatcharakon, P; Kongkam, P; Ponuthai, Y; Rerknimitr, R; Ridtitid, W; Thanapirom, K; Treeprasertsuk, S; Viriyautsahakul, V, 2014
)
0.88
"Propofol infusion is safe and shows no difference in outcome from the midazolam and meperidine sedation for the DBE procedure."( The safety of propofol infusion compared to midazolam and meperidine intravenous bolus for patients undergoing double balloon enteroscopy.
Angsuwatcharakon, P; Kongkam, P; Ponuthai, Y; Rerknimitr, R; Ridtitid, W; Thanapirom, K; Treeprasertsuk, S; Viriyautsahakul, V, 2014
)
0.9
"6 mg/kg) plus nitrous oxide (30%-50%) sedation are both safe while providing dental treatment to children with behavior problems."( Comparison of oral midazolam with combination of oral midazolam and nitrous oxide inhalation in relation to safety of dental sedation in young children.
Al-Zahrani, AM; Sheta, SA; Wyne, AH, 2011
)
0.7
" Ongoing monitoring of this particular adverse event will be required with a sustained patient safety message to health services to maintain awareness of the issue and reduction in the number of midazolam-related errors."( Reducing risk of overdose with midazolam injection in adults: an evaluation of change in clinical practice to improve patient safety in England.
Flood, C; Lamont, T; Mansaray, M; Marsh, R; Matthew, L; Patel, B, 2015
)
0.89
" Due to inconsistency in side effect reporting, the authors suggest the application of a standardised adverse event reporting tool for future studies of sedation in paediatric dentistry."( Reported side effects of intravenous midazolam sedation when used in paediatric dentistry: a review.
Ashley, PF; Lourenço-Matharu, L; Papineni McIntosh, A, 2015
)
0.69
" There was no apparent relationship between adverse event frequency or intensity and doravirine dose."( Safety, tolerability and pharmacokinetics of doravirine, a novel HIV non-nucleoside reverse transcriptase inhibitor, after single and multiple doses in healthy subjects.
Ancona, JK; Anderson, MS; Butterton, JR; Cilissen, C; De Lepeleire, I; Dockendorf, MF; Gilmartin, J; Guo, Y; Liu, R; Tetteh, E; Van Bortel, L; Wagner, JA, 2015
)
0.42
" No serious adverse effects were seen in both groups."( Efficacy and safety of intramuscular midazolam versus rectal diazepam in controlling status epilepticus in children.
Azizi Malamiri, R; Fayezi, A; Jafari, M; Maraghi, E; Momen, AA; Nikkhah, A; Riahi, K, 2015
)
0.69
"Tracheal intubation in PICUs is often associated with adverse tracheal intubation-associated events."( Current medication practice and tracheal intubation safety outcomes from a prospective multicenter observational cohort study.
Brown, CA; Howell, JD; Hsing, DD; Montgomery, V; Nadkarni, VM; Nishisaki, A; Parker, MM; Tarquinio, KM; Turner, DA; Walls, RM, 2015
)
0.42
" Adverse tracheal intubation-associated events were defined a priori."( Current medication practice and tracheal intubation safety outcomes from a prospective multicenter observational cohort study.
Brown, CA; Howell, JD; Hsing, DD; Montgomery, V; Nadkarni, VM; Nishisaki, A; Parker, MM; Tarquinio, KM; Turner, DA; Walls, RM, 2015
)
0.42
" To compare the safety profiles of propofol and other similar anesthetics such as diazepam, lorazepam, and midazolam, we evaluated their uses and related adverse drug reactions (ADRs) using Korean Adverse Event Reporting System (KAERS) data."( Increased use in propofol and reported patterns of adverse events among anesthetics in Korea.
Kim, MH; Park, BJ; Park, HJ; Shin, JY, 2015
)
0.63
" No severe adverse events were observed."( The Efficacy and Safety of Procedural Sedoanalgesia with Midazolam and Ketamine in Pediatric Hematology.
Çakmak, E; Demirsoy, U; Gelen, SA; Sarper, N; Zengin, E, 2015
)
0.66
"The purpose of this study was to evaluate patient safety, in terms of adverse events, alterations in blood pressure or oxygen saturation (SpO2) in two routine sedation procedures, with and without intravenous analgesia."( Safety of adjunct pre-emptive intravenous tramadol with midazolam sedation for third molar surgery.
Eriksson, LB; Tegelberg, Å, 2015
)
0.66
"The results confirm that pre-emptive intravenous tramadol, administered at 1 mg/kg body weight as an adjunct to midazolam sedation for third molar surgery, offers a safe method."( Safety of adjunct pre-emptive intravenous tramadol with midazolam sedation for third molar surgery.
Eriksson, LB; Tegelberg, Å, 2015
)
0.87
" Intranasal midazolam had adverse effects on nasal mucosa."( Cytotoxic Effects of Intranasal Midazolam on Nasal Mucosal Tissue.
Değer, A; Ital, I; Kasim, CM; Kucur, C; Oghan, F; Ozbay, I, 2015
)
1.08
" Adverse events, oxygen saturation, and vital signs were recorded."( Pharmacokinetics, pharmacodynamics, and safety of USL261, a midazolam formulation optimized for intranasal delivery, in a randomized study with healthy volunteers.
Bancke, LL; Dworak, HA; Gidal, BE; Halvorsen, MB; Rodvold, KA, 2015
)
0.66
" No serious adverse events (SAEs) or deaths were reported, and no treatment-emergent adverse events (TEAEs) led to study discontinuation."( Pharmacokinetics, pharmacodynamics, and safety of USL261, a midazolam formulation optimized for intranasal delivery, in a randomized study with healthy volunteers.
Bancke, LL; Dworak, HA; Gidal, BE; Halvorsen, MB; Rodvold, KA, 2015
)
0.66
"The study investigated patient discharge parameters and postdischarge adverse events after discharge among children who received oral conscious sedation for dental treatment."( Oral Sedation Postdischarge Adverse Events in Pediatric Dental Patients.
Huang, A; Tanbonliong, T, 2015
)
0.42
" No serious adverse events were seen, and minor sedation-related adverse events occurred with similar frequency in both groups (8."( Capnographic Monitoring of Moderate Sedation During Low-Risk Screening Colonoscopy Does Not Improve Safety or Patient Satisfaction: A Prospective Cohort Study.
Barnett, S; Bukoye, B; Hung, A; Leffler, DA; Sheehan, J; Sheth, SG; Tsao, R, 2016
)
0.43
" These data suggest that routine capnography in this setting may not be cost effective and that EtCO2 might be reserved for patients at higher risk of adverse events."( Capnographic Monitoring of Moderate Sedation During Low-Risk Screening Colonoscopy Does Not Improve Safety or Patient Satisfaction: A Prospective Cohort Study.
Barnett, S; Bukoye, B; Hung, A; Leffler, DA; Sheehan, J; Sheth, SG; Tsao, R, 2016
)
0.43
" This concept was defined based on the combination of the receipt of high-doses of midazolam or propofol, poor tolerance, use of reversal agents or sedation-related adverse events."( Safety and risk factors for difficult endoscopist-directed ERCP sedation in daily practice: a hospital-based case-control study.
Álvarez Suárez, B; Castro Ortiz, E; Dacal Rivas, A; Fernández López, A; González Ramírez, A; González Soler, R; Lancho Seco, Á; López Baz, A; López Roses, L; Martí Marqués, E; Pérez-Cuadrado Robles, E; Tardáguila García, D, 2016
)
0.66
"56%), sedation-related adverse events (n = 14, 22."( Safety and risk factors for difficult endoscopist-directed ERCP sedation in daily practice: a hospital-based case-control study.
Álvarez Suárez, B; Castro Ortiz, E; Dacal Rivas, A; Fernández López, A; González Ramírez, A; González Soler, R; Lancho Seco, Á; López Baz, A; López Roses, L; Martí Marqués, E; Pérez-Cuadrado Robles, E; Tardáguila García, D, 2016
)
0.43
" Secondary outcomes included the rate of adverse events, intensive care unit (ICU) and hospital length of stay, hospital mortality and long-term neurological outcome, assessed with the extended Glasgow outcome scale (GOS-E) at discharge and at six 6 months."( Midazolam and thiopental for the treatment of refractory status epilepticus: a retrospective comparison of efficacy and safety.
Bellante, F; Créteur, J; Depondt, C; Gaspard, N; Legros, B; Taccone, FS, 2016
)
1.88
" Adverse events are as follows."( Canadian Association of Gastroenterology Indicators of Safety Compromise following Colonoscopy in Clinical Practice.
Borgaonkar, MR; Evans, B; Hickey, N; Lougheed, M; Marcoux, C; McGrath, J; O'Leary, M; Pace, D, 2016
)
0.43
" There was no significant difference in time to obey verbal commands, proportion of time spent in target sedation, adverse events, death, or length of hospital stay."( Safety and Efficacy of Volatile Anesthetic Agents Compared With Standard Intravenous Midazolam/Propofol Sedation in Ventilated Critical Care Patients: A Meta-analysis and Systematic Review of Prospective Trials.
Beattie, WS; Ferguson, ND; Jerath, A; Lightfoot, N; Panckhurst, J; Parotto, M; Steel, A; Wasowicz, M, 2017
)
0.68
"Volatile-based sedation demonstrates a reduction in time to extubation, with no increase in short-term adverse outcomes."( Safety and Efficacy of Volatile Anesthetic Agents Compared With Standard Intravenous Midazolam/Propofol Sedation in Ventilated Critical Care Patients: A Meta-analysis and Systematic Review of Prospective Trials.
Beattie, WS; Ferguson, ND; Jerath, A; Lightfoot, N; Panckhurst, J; Parotto, M; Steel, A; Wasowicz, M, 2017
)
0.68
" No sedation adverse events were registered CONCLUSION: Propofol is more effective and at least as safe as midazolam for procedural sedation in the ED."( Propofol versus midazolam for procedural sedation in the emergency department: A study on efficacy and safety.
Beije, F; Bens, BWJ; Bosch, MGE; Feenstra, R; Lameijer, H; Pol, A; Sikkema, YT; Ter Avest, E, 2017
)
1.01
" Adverse events are related to inappropriate respiratory management, mostly originating from an overdose of sedatives."( Optimal and safe standard doses of midazolam and propofol to achieve patient and doctor satisfaction with dental treatment: A prospective cohort study.
Gotoh, K; Iijima, T; Masuda, R; Nishimura, A; Nonaka, M; Oka, S, 2017
)
0.73
" No serious adverse events were reported."( Optimal and safe standard doses of midazolam and propofol to achieve patient and doctor satisfaction with dental treatment: A prospective cohort study.
Gotoh, K; Iijima, T; Masuda, R; Nishimura, A; Nonaka, M; Oka, S, 2017
)
0.73
" Although this level of sedation is relatively light, memory loss and an absence of unintentional patient movements can be expected without adverse events."( Optimal and safe standard doses of midazolam and propofol to achieve patient and doctor satisfaction with dental treatment: A prospective cohort study.
Gotoh, K; Iijima, T; Masuda, R; Nishimura, A; Nonaka, M; Oka, S, 2017
)
0.73
" Fortunately, electronic monitors have contributed to a reduction in the associated respiratory adverse events (RAEs)."( Detection of Respiratory Adverse Events in Pediatric Dental Patients Sedated With 0.75mg/Kg of Midazolam and Oxygen by Continuous Pretracheal Auscultation: A Prospective Randomized Controlled Trial.
Hadjittofi, C; Hoash, N; Kharouba, J; Matter, I; Moaddi, B; Parisinos, CA; Peretz, B; Somri, M,
)
0.35
" Anesthesia onset time, total number of intraoperative children movements, hemodynamics (heart rate, arterial pressure, pulse oxygen saturation (SpO2), respiratory rate), total cumulative dose of dexmedetomidine and remifentanil, the amount of midazolam and lidocaine, time to first dose of rescue midazolam and lidocaine, postoperative recovery time, adverse events, bronchoscopist satisfaction score were recorded."( The safety and efficacy of dexmedetomidine-remifentanil in children undergoing flexible bronchoscopy: A retrospective dose-finding trial.
Jin, S; Li, X; Li, Y; Wang, X; Zhang, D, 2017
)
0.64
" We compared sedation and recovery times, medication doses, and adverse events between groups."( Bolus Administration of Fentanyl and Midazolam for Colonoscopy Increases Endoscopy Unit Efficiency and Safety Compared With Titrated Sedation.
Boyd, A; Finn, RT; Gellad, ZF; Lin, L, 2017
)
0.73
"The results of our study showed that the use of IV midazolam and ketamine during upper endoscopy in children was safe and effective."( Efficacy and safety of midazolam and ketamine in paediatric upper endoscopy.
Artan, R; Basturk, A; Yılmaz, A, 2017
)
1.02
" The time of stay in the recovery room and adverse events were reviewed through the nursing records."( Efficacy and safety of flumazenil injection for the reversal of midazolam sedation after elective outpatient endoscopy.
Kim, JH; Lee, SP; Lee, SY; Park, HS; Shim, CS; Sung, IK, 2018
)
0.72
" No significant differences were found in the number of patients with pain (VAS ≥1), adverse events and discomfort between the two groups."( Efficacy and safety of flumazenil injection for the reversal of midazolam sedation after elective outpatient endoscopy.
Kim, JH; Lee, SP; Lee, SY; Park, HS; Shim, CS; Sung, IK, 2018
)
0.72
"The time in the recovery room after flumazenil administration was significantly shortened, and the use of the drug did not increase the risk of adverse events or discomfort."( Efficacy and safety of flumazenil injection for the reversal of midazolam sedation after elective outpatient endoscopy.
Kim, JH; Lee, SP; Lee, SY; Park, HS; Shim, CS; Sung, IK, 2018
)
0.72
" There were no treatment-emergent serious adverse events."( A phase III study evaluating the efficacy and safety of remimazolam (CNS 7056) compared with placebo and midazolam in patients undergoing colonoscopy.
Barish, CF; Bernstein, D; Bhandari, R; Cash, BD; DeMicco, MP; Desta, T; Etzkorn, K; Pruitt, R; Quirk, D; Rex, DK; Schaeffer, C; Sullivan, S; Tiongco, F, 2018
)
0.69
" Having safe and fast means of providing sedation and anxiolysis to children is important for the child's tolerance of the procedure, parent satisfaction and efficient patient flow in the ED."( Adverse events and satisfaction with use of intranasal midazolam for emergency department procedures in children.
Laurich, VM; Malia, L; Sturm, JJ, 2019
)
0.76
" Data collected included last solid and liquid intake, procedure performed, sedation depth, adverse events and parent and provider satisfaction."( Adverse events and satisfaction with use of intranasal midazolam for emergency department procedures in children.
Laurich, VM; Malia, L; Sturm, JJ, 2019
)
0.76
" There were no adverse events experienced by any patients."( Adverse events and satisfaction with use of intranasal midazolam for emergency department procedures in children.
Laurich, VM; Malia, L; Sturm, JJ, 2019
)
0.76
"Our data suggest that short NPO of both solids and liquids are safe for the use of INM."( Adverse events and satisfaction with use of intranasal midazolam for emergency department procedures in children.
Laurich, VM; Malia, L; Sturm, JJ, 2019
)
0.76
" Our findings suggest that local anaesthesia with conscious sedation is a safe and feasible option for cardiac device implantation procedures, including complex procedures."( Feasibility and safety of using local anaesthesia with conscious sedation during complex cardiac implantable electronic device procedures.
Jánosi, RA; Kaya, E; Lortz, J; Rassaf, T; Südkamp, H, 2018
)
0.48
"Recent studies have shown that etomidate is associated with fewer serious adverse events than propofol and has a noninferior sedative effect."( Efficacy and safety of etomidate-midazolam for screening colonoscopy in the elderly: A prospective double-blinded randomized controlled study.
Choi, HS; Choi, SJ; Chun, HJ; Jeen, YT; Keum, B; Kim, CD; Kim, ES; Kim, SH; Kim, W; Lee, BJ; Lee, HS; Lee, JM; Min, G; Park, JJ, 2018
)
0.76
" The primary outcome was all cardiopulmonary adverse events."( Efficacy and safety of etomidate-midazolam for screening colonoscopy in the elderly: A prospective double-blinded randomized controlled study.
Choi, HS; Choi, SJ; Chun, HJ; Jeen, YT; Keum, B; Kim, CD; Kim, ES; Kim, SH; Kim, W; Lee, BJ; Lee, HS; Lee, JM; Min, G; Park, JJ, 2018
)
0.76
"The incidence of cardiopulmonary adverse events was higher in the propofol group (72."( Efficacy and safety of etomidate-midazolam for screening colonoscopy in the elderly: A prospective double-blinded randomized controlled study.
Choi, HS; Choi, SJ; Chun, HJ; Jeen, YT; Keum, B; Kim, CD; Kim, ES; Kim, SH; Kim, W; Lee, BJ; Lee, HS; Lee, JM; Min, G; Park, JJ, 2018
)
0.76
" Our results globally overlap those of wider series and reinforce the perception that local anesthetic semi-flexible pleuroscopy is a well-tolerated, safe and highly accurate diagnostic and therapeutic tool which has proved to be both feasible and effective in our experience."( Effectiveness and safety of local anesthetic, semi-flexible pleuroscopy - experience from a peripheral hospital.
Ferreira, L; Gomes, R; Rodrigues, LV; Samouco, G; Santos, C,
)
0.13
" The primary outcome measures were adverse events and failed laceration repair."( Safety and effectiveness of intranasal midazolam and fentanyl used in combination in the pediatric emergency department.
Cosgrove, P; Kienstra, AJ; Ryan, PM; Vezzetti, R; Wilkinson, M, 2019
)
0.78
" There were no serious adverse events reported."( Safety and effectiveness of intranasal midazolam and fentanyl used in combination in the pediatric emergency department.
Cosgrove, P; Kienstra, AJ; Ryan, PM; Vezzetti, R; Wilkinson, M, 2019
)
0.78
"Our results suggest that the combination of INM and INF may be a safe and effective strategy for procedural sedation in young children undergoing simple laceration repair."( Safety and effectiveness of intranasal midazolam and fentanyl used in combination in the pediatric emergency department.
Cosgrove, P; Kienstra, AJ; Ryan, PM; Vezzetti, R; Wilkinson, M, 2019
)
0.78
" However, adverse events (AEs) may occur more frequently in patients with cirrhosis due to altered MDZ metabolism."( Safety and effectiveness of midazolam for cirrhotic patients undergoing endoscopic variceal ligation.
Jang, DK; Jo, HB; Kang, HW; Kim, JH; Koh, MS; Lee, JH; Lee, JK; Lim, YJ, 2018
)
0.77
"Remimazolam administered under the supervision of a pulmonologist was effective and safe for moderate sedation during flexible bronchoscopy."( Safety and Efficacy of Remimazolam Compared With Placebo and Midazolam for Moderate Sedation During Bronchoscopy.
Akulian, J; Callahan, SP; Chen, A; Feldman, G; Lorch, DG; Ndukwu, I; Ostroff, R; Pastis, NJ; Pritchett, MA; Schippers, F; Shojaee, S; Silvestri, GA; Tanner, NT; Wahidi, M; Yarmus, LB, 2019
)
0.76
" The safe preparation of medications during resuscitation requires attention, time and resources, and can be a source of medication error."( Predrawn prehospital medications are microbiologically safe for up to 48 hours.
Foster, A; Garner, A; Gutierrez, CH; Kitcher, J; Soeyland, T; Vidler, S, 2018
)
0.48
"Predrawing of the eight studied medications for urgent prehospital procedures appears to be a microbiologically safe practice with syringe dwell times up to 48 hours."( Predrawn prehospital medications are microbiologically safe for up to 48 hours.
Foster, A; Garner, A; Gutierrez, CH; Kitcher, J; Soeyland, T; Vidler, S, 2018
)
0.48
" The secondary endpoints were postoperative awareness, technical success rate, frequency of body movement, patient and operator satisfaction, cardiorespiratory dynamics during EIS, and adverse events."( Propofol is a more effective and safer sedative agent than midazolam in endoscopic injection sclerotherapy for esophageal varices in patients with liver cirrhosis: a randomized controlled trial.
Hashimoto, M; Hikichi, T; Irie, H; Kikuchi, H; Konno, N; Nakamura, J; Obara, K; Ohira, H; Sato, Y; Sugimoto, M; Suzuki, R; Takagi, T; Takasumi, M; Watanabe, K, 2018
)
0.72
" No adverse events were observed."( Propofol is a more effective and safer sedative agent than midazolam in endoscopic injection sclerotherapy for esophageal varices in patients with liver cirrhosis: a randomized controlled trial.
Hashimoto, M; Hikichi, T; Irie, H; Kikuchi, H; Konno, N; Nakamura, J; Obara, K; Ohira, H; Sato, Y; Sugimoto, M; Suzuki, R; Takagi, T; Takasumi, M; Watanabe, K, 2018
)
0.72
" Adverse Event: Six hours after starting midazolam infusion he started developing pulsus bigeminus and bradycardia and eventual death after two hours."( Cardiotoxicity Associated with Midazolam in a Patient with Diphtheria.
Gohil, JR; Jindal, S, 2019
)
1.07
"The exclusively cardiological procedure of deep sedation seems to be safe and effective."( Safety and efficacy of a cardiologist-only approach to deep sedation for electrical cardioversion.
Bolzan, B; Borio, G; Morani, G; Ribichini, FL, 2019
)
0.51
" The outcome measures were amount of midazolam, adverse events associated with sedation, and hemodynamics."( Dexmedetomidine is safe and reduces the additional dose of midazolam for sedation during endoscopic retrograde cholangiopancreatography in very elderly patients.
Andoh, A; Bamba, S; Fujimoto, T; Hasegawa, H; Imai, T; Inatomi, O; Nishida, A; Sugimoto, M; Takahashi, K; Yamashita, N; Yokota, Y, 2018
)
1
" Adverse events were observed in three patients; one had mild respiratory depression that required supplemental oxygen and bag-valve-mask ventilation."( Efficacy, safety, and pharmacokinetics of intravenous midazolam in Japanese children with status epilepticus.
Fukuyama, T; Hamano, SI; Miki, M; Osawa, M; Sugai, K; Tabata, T, 2019
)
0.76
"The present study shows that ERCP technique is safe under conscious sedation as it delivers balanced tranquillity."( Safety of Conscious Sedation in Patients Undergoing Endoscopic Retrograde Cholangio Pancreatography.
Anwar, A; Kamani, L; Memon, AL, 2018
)
0.48
"In a selected population of pediatric patients, buccal dexmedetomidine with or without midazolam provides adequate sedation for most MRI studies with few adverse effects, but given a failure rate of almost 20%, modifications to buccal dexmedetomidine dosing should be investigated."( Safety and Efficacy of Buccal Dexmedetomidine for MRI Sedation in School-Aged Children.
Boriosi, JP; Eickhoff, JC; Hollman, GA, 2019
)
0.74
" This paper delineates the findings related to the pharmacokinetics, adverse effects and drug-drug interactions as well as associated therapeutic implications for safe midazolam use."( Midazolam: Safety of use in palliative care: A systematic critical review.
Oduah, MT; Sopata, M; Stachowiak-Szymczak, K; Szymański, K; Zaporowska-Stachowiak, I; Łuczak, J, 2019
)
2.15
"5%) discontinued because of a treatment-emergent adverse event (TEAE) during the TDP and none during the CP."( Safety and efficacy of midazolam nasal spray in the outpatient treatment of patients with seizure clusters-a randomized, double-blind, placebo-controlled trial.
Detyniecki, K; Meng, TC; Pullman, WE; Sequeira, DJ; Van Ess, PJ; Wheless, JW, 2019
)
0.82
" Adverse events in CAPS patients were recorded."( Computer-Assisted Propofol Sedation for Esophagogastroduodenoscopy Is Effective, Efficient, and Safe.
Beecher, R; Chiorean, M; Drennan, F; Gluck, M; Koch, J; Kozarek, RA; La Selva, D; Larsen, M; Lin, OS; McCormick, S; Ross, A; Tombs, D; Venu, N; Weigel, W, 2019
)
0.51
" There were no other serious adverse events."( Computer-Assisted Propofol Sedation for Esophagogastroduodenoscopy Is Effective, Efficient, and Safe.
Beecher, R; Chiorean, M; Drennan, F; Gluck, M; Koch, J; Kozarek, RA; La Selva, D; Larsen, M; Lin, OS; McCormick, S; Ross, A; Tombs, D; Venu, N; Weigel, W, 2019
)
0.51
" Patients were monitored for treatment-emergent adverse events (TEAEs) throughout, and the main seizure-related outcome was treatment success, defined as seizure termination within 10 minutes and no recurrence 10 minutes-6 hours after drug administration."( Safety and efficacy of midazolam nasal spray in the outpatient treatment of patients with seizure clusters: An open-label extension trial.
Detyniecki, K; Meng, TC; Pullman, WE; Sequeira, DJ; Van Ess, PJ; Wheless, JW, 2019
)
0.82
"This retrospective cohort study of cirrhotic patients undergoing endoscopy from a large academic medical center between 2010 and 2014 examined extensive clinical data including the following: past history, physical findings, laboratory results, and procedural adverse events."( Sedation During Endoscopy in Patients with Cirrhosis: Safety and Predictors of Adverse Events.
Edelson, J; Rockey, DC; Suarez, AL; Zhang, J, 2020
)
0.56
" There was no difference in the frequency of adverse events in MAC and moderate sedation groups, with a total of 15 adverse events (7/1157 MAC and 8/1461 moderate sedation)."( Sedation During Endoscopy in Patients with Cirrhosis: Safety and Predictors of Adverse Events.
Edelson, J; Rockey, DC; Suarez, AL; Zhang, J, 2020
)
0.56
" Oral midazolam has been shown to be safe in various procedures."( Safety of Premedication with Oral Midazolam before Rhinoplasty as Indicated by Intraoperative Levels of Blood Oxygen Saturation.
Frand, J; Harel, M; Leibou, L; Shalom, A, 2019
)
1.27
"To evaluate the safety of premedication with oral midazolam prior to rhinoplasty by analyzing the intraoperative blood oxygen saturation levels as predictors of adverse respiratory events."( Safety of Premedication with Oral Midazolam before Rhinoplasty as Indicated by Intraoperative Levels of Blood Oxygen Saturation.
Frand, J; Harel, M; Leibou, L; Shalom, A, 2019
)
1.05
"Remimazolam was safe and well tolerated in healthy Chinese participants."( Safety, pharmacokinetic and pharmacodynamic properties of single ascending dose and continuous infusion of remimazolam besylate in healthy Chinese volunteers.
Cui, YM; Li, LE; Liang, Y; Sheng, XY; Yang, XY; Ye, X; Zhao, X, 2020
)
0.56
"Both propofol and midazolam (± short-acting opioids) result in high patient satisfaction and appear to be safe for use in colonoscopy."( Propofol versus midazolam with or without short-acting opioids for sedation in colonoscopy: a systematic review and meta-analysis of safety, satisfaction, and efficiency outcomes.
Acuna, SA; Baxter, NN; Dossa, F; Keng, C; Medeiros, B, 2020
)
1.24
"Propofol-based sedation is widely used in ERCP procedures, but adverse respiratory or cardiovascular events commonly occur."( Efficacy and safety of intravenous lidocaine in propofol-based sedation for ERCP procedures: a prospective, randomized, double-blinded, controlled trial.
Ji, R; Li, YQ; Liu, C; Liu, J; Liu, X; Peng, LP, 2020
)
0.56
"An efficient, well tolerated, and safe emergency treatment with a rapid onset of action is needed to prevent seizure clusters and to terminate prolonged seizures and status epilepticus."( Efficacy, Tolerability, and Safety of Concentrated Intranasal Midazolam Spray as Emergency Medication in Epilepsy Patients During Video-EEG Monitoring.
Balaban, Ü; Fuest, S; Herrmann, E; Kay, L; Knake, S; Reif, PS; Rosenow, F; Schubert-Bast, S; Strzelczyk, A; von Blomberg, A; Zöllner, JP, 2020
)
0.8
" Treatment-emergent adverse events (TEAEs) were also evaluated."( Efficacy, Tolerability, and Safety of Concentrated Intranasal Midazolam Spray as Emergency Medication in Epilepsy Patients During Video-EEG Monitoring.
Balaban, Ü; Fuest, S; Herrmann, E; Kay, L; Knake, S; Reif, PS; Rosenow, F; Schubert-Bast, S; Strzelczyk, A; von Blomberg, A; Zöllner, JP, 2020
)
0.8
" In-MDZ was well tolerated without major adverse events."( Efficacy, Tolerability, and Safety of Concentrated Intranasal Midazolam Spray as Emergency Medication in Epilepsy Patients During Video-EEG Monitoring.
Balaban, Ü; Fuest, S; Herrmann, E; Kay, L; Knake, S; Reif, PS; Rosenow, F; Schubert-Bast, S; Strzelczyk, A; von Blomberg, A; Zöllner, JP, 2020
)
0.8
"We conclude that in-MDZ is a safe and efficient treatment option to prevent short-term recurrence of seizures."( Efficacy, Tolerability, and Safety of Concentrated Intranasal Midazolam Spray as Emergency Medication in Epilepsy Patients During Video-EEG Monitoring.
Balaban, Ü; Fuest, S; Herrmann, E; Kay, L; Knake, S; Reif, PS; Rosenow, F; Schubert-Bast, S; Strzelczyk, A; von Blomberg, A; Zöllner, JP, 2020
)
0.8
"Data are limited regarding the impact of age and sedation on cardiocerebrovascular disease (CCD) adverse events after GI endoscopy."( Impacts of age and sedation on cardiocerebrovascular adverse events after diagnostic GI endoscopy: a nationwide population-based study.
Jung, HK; Jung, SA; Kim, MH; Kim, SE; Kim, SY; Moon, CM; Shim, KN, 2020
)
0.56
"CCD adverse events after diagnostic endoscopy were significantly frequent in individuals with older age (70-99 years) and/or sedation during endoscopy."( Impacts of age and sedation on cardiocerebrovascular adverse events after diagnostic GI endoscopy: a nationwide population-based study.
Jung, HK; Jung, SA; Kim, MH; Kim, SE; Kim, SY; Moon, CM; Shim, KN, 2020
)
0.56
"8% in group A), recovery profile or the incidence or severity of adverse events (AEs) or adverse drug reactions (ADRs)."( Safety and efficacy of remimazolam in induction and maintenance of general anesthesia in high-risk surgical patients (ASA Class III): results of a multicenter, randomized, double-blind, parallel-group comparative trial.
Doi, M; Hirata, N; Morimatsu, H; Morisaki, H; Sakamoto, A; Suzuki, T, 2020
)
0.56
" Adverse events and adverse drug reactions (ADRs) were monitored for safety."( Efficacy and safety of remimazolam versus propofol for general anesthesia: a multicenter, single-blind, randomized, parallel-group, phase IIb/III trial.
Doi, M; Morita, K; Sakamoto, A; Suzuki, T; Takeda, J; Yamakage, M, 2020
)
0.56
" We characterized the distribution of infant characteristics and evaluated the relationship between drug administration and any adverse event."( Comparative safety profile of chloral hydrate versus other sedatives for procedural sedation in hospitalized infants.
Balevic, S; Chu, V; Clark, R; Crenshaw, EG; Dallefeld, SH; Daniel, KR; Gilleskie, ML; Greenberg, RG; Kumar, KR; Smith, DS; Smith, PB; Zimmerman, KO, 2020
)
0.56
" Adverse events occurred in 41 (6%) infants."( Comparative safety profile of chloral hydrate versus other sedatives for procedural sedation in hospitalized infants.
Balevic, S; Chu, V; Clark, R; Crenshaw, EG; Dallefeld, SH; Daniel, KR; Gilleskie, ML; Greenberg, RG; Kumar, KR; Smith, DS; Smith, PB; Zimmerman, KO, 2020
)
0.56
"Administration of chloral hydrate to hospitalized infants undergoing minor procedures is associated with a lower risk for adverse events compared to other sedatives."( Comparative safety profile of chloral hydrate versus other sedatives for procedural sedation in hospitalized infants.
Balevic, S; Chu, V; Clark, R; Crenshaw, EG; Dallefeld, SH; Daniel, KR; Gilleskie, ML; Greenberg, RG; Kumar, KR; Smith, DS; Smith, PB; Zimmerman, KO, 2020
)
0.56
"Evaluate adverse events associated with oral midazolam as a perioperative anxiolytic during dermatologic surgery and assess whether an enhanced monitoring approach is associated with an increased detection rate."( Safety of Oral Midazolam as a Perioperative Anxiolytic for Outpatient Dermatologic Procedures.
Arpey, CJ; Baum, CL; Bezalel, SA; Brewer, JD; Otley, CC; Roenigk, RK, 2020
)
1.17
" The number of procedures, type of procedures, dose in milligrams, number of doses, major and minor adverse events, and vital signs were recorded."( Safety of Oral Midazolam as a Perioperative Anxiolytic for Outpatient Dermatologic Procedures.
Arpey, CJ; Baum, CL; Bezalel, SA; Brewer, JD; Otley, CC; Roenigk, RK, 2020
)
0.91
" There were zero major adverse events in both groups."( Safety of Oral Midazolam as a Perioperative Anxiolytic for Outpatient Dermatologic Procedures.
Arpey, CJ; Baum, CL; Bezalel, SA; Brewer, JD; Otley, CC; Roenigk, RK, 2020
)
0.91
"Oral midazolam administration was not associated with major adverse events including in the more intensively monitored group."( Safety of Oral Midazolam as a Perioperative Anxiolytic for Outpatient Dermatologic Procedures.
Arpey, CJ; Baum, CL; Bezalel, SA; Brewer, JD; Otley, CC; Roenigk, RK, 2020
)
1.42
" No significant differences were observed in diagnostic yield and procedure time between the 2 groups, and no severe adverse events were noted in the elderly group."( Comfort and safety of bronchoscopy performed under sedation and local anesthesia in elderly patients.
Hara, M; Ise, S; Izumi, M; Kawasaki, M; Nagaoka, A; Noda, N; Ose, M; Tatsuta, M; Wakamatsu, K, 2020
)
0.56
" Safety and tolerability outcomes included treatment-emergent adverse events (TEAEs)."( Safety and efficacy of midazolam nasal spray for the treatment of intermittent bouts of increased seizure activity in the epilepsy monitoring unit: A double-blind, randomized, placebo-controlled trial.
Choi, EJ; Cleveland, JM; King, A; Meng, TC; Pullman, WE; Sequeira, DJ; Sinha, SR; Spencer, DC; Van Ess, PJ; Wheless, JW, 2020
)
0.87
" We reviewed adverse effects of clonidine occurring in this indication."( Safety of clonidine used for long-term sedation in paediatric intensive care: A systematic review.
Ahne, G; Eberl, S; Neubert, A; Standing, J; Toni, I, 2021
)
0.62
" The purpose of this article is to measure the frequency of adverse anesthetic events related to ambulatory surgical procedures performed under intravenous (IV) sedation by the Division of Oral and Maxillofacial Surgery at the Mayo Clinic during a 15-year period using the team anesthesia model."( Safety of Outpatient Procedural Sedation Administered by Oral and Maxillofacial Surgeons: The Mayo Clinic Experience in 17,634 Sedations (2004 to 2019).
Arce, K; Ettinger, KS; Fillmore, WJ; Heggestad, BT; Nathan, JM; Van Ess, JM; Viozzi, CF; Wiemer, SJ, 2021
)
0.62
" The primary outcome variable of interest was the presence of anesthetic-related adverse events (AEs) consistent with the World Society of Intravenous Anesthesia International Sedation Task Force's intervention-based definitions of adverse anesthetic events."( Safety of Outpatient Procedural Sedation Administered by Oral and Maxillofacial Surgeons: The Mayo Clinic Experience in 17,634 Sedations (2004 to 2019).
Arce, K; Ettinger, KS; Fillmore, WJ; Heggestad, BT; Nathan, JM; Van Ess, JM; Viozzi, CF; Wiemer, SJ, 2021
)
0.62
"1%) and 0% mortality rate reported in this study demonstrate that the anesthesia team model used by oral and maxillofacial surgeons compares favorably to standardized intervention-based adverse anesthetic event outcomes reported by other nonanesthesiology specialties routinely performing outpatient procedural sedation."( Safety of Outpatient Procedural Sedation Administered by Oral and Maxillofacial Surgeons: The Mayo Clinic Experience in 17,634 Sedations (2004 to 2019).
Arce, K; Ettinger, KS; Fillmore, WJ; Heggestad, BT; Nathan, JM; Van Ess, JM; Viozzi, CF; Wiemer, SJ, 2021
)
0.62
"Endoscopist directed nurse administered propofol sedation (EDNAPS) is widely considered to be safe and efficient, but there are limited data from the Australian health-care setting, and Australian sedation guidelines do not support the practice."( Prospective audit of the safety of endoscopist-directed nurse-administered propofol sedation in an Australian referral hospital.
Boyd, P; Gilhotra, R; Gururatsakul, M; Lee, R; McGowan, C; Ombiga, J; Ponnuswamy, SK; Whittaker, D, 2021
)
0.62
"Endoscopist directed nurse administered propofol sedation is a safe way of performing endoscopic sedation in low-risk patients in the hospital setting."( Prospective audit of the safety of endoscopist-directed nurse-administered propofol sedation in an Australian referral hospital.
Boyd, P; Gilhotra, R; Gururatsakul, M; Lee, R; McGowan, C; Ombiga, J; Ponnuswamy, SK; Whittaker, D, 2021
)
0.62
"Sedation for upper gastrointestinal endoscopy (UGIE) in patients with cirrhosis is theoretically associated with high incidence of adverse events due to low levels of binding proteins and decreased hepatic clearance of drugs."( Safety of balanced propofol and midazolam in upper gastrointestinal endoscopy for sedation in cirrhotic patients.
Alam, L; Alam, M; Khattak, MA, 2021
)
0.9
" The primary outcomes included the adverse effects and anxiety level."( Effectiveness and safety of oral sedation in adult patients undergoing dental procedures: a systematic review.
Araújo, JO; Bergamaschi, CC; de Andrade, NK; Guimarães, CC; Lopes, LC; Motta, RHL; Ramacciato, JC, 2021
)
0.62
"To determine the frequency, severity and duration of adverse events including myoclonus, pain on injection, hypersalivation, regurgitation and apnoea after administration of midazolam or saline followed by etomidate in hydromorphone premedicated dogs."( Descriptive assessment of adverse events associated with midazolam-etomidate versus saline-etomidate in healthy hydromorphone premedicated dogs.
Calbay, R; da Cunha, AF; Hofmeister, EH; Jones, TL, 2021
)
1.06
" Further investigation is needed to determine if midazolam reduced the incidence of adverse events or improved the induction quality when combined with hydromorphone and etomidate."( Descriptive assessment of adverse events associated with midazolam-etomidate versus saline-etomidate in healthy hydromorphone premedicated dogs.
Calbay, R; da Cunha, AF; Hofmeister, EH; Jones, TL, 2021
)
1.12
" This retrospective study, evaluates intramuscular midazolam as a safe option for anxiolysis during spasticity management injections."( The use and safety of intramuscular midazolam during in-office botulinum toxin injections in pediatric patients.
Alwasiah, N; Mian, MN; Savitz, A,
)
0.66
" Safety evaluations included respiratory depression and the frequency of treatment-emergent adverse events (TEAEs)."( A Phase 3 open-label study of the efficacy, safety and pharmacokinetics of buccally administered midazolam hydrochloride for the treatment of status epilepticus in pediatric Japanese subjects.
Benitez, A; Fournier, M; Kugler, AR; Takeda, S; Yoshinaga, H, 2021
)
0.84
" No serious adverse events/deaths were reported."( Napabucasin Drug-Drug Interaction Potential, Safety, Tolerability, and Pharmacokinetics Following Oral Dosing in Healthy Adult Volunteers.
Brantley, SJ; Dai, X; Goulet, MT; Hard, ML; Hitron, M; Karol, MD; McLaughlin, CF, 2021
)
0.62
" Efficacy was measured by completing the induction of anesthesia without rescue sedation; and safety was defined as no severe adverse events."( Safety and efficacy of remimazolam compared with propofol in induction of general anesthesia.
Dai, G; Duan, F; Liao, M; Pei, L; Zhang, X; Zhang, Y; Zhao, Z; Zhu, M, 2021
)
0.62
"Remimazolam is a safe and effective sedative drug during induction with less adverse effects for general anesthesia in ASA I or II patients."( Safety and efficacy of remimazolam compared with propofol in induction of general anesthesia.
Dai, G; Duan, F; Liao, M; Pei, L; Zhang, X; Zhang, Y; Zhao, Z; Zhu, M, 2021
)
0.62
" However, there are no reports of an association of adverse events and examination success rates with patient medical backgrounds using a combination of these sedatives."( Patient background related to success and adverse event in pediatric sedated MRI.
Akiyama, L; Fujii, K; Hiramoto, R; Kawasaki, Y; Konda, Y; Mihira, H; Ozawa, Y; Shiko, Y, 2022
)
0.72
" Outcomes were sedation success and adverse events, including oxygen desaturation."( Patient background related to success and adverse event in pediatric sedated MRI.
Akiyama, L; Fujii, K; Hiramoto, R; Kawasaki, Y; Konda, Y; Mihira, H; Ozawa, Y; Shiko, Y, 2022
)
0.72
" The only adverse event was oxygen desaturation (11."( Patient background related to success and adverse event in pediatric sedated MRI.
Akiyama, L; Fujii, K; Hiramoto, R; Kawasaki, Y; Konda, Y; Mihira, H; Ozawa, Y; Shiko, Y, 2022
)
0.72
"The number of therapeutic endoscopic procedures in elderly individuals keeps increasing and this population has a high risk of adverse events related to sedation and general anesthesia."( Efficacy and safety of endoscopic retrograde cholangiopancreatography in the very elderly by using a combination of intravenous midazolam, ketamine and pethidine.
Cetin, MF; Tokmak, S; Torun, S, 2021
)
0.83
" Adverse events (AEs) included: hypoxia (oxygen saturation < 90%); hypotension [(a) systolic blood pressure < 90 mm Hg, (b) systolic blood pressure decline of >50 mm Hg, (c) decline in mean arterial pressure of >30%]; bradycardia (heart rate of < 40 beats/min)."( Safety Profile of Endoscopist-directed Balanced Propofol Sedation for Procedural Sedation: An Experience at a Hospital-based Endoscopy Unit.
Fatima, H; Imperiale, T, 2022
)
0.72
"EDBPS is safe for endoscopic sedation."( Safety Profile of Endoscopist-directed Balanced Propofol Sedation for Procedural Sedation: An Experience at a Hospital-based Endoscopy Unit.
Fatima, H; Imperiale, T, 2022
)
0.72
"Dexmedetomidine is a safe and effective adjunct to propofol."( Safety and Efficacy of IV Dexmedetomidine as an Adjunct to Propofol to Sedate Anxious and Uncooperative Pediatric Dental Patients: A Randomized Controlled Trial.
Gauba, K; Goyal, A; Jain, K; Kapur, A; Rehman, F, 2021
)
0.62
" Primary variables: treatment-emergent adverse events (TEAEs; Parts A and B); area under the plasma concentration-time curve (AUC) and maximum plasma concentration of midazolam and α-hydroxymidazolam (Part C)."( Pharmacokinetics, pharmacodynamics and safety of BAY 2433334, a novel activated factor XI inhibitor, in healthy volunteers: A randomized phase 1 multiple-dose study.
Distler, J; Heckmann, M; Kanefendt, F; Koechel, A; Kubitza, D; Schwers, S, 2022
)
0.92
"Reviews of the sedation logs of 1,785 sedation visits are compared with emphasis on what dosing proves both safe and effective for differing levels of challenging pediatric behavior."( Retrospective Comparisons of the Efficacy and Safety of Variable dosing of Midazolam with and without Meperidine for Management of Varying Levels of Anxiety of Pediatric Dental Patients: 35 years of Sedation Experience.
Nathan, JE, 2022
)
0.95
"Where Mep was used, success rates were consistently higher; working times were significantly prolonged and greater control was provided to avoid adverse reactions by virtue of reversal capability for both agents."( Retrospective Comparisons of the Efficacy and Safety of Variable dosing of Midazolam with and without Meperidine for Management of Varying Levels of Anxiety of Pediatric Dental Patients: 35 years of Sedation Experience.
Nathan, JE, 2022
)
0.95
"5 mg/kg Mep offers the most effective and safe results to overcome need for restraint for moderate and severe levels of anxiety, respectively."( Retrospective Comparisons of the Efficacy and Safety of Variable dosing of Midazolam with and without Meperidine for Management of Varying Levels of Anxiety of Pediatric Dental Patients: 35 years of Sedation Experience.
Nathan, JE, 2022
)
0.95
" CONCLUSIONS High-dose dexmedetomidine with a single dose of midazolam might be an effective combination at the induction stage for pediatric sedation for MRI, with very few adverse events."( Safety of Dexmedetomidine as an Alternative Pediatric Magnetic Resonance Imaging (MRI) Sedative: A Retrospective Single-Center Study.
Bukauskas, T; Liaudanskytė, K; Lukošienė, L; Macas, A; Razlevičė, I; Stremaitytė, V, 2022
)
0.96
"Perioperative respiratory adverse events (PRAEs) are the most common complication during pediatric anesthesia, and they may be affected by the administration of preoperative sedatives."( Effect of Intranasal Dexmedetomidine or Midazolam for Premedication on the Occurrence of Respiratory Adverse Events in Children Undergoing Tonsillectomy and Adenoidectomy: A Randomized Clinical Trial.
Chen, C; Liu, H; Shen, F; Wang, X; Xia, J; Xu, Y; Zhang, Q; Zhang, Y, 2022
)
0.99
"76), but no other serious clinical adverse events were observed."( Effect of Intranasal Dexmedetomidine or Midazolam for Premedication on the Occurrence of Respiratory Adverse Events in Children Undergoing Tonsillectomy and Adenoidectomy: A Randomized Clinical Trial.
Chen, C; Liu, H; Shen, F; Wang, X; Xia, J; Xu, Y; Zhang, Q; Zhang, Y, 2022
)
0.99
" The fundamentals of providing safe sedation include careful patient assessment, patient preparation, a good understanding of the complexity of treatment, and an appropriately trained team."( Safe intravenous sedation for oral surgery in a primary care setting.
Nayani-Low, S; Patel, J, 2022
)
0.72
" The efficacy and safety of the sedations including sedation time intervals, nausea score, vomiting episodes, pain score, adverse effects, and parent's satisfaction were evaluated."( The efficacy and safety of midazolam with fentanyl versus midazolam with ketamine for bedside invasive procedural sedation in pediatric oncology patients: A randomized, double-blinded, crossover trial.
Lertvivatpong, N; Malaithong, W; Monsereenusorn, C; Photia, A; Rujkijyanont, P; Traivaree, C, 2022
)
1.02
"Analyses were performed to investigate relationships between dose administered, age, individual reactions, adverse effects and changes in dive physiology."( Using a combination of midazolam and butorphanol is a safe and effective reversible field sedation protocol for Weddell seal (Leptonychotes weddellii) pups.
Brodie, E; Harris, HS; Johnson, S; Liwanag, HEM; Pearson, LE; Whitmer, ER; Whoriskey, S, 2022
)
1.03
"2 mg/kg) provided safe and effective sedation, with reversible effects, in Weddell seal pups."( Using a combination of midazolam and butorphanol is a safe and effective reversible field sedation protocol for Weddell seal (Leptonychotes weddellii) pups.
Brodie, E; Harris, HS; Johnson, S; Liwanag, HEM; Pearson, LE; Whitmer, ER; Whoriskey, S, 2022
)
1.03
"The combination of intranasal midazolam-butorphanol and intramuscular alfaxalone at the doses examined was a safe and effective method for sedating Quaker parrots."( Intranasal butorphanol and midazolam administered prior to intramuscular alfaxalone provides safe and effective sedation in Quaker parrots (Myiopsitta monachus).
Conner, CM; Hoppes, SM; Simon, BT; Stevens, BJ, 2022
)
1.31
" However, cardiac and pulmonary adverse events are the primary concerns associated with the use of these sedatives."( Efficacy and safety of remimazolam tosylate for sedation during upper gastrointestinal endoscopy: study protocol for a multicenter randomized controlled trial.
Chen, C; Huai, X; Su, D; Su, Z; Zhang, X; Zhou, J; Zhu, H, 2022
)
0.72
" Adverse events will be recorded to evaluate safety."( Efficacy and safety of remimazolam tosylate for sedation during upper gastrointestinal endoscopy: study protocol for a multicenter randomized controlled trial.
Chen, C; Huai, X; Su, D; Su, Z; Zhang, X; Zhou, J; Zhu, H, 2022
)
0.72
" Condition of parental separation, anesthesia induction or facemask acceptance, sedation level, different hemodynamic parameters and adverse events were considered as the outcomes in our study."( Efficacy and safety of intranasal midazolam versus intranasal ketamine as sedative premedication in pediatric patients: a meta-analysis of randomized controlled trials.
Chen, S; Fu, Y; Huang, L; Jia, ZJ; Lang, B; Wang, H; Zeng, L; Zhang, L; Zhang, Q, 2022
)
1
" Current evidences also indicated that the differences of various adverse effects between two groups were not significant."( Efficacy and safety of intranasal midazolam versus intranasal ketamine as sedative premedication in pediatric patients: a meta-analysis of randomized controlled trials.
Chen, S; Fu, Y; Huang, L; Jia, ZJ; Lang, B; Wang, H; Zeng, L; Zhang, L; Zhang, Q, 2022
)
1
"To determine the anesthetic approach with the least adverse events and better cardiorespiratory stability profile, used in infants undergoing laser photocoagulation for retinopathy of prematurity."( Safety profile of anesthetic modalities during laser treatment for retinopathy of prematurity: a systematic review.
Arvanitaki, Z; Gavriilidou, A; Haidich, AB; Mataftsi, A; Seliniotaki, AK; Ziakas, N, 2023
)
0.91
" Dexmedetomidine has a safe profile in the pediatric population and can therefore represent an interesting alternative."( Prospective, randomized, double-blind, double-dummy, active-controlled, phase 3 clinical trial comparing the safety and efficacy of intranasal dexmedetomidine to oral midazolam as premedication for propofol sedation in pediatric patients undergoing magnet
Caruso, G; De Pooter, F; Fils, JF; Giancursio, M; Schmartz, D; Van der Linden, P; Wabelo, ON, 2023
)
1.11
" Adverse events occurred in eight patients (1."( Safety of endoscopic ultrasound-guided fine-needle aspiration for pancreatic solid mass in the elderly: A single-center retrospective study.
Iino, Y; Kan, M; Kato, N; Kusakabe, Y; Nagashima, H; Ohno, I; Ohyama, H; Okitsu, K; Ouchi, M; Sekine, Y; Sugihara, C; Takahashi, K; Takiguchi, Y; Toyama, S; Yamada, N, 2023
)
0.91
"Our analysis suggests that EUS-FNA for pancreatic solid masses can be safely performed in patients aged >80 years without increasing the adverse event rate compared to nonelderly patients aged <80 years."( Safety of endoscopic ultrasound-guided fine-needle aspiration for pancreatic solid mass in the elderly: A single-center retrospective study.
Iino, Y; Kan, M; Kato, N; Kusakabe, Y; Nagashima, H; Ohno, I; Ohyama, H; Okitsu, K; Ouchi, M; Sekine, Y; Sugihara, C; Takahashi, K; Takiguchi, Y; Toyama, S; Yamada, N, 2023
)
0.91
" However, it is important to find safer and more effective sedation agents, considering the adverse effects associated with current agents."( Efficacy and safety of remimazolam besilate for sedation in outpatients undergoing impacted third molar extraction: a prospective exploratory study.
Aikawa, T; Doi, M; Imado, E; Imamura, S; Kamio, H; Mukai, A; Oda, A; Ono, S; Oue, K; Sakuma, M; Sasaki, U; Shimizu, Y; Takahashi, T; Yoshida, M, 2023
)
0.91
" The primary endpoint was the sedation success rate with remimazolam monotherapy, and the secondary endpoints included induction time, recovery time, time until discharge, remimazolam dose, respiratory and circulatory dynamics, and frequency of adverse events."( Efficacy and safety of remimazolam besilate for sedation in outpatients undergoing impacted third molar extraction: a prospective exploratory study.
Aikawa, T; Doi, M; Imado, E; Imamura, S; Kamio, H; Mukai, A; Oda, A; Ono, S; Oue, K; Sakuma, M; Sasaki, U; Shimizu, Y; Takahashi, T; Yoshida, M, 2023
)
0.91
" Laboratory tests, adverse events, and the length of ICU stay were considered secondary outcomes."( Remimazolam tosylate's long-term sedative properties in ICU patients on mechanical ventilation: effectiveness and safety.
Li, G; Liao, Z; Wang, L; Xia, W; Yao, Z; Zhan, L, 2023
)
0.91
" The Richmond Agitation and Sedation Scale scores, length of ICU stay, and occurrence of adverse events did not exhibit significant differences between the two groups."( Remimazolam tosylate's long-term sedative properties in ICU patients on mechanical ventilation: effectiveness and safety.
Li, G; Liao, Z; Wang, L; Xia, W; Yao, Z; Zhan, L, 2023
)
0.91
"Remimazolam tosylate did not increase the total inpatient cost, the incidence of adverse events, and ICU mortality in patients with mechanical ventilation."( Remimazolam tosylate's long-term sedative properties in ICU patients on mechanical ventilation: effectiveness and safety.
Li, G; Liao, Z; Wang, L; Xia, W; Yao, Z; Zhan, L, 2023
)
0.91
" Other procedural time parameters, satisfaction profiles, and adverse effects were thoroughly evaluated."( Safety and efficacy of remimazolam compared with midazolam during bronchoscopy: a single-center, randomized controlled study.
Cho, JY; Choe, KH; Chung, JM; Han, JH; Kim, EG; Kim, M; Kim, SH; Lee, KM; Seok, JW; Seong, C; Shin, YM; Yang, B; Yang, J, 2023
)
1.16

Pharmacokinetics

Pharmacokinetic profiles of midazolam were similar for all four species, especially with regard to the area under the plasma drug concentration-time curve. This pharmacokinetic and pharmacodynamic analysis does not provide evidence for different dosing of midzolam in children with Down syndrome after cardiac surgery.

ExcerptReferenceRelevance
" By means of pharmacodynamic models, the effects on the CBF could be predicted from the arterial drug concentrations."( Ketamine and midazolam decrease cerebral blood flow and consequently their own rate of transport to the brain: an application of mass balance pharmacokinetics with a changing regional blood flow.
Akeson, J; Björkman, S; Messeter, K; Nilsson, F; Roth, B, 1992
)
0.65
"The pharmacokinetic and pharmacodynamic interaction between the benzodiazepine agonist midazolam and antagonist flumazenil was quantified in vivo in rats, using effect parameters derived from aperiodic EEG analysis."( In vivo characterization of the pharmacodynamic interaction of a benzodiazepine agonist and antagonist: midazolam and flumazenil.
Danhof, M; Mandema, JW; Tukker, E, 1992
)
0.72
" The pharmacokinetic profile was affected by age, sex and anaesthetic technique."( Effect of age, sex and anaesthetic technique on the pharmacokinetics of atracurium.
Hunter, JM; Parker, CJ; Snowdon, SL, 1992
)
0.28
"9 l/kg, mean elimination half-life was 77 +/- 18 min, and clearance was 27 +/- 3 ml/kg/min."( Pharmacokinetics and preliminary observations of behavioral changes following administration of midazolam to dogs.
Court, MH; Greenblatt, DJ, 1992
)
0.5
"The pharmacokinetic and pharmacodynamic interactions between the benzodiazepine agonist midazolam, on one hand, and the partial agonist bretazenil and inverse agonist Ro 19-4603, on the other, were characterized in vivo in rats using effect parameters derived from quantitative EEG analysis."( In vivo modeling of the pharmacodynamic interaction between benzodiazepines which differ in intrinsic efficacy.
Danhof, M; Kuck, MT; Mandema, JW, 1992
)
0.51
"Midazolam is a water soluble benzodiazepine, with a short elimination half-life in adults and children."( Pharmacokinetics of midazolam during continuous infusion in critically ill neonates.
Beaufils, F; Burtin, P; Daoud, P; Jacqz-Aigrain, E; Maherzi, S, 1992
)
2.05
" Plasma drug concentrations for pharmacokinetic calculations were estimated from samples drawn up to 24 hours after drug intake."( Exercise alters the pharmacokinetics of midazolam.
Laitinen, LA; Lindqvist, A; Olkkola, KT; Seppälä, T; Strömberg, C; Vanakoski, J, 1992
)
0.55
"Measurements included plasma concentration time profiles of midazolam and pharmacokinetic parameters, such as elimination half-life, clearance, and volume of distribution."( Pharmacokinetics of midazolam administered by continuous intravenous infusion to intensive care patients.
Crevoisier, C; Fritz, ME; Malacrida, R; Suter, PM, 1992
)
0.85
" Consequently, its plasma elimination half-life after discontinuation was also greatly prolonged, but this shouldn't cause very prolonged sedative effects since this metabolite is much less active than the parent drug."( The effects of acute changes in renal function on the pharmacokinetics of midazolam during long-term infusion in ICU patients.
Driessen, JJ; Guelen, PJ; Vree, TB, 1991
)
0.51
" The potential exists for many clinically significant pharmacokinetic interactions between these and other concurrently administered drugs."( Pharmacokinetic interactions with calcium channel antagonists (Part I).
Bottorff, MB; Myre, SA; Schlanz, KD, 1991
)
0.28
" Reanalysis of the EEG data using mean population pharmacokinetic parameters as input to the pharmacodynamic model led to poorer estimation of the pharmacodynamic parameters: particularly EC50."( A population analysis of the pharmacokinetics and pharmacodynamics of midazolam in the rat.
Aarons, L; Danhof, M; Mandema, JW, 1991
)
0.52
" After both routes of administration the half-life was similar (2."( Pharmacokinetics of midazolam in children: comparative study of intranasal and intravenous administration.
Delaunay, L; Murat, I; Olive, G; Pons, G; Rey, E; Richard, MO; Saint-Maurice, C, 1991
)
0.6
" Clearance, volume of distribution, and terminal elimination (beta) half-life were estimated from a biexponential fit of the serial plasma midazolam concentrations."( Pharmacokinetic and pharmacodynamic study of midazolam in children during esophagogastroduodenoscopy.
Aravind, MK; Brennan, S; Kauffman, RE; Tolia, V, 1991
)
0.74
" In particular, the elimination half-life was prolonged (10."( Postoperative sedation with midazolam in heart surgery patients: pharmacokinetic considerations.
Maitre, PO, 1990
)
0.57
" Pharmacokinetic analysis in 20 patients showed that the elimination half-life of propofol was prolonged (470 minutes) and clearance was reduced (1."( Propofol sedation after open heart surgery. A clinical and pharmacokinetic study.
Carson, IW; Collier, PS; Elliott, P; Lyons, SM; McMurray, TJ, 1990
)
0.28
" Arterial plasma concentration and electroencephalogram voltage were related with nonparameteric and parametric pharmacodynamic models."( Electroencephalographic effects of benzodiazepines. II. Pharmacodynamic modeling of the electroencephalographic effects of midazolam and diazepam.
Bührer, M; Crevoisier, C; Maitre, PO; Stanski, DR, 1990
)
0.49
"Midazolam is a water soluble benzodiazepine, with a short elimination half-life in adults and children."( Pharmacokinetics of midazolam in critically ill neonates.
Jacqz-Aigrain, E; Robieux, I; Wood, C, 1990
)
2.05
"Differences in pharmacokinetic data of aminoglycosides, ceftazidime and ceftriaxone between intensive care patients and volunteers or patients who are less severely ill, are described."( Pharmacokinetics of antibiotics in critically ill patients.
van Dalen, R; Vree, TB, 1990
)
0.28
"It has recently been shown by several investigators that the half-life (t1/2) of midazolam is prolonged (greater than 7 h) in a small proportion of the population."( Increased volume of distribution prolongs midazolam half-life.
Khoo, KC; Patel, IH; Soni, PP; Wills, RJ, 1990
)
0.77
"The pharmacokinetic parameters of 16 patients in the intensive care unit, sedated with midazolam, were evaluated."( Decreased plasma albumin concentration results in increased volume of distribution and decreased elimination of midazolam in intensive care patients.
Dirksen, MS; Driessen, JJ; Guelen, PJ; Hafkenscheid, JC; Janssen, TJ; Shimoda, M; Termond, EF; van Dalen, R; Vree, TB, 1989
)
0.71
"In children, rectal midazolam is being used increasingly for premedication, as this substance is reported to have a short half-life and rapid action."( [Pharmacokinetic studies following intravenous and rectal administration of midazolam in children].
Danner, U; Gruber, RG; Knoll, R; Kraus, GB, 1989
)
0.83
"721 h-1), and longer elimination half-life (7."( Pharmacokinetics of midazolam following intravenous and oral administration in patients with chronic liver disease and in healthy subjects.
Crevoisier, C; Himberg, JJ; Pentikäinen, PJ; Välisalmi, L, 1989
)
0.6
" The aims of this study were to determine the pharmacokinetic data of midazolam following different doses and to test whether a correlation exists between its plasma level and sedative effect."( [The pharmacokinetics of midazolam following intramuscular administration].
Asskali, F; Behne, M; Förster, H; Janshon, G, 1989
)
0.81
" The pharmacokinetic parameters of midazolam were determined using both moment analysis and the program NONMEM."( Pharmacokinetics of midazolam in patients recovering from cardiac surgery.
Crevoisier, C; Funk, B; Ha, HR; Maitre, PO, 1989
)
0.88
"The pharmacodynamic interaction between midazolam and the specific benzodiazepine antagonist Ro 15-1788 has been investigated in six healthy male volunteers."( Pharmacodynamic interaction between midazolam and a specific benzodiazepine antagonist in humans.
Klotz, U; Ludwig, L; Reimann, IW; Ziegler, G, 1985
)
0.81
"5 mg dose, the Cmax and AUC parameters of both midazolam and 1-hydroxymethylmidazolam increased proportionally after the 15 mg dose and more than proportionally after the 30 mg dose."( Dose dependent pharmacokinetics of midazolam.
Blumenthal, HP; Bornemann, LD; Colburn, WA; Crews, T; Min, BH; Patel, IH; Rees, MM, 1985
)
0.8
" The pharmacokinetic parameters based on gas-liquid chromatographic measurements were quite comparable with those in young, healthy persons published earlier."( Midazolam as an intravenous induction agent in the elderly: a clinical and pharmacokinetic study.
Aaltonen, L; Himberg, JJ; Hovi-Viander, M; Kanto, J, 1986
)
1.71
"The authors studied the pharmacokinetic behaviour of a new benzodiazepine, midazolam, after a single oral administration in a group of five patients of both sexes, suffering from compensated alcoholic cirrhosis."( A pharmacokinetic study on midazolam in compensated liver cirrhosis.
Ascalone, V; Cisternino, M; Colombi Zinelli, L; Rinetti, M, 1985
)
0.8
"58 litre kg-1, resulting in a terminal half-life of 112 min."( Pharmacokinetics of alfentanil in total i.v. anaesthesia.
Hartvig, P; Nilsson, A; Persson, MP, 1988
)
0.27
"The usefulness of radioreceptor assay (RRA) in the pharmacokinetic studies on midazolam - the first benzodiazepine with water-soluble salts - was compared with that of gas liquid chromatography (GLC) in 18 patients operated on under local anesthesia in supine position."( The usefulness of radioreceptor assay and gas liquid chromatography in pharmacokinetic studies on midazolam.
Aaltonen, L; Himberg, JJ; Kanto, J; Vuori, A, 1985
)
0.71
" The short elimination half-life of midazolam (2."( Age and nature of operation influence the pharmacokinetics of midazolam.
Collier, PS; Dundee, JW; Elliott, P; Halliday, NJ; Harper, KW; Lowry, KG, 1985
)
0.78
"3 mg kg-1 was given as a single dose to three groups of children undergoing cardiac surgery to determine its pharmacokinetic profile in this situation."( A pharmacokinetic study of midazolam in paediatric patients undergoing cardiac surgery.
Carson, IW; Collier, PS; Dundee, JW; Howard, PJ; Lyons, SM; Mathews, HM; Orr, IA, 1988
)
0.57
" Based on the pharmacokinetic parameters determined for Group 1, dogs in Group 2 (n = 4) received Mid as a continuous infusion of 21 micrograms kg-1 min-1 for 5 hr accompanied by an initial loading dose (3 mg/kg infused over 20 min) designed to produce a stable [MID] of 1000 ng/ml in plasma."( Pharmacokinetics and pharmacodynamics of midazolam in the enflurane-anesthetized dog.
Hall, RI; Hug, CC; Szlam, F, 1988
)
0.54
" Comparison of young men vs elderly men, young women vs elderly women, young men vs young women, elderly men vs elderly women, and young women OCS-users vs young women non-OCS users indicated no substantial differences in the pharmacokinetic profile of midazolam between groups except for the comparison between the young and elderly men groups."( Effects of age, gender and oral contraceptives on intramuscular midazolam pharmacokinetics.
Holazo, AA; Patel, IH; Winkler, MB, 1988
)
0.69
" In only one patient was midazolam serum elimination half-life less than 2 hours and in six patients the half-life was greater than 10 hours."( Clinical pharmacokinetics of midazolam in intensive care patients, a wide interpatient variability?
de Jong, M; Janknegt, R; Oldenhof, H; Steenhoek, A, 1988
)
0.87
" Using the two-compartment model we estimated distribution half-life (t1/2a), elimination half-life (t1/2el), clearance (Cl), and volumes of distribution (Vz = volume in elimination phase)."( [The pharmacokinetics of midazolam in various kinds of anesthesia].
Asskali, F; Behne, M; Förster, H; Kessler, P; Seiz, W; Zobel, R, 1987
)
0.58
"94 litre kg-1) and terminal half-life (3."( Pharmacokinetics of midazolam in total i.v. anaesthesia.
Hartvig, P; Nilsson, A; Persson, P; Tamsen, A, 1987
)
0.6
" The pharmacokinetic variables describing the absorption and disposition of midazolam were determined in five of the volunteers."( Dose-finding and pharmacokinetic study of intramuscular midazolam.
Avram, MJ; Caldwell, NJ; Fragen, RJ, 1987
)
0.75
"Diazepam, flunitrazepam and midazolam have different pharmacokinetic properties, their biological halflives for instance, being 24 to 48 hours, 4,5 hours and 2,5 hours respectively."( [Clinical pharmacokinetics of midazolam, flunitrazepam and diazepam (author's transl)].
Lauven, PM; Schüttler, J; Schwilden, H; Stoeckel, H, 1981
)
0.85
"83 h and there was no significant difference between the mean terminal half-life values obtained for the three midazolam formulations."( The pharmacokinetics of midazolam in man.
Brophy, TO; Eadie, MJ; Smith, MT, 1981
)
0.78
" The pharmacokinetic properties of these newer drugs can best be understood by their categorisation according to range of elimination half-life and pathway of metabolism (oxidation versus conjugation)."( Clinical pharmacokinetics of the newer benzodiazepines.
Abernethy, DR; Divoll, M; Greenblatt, DJ; Ochs, HR; Shader, RI,
)
0.13
"The pharmacokinetic behaviour and the bioavailability of midazolam were investigated in six volunteers after intravenous (0."( Pharmacokinetics and bioavailability of midazolam in man.
Eckert, M; Heizmann, P; Ziegler, WH, 1983
)
0.78
"The pharmacokinetics and their relation to the pharmacodynamic properties of midazolam, the first water-soluble benzodiazepine derivative, are reviewed."( Pharmacokinetics and the sedative effect of midazolam.
Allonen, H; Kanto, J, 1983
)
0.76
" The pharmacokinetic and protein binding parameters in man as well as the ex vivo receptor binding parameters in rat brain for three benzodiazepine induction agents, diazepam, lorazepam and midazolam, were used to develop and test a pharmacokinetic/pharmacodynamic/receptor binding model."( A pharmacokinetic/pharmacodynamic/receptor binding model to predict the onset and duration of pharmacological activity of the benzodiazepines.
Bautz, G; Colburn, WA; Horst, WD; Jack, ML; O'Brien, RA; Spirt, NM; Zanko, M, 1983
)
0.46
"Large differences exist among the various benzodiazepines with regard to their pharmacokinetic properties and metabolism in man."( Pharmacokinetics of benzodiazepines: metabolic pathways and plasma level profiles.
Breimer, DD; Jochemsen, R, 1984
)
0.27
" In addition, the pharmacodynamic response to the new sedative/hypnotic benzodiazepine was characterised by a pencil tracking test, sedation index formed from visual analogue scales, and choice reaction time."( Chronopharmacokinetic study with prolonged infusion of midazolam.
Klotz, U; Reimann, IW,
)
0.38
" The pharmacokinetic parameters in CRF patients were compared with those of healthy volunteers matched for age, sex, and body size with the CRF patients."( The pharmacokinetics of midazolam in chronic renal failure patients.
Abernethy, DR; Greenblatt, DJ; Reves, JG; Smith, LR; Vinik, HR, 1983
)
0.57
" The serum levels of the parent drug and its active metabolites were determined in six cases by a radioreceptor assay and pharmacokinetic parameters were calculated on the basis of these levels by a two-compartment open model."( Pharmacokinetics and sedative effect of midazolam in connection with caesarean section performed under epidural analgesia.
Aaltonen, L; Aärimaa, L; Erkkola, R; Kanto, J, 1984
)
0.54
" After intravenous dosing, the mean (+/- SD) elimination half-life (2."( Pharmacokinetics of midazolam in the aged.
Brophy, TO; Eadie, MJ; Heazlewood, V; Smith, MT; Tyrer, JH, 1984
)
0.59
" Dosage rules based on pharmacokinetic principles, for repeated administration and infusion are outlined for the induction, maintenance and termination of anaesthesia."( [Principles of clinical pharmacokinetics in anaesthesiology (author's transl)].
Lauven, PM; Schüttler, J; Schwilden, H; Stoeckel, H, 1982
)
0.26
" The utility of the RIA for the pharmacokinetic evaluation of midazolam is illustrated with plasma concentration profiles of the drug obtained in subjects who had received midazolam intravenously, intramuscularly and orally."( Midazolam: radioimmunoassay for pharmacokinetic studies in man.
Dixon, R; Lucek, R; Todd, D; Walser, A, 1982
)
1.95
" The half-life of the slow redistribution and elimination phase (beta-phase) amounted to a mean of about 150 min."( [Pharmacokinetics of midazolam in man (author's transl)].
Greenblatt, DJ; Lauven, PM; Ochs, H; Stoeckel, H, 1981
)
0.58
" In sessions 2 and 3, a computer-controlled infusion of midazolam with individual volunteer pharmacokinetic data was administered, targeting a plasma concentration corresponding to a light or deep level of sedation (20% or 80% of the maximal midazolam electroencephalographic effect) for a period of 210 minutes."( Pharmacodynamic modeling of the electroencephalographic effects of flumazenil in healthy volunteers sedated with midazolam.
Egan, TD; Egan, TE; Fiset, P; Lemmens, HL; Shafer, SL; Stanski, DR, 1995
)
0.75
"The pharmacokinetic and pharmacodynamic interactions between midazolam and ethanol were studied in the rat in vivo."( Pharmacodynamic interaction between midazolam and a low dose of ethanol in vivo.
Danhof, M; Hoyo-Vadillo, C; Mandema, JW, 1995
)
0.81
" Pharmacokinetic and pharmacodynamic data were simultaneously fitted to a semiparametric model."( Simultaneous modeling of the pharmacokinetics and pharmacodynamics of midazolam and diazepam.
Choma, N; Crews, T; DeFeo, TM; Limjuco, R; Milla, G; Mould, DR; Patel, IH; Reele, S, 1995
)
0.53
" Simulations of the times required for 20%, 50%, and 80% decreases in midazolam concentrations after stopping an infusion that maintains a constant plasma midazolam concentration were performed, comparing pharmacokinetic variables from this study with previously published values."( Midazolam pharmacokinetics in patients undergoing abdominal aortic surgery.
Hudson, RJ, 1994
)
1.97
") using a pharmacokinetic model-driven drug infusion device to achieve a plasma midazolam concentration that was held constant for the 10-min duration of the study."( Aging increases pharmacodynamic sensitivity to the hypnotic effects of midazolam.
Bai, SA; Jacobs, JR; Marty, J; Reves, JG; Smith, LR; White, WD, 1995
)
0.75
" Median (range) values of pharmacokinetic parameters for sufentanil were: t1/2,z = 16 (7-49) h; CL = 1215 (519-2550) ml min-1; CLR = 7 (2-38) ml min-1; Vss = 10."( Pharmacokinetics and effects on intracranial pressure of sufentanil in head trauma patients.
Bause, H; Klotz, U; Krishna, DR; Pohl, S; Scholz, J; Schulte am Esch, J; Schulz, M, 1994
)
0.29
" There was a large interindividual variability for the pharmacokinetic parameters."( Population pharmacokinetics of midazolam in neonates.
Betremieux, P; Burtin, P; Desplanques, L; Girard, P; Jacqz-Aigrain, E; Lenclen, R; Magny, JF; Mussat, P; Tehiry, C, 1994
)
0.57
" To determine whether there are parallel or divergent rates of elimination of the two drugs between individuals, the pharmacokinetic profiles of midazolam and flumazenil were studied simultaneously in 12 adult male volunteers."( Midazolam and flumazenil pharmacokinetics and pharmacodynamics following simultaneous administration to human volunteers.
Gin, T; Oh, TE; Short, TG; Tam, YH; Tan, P; Young, KK, 1994
)
1.93
" All infusions were administered via pharmacokinetic model-controlled syringe pumps programmed to maintain a constant plasma concentration."( Pharmacokinetic interactions between midazolam and propofol: an infusion study.
Short, TG; Tan, P; Teh, J; Wong, J, 1994
)
0.56
" Changes in the pharmacodynamics due to the sauna were consistent with the pharmacokinetic findings: midazolam decreased flicker recognition and induced exophoria significantly less during the early sauna period than in the control session, whereas ephedrine made the volunteers subjectively more alert at that time."( Effects of a sauna on the pharmacokinetics and pharmacodynamics of midazolam and ephedrine in healthy young women.
Seppälä, T; Strömberg, C; Vanakoski, J, 1993
)
0.74
" The elimination half-life of midazolam was about 3 times longer in hepatectomy group (24."( [Pharmacokinetics of midazolam in patients with liver damage for hepatectomy].
Hirasaki, A; Iwasaki, T; Konishi, H; Nishiyama, T; Seto, K; Toda, N, 1993
)
0.89
" A four-parameter threshold pharmacodynamic model was fitted to the data in each patient."( Effect of age, gender and anaesthetic technique on the pharmacodynamics of atracurium.
Hunter, JM; Parker, CJ; Snowdon, SL, 1993
)
0.29
"The accuracy of a computer-controlled infusion of midazolam, based on previously published pharmacokinetic parameters, was tested prospectively in 12 adult female patients undergoing general anaesthesia."( Pharmacokinetic model-controlled infusion of midazolam. A prospective evaluation during general anaesthesia.
Oh, TE; Short, TG; Tam, YH; Tan, P, 1993
)
0.8
" Midazolam data were consistent with a three-compartment model with a mean (SD) elimination half-life of 107 (30) min, total body clearance of 15."( Pharmacokinetics of flumazenil and midazolam.
Brown, AG; Chan, K; Jones, RD; Mya, GH; Roulson, CJ; Smith, ID, 1993
)
1.47
" The elimination phase half-life of midazolam was about twice as long as reported earlier in healthy adult volunteers, but ageing did not affect the elimination of flunitrazepam."( Midazolam and flunitrazepam: pharmacokinetics and effects on night time respiration and body movements in the elderly.
Alihanka, J; Himberg, JJ; Kanto, J; Rajala, T; Seppälä, M; Sourander, L, 1993
)
2
"The pharmacokinetic and pharmacodynamic interaction between azithromycin (CAS 83905-01-5), an azalide antibiotic, and midazolam (CAS 59467-70-8), a short-acting hypnotic agent, was investigated in an open, three-way cross-over study, including erythromycin (CAS 114-07-8) as a positive control."( Influence of the antibiotics erythromycin and azithromycin on the pharmacokinetics and pharmacodynamics of midazolam.
Laufen, H; Leitold, M; Scharpf, F; Wildfeuer, A; Yeates, RA; Zimmermann, T, 1996
)
0.72
" The bioavailability values assessed from DRL performance also agree with the measured pharmacokinetic values."( Pharmacokinetics and bioavailability of midazolam after intravenous, subcutaneous, intraperitoneal and oral administration under a chronic food-limited regimen: relating DRL performance to pharmacokinetics.
Lau, CE; Ma, F; Smith, C; Wang, Y, 1996
)
0.56
" Midazolam Cmax was increased and its t1/2 beta was prolonged during the sauna session, but the clinical relevance of the findings appears to be modest."( Effects of heat exposure in a Finnish sauna on the pharmacokinetics and metabolism of midazolam.
Idänpään-Heikkilä, JJ; Olkkola, KT; Seppälä, T; Vanakoski, J, 1996
)
1.43
" We describe the first set of experiments which directly measure agonist-induced changes in both pharmacodynamic effects and pharmacokinetic parameters simultaneously and which demonstrate the feasibility of these studies in man."( Benzodiazepine site pharmacokinetic/pharmacodynamic quantification in man: direct measurement of drug occupancy and effects on the human brain in vivo.
Bloomfield, PM; Cunningham, VJ; Gunn, RN; Malizia, AL; Nutt, DJ; Waters, SH; Wilson, SJ, 1996
)
0.29
" No significant differences were found between the Vietnamese and Caucasian groups with regard to distribution half-life of midazolam (8."( Pharmacokinetics of midazolam in Vietnamese subjects.
Balson, KR; Elliott, SL; McAlindon, ME; Morgan, DJ; Richmond, BH; Yeomans, ND, 1996
)
0.82
"This study investigated the pharmacodynamic effects and sedative potential of midazolam administered by the intranasal route to adult volunteers."( Intranasal administration of midazolam: pharmacokinetic and pharmacodynamic properties and sedative potential.
Braham, RL; Fukuta, O; Kurosu, K; Yanase, H,
)
0.65
"This study in rats was performed to explore whether the inhibitory effect of midazolam on the development of acute tolerance to the analgesic effect of alfentanil is due to pharmacokinetic mechanisms."( Effect of midazolam on development of acute tolerance to alfentanil: the role of pharmacokinetic interactions.
Arthur, GR; Bradley, EL; Kissin, I; Lee, SS, 1997
)
0.93
" Midazolam concentrations were also measured and pharmacokinetic parameters determined using a population modelling package."( Haemodynamic responses and population pharmacokinetics of midazolam following administration to ventilated, preterm neonates.
Charles, BG; Gray, PH; Harte, GJ; Lee, TC; Steer, PA, 1997
)
1.45
" Pharmacokinetic data were fitted using iterative two-stage analysis to a two-compartment model."( Pharmacokinetics and pharmacodynamics of midazolam after intranasal administration.
Burstein, AH; Forrest, A; Gengo, FM; Hatton, M; Modica, R, 1997
)
0.56
" Blood samples were collected frequently for pharmacokinetic determinations (two-compartment model)."( Integrated pharmacokinetics and pharmacodynamics of Ro 48-6791, a new benzodiazepine, in comparison with midazolam during first administration to healthy male subjects.
Cohen, AF; Dingemanse, J; Massarella, J; Oberyé, JJ; Roncari, G; Schoemaker, RC; Segala, P; van Gerven, JM; van Oostenbruggen, MF; Zell, M, 1997
)
0.51
" Ro 48-6792, a metabolite of Ro 48-6791, showed a considerably longer half-life than the parent compound."( Integrated pharmacokinetics and pharmacodynamics of Ro 48-6791, a new benzodiazepine, in comparison with midazolam during first administration to healthy male subjects.
Cohen, AF; Dingemanse, J; Massarella, J; Oberyé, JJ; Roncari, G; Schoemaker, RC; Segala, P; van Gerven, JM; van Oostenbruggen, MF; Zell, M, 1997
)
0.51
" The metabolite Ro 61-2466 had a longer half-life than the parent compound Ro 48-8684."( Integrated pharmacokinetics and pharmacodynamics of Ro 48-8684, a new benzodiazepine, in comparison with midazolam during first administration to healthy male subjects.
Cohen, AF; Dingemanse, J; Heizmann, P; Keesmaat, P; Kooyman, H; Massarella, J; Roncari, G; Schoemaker, RC; van Gerven, JM; Zell, M, 1997
)
0.51
"In the present investigation, the extent of arteriovenous concentration differences of midazolam in rats was quantified, and the consequences of these differences on the pharmacodynamic estimates were determined."( Relevance of arteriovenous concentration differences in pharmacokinetic-pharmacodynamic modeling of midazolam.
Danhof, M; Herben, VM; Mandema, JW; Tuk, B, 1998
)
0.74
"This report includes a recalculation of the pooled data of 2 pharmacokinetic and pharmacodynamic studies of the interaction between the hypnotic midazolam and the antibiotics erythromycin, clarithromycin (macrolides), and azithromycin (an azalide)."( Pharmacokinetic and pharmacodynamic interaction study between midazolam and the macrolide antibiotics, erythromycin, clarithromycin, and the azalide azithromycin.
Laufen, H; Schumacher, T; Yeates, RA; Zimmermann, T, 1997
)
0.74
"To determine whether age-dependent pharmacokinetic and pharmacodynamic alterations account for a more pronounced response to benzodiazepines among elderly patients."( Pharmacokinetics and the pharmacodynamic action of midazolam in young and elderly patients undergoing tooth extraction.
Dilger, K; Klotz, U; Mikus, G; Platten, HP; Schweizer, E, 1998
)
0.55
"Elderly patients are more sensitive to the sedative action of midazolam than young patients, and the sensitivity is caused by age-dependent pharmacodynamic alterations."( Pharmacokinetics and the pharmacodynamic action of midazolam in young and elderly patients undergoing tooth extraction.
Dilger, K; Klotz, U; Mikus, G; Platten, HP; Schweizer, E, 1998
)
0.79
"To compare the pharmacokinetic behaviour of doxacurium in patients undergoing normothermic or hypothermic cardiopulmonary bypass (CPB) for coronary artery bypass graft surgery."( Pharmacokinetics of doxacurium during normothermic and hypothermic cardiopulmonary bypass surgery.
Asokumar, B; Cheng, D; Chung, F; Peniston, C; Sandler, A; Varin, F, 1998
)
0.3
" Timed blood and urine samples were collected and pharmacokinetic parameters were estimated using a non-compartmental approach."( Pharmacokinetics of doxacurium during normothermic and hypothermic cardiopulmonary bypass surgery.
Asokumar, B; Cheng, D; Chung, F; Peniston, C; Sandler, A; Varin, F, 1998
)
0.3
"For the normothermic and hypothermic groups, terminal elimination half-life (t1/2 beta) was 100."( Pharmacokinetics of doxacurium during normothermic and hypothermic cardiopulmonary bypass surgery.
Asokumar, B; Cheng, D; Chung, F; Peniston, C; Sandler, A; Varin, F, 1998
)
0.3
" A wide interpatient variability of the main pharmacokinetic parameters of midazolam was found."( Pharmacokinetics of midazolam and its main metabolite 1-hydroxymidazolam in intensive care patients.
Boulieu, R; Fisher, C; Lehmann, B; Morlet, D; Salord, F,
)
0.69
" The objective of the present study was to determine pharmacokinetic data from individual plasma concentration profiles obtained following intravenous and buccal administration of midazolam."( Midazolam pharmacokinetics following intravenous and buccal administration.
Alincic, S; Schwagmeier, R; Striebel, HW, 1998
)
1.93
"The pharmacokinetic data presented in this study demonstrate a high bioavailability and reliable plasma concentrations following buccal midazolam."( Midazolam pharmacokinetics following intravenous and buccal administration.
Alincic, S; Schwagmeier, R; Striebel, HW, 1998
)
1.95
" Animals received a single injection of MDZ (pharmacokinetic study, 10 mg/kg; pharmacodynamic study, 55."( Effects of glucocorticoids on pharmacokinetics and pharmacodynamics of midazolam in rats.
Asoh, M; Kobayashi, S; Kumai, T; Nakura, H; Tanaka, M; Tateishi, T; Watanabe, M, 1998
)
0.53
"5-30 Hz) of the EEG as derived by Fast Fourier Transformation analysis was used as pharmacodynamic endpoint."( Adaptive changes in the pharmacodynamics of midazolam in different experimental models of epilepsy: kindling, cortical stimulation and genetic absence epilepsy.
Cleton, A; Danhof, M; Voskuyl, RA, 1998
)
0.56
" Midazolam population pharmacokinetic parameters were estimated using NONMEM."( Population pharmacokinetics of midazolam administered by target controlled infusion for sedation following coronary artery bypass grafting.
Barr, J; Donner, A; Geller, E; Ramsay, J; Shafer, SL; Sladen, R; Somma, J; Zomorodi, K, 1998
)
1.5
" Typical pharmacokinetic parameters were V1 = 32."( Population pharmacokinetics of midazolam administered by target controlled infusion for sedation following coronary artery bypass grafting.
Barr, J; Donner, A; Geller, E; Ramsay, J; Shafer, SL; Sladen, R; Somma, J; Zomorodi, K, 1998
)
0.59
"The intersubject variability and predictability of the three-compartment pharmacokinetic model are similar to those of other intravenous anesthetic drugs."( Population pharmacokinetics of midazolam administered by target controlled infusion for sedation following coronary artery bypass grafting.
Barr, J; Donner, A; Geller, E; Ramsay, J; Shafer, SL; Sladen, R; Somma, J; Zomorodi, K, 1998
)
0.59
" Pharmacodynamic parameters were derived using NONMEM."( Population pharmacodynamics of midazolam administered by target controlled infusion in SICU patients after CABG surgery.
Donner, A; Geller, E; Ramsay, J; Shafer, SL; Sladen, R; Somma, J; Zomorodi, K, 1998
)
0.59
" A population analysis was conducted using a two-compartment pharmacokinetic model using the NONMEM program."( Population pharmacokinetic modeling in very premature infants receiving midazolam during mechanical ventilation: midazolam neonatal pharmacokinetics.
Charles, BG; Flenady, VJ; Gray, PH; Harte, GJ; Lee, TC; Steer, PA, 1999
)
0.54
" Serum KCZ concentrations showed an apparent nonlinear pattern of decline with a short half-life (1."( Pharmacokinetics and electroencephalographic effects of ketoconazole in the rat.
Durol, AL; Greenblatt, DJ; Kotegawa, T; Laurijssens, BE, 1999
)
0.3
"The pharmacodynamic interaction between midazolam and its active metabolite alpha-OH-midazolam was investigated to evaluate whether estimates of relevant pharmacodynamic parameters are possible after administration of a mixture of the two."( Characterization of the pharmacodynamic interaction between parent drug and active metabolite in vivo: midazolam and alpha-OH-midazolam.
Danhof, M; Herben, VM; Mandema, JW; Tuk, B; van Oostenbruggen, MF, 1999
)
0.79
"5-30 Hz) of the EEG was used as pharmacodynamic endpoint."( Rate of change of blood concentrations is a major determinant of the pharmacodynamics of midazolam in rats.
Cleton, A; Danhof, M; Mazee, D; Voskuyl, RA, 1999
)
0.53
" Pharmacokinetic data were derived from arterial blood samples with use of a three-compartment model."( The effect of age on the pharmacokinetics and pharmacodynamics of midazolam.
Albrecht, S; Dingemanse, J; Geisslinger, G; Hering, W; Ihmsen, H; Schüttler, J; Schwilden, H, 1999
)
0.54
" Pharmacokinetic parameters were similar in both groups (clearance, 399+/-91 and 388+/-97 mL/min; steady-state volume of distribution, 85+/-22 and 104 +/-11 L in young and elderly subjects, respectively)."( The effect of age on the pharmacokinetics and pharmacodynamics of midazolam.
Albrecht, S; Dingemanse, J; Geisslinger, G; Hering, W; Ihmsen, H; Schüttler, J; Schwilden, H, 1999
)
0.54
" The aim of the present investigation is to compare the pharmacokinetic parameters of midazolam tablets administered by the sublingual and intravenous routes in 6 rabbits to determine the bioequivalence between these routes."( Pharmacokinetics of midazolam: comparison of sublingual and intravenous routes in rabbit.
Barthélémy, C; Brunet, C; Cazin, JC; Cazin, M; Chatelier, D; Dine, T; Gressier, B; Luyckx, M; Odou, P; Robert, H,
)
0.68
"To examine the effect of propofol on the pharmacokinetics of midazolam in vivo and to elucidate the mechanism of the pharmacokinetic changes of midazolam by propofol with the use of human liver microsomes and recombinant CYP3A4."( Propofol decreases the clearance of midazolam by inhibiting CYP3A4: an in vivo and in vitro study.
Asada, A; Hamaoka, N; Hase, I; Ishizaki, T; Mizutani, K; Nakamoto, T; Oda, Y, 1999
)
0.82
"005) and the mean elimination half-life was prolonged by 61% (P = ."( Propofol decreases the clearance of midazolam by inhibiting CYP3A4: an in vivo and in vitro study.
Asada, A; Hamaoka, N; Hase, I; Ishizaki, T; Mizutani, K; Nakamoto, T; Oda, Y, 1999
)
0.58
" The Medline electronic database from 1966 through 1998 was used to identify clinical studies of the pharmacokinetic effect of drugs on these three benzodiazepines."( Pharmacokinetic and pharmacodynamic consequences of metabolism-based drug interactions with alprazolam, midazolam, and triazolam.
Balian, JD; Flockhart, DA; Yuan, R, 1999
)
0.52
"Several statistical regression models and artificial neural networks were used to predict the hepatic drug clearance in humans from in vitro (hepatocyte) and in vivo pharmacokinetic data and to identify the most predictive models for this purpose."( Combining in vitro and in vivo pharmacokinetic data for prediction of hepatic drug clearance in humans by artificial neural networks and multivariate statistical techniques.
Coassolo, P; Lavé, T; Schneider, G, 1999
)
0.3
" Pharmacodynamic measurements included (1) sedation score using a 5-point scale at baseline and 10-, 20-, and 30-minute postdose intervals and (2) anxiety score using a 4-point scale at the time of separation from caretakers and, when applicable, at the time of mask anesthetic induction."( Pediatric pharmacodynamics of midazolam oral syrup. Pediatric Pharmacology Research Unit Network.
Akbari, B; Blumer, J; Kearns, G; Khoo, KC; Marshall, J; Rodarte, A, 2000
)
0.6
"The pharmacodynamic (PD) interaction between the benzodiazepine agonist midazolam and the alpha(2)-adrenergic agonist dexmedetomidine was characterized for defined measures of anesthetic action and cardiovascular and ventilatory side effects in 33 rats."( Quantification of pharmacodynamic interactions between dexmedetomidine and midazolam in the rat.
Bol, CJ; Mandema, JW; Tang, JP; Vogelaar, JP, 2000
)
0.77
" Post-injection delays in either environment yielded performances that mirrored the pharmacokinetic profile operative at the corresponding time-delay points."( Post-injection delays in experimental chambers, but not in home cages, produce both sensitization and tolerance of operant behaviour to midazolam: relation to pharmacokinetics.
Falk, JL; Lau, CE; Nguyen, KN; Sun, L, 2000
)
0.51
"To evaluate the prospective predictive accuracy and the quality of anesthesia of pharmacokinetic model-driven infusion of sufentanil and midazolam designed to establish and maintain a plasma level of drug during cardiac surgery."( Pharmacokinetic model-driven infusion of sufentanil and midazolam during cardiac surgery: assessment of the prospective predictive accuracy and the quality of anesthesia.
Barvais, L; Cantraine, F; Coussaert, E; d'Hollander, A; Heitz, D; Maes, V; Schmartz, D, 2000
)
0.76
"Pharmacokinetic model-driven infusion of sufentanil and midazolam using the pharmacokinetic sets of Gepts et al and Maitre et al is a safe and accurate anesthetic technique before CPB in adult patients undergoing cardiac surgery when high sufentanil (1 to 10 ng/mL) and low midazolam (100 ng/mL) predicted plasma concentrations are targeted."( Pharmacokinetic model-driven infusion of sufentanil and midazolam during cardiac surgery: assessment of the prospective predictive accuracy and the quality of anesthesia.
Barvais, L; Cantraine, F; Coussaert, E; d'Hollander, A; Heitz, D; Maes, V; Schmartz, D, 2000
)
0.8
" The values for percent 14C exhaled during the first hour (for EBT) and the pharmacokinetic parameters of midazolam (AUC, Cmax, t1/2) were not affected following multiple once-daily oral doses of simvastatin 80 mg."( Simvastatin does not affect CYP3A activity, quantified by the erythromycin breath test and oral midazolam pharmacokinetics, in healthy male subjects.
Brucker, MJ; Gagliano, K; Gillen, L; Greenberg, HE; McLoughlin, D; Prueksaritanont, T; Rogers, JD; Vega, JM; Waldman, SA; Wong, PH, 2000
)
0.74
" In conclusion, it was demonstrated that DEX pretreatment affects not only P-gp-mediated disposition of Rho123 but also pharmacokinetic interactions of P-gp/CYP3A-related compounds with Rho123, probably because concentrations of substrates/inhibitors at target sites such as the intestine and liver are varied."( Pharmacokinetic interaction of cytochrome P450 3A-related compounds with rhodamine 123, a P-glycoprotein substrate, in rats pretreated with dexamethasone.
Murakami, T; Nagai, J; Nasu, R; Sanemasa, M; Takano, M; Yumoto, R, 2001
)
0.31
"We investigated the relationship between the pharmacokinetic variables of oral midazolam and patients' state/trait anxiety and personality."( The effect of anxiety and personality on the pharmacokinetics of oral midazolam.
Eisenhardt, S; Martens-Lobenhoffer, J; Meyer, FP; Röse, W; Tröger, U, 2001
)
0.77
"We conclude that personality traits and anxiety levels had no effect on the pharmacokinetic variables of midazolam."( The effect of anxiety and personality on the pharmacokinetics of oral midazolam.
Eisenhardt, S; Martens-Lobenhoffer, J; Meyer, FP; Röse, W; Tröger, U, 2001
)
0.76
"The aim of this study was to predict the disposition of midazolam in individual surgical patients by physiologically based pharmacokinetic (PBPK) modeling and explore the causes of interindividual variability."( Prediction of the disposition of midazolam in surgical patients by a physiologically based pharmacokinetic model.
Benoni, G; Berling, BM; Björkman, S; Wada, DR, 2001
)
0.84
" Pharmacokinetics parameters of midazolam were as follows: Cmax (191 +/- 17) nmol/L, tmax (1."( Single plasma sampling to predict oral clearance of CYP3A probe midazolam.
Cheng, ZN; Huang, SL; Ou-Yang, DS; Zhou, HH; Zhu, B, 2001
)
0.83
" Eligible study patients were enrolled into one of three study arms: Arm I (midazolam/metabolite pharmacokinetic evaluation after oral administration of a syrup formulation), Arm II (the absolute bioavailability of midazolam syrup), and Arm III (midazolam and metabolite pharmacokinetics after IV administration)."( The single-dose pharmacokinetics of midazolam and its primary metabolite in pediatric patients after oral and intravenous administration.
Akbari, B; Blumer, JL; Kearns, GL; Khoo, KC; Pou, S; Reed, MD; Rodarte, A, 2001
)
0.82
"The object of this study was to investigate the influence of midazolam on the plasma concentrations and pharmacokinetic parameters of lidocaine in rabbits."( The influence of midazolam on plasma concentrations and pharmacokinetic parameters of lidocaine in rabbits.
Orszulak-Michalak, D; Owczarek, J; Wiktorowska-Owczarek, AK, 2002
)
0.9
" No differences in pharmacokinetic or pharmacodynamic parameters were found between day 1 and day 7 in either group."( Effect of 7-day exposure to midazolam on electroencephalogram pharmacodynamics in rats: a model to study multiple pharmacokinetic-pharmacodynamic relationships in individual animals.
Greenblatt, DJ; Laurijssens, BE, 2002
)
0.61
"To investigate the pharmacokinetic and pharmacodynamic profile of midazolam administered as a concentrated intranasal spray, compared with intravenous midazolam, in healthy adult subjects."( Pharmacokinetics and pharmacodynamics of midazolam administered as a concentrated intranasal spray. A study in healthy volunteers.
Brekelmans, GJ; de Haan, GJ; Edelbroek, PM; Jonker, DM; Knoester, PD; Van Der Hoeven, RT; Vermeij, TA, 2002
)
0.82
" The total plasma concentrations of midazolam and the metabolite 1-hydroxymidazolam after both intranasal and intravenous administration were described with a single pharmacokinetic model."( Pharmacokinetics and pharmacodynamics of midazolam administered as a concentrated intranasal spray. A study in healthy volunteers.
Brekelmans, GJ; de Haan, GJ; Edelbroek, PM; Jonker, DM; Knoester, PD; Van Der Hoeven, RT; Vermeij, TA, 2002
)
0.86
" A great interindividual variability on pharmacokinetic and pharmacodynamic response was observed."( [Sedation induced by midazolam in intensive care: pharmacologic and pharmacokinetic aspects].
Bastien, O; Bolon, M; Boulieu, R; Flamens, C; Paulus, S, 2002
)
0.63
"According to midazolam pharmacokinetic and pharmacodynamic variability, an individual dosage adjustment is essential for long-term sedation."( [Sedation induced by midazolam in intensive care: pharmacologic and pharmacokinetic aspects].
Bastien, O; Bolon, M; Boulieu, R; Flamens, C; Paulus, S, 2002
)
1
" Also some other drugs may change pharmacokinetics of procainamide, for example the iv anesthetics influence on pharmacokinetic parameters of procainamide."( Influence of midazolam on pharmacokinetic parameters of procainamide in rabbits.
Orszulak-Michalak, D; Owczarek, J; Wiktorowska-Owczarek, AK,
)
0.5
" Pharmacokinetic variables were determined by noncompartmental analysis."( The influence of parecoxib, a parenteral cyclooxygenase-2 specific inhibitor, on the pharmacokinetics and clinical effects of midazolam.
Feldman, J; Ibrahim, A; Karim, A; Kharasch, E, 2002
)
0.52
"Thirty-two patients were enrolled, of whom 31 had full pharmacokinetic data sets."( Explaining interindividual variability of docetaxel pharmacokinetics and pharmacodynamics in Asians through phenotyping and genotyping strategies.
Fan, L; Goh, BC; Guo, JY; Lamba, J; Lee, HS; Lee, SC; Lim, HL; Lim, R; Ong, AB; Schuetz, E; Wang, LZ, 2002
)
0.31
"The pharmacokinetic and pharmacodynamic interactions of ethanol with the full benzodiazepine agonist midazolam, the partial agonist bretazenil and the benzodiazepine BZ1 receptor subtype selective agonist zolpidem have been determined in the rat in vivo, using an integrated pharmacokinetic-pharmacodynamic approach."( Mechanism-based pharmacodynamic modeling of the interaction of midazolam, bretazenil, and zolpidem with ethanol.
Danhof, M; Tuk, B; van Gool, T, 2002
)
0.77
" The aim of the study was to investigate the influence of midazolam on the plasma concentrations and pharmacokinetic parameters of verapamil after intravenous bolus administration in rabbits during 2 h of observation."( Influence of midazolam on pharmacokinetics of verapamil in rabbits.
Orszulak-Michalak, D; Owczarek, J; Wiktorowska-Owczarek, AK,
)
0.74
"The objective of this study was to characterize quantitatively the pharmacodynamic interaction between midazolam (MDL), an allosteric modulator of the gamma-aminobutyric acid subtype A (GABAA) receptor, and tiagabine (TGB), an inhibitor of synaptic GABA uptake."( Pharmacodynamic analysis of the interaction between tiagabine and midazolam with an allosteric model that incorporates signal transduction.
Danhof, M; Edelbroek, PM; Jonker, DM; Piotrovsky, VK; Vermeij, DA; Voskuyl, RA, 2003
)
0.77
"5- to 30-Hz frequency band was used as the pharmacodynamic end point."( Pharmacodynamic analysis of the interaction between tiagabine and midazolam with an allosteric model that incorporates signal transduction.
Danhof, M; Edelbroek, PM; Jonker, DM; Piotrovsky, VK; Vermeij, DA; Voskuyl, RA, 2003
)
0.56
" A significant pharmacokinetic interaction with TGB was observed."( Pharmacodynamic analysis of the interaction between tiagabine and midazolam with an allosteric model that incorporates signal transduction.
Danhof, M; Edelbroek, PM; Jonker, DM; Piotrovsky, VK; Vermeij, DA; Voskuyl, RA, 2003
)
0.56
"We conclude that the in vivo pharmacodynamic interaction between MDL and TGB is additive rather than synergistic."( Pharmacodynamic analysis of the interaction between tiagabine and midazolam with an allosteric model that incorporates signal transduction.
Danhof, M; Edelbroek, PM; Jonker, DM; Piotrovsky, VK; Vermeij, DA; Voskuyl, RA, 2003
)
0.56
"5 mg/kg) administration of MDZ, and pharmacokinetic parameters were estimated by fitting to a noncompartmental model."( Expression of the human CYP3A4 gene in the small intestine of transgenic mice: in vitro metabolism and pharmacokinetics of midazolam.
Akiyama, TE; Cheung, C; Elizondo, G; Feigenbaum, L; Gonzalez, FJ; Granvil, CP; Krausz, KW; Yu, AM, 2003
)
0.53
"The pharmacokinetic profile of midazolam (MDZ) and its major metabolites 1'-OH-midazolam (1'OH-MDZ) and 4-OH-midazolam (4OH-MDZ) was investigated in rats."( Impact of Solutol HS 15 on the pharmacokinetic behavior of midazolam upon intravenous administration to male Wistar rats.
Bittner, B; Flament, C; González, RC; Isel, H, 2003
)
0.85
"The aim of the study was to assess the performance of a bayesian program (PKS System, Abbott) for predicting midazolam concentrations and pharmacokinetic parameters in intensive care patients by comparing the pharmacokinetic parameters estimated by PKS to those calculated according to rich data."( Evaluation of the estimation of midazolam concentrations and pharmacokinetic parameters in intensive care patients using a bayesian pharmacokinetic software (PKS) according to sparse sampling approach.
Bastien, O; Bolon, M; Boulieu, R; Flamens, C; Paulus, S; Salord, F, 2003
)
0.81
"Prospective population pharmacokinetic study."( Population pharmacokinetics and metabolism of midazolam in pediatric intensive care patients.
de Hoog, M; de Wildt, SN; van den Anker, JN; van der Giesen, E; Vinks, AA, 2003
)
0.58
" A population analysis was conducted via a two-compartment pharmacokinetic model by the NPEM program."( Population pharmacokinetics and metabolism of midazolam in pediatric intensive care patients.
de Hoog, M; de Wildt, SN; van den Anker, JN; van der Giesen, E; Vinks, AA, 2003
)
0.58
"We describe population and individual midazolam pharmacokinetic parameter estimates in pediatric intensive care patients by using a population modeling approach."( Population pharmacokinetics and metabolism of midazolam in pediatric intensive care patients.
de Hoog, M; de Wildt, SN; van den Anker, JN; van der Giesen, E; Vinks, AA, 2003
)
0.85
" Population pharmacokinetic analysis and model building was conducted using WinNonMix (Pharsight Corporation, Mountain View, CA)."( Pharmacokinetics of midazolam in neonates undergoing extracorporeal membrane oxygenation.
Firmin, RK; Lawson, G; McCormack, P; Mulla, H; Upton, DR, 2003
)
0.64
"These results reveal significantly increased volume of distribution and plasma half-life in neonates receiving extracorporeal membrane oxygenation."( Pharmacokinetics of midazolam in neonates undergoing extracorporeal membrane oxygenation.
Firmin, RK; Lawson, G; McCormack, P; Mulla, H; Upton, DR, 2003
)
0.64
"Plasma concentration-time profiles of sufentanil and pharmacokinetic parameters such as initial postinfusion half-life (t(1/2alpha)), elimination half-life (t(1/2beta)), total clearance (Cl), volume of distribution (Vdbeta), and time required to obtain a 50% decrease in plasma concentration (tcp(0/2))."( Pharmacokinetics of long-term sufentanil infusion for sedation in ICU patients.
Assoune, P; Boudaoud, S; Ethuin, F; Eurin, B; Jacob, L; Le Moing, JP; Leblanc, I; Levron, JC; Marie, O; Troje, C, 2003
)
0.32
"The pharmacokinetic analysis of sufentanil for ICU sedation revealed increased volume of distribution and elimination half-life."( Pharmacokinetics of long-term sufentanil infusion for sedation in ICU patients.
Assoune, P; Boudaoud, S; Ethuin, F; Eurin, B; Jacob, L; Le Moing, JP; Leblanc, I; Levron, JC; Marie, O; Troje, C, 2003
)
0.32
"The objective of the present investigation was to characterize the pharmacodynamic interaction between the synthetic neuroactive steroid alphaxalone and the benzodiazepine midazolam."( Mechanism-based modeling of the pharmacodynamic interaction of alphaxalone and midazolam in rats.
Danhof, M; Huntjens, DR; Peletier, LA; van der Graaf, PH; Visser, SA, 2003
)
0.74
"The objective of this study was to investigate pharmacokinetic and pharmacodynamic interactions between midazolam and fluoxetine, fluvoxamine, nefazodone, and ketoconazole."( Pharmacokinetic and pharmacodynamic interactions of oral midazolam with ketoconazole, fluoxetine, fluvoxamine, and nefazodone.
Alfaro, CL; Ereshefsky, L; Lam, YW; Miller, M, 2003
)
0.78
" Population pharmacokinetic models were developed using the Non-Linear Mixed Effect Modelling (NONMEM) program."( Comparative population pharmacokinetics of lorazepam and midazolam during long-term continuous infusion in critically ill patients.
Danhof, M; de Jongh, J; Strack van Schijndel, RM; Swart, EL; Thijs, LG; Zuideveld, KP, 2004
)
0.57
"The primary objectives of the present study were to establish whether there was a pharmacokinetic or pharmacodynamic interaction between the probe drugs caffeine (CYP1A2), tolbutamide (CYP2C9), debrisoquine (CYP2D6), chlorzoxazone (CYP2E1) and midazolam (CYP3A4), when administered in combination as a cocktail."( Pharmacokinetic and pharmacodynamic assessment of a five-probe metabolic cocktail for CYPs 1A2, 3A4, 2C9, 2D6 and 2E1.
Aherne, Z; Blakey, GE; Lockton, JA; Norwood, P; Perrett, J; Plume, J; Russell, M, 2004
)
0.51
" Blood pressure and blood glucose measurements were used to assess pharmacodynamic interactions."( Pharmacokinetic and pharmacodynamic assessment of a five-probe metabolic cocktail for CYPs 1A2, 3A4, 2C9, 2D6 and 2E1.
Aherne, Z; Blakey, GE; Lockton, JA; Norwood, P; Perrett, J; Plume, J; Russell, M, 2004
)
0.32
"The five probe drugs when coadministered, in this dosing regimen, demonstrated no evidence of either a metabolic or pharmacodynamic interaction that might confound the conclusions drawn during a cocktail study."( Pharmacokinetic and pharmacodynamic assessment of a five-probe metabolic cocktail for CYPs 1A2, 3A4, 2C9, 2D6 and 2E1.
Aherne, Z; Blakey, GE; Lockton, JA; Norwood, P; Perrett, J; Plume, J; Russell, M, 2004
)
0.32
" A comparison is also presented between several methods based on animal pharmacokinetic data, using the same set of proprietary compounds, and it lends further support for the use of this method, as opposed to methods that require the gathering of pharmacokinetic data in laboratory animals."( Prediction of human volume of distribution values for neutral and basic drugs. 2. Extended data set and leave-class-out statistics.
Gao, F; Lombardo, F; Obach, RS; Shalaeva, MY, 2004
)
0.32
" The mean time-plasma concentration data were fit to standard pharmacokinetic models."( Pharmacokinetic studies of intramuscular midazolam in guinea pigs challenged with soman.
Byers, CE; Capacio, BR; McDonough, JH; Merk, KA; Smith, JR, 2004
)
0.59
" The pharmacokinetic profile of intravenous midazolam was characterized before and after itraconazole administration (200 mg once daily for 4 days) and also after rifampin (INN, rifampicin) pretreatment (600 mg once daily for 10 days), with a washout period of 2 weeks in between."( Effect of the CYP3A5 genotype on the pharmacokinetics of intravenous midazolam during inhibited and induced metabolic states.
Cho, JY; Chung, JY; Hong, KS; Jang, IJ; Kim, JR; Lim, HS; Liu, KH; Oh, DS; Shin, JG; Shin, SG; Yi, SY; Yu, KS, 2004
)
0.82
"The pharmacokinetic profiles of midazolam and of its hydroxy metabolites did not show differences between the genotype groups under basal and induced metabolic conditions."( Effect of the CYP3A5 genotype on the pharmacokinetics of intravenous midazolam during inhibited and induced metabolic states.
Cho, JY; Chung, JY; Hong, KS; Jang, IJ; Kim, JR; Lim, HS; Liu, KH; Oh, DS; Shin, JG; Shin, SG; Yi, SY; Yu, KS, 2004
)
0.84
" Based on our findings that there is no relationship between pharmacokinetic parameters and pharmacodynamic outcome, we recommend that midazolam dosing should be titrated according to the desired clinical effect in combination with a validated assessment instrument, eg, the COMFORT scale."( Pharmacodynamics of midazolam in pediatric intensive care patients.
de Hoog, M; de Wildt, SN; Joosten, KF; van den Anker, JN; van Dijk, M; Vinks, AA, 2005
)
0.86
"Abstinent male alcohol dependent subjects underwent [11C]flumazenil PET to measure occupancy of BDZ receptors by midazolam whilst recording its pharmacodynamic effects on behavioural and physiological measures."( GABA-benzodiazepine receptor function in alcohol dependence: a combined 11C-flumazenil PET and pharmacodynamic study.
Brooks, DJ; Cunningham, VJ; Feeney, A; Lingford-Hughes, AR; Nutt, DJ; Stevenson, B; Wilson, SJ, 2005
)
0.54
"To create a general physiologically based pharmacokinetic (PBPK) model for drug disposition in infants and children, covering the age range from birth to adulthood, and to evaluate it with theophylline and midazolam as model drugs."( Prediction of drug disposition in infants and children by means of physiologically based pharmacokinetic (PBPK) modelling: theophylline and midazolam as model drugs.
Björkman, S, 2005
)
0.72
" Volume of distribution (V dss), total and renal clearance (CL and CL R) and elimination half-life (t(1/2)) were estimated by PBPK modelling, as functions of age, and compared with literature data."( Prediction of drug disposition in infants and children by means of physiologically based pharmacokinetic (PBPK) modelling: theophylline and midazolam as model drugs.
Björkman, S, 2005
)
0.53
" Prediction of the disposition of theophylline and midazolam, two model drugs with dissimilar physicochemical and pharmacokinetic characteristics, yielded results that generally tallied with literature data."( Prediction of drug disposition in infants and children by means of physiologically based pharmacokinetic (PBPK) modelling: theophylline and midazolam as model drugs.
Björkman, S, 2005
)
0.78
"We previously established a method to predict the drug metabolism capacity of injured liver based on pharmacokinetic estimation of the amount of cytochrome P450 (CYP) in vivo (PKCYP test), by introducing the apparent liver-to-blood free concentration gradient in vivo (qg) as a parameter."( Prediction of theophylline clearance in CCl4-treated rats using in vivo CYP1A2 and CYP3A2 contents assessed with the PKCYP test.
Isawa, M; Kose, N; Nakashima, E; Sai, Y; Suwa, T; Yamamoto, K, 2005
)
0.33
" Midazolam concentrations in plasma were determined using liquid chromatography-mass spectrometry, and pharmacokinetic variables were calculated using noncompartmental analysis."( Effect of common CYP3A4 and CYP3A5 variants on the pharmacokinetics of the cytochrome P450 3A phenotyping probe midazolam in cancer patients.
Ahn, D; Baker, SD; Bates, SE; Cusatis, G; Figg, WD; Ingersoll, RG; Lepper, ER; Mathijssen, RH; Permenter, M; Price, DK; Ries, N; Schenk, PW; Smith, NF; Sparreboom, A; van Schaik, RH; Verweij, J, 2005
)
1.45
"We investigated the propagation of population pharmacokinetic information across clinical studies by applying Bayesian techniques."( Propagation of population pharmacokinetic information using a Bayesian approach: comparison with meta-analysis.
Aarons, L; Dokoumetzidis, A, 2005
)
0.33
"The objective of the present investigation was to develop a population pharmacodynamic model for midazolam- and lorazepam-induced sedation upon long-term continuous infusion in critically ill patients."( Population pharmacodynamic modelling of lorazepam- and midazolam-induced sedation upon long-term continuous infusion in critically ill patients.
Danhof, M; de Jongh, J; Strack van Schijndel, RM; Swart, EL; Thijs, LG; Zuideveld, KP, 2006
)
0.8
"The pharmacokinetics of lorazepam and midazolam was described with previously proposed pharmacokinetic models."( Population pharmacodynamic modelling of lorazepam- and midazolam-induced sedation upon long-term continuous infusion in critically ill patients.
Danhof, M; de Jongh, J; Strack van Schijndel, RM; Swart, EL; Thijs, LG; Zuideveld, KP, 2006
)
0.85
"The population pharmacodynamic model shows a similarly wide intra- and inter-individual variability in the pharmacodynamics of both lorazepam and midazolam."( Population pharmacodynamic modelling of lorazepam- and midazolam-induced sedation upon long-term continuous infusion in critically ill patients.
Danhof, M; de Jongh, J; Strack van Schijndel, RM; Swart, EL; Thijs, LG; Zuideveld, KP, 2006
)
0.78
" Suggested methods to improve our knowledge without performing conventional full-scale investigations include population pharmacokinetic studies, allometric scaling of drug disposition according to bodyweight and in silico prediction of pharmacokinetics."( Prediction of cytochrome p450-mediated hepatic drug clearance in neonates, infants and children : how accurate are available scaling methods?
Björkman, S, 2006
)
0.33
" Serial blood samples were collected predose and up to 24 hours after each MDZ dose for pharmacokinetic (PK) evaluation."( Effect of R667, a novel emphysema agent, on the pharmacokinetics of midazolam in healthy men.
Brennan, BJ; Brown, AB; Davies, BE; Gooden, C; Kolis, SJ; Rutman, O, 2006
)
0.57
" Saquinavir pharmacokinetic parameter values were determined using noncompartmental methods and compared between males and females."( Lack of sex-related differences in saquinavir pharmacokinetics in an HIV-seronegative cohort.
Alfaro, RM; Falloon, J; Formentini, E; Natarajan, V; Penzak, SR; Robertson, SM, 2006
)
0.33
"There was no significant difference in saquinavir AUC(0-8) or any other pharmacokinetic parameter value between the sexes."( Lack of sex-related differences in saquinavir pharmacokinetics in an HIV-seronegative cohort.
Alfaro, RM; Falloon, J; Formentini, E; Natarajan, V; Penzak, SR; Robertson, SM, 2006
)
0.33
" Caution must be exercised when extrapolating pharmacokinetic data from healthy volunteer studies (including sex-based pharmacokinetic differences) to HIV-infected populations or to patients receiving additional concurrent medications."( Lack of sex-related differences in saquinavir pharmacokinetics in an HIV-seronegative cohort.
Alfaro, RM; Falloon, J; Formentini, E; Natarajan, V; Penzak, SR; Robertson, SM, 2006
)
0.33
" Plasma concentrations of midazolam, alpha-hydroxymidazolam, and voriconazole were determined for 24 hours and pharmacodynamic variables measured for 12 hours."( Effect of voriconazole on the pharmacokinetics and pharmacodynamics of intravenous and oral midazolam.
Laine, K; Leino, K; Neuvonen, PJ; Olkkola, KT; Saari, TI; Valtonen, M, 2006
)
0.85
"Conventional methods to forecast CYP3A-mediated drug-drug interactions have not employed stochastic approaches that integrate pharmacokinetic (PK) variability and relevant covariates to predict inhibition in terms of probability and uncertainty."( Stochastic prediction of CYP3A-mediated inhibition of midazolam clearance by ketoconazole.
Chien, JY; Ernest, CS; Gorski, JC; Hall, SD; Lucksiri, A; Wrighton, SA, 2006
)
0.58
" Recent studies with a 103-compound dataset suggested that scaling from monkey pharmacokinetic data tended to be the most accurate method for predicting human clearance."( Extrapolation of preclinical pharmacokinetics and molecular feature analysis of "discovery-like" molecules to predict human pharmacokinetics.
Evans, CA; Jolivette, LJ; Nagilla, R; Ward, KW, 2006
)
0.33
" Posterior Bayesian estimates of vinorelbine clearance were obtained for each patient using population pharmacokinetic modeling."( Predictors of vinorelbine pharmacokinetics and pharmacodynamics in patients with cancer.
Ackland, SP; Balleine, RL; Blair, EY; Clarke, CL; Collins, M; Evans, S; Farlow, D; Garg, MB; Gurney, H; Hoskins, JM; Mann, GJ; McLachlan, AJ; Rivory, LP; Wong, M, 2006
)
0.33
"Specific indicators of drug clearance provide predictive information about vinorelbine pharmacokinetics, and body-surface area, probably reflecting normal bone marrow reserve, provides an additional pharmacodynamic indicator."( Predictors of vinorelbine pharmacokinetics and pharmacodynamics in patients with cancer.
Ackland, SP; Balleine, RL; Blair, EY; Clarke, CL; Collins, M; Evans, S; Farlow, D; Garg, MB; Gurney, H; Hoskins, JM; Mann, GJ; McLachlan, AJ; Rivory, LP; Wong, M, 2006
)
0.33
" In an attempt to explain this variability, three pharmacokinetic studies were carried out in healthy volunteers to investigate the relationship between exposure to gefitinib and cytochrome P450 (CYP) 3A phenotype (study 1), CYP3A5 genotype (study 2) and CYP2D6 genotype (study 3)."( Exploring the relationship between expression of cytochrome P450 enzymes and gefitinib pharmacokinetics.
Cantarini, MV; Fuhr, R; Holt, A; Swaisland, HC, 2006
)
0.33
" In study 2, 73 healthy volunteers with previously defined single-dose gefitinib pharmacokinetic profiles were genotyped for CYP3A5."( Exploring the relationship between expression of cytochrome P450 enzymes and gefitinib pharmacokinetics.
Cantarini, MV; Fuhr, R; Holt, A; Swaisland, HC, 2006
)
0.33
" Noncompartmental analysis was used to estimate pharmacokinetic parameters."( Pharmacokinetics and pharmacodynamics of a new intranasal midazolam formulation in healthy volunteers.
Archer, SM; Clinch, T; Kelly, TH; Record, KA; Rudy, AC; Wermeling, DP, 2006
)
0.58
" AQUAVAN injection (fospropofol disodium), a phosphorylated prodrug of propofol, is an investigational agent possessing a unique and distinct pharmacokinetic and pharmacodynamic profile."( Pharmacokinetic and pharmacodynamic characteristics of medications used for moderate sedation.
Gan, TJ, 2006
)
0.33
"Prediction of the exposure of neonates, infants and children to xenobiotics is likely to be more successful using physiologically based pharmacokinetic models than simplistic allometric scaling, particularly in younger children."( Prediction of the clearance of eleven drugs and associated variability in neonates, infants and children.
Johnson, TN; Rostami-Hodjegan, A; Tucker, GT, 2006
)
0.33
" In vitro enzyme pharmacokinetic parameters (maximum rate of metabolism [Vmax] and Michaelis-Menten constant [Km]) and in vivo clearance data were obtained from the literature."( Prediction of the clearance of eleven drugs and associated variability in neonates, infants and children.
Johnson, TN; Rostami-Hodjegan, A; Tucker, GT, 2006
)
0.33
"The in silico prediction of pharmacokinetic behaviour in paediatric patients is not intended to replace clinical studies."( Prediction of the clearance of eleven drugs and associated variability in neonates, infants and children.
Johnson, TN; Rostami-Hodjegan, A; Tucker, GT, 2006
)
0.33
"The aim of this study was to evaluate whether curcumin could modulate P-glycoprotein (P-gp) and CYP3A expression, and in turn modify the pharmacokinetic profiles of P-gp and CYP3A substrates in male Sprague-Dawley rats."( Impact of curcumin-induced changes in P-glycoprotein and CYP3A expression on the pharmacokinetics of peroral celiprolol and midazolam in rats.
Lim, LY; Tan, TM; Zhang, W, 2007
)
0.55
" This method was sensitive and reliable enough for pharmacokinetic studies on healthy volunteers, and was applied for the measurement of CYP3A activity in humans after an intravenous (1mg) and a single-oral administration (2mg) of subtherapeutic MDZ dose."( A developed determination of midazolam and 1'-hydroxymidazolam in plasma by liquid chromatography-mass spectrometry: application of human pharmacokinetic study for measurement of CYP3A activity.
Kanazawa, H; Murakami, I; Shimizu, M; Sugawara, K; Tamura, HO; Tateishi, T; Uno, T, 2007
)
0.63
"Because information on the optimal dose of midazolam for sedation of nonventilated infants after major surgery is scant, a population pharmacokinetic and pharmacodynamic model is developed for this specific group."( Pharmacokinetics and pharmacodynamics of midazolam and metabolites in nonventilated infants after craniofacial surgery.
Danhof, M; Dejongh, J; Knibbe, CA; Mathôt, RA; Peeters, MY; Prins, SA; Tibboel, D; van Schaik, RH; Warris, C, 2006
)
0.86
" Population pharmacokinetic and pharmacodynamic modeling was performed using NONMEM V (GloboMax LLC, Hanover, MD)."( Pharmacokinetics and pharmacodynamics of midazolam and metabolites in nonventilated infants after craniofacial surgery.
Danhof, M; Dejongh, J; Knibbe, CA; Mathôt, RA; Peeters, MY; Prins, SA; Tibboel, D; van Schaik, RH; Warris, C, 2006
)
0.6
" Midazolam has a higher clearance and shorter half-life than other benzodiazepines, and prolonged sedation is achieved with continuous infusion."( Clinical pharmacokinetic monitoring of midazolam in critically ill patients.
Ensom, MH; Spina, SP, 2007
)
1.52
" In this study, we aim to predict the effect of the CYP3A4 inhibitors, itraconazole (ITZ) and its primary metabolite, hydroxyitraconazole (OH-ITZ) on the pharmacokinetics of the anesthetic, midazolam (MDZ) and its metabolites, 1' hydroxymidazolam (1OH-MDZ) and 1' hydroxymidazolam glucuronide (1OH-MDZ-Glu) using mechanistic whole body physiologically-based pharmacokinetic simulation models."( Dynamically simulating the interaction of midazolam and the CYP3A4 inhibitor itraconazole using individual coupled whole-body physiologically-based pharmacokinetic (WB-PBPK) models.
Edginton, AN; Jang, IJ; Niederalt, C; Sevestre, M; Vossen, M; Willmann, S, 2007
)
0.79
" A pharmacokinetic mechanism for the cranberry juice-warfarin interaction seems unlikely."( Effects of daily ingestion of cranberry juice on the pharmacokinetics of warfarin, tizanidine, and midazolam--probes of CYP2C9, CYP1A2, and CYP3A4.
Backman, JT; Lilja, JJ; Neuvonen, PJ, 2007
)
0.56
" The pharmacokinetic findings are compatible with a more rapid and extensive initial effect of IV morphine compared with IM."( Serum and cerebrospinal fluid morphine pharmacokinetics after single doses of intravenous and intramuscular morphine after hip replacement surgery.
Borchgrevink, PC; Dale, O; Klepstad, P; Nilsen, T; Thoner, J; Tveita, T, 2007
)
0.34
" This study was undertaken to estimate whether the CYP3A5 genotype can explain a relevant portion of pharmacokinetic interindividual variability."( Impact of the CYP3A5 genotype on midazolam pharmacokinetics and pharmacodynamics during intensive care sedation.
Bachmakov, I; Bremer, F; Fromm, MF; König, J; Schüttler, J; Schwilden, H, 2007
)
0.62
" Pharmacokinetic profiles of midazolam were similar for all four species, especially with regard to the area under the plasma drug concentration-time curve."( Plasma pharmacokinetics of midazolam in chickens, turkeys, pheasants and bobwhite quail.
Cortright, KA; Craigmill, AL; Wetzlich, SE, 2007
)
0.93
" We sought to use the rat as an in vivo screening model to predict pharmacokinetic interactions with ketoconazole."( Development of an in vivo rat screen model to predict pharmacokinetic interactions of CYP3A4 substrates.
Caporuscio, C; Cornelius, G; Mandlekar, SV; Marathe, PH; Rose, AV; Sleczka, B; Wang, J, 2007
)
0.34
" Serial plasma samples were collected for pharmacokinetic analyses."( The effect of multiple-dose, oral rifaximin on the pharmacokinetics of intravenous and oral midazolam in healthy volunteers.
Bettenhausen, DK; Connolly, M; Forbes, WP; Pentikis, HS; Trapnell, CB, 2007
)
0.56
"The pharmacokinetic parameters of single-dose intravenous or oral midazolam were determined alone and after coadministration of rifaximin for 3 and 7 days."( The effect of multiple-dose, oral rifaximin on the pharmacokinetics of intravenous and oral midazolam in healthy volunteers.
Bettenhausen, DK; Connolly, M; Forbes, WP; Pentikis, HS; Trapnell, CB, 2007
)
0.8
" Concentration of aminoacids (triptophan, tirosyn) in the blood is synshronized with the course of pharmacokinetic of the psychotropic preparation and functional state of serotoninergic system."( [Functional state of serotoninergic system on a background of different pharmacokinetic of Midazolam].
Arveladze, MN; Kapanadze, LR; Zurabashvili, ZA,
)
0.35
" The data were evaluated using a mechanistic pharmacokinetic approach in NONMEM."( Pharmacodynamics of carbamazepine-mediated induction of CYP3A4, CYP1A2, and Pgp as assessed by probe substrates midazolam, caffeine, and digoxin.
Cederberg, J; Dahl, ML; Karlsson, MO; Magnusson, MO; Sandström, R, 2008
)
0.56
"750) or apparent half-life (P = ."( Lack of a pharmacokinetic effect of raltegravir on midazolam: in vitro/in vivo correlation.
DeNoia, EP; Ghosh, K; Gottesdiener, KM; Hanley, WD; Iwamoto, M; Kassahun, K; Lu, P; Mangin, E; Petry, AS; Rhoton, A; Stone, JA; Troyer, MD; Wagner, JA; Wenning, LA, 2008
)
0.6
" UDCA did not affect the pharmacokinetic and pharmacodynamic parameters of intravenous and oral MDZ administrations."( Effects of ursodeoxycholic acid on the pharmacokinetics and pharmacodynamics of intravenous and oral midazolam in healthy volunteers.
Inui, N; Luo, J; Misaka, S; Ohashi, K; Takeuchi, K; Uchida, S; Watanabe, H; Yamada, S; Yan, D; Yang, Y, 2008
)
0.56
" Because it was known from the literature that the half-life of midazolam can increase at high dosage, the kinetics of midazolam (MDZ), 1'-hydroxymidazolam, and 4-hydroxymidazolam were assessed at steady state (dosage 1 mg/min) and after stopping treatment."( Pharmacokinetics of midazolam and metabolites in a patient with refractory status epilepticus treated with extraordinary doses of midazolam.
Bodmer, M; Grignaschi, N; Haschke, M; Krähenbühl, S; Kummer, O; Link, B; Ruegg, S, 2008
)
0.91
" Pharmacokinetic parameters of midazolam and dextromethorphan were assessed alone and in the presence of AMD070."( Pharmacokinetic effect of AMD070, an Oral CXCR4 antagonist, on CYP3A4 and CYP2D6 substrates midazolam and dextromethorphan in healthy volunteers.
Becker, S; Calandra, GB; Chee, P; Everts, S; Hendrix, CW; MacFarland, RT; Nyunt, MM; Scarborough, R, 2008
)
0.85
" pharmacokinetic data on 670 drugs representing, to our knowledge, the largest publicly available set of human clinical pharmacokinetic data."( Trend analysis of a database of intravenous pharmacokinetic parameters in humans for 670 drug compounds.
Lombardo, F; Obach, RS; Waters, NJ, 2008
)
0.35
" A population pharmacokinetic analysis of the paracetamol plasma concentration time-profiles was undertaken using nonlinear mixed effects models."( Pharmacokinetics and analgesic effects of intravenous propacetamol vs rectal paracetamol in children after major craniofacial surgery.
Anderson, BJ; Mathot, RA; Prins, SA; Searle, S; Tibboel, D; Van Dijk, M; Van Leeuwen, P, 2008
)
0.35
" Pharmacokinetic parameters were standardized to a 70 kg person using allometric '1/4 power' models."( Pharmacokinetics and analgesic effects of intravenous propacetamol vs rectal paracetamol in children after major craniofacial surgery.
Anderson, BJ; Mathot, RA; Prins, SA; Searle, S; Tibboel, D; Van Dijk, M; Van Leeuwen, P, 2008
)
0.35
" Plasma concentration-time data were fitted using pharmacokinetic models."( Pharmacokinetics and clinical efficacy of midazolam in children with severe malaria and convulsions.
Edwards, G; Kokwaro, GO; Muchohi, SN; Newton, CR; Ogutu, BR; Ward, SA, 2008
)
0.61
" midazolam formulation resulted in rapid absorption and attained plasma concentrations that correlated with pharmacodynamic effects."( A pharmacokinetic and pharmacodynamic study, in healthy volunteers, of a rapidly absorbed intranasal midazolam formulation.
Archer, SM; Record, KA; Rudy, AC; Wermeling, DP, 2009
)
1.48
" We have developed a whole body physiologically based pharmacokinetic (PBPK) model to explore the effects of pregnancy on pharmacokinetics."( Physiologically based pharmacokinetic model of midazolam disposition during pregnancy.
Andrew, MA; Hebert, MF; Vicini, P, 2008
)
0.6
" The elimination half-life of midazolam administered intravenously (5 mg kg(-1)) or orally (15 mg kg(-1)) was significantly decreased by 70% and 73%, respectively, 24 h after a single oral administration of ursodeoxycholic acid (UDCA, 300 mg kg(-1)) in rats."( Effect of ursodeoxycholic acid on the pharmacokinetics of midazolam and CYP3A in the liver and intestine of rats.
Ito, Y; Kurosawa, S; Uchida, S; Yamada, S, 2009
)
0.89
" Because of the potential for drug interactions, it is important to determine the effects of posaconazole on the pharmacokinetic properties of midazolam."( Effects of oral posaconazole on the pharmacokinetic properties of oral and intravenous midazolam: a phase I, randomized, open-label, crossover study in healthy volunteers.
Krishna, G; Ma, L; Martinho, M; McLeod, J; Moton, A; Savant, I; Seiberling, M, 2009
)
0.78
"The aim of this study was to compare the effects of oral administration of posaconazole versus ketoconazole on the pharmacokinetic properties of orally and intravenously administered midazolam."( Effects of oral posaconazole on the pharmacokinetic properties of oral and intravenous midazolam: a phase I, randomized, open-label, crossover study in healthy volunteers.
Krishna, G; Ma, L; Martinho, M; McLeod, J; Moton, A; Savant, I; Seiberling, M, 2009
)
0.77
" Pharmacokinetic parameters, including C(max), C(min) (before azole administration), terminal-phase t(1/2) (t(1/2z)), and AUC to final measurable sampling time (AUC(tf)), were calculated using noncompartmental methods, and drug interactions were evaluated using analysis of variance."( Effects of oral posaconazole on the pharmacokinetic properties of oral and intravenous midazolam: a phase I, randomized, open-label, crossover study in healthy volunteers.
Krishna, G; Ma, L; Martinho, M; McLeod, J; Moton, A; Savant, I; Seiberling, M, 2009
)
0.58
"The combined administration of anesthetics has been associated with pharmacokinetic interactions that induce concentration changes of up to 30%."( Mixed-effects modeling of the influence of midazolam on propofol pharmacokinetics.
Dahan, A; Lichtenbelt, BJ; Olofsen, E; van Kleef, JW; Vuyk, J, 2009
)
0.62
" Inclusion of mean arterial blood pressure further improved the propofol pharmacokinetic model."( Mixed-effects modeling of the influence of midazolam on propofol pharmacokinetics.
Dahan, A; Lichtenbelt, BJ; Olofsen, E; van Kleef, JW; Vuyk, J, 2009
)
0.62
" In addition, a reduction in mean arterial blood pressure is associated with propofol pharmacokinetic alterations that increase the blood propofol concentration."( Mixed-effects modeling of the influence of midazolam on propofol pharmacokinetics.
Dahan, A; Lichtenbelt, BJ; Olofsen, E; van Kleef, JW; Vuyk, J, 2009
)
0.62
" Semiphysiologically based pharmacokinetic (PBPK) models were developed for DTZ and MDZ with the major metabolite of DTZ, N-desmethyldiltiazem (nd-DTZ), incorporated in the DTZ model."( Semiphysiologically based pharmacokinetic models for the inhibition of midazolam clearance by diltiazem and its major metabolite.
Gorski, JC; Hall, SD; Jones, DR; Quinney, SK; Zhang, X, 2009
)
0.59
"05) were observed between groups 1 and 2 in the pharmacokinetic parameters of both enantiomers."( Influence of glomerular filtration rate on the pharmacokinetics of cyclophosphamide enantiomers in patients with lupus nephritis.
Coelho, EB; Dantas, M; de Miranda Silva, C; Donadi, EA; Fernandes, BJ; Lanchote, VL; Marques, MP; Silva, LM, 2009
)
0.35
" Pharmacokinetic investigations of oral midazolam administration at 15 mg were performed both before and at the end of the SchE treatment period."( Effects of Schisandra sphenanthera extract on the pharmacokinetics of midazolam in healthy volunteers.
Li, Q; Wu, XC; Xin, HW; Xiong, L; Yu, AR, 2009
)
0.85
" No significant differences were observed in the other pharmacokinetic parameters of 1'-hydroxy midazolam."( Effects of Schisandra sphenanthera extract on the pharmacokinetics of midazolam in healthy volunteers.
Li, Q; Wu, XC; Xin, HW; Xiong, L; Yu, AR, 2009
)
0.8
"ESRD can affect the pharmacokinetic disposition of drugs subject to nonrenal clearance."( ESRD impairs nonrenal clearance of fexofenadine but not midazolam.
Frye, RF; Himmelfarb, J; Le, P; Leblond, FA; Naud, J; Nolin, TD; Pichette, V; Sadr, H, 2009
)
0.6
" These results show that the cynomolgus monkey can be a predictive in vivo animal model of PXR-mediated induction of human CYP3A4 and can provide a useful assessment of the resulting pharmacokinetic changes of affected drugs."( Evaluation of cynomolgus monkey pregnane X receptor, primary hepatocyte, and in vivo pharmacokinetic changes in predicting human CYP3A4 induction.
Anthony, MN; Dinchuk, JE; Dulac, HA; Grace, JE; Kim, S; Mosure, KW; Orcutt, T; Pizzano, J; Sauer, MB; Simmermacher, J; Sinz, M; Vuppugalla, R; Zoeckler, ME, 2010
)
0.36
" A semiphysiologically based pharmacokinetic model was developed for clarithromycin and midazolam metabolism, incorporating hepatic and intestinal metabolism by CYP3A and non-CYP3A mechanisms."( Physiologically based pharmacokinetic model of mechanism-based inhibition of CYP3A by clarithromycin.
Gorski, JC; Hall, SD; Li, L; Lucksiri, A; Quinney, SK; Zhang, X, 2010
)
0.58
" The pharmacokinetic parameters (Cmax and AUC0-inf) of the main metabolite Org 26761 were proportional to dose."( Pharmacodynamic and pharmacokinetic effects of the intravenous CB1 receptor agonist Org 26828 in healthy male volunteers.
Cohen, AF; de Kam, ML; Kleijn, HJ; Passier, PC; van Gerven, JM; Zuurman, L, 2010
)
0.36
"* Short-term administration of low-dose ritonavir increases area under the plasma concentration curve following oral midazolam by a factor of 28."( Inhibition of oral midazolam clearance by boosting doses of ritonavir, and by 4,4-dimethyl-benziso-(2H)-selenazine (ALT-2074), an experimental catalytic mimic of glutathione oxidase.
Berkowitz, N; Court, MH; Greenblatt, DJ; Harmatz, JS; MacNab, MW; Oleson, LE; Peters, DE; Zinny, MA, 2009
)
0.89
"We evaluated whether 'boosting' doses of ritonavir can serve as a positive control inhibitor for pharmacokinetic drug-drug interaction studies involving cytochrome P450 3A (CYP3A)."( Inhibition of oral midazolam clearance by boosting doses of ritonavir, and by 4,4-dimethyl-benziso-(2H)-selenazine (ALT-2074), an experimental catalytic mimic of glutathione oxidase.
Berkowitz, N; Court, MH; Greenblatt, DJ; Harmatz, JS; MacNab, MW; Oleson, LE; Peters, DE; Zinny, MA, 2009
)
0.68
"These pharmacokinetic data show that intravenous telavancin administered at the intended therapeutic dose does not affect the pharmacokinetics of intravenous midazolam."( Effect of Telavancin on the pharmacokinetics of the cytochrome P450 3A probe substrate midazolam: a randomized, double-blind, crossover study in healthy subjects.
Ballow, CH; Barriere, SL; Goldberg, MR; Kitt, MM; Wong, SL, 2010
)
0.78
" Population pharmacokinetic modeling identified a significant relationship between temperature and clearance and intercompartmental clearance for midazolam."( Mild hypothermia alters midazolam pharmacokinetics in normal healthy volunteers.
Bies, RR; Callaway, CW; Empey, PE; Hostler, D; Kochanek, PM; Poloyac, SM; Rittenberger, JC; Tortorici, MA; Zhou, J, 2010
)
0.87
" Plasma concentrations for midazolam and its metabolite 1-hydroxymidazolam were measured and fitted to a noncompartmental model to estimate the pharmacokinetic parameters."( Effects of oral clotrimazole troches on the pharmacokinetics of oral and intravenous midazolam.
Baum, CL; Camp, JR; Chan, LN; Jeong, HY; Molokie, RE; Shord, SS; Vasquez, EM; Xie, H, 2010
)
0.88
" Inclusion of heart rate further improved the pharmacokinetic model of midazolam."( Propofol reduces the distribution and clearance of midazolam.
Dahan, A; Lichtenbelt, BJ; Olofsen, E; Struys, MM; van Kleef, JW; Vuyk, J, 2010
)
0.85
" In addition, inclusion of heart rate as a covariate improved the pharmacokinetic model of midazolam predominantly through a reduction in the intraindividual variability."( Propofol reduces the distribution and clearance of midazolam.
Dahan, A; Lichtenbelt, BJ; Olofsen, E; Struys, MM; van Kleef, JW; Vuyk, J, 2010
)
0.83
" Safety and pharmacokinetic parameters were determined for doses ranging from 5 to 30 mg."( Human safety and pharmacokinetic study of intramuscular midazolam administered by autoinjector.
Atkinson, AJ; Burback, BL; Corwin, MJ; Hong, SP; Johnson, JD; Reichard, DW, 2010
)
0.61
" Pharmacokinetic changes are expected because of extracorporeal circulation and maturation."( Population pharmacokinetics of midazolam and its metabolites during venoarterial extracorporeal membrane oxygenation in neonates.
Ahsman, MJ; Hanekamp, M; Mathot, RA; Tibboel, D; Wildschut, ED, 2010
)
0.65
" Pharmacokinetic parameters were obtained by non-compartmental and two-compartmental models."( Pharmacokinetics and pharmacodynamics of nasally delivered midazolam.
Briellmann, TA; Drewe, J; Dussy, FE; Fröhlich, J; Haschke, M; Hofmann, S; Imanidis, G; Krähenbühl, S; Surber, C; Suter, K; Witschi, R, 2010
)
0.6
" The pharmacodynamic effects after the low-dose nasal formulations were comparable with those after 1 mg intravenous midazolam."( Pharmacokinetics and pharmacodynamics of nasally delivered midazolam.
Briellmann, TA; Drewe, J; Dussy, FE; Fröhlich, J; Haschke, M; Hofmann, S; Imanidis, G; Krähenbühl, S; Surber, C; Suter, K; Witschi, R, 2010
)
0.81
") treatment decreased midazolam clearance by 16%, with increases in the AUC by 22% and the half-life by 14%."( A pharmacodynamic-pharmacokinetic (PD-PK) study on the effects of Danshen (Salvia miltiorrhiza) on midazolam, a model CYP3A probe substrate, in the rat.
Lee, WY; Or, PM; Wang, X; Yeung, JH; Zhou, X, 2010
)
0.89
"Physiological-based pharmacokinetic models have been used to describe midazolam clearance (CL) maturation."( A maturation model for midazolam clearance.
Anderson, BJ; Larsson, P, 2011
)
0.91
" Predicted CL changes with age based on this model were in close agreement with physiologically based pharmacokinetic (PBPK) models."( A maturation model for midazolam clearance.
Anderson, BJ; Larsson, P, 2011
)
0.68
"Previously published pharmacokinetic parameters can be used to develop maturation models that address gaps in current knowledge regarding the influence of age on a drug's disposition."( A maturation model for midazolam clearance.
Anderson, BJ; Larsson, P, 2011
)
0.68
" Blood samples were collected periodically in both phases and analyzed for parent drugs and metabolites (dextrorphan, 4'-hydroxy-flurbiprofen and 1'-hydroxy-midazolam) to calculate pharmacokinetic parameters."( Drug metabolism in hemorrhagic shock: pharmacokinetics of selective markers of cytochrome-P450 2C9, 2D6, and 3A4 enzyme activities in a porcine model.
Beilman, GJ; Kumar, A; Mann, HJ; Remmel, RP, 2011
)
0.57
" A known DDI between single oral doses of the CYP3A substrate midazolam (5 mg) and the inhibitor ketoconazole (400 mg) was simulated using a physiologically based pharmacokinetic simulator SimCyp in virtual subjects."( Bioavailability considerations in evaluating drug-drug interactions using the population pharmacokinetic approach.
Duan, JZ; Jackson, AJ; Zhao, P, 2011
)
0.61
"To clarify whether alterations in midazolam pharmacokinetics resulting from changes in cytochrome P450 3A (CYP3A) activity lead to changes in its pharmacodynamic effects, benzodiazepine receptor occupancy was measured in the brain of rats after oral administration of midazolam."( Evaluation of the pharmacokinetic interaction of midazolam with ursodeoxycholic acid, ketoconazole and dexamethasone by brain benzodiazepine receptor occupancy.
Kagawa, Y; Kato, Y; Kurosawa, S; Misaka, S; Uchida, S; Yamada, S; Yoshida, A, 2011
)
0.9
"The results indicate that pharmacokinetic changes such as altered CYP3A activity significantly influence the pharmacodynamic effect of midazolam by affecting occupancy of benzodiazepine receptors in the brain."( Evaluation of the pharmacokinetic interaction of midazolam with ursodeoxycholic acid, ketoconazole and dexamethasone by brain benzodiazepine receptor occupancy.
Kagawa, Y; Kato, Y; Kurosawa, S; Misaka, S; Uchida, S; Yamada, S; Yoshida, A, 2011
)
0.83
" Neither the genotype nor the apple juice showed significant effects on the pharmacokinetics of midazolam except for a marginally significant decrease in Cmax after administration with apple juice."( The effects of the SLCO2B1 c.1457C > T polymorphism and apple juice on the pharmacokinetics of fexofenadine and midazolam in humans.
Imai, H; Imanaga, J; Kotegawa, T; Ohashi, K; Ohyama, T; Shirasaka, Y; Tamai, I; Tateishi, T; Tsutsumi, K; Yoshizato, T, 2011
)
0.8
" Pharmacokinetic analyses were performed on day 1 without sorafenib and day 28 after steady-state sorafenib exposure; sorafenib pharmacokinetics were evaluated on day 28."( Interaction of sorafenib and cytochrome P450 isoenzymes in patients with advanced melanoma: a phase I/II pharmacokinetic interaction study.
Flaherty, KT; Frye, RF; Lathia, C; O'Dwyer, PJ; Redlinger, M; Rosen, M; Schuchter, L, 2011
)
0.37
"In this small Japanese adult volunteer population receiving single subtherapeutic doses of midazolam, 2 weeks' consumption of pomegranate juice did not significantly alter the pharmacokinetic profile of midazolam compared with that of the control."( Effect of 2 weeks' consumption of pomegranate juice on the pharmacokinetics of a single dose of midazolam: an open-label, randomized, single-center, 2-period crossover study in healthy Japanese volunteers.
Inui, N; Kosuge, K; Misaka, S; Nakamura, R; Takahashi, N; Takeuchi, K; Uchida, S; Watanabe, H; Yamada, S, 2011
)
0.81
" Ethnic differences in pharmacokinetic parameters of midazolam using non-compartmental methods and anova and Kruskal-Wallis rank test."( Pharmacokinetics of midazolam tablet in different Chinese ethnic groups.
Guo, T; Mao, GF; Su, XY; Xia, DY; Zhao, LS, 2011
)
0.94
" Midazolam terminal half-life (t(1/2z)) were 3·0 ± 0·8, 2·2 ± 0·7, 1·9 ± 0·7, 3·5 ± 1·9, 3·8 ± 2·3 h for Hans, Mongolians, Uygurs, Huis and Koreans, respectively."( Pharmacokinetics of midazolam tablet in different Chinese ethnic groups.
Guo, T; Mao, GF; Su, XY; Xia, DY; Zhao, LS, 2011
)
1.6
" Clinical studies on the effect of these stressors on drug pharmacokinetics demonstrate that the likelihood of pharmacokinetic alteration is dependent on drug properties and the intensity of the stressor."( Simulation of differential drug pharmacokinetics under heat and exercise stress using a physiologically based pharmacokinetic modeling approach.
Cheung, B; Edginton, A; Peng, HT; Sidhu, P, 2011
)
0.37
" The present study evaluated pharmacokinetic parameters and safety/tolerability upon coadministration of brivanib alaninate and midazolam."( Lack of effect of brivanib on the pharmacokinetics of midazolam, a CYP3A4 substrate, administered intravenously and orally in healthy participants.
Clemens, PL; Dhar, A; Kollia, G; Lathers, D; Masson, E; Syed, S; Walters, I, 2012
)
0.83
" Pharmacokinetic data (ie, C(max), T(max), t(½), and AUC) were analyzed using a 2-compartment model."( Pharmacokinetics and tolerability of nasal versus intravenous midazolam in healthy Dutch volunteers: a single-dose, randomized-sequence, open-label, 2-period crossover pilot study.
de Krom, MC; Fiddelers, AA; Marcus, MA; Neef, C; Theunissen, HM; van der Kuy, PH; Veldhorst-Janssen, NM, 2011
)
0.61
" Midazolam, 1'-hydroxymidazolam, digoxin, and telaprevir concentrations in plasma and digoxin concentrations in urine were measured and pharmacokinetic parameters calculated."( Effect of telaprevir on the pharmacokinetics of midazolam and digoxin.
Alves, K; Chandorkar, G; Farmer, HF; Garg, V; Smith, F; van Heeswijk, RP, 2012
)
1.54
" The pharmacokinetic behavior of remimazolam was linear and its systemic clearance approximately 3 times that of midazolam."( A placebo- and midazolam-controlled phase I single ascending-dose study evaluating the safety, pharmacokinetics, and pharmacodynamics of remimazolam (CNS 7056): Part I. Safety, efficacy, and basic pharmacokinetics.
Antonik, LJ; Borkett, KM; Goldwater, DR; Kilpatrick, GJ; Tilbrook, GS, 2012
)
0.94
" Population pharmacokinetic and pharmacodynamic modeling of the data was undertaken and the parameters obtained were used for Monte-Carlo simulations of alternative dosing regimens."( A placebo- and midazolam-controlled phase I single ascending-dose study evaluating the safety, pharmacokinetics, and pharmacodynamics of remimazolam (CNS 7056): Part II. Population pharmacokinetic and pharmacodynamic modeling and simulation.
Borkett, KM; Kilpatrick, GJ; Tilbrook, GS; Wiltshire, HR, 2012
)
0.73
"A 4-compartment mammillary pharmacokinetic model of midazolam and a physiologically based recirculation model of remimazolam were fitted to the observed plasma levels."( A placebo- and midazolam-controlled phase I single ascending-dose study evaluating the safety, pharmacokinetics, and pharmacodynamics of remimazolam (CNS 7056): Part II. Population pharmacokinetic and pharmacodynamic modeling and simulation.
Borkett, KM; Kilpatrick, GJ; Tilbrook, GS; Wiltshire, HR, 2012
)
0.98
"Population pharmacokinetic and pharmacodynamic models developed for remimazolam and midazolam fitted the observed data well."( A placebo- and midazolam-controlled phase I single ascending-dose study evaluating the safety, pharmacokinetics, and pharmacodynamics of remimazolam (CNS 7056): Part II. Population pharmacokinetic and pharmacodynamic modeling and simulation.
Borkett, KM; Kilpatrick, GJ; Tilbrook, GS; Wiltshire, HR, 2012
)
0.96
"The objective of this investigation was to assess the performance of an allometric model as the basis for interpolating drug exposure in the context of pharmacokinetic bridging across paediatric subpopulations."( Scaling of pharmacokinetics across paediatric populations: the lack of interpolative power of allometric models.
Cella, M; Danhof, M; de Wildt, SN; Della Pasqua, O; Knibbe, C; Van Gerven, J, 2012
)
0.38
" time curve (AUC), in children and adolescents was interpolated based on pharmacokinetic parameter distributions obtained from the model describing infants, toddlers and adults (model 1)."( Scaling of pharmacokinetics across paediatric populations: the lack of interpolative power of allometric models.
Cella, M; Danhof, M; de Wildt, SN; Della Pasqua, O; Knibbe, C; Van Gerven, J, 2012
)
0.38
"The two pharmacokinetic models accurately described midazolam exposure in the population on which they were built."( Scaling of pharmacokinetics across paediatric populations: the lack of interpolative power of allometric models.
Cella, M; Danhof, M; de Wildt, SN; Della Pasqua, O; Knibbe, C; Van Gerven, J, 2012
)
0.63
"In the first DDI study, coadministration of ketoconazole (a CYP3A4 inhibitor) and clobazam increased clobazam's area under the concentration time curve from time zero extrapolated to infinity (AUC(0-∞) ) 54% and decreased clobazam's maximum plasma concentration (C(max) ) by 15% versus administration of clobazam alone, but the combination affected these pharmacokinetic parameters for N-CLB to a lesser degree."( Pharmacokinetic drug interactions between clobazam and drugs metabolized by cytochrome P450 isoenzymes.
Bekersky, I; Blum, RA; Tolbert, D; Walzer, M, 2012
)
0.38
" The pharmacodynamic (PD) effects were assessed using quantitative electroencephalography (EEG)."( Intranasal midazolam: pharmacokinetics and pharmacodynamics assessed by quantitative EEG in healthy volunteers.
Deuster, S; Donzelli, M; Drewe, J; Fuhr, P; Hardmeier, M; Haschke, M; Krähenbühl, S; Pflüger, M; Rüegg, S; Suter, K; Zimmermann, R, 2012
)
0.77
" Pharmacokinetic analysis, on whole blood, revealed rapid absorption of the administered midazolam with a higher C(max) in PXB compared to SCID."( Pharmacokinetics and metabolism of midazolam in chimeric mice with humanised livers.
Hutchison, M; Morikawa, Y; Pickup, K; Samuelsson, K; Sarda, S; Schulz-Utermoehl, T; Swales, JG; Wilson, ID, 2012
)
0.87
"Population pharmacokinetic modeling was performed using a joint dataset of 3 studies conducted previously: study 1: pediatric intensive care patients requiring sedation in the intensive care unit; study 2: pediatric oncology patients undergoing an invasive procedure; study 3: otherwise healthy infants admitted for postoperative monitoring after elective major craniofacial surgery."( Critical illness is a major determinant of midazolam clearance in children aged 1 month to 17 years.
Danhof, M; de Wildt, SN; Ince, I; Knibbe, CA; Murry, DJ; Peeters, MY; Tibboel, D, 2012
)
0.64
" We have used a pregnancy physiologically based pharmacokinetic (p-PBPK) model to assess the likely impact of pregnancy on three model compounds, namely caffeine, metoprolol and midazolam, based on the knowledge of their disposition in nonpregnant women and information from in vitro studies."( A pregnancy physiologically based pharmacokinetic (p-PBPK) model for disposition of drugs metabolized by CYP1A2, CYP2D6 and CYP3A4.
Abduljalil, K; Gaohua, L; Jamei, M; Johnson, TN; Rostami-Hodjegan, A, 2012
)
0.57
" The aim of this study was to determine whether a commercially available curcuminoid/piperine extract alters the pharmacokinetic disposition of probe drugs for these enzymes in human volunteers."( Effect of a herbal extract containing curcumin and piperine on midazolam, flurbiprofen and paracetamol (acetaminophen) pharmacokinetics in healthy volunteers.
Badmaev, V; Court, MH; Greenblatt, DJ; Hanley, MJ; Harmatz, JS; Hazarika, S; Majeed, M; Masse, G; Volak, LP, 2013
)
0.63
" Following single doses of ACT-178882, t1/2 and tmax varied from 18."( Clinical pharmacology of single- and multiple-ascending doses of ACT-178882, a new direct renin inhibitor, and its pharmacokinetic interaction with food and midazolam.
Binkert, C; Dingemanse, J; Nicolas, L, 2013
)
0.59
"Predicted metabolic drug clearances (CLPT ) were determined using in vitro-in vivo extrapolation coupled with physiological-based pharmacokinetic modelling and simulation (IVIVE-PBPK) in Simcyp®."( Predicted metabolic drug clearance with increasing adult age.
Doogue, MP; Jensen, BP; Patel, F; Polasek, TM; Sorich, MJ; Wiese, MD, 2013
)
0.39
"4) in the maximum plasma concentration (C(max)), area under the concentration-time curve from time 0 to infinity (AUC(0-∞)), and terminal half-life (t(1/2)), respectively, of midazolam; the time to peak plasma concentration (t(max)) was unchanged."( Pharmacokinetic interactions of almorexant with midazolam and simvastatin, two CYP3A4 model substrates, in healthy male subjects.
Alessi, F; Dingemanse, J; Hoch, M; Hoever, P; Theodor, R, 2013
)
0.84
" The systemic half-life was short and the systemic clearance rate was higher than hepatic blood flow."( Clinical pharmacokinetics, metabolism, and drug-drug interaction of carfilzomib.
Alsina, M; Badros, A; Bomba, D; Fang, Y; Infante, JR; Kirk, C; Li, J; Papadopoulos, K; Wang, Z; Wong, A; Woo, T; Yang, J, 2013
)
0.39
"Focusing on the genetic similarity of CYP3A subfamily enzymes (CYP3A4 and CYP3A5) between monkeys and humans, we have attempted to provide a single-species approach to predicting human hepatic clearance (CLh) of CYP3A4 substrates using pharmacokinetic parameters in cynomolgus monkeys following intravenous administrations."( A new approach to predicting human hepatic clearance of CYP3A4 substrates using monkey pharmacokinetic data.
Houjo, T; Ishigai, M; Kato, M; Ogawa, K, 2013
)
0.39
"Conventional mammillary models are frequently used for pharmacokinetic (PK) analysis when only blood or plasma data are available."( Applications of minimal physiologically-based pharmacokinetic models.
Cao, Y; Jusko, WJ, 2012
)
0.38
"A two-compartment pharmacokinetic model best describes the data."( Pharmacokinetics of midazolam in resuscitated patients treated with moderate hypothermia.
Bastiaans, DE; Derijks, LJ; Swart, EL; van Akkeren, JP, 2013
)
0.71
" Plasma samples obtained, up to 24 hr after dosing, from four male and four female Microminipigs were analyzed by liquid chromatography tandem mass spectrometry to estimate typical pharmacokinetic parameters for each analyte."( Simultaneous pharmacokinetics assessment of caffeine, warfarin, omeprazole, metoprolol, and midazolam intravenously or orally administered to Microminipigs.
Iwasaki, K; Izumi, H; Kusumoto, S; Mogi, M; Murayama, N; Shimizu, M; Takehara, H; Toda, A; Utoh, M; Yamazaki, H, 2012
)
0.6
"We conducted a pharmacokinetic (PK) study and a pharmacodynamic (PD) study to assess whether Roux-en-Y gastric bypass (RYGB) surgery is associated with significant changes to PK and PD of oral medications."( Pharmacokinetic and pharmacodynamic alterations in the Roux-en-Y gastric bypass recipients.
Chalasani, N; Hall, SD; Jones, DR; Mattar, S; Tandra, S; Vuppalanchi, R, 2013
)
0.39
" Compared with controls, the RYGB group had brisk natriuresis, with significantly lower tmax for urine sodium (1."( Pharmacokinetic and pharmacodynamic alterations in the Roux-en-Y gastric bypass recipients.
Chalasani, N; Hall, SD; Jones, DR; Mattar, S; Tandra, S; Vuppalanchi, R, 2013
)
0.39
"RYGB recipients have significantly shorter tmax for the studied orally administered medications, but otherwise no other significant changes in PK were reported."( Pharmacokinetic and pharmacodynamic alterations in the Roux-en-Y gastric bypass recipients.
Chalasani, N; Hall, SD; Jones, DR; Mattar, S; Tandra, S; Vuppalanchi, R, 2013
)
0.39
"Potential differences in pharmacokinetics (PK) between healthy subjects and patients with cancer were investigated using a physiologically based pharmacokinetic approach integrating demographic and physiological data from patients with cancer."( A physiologically based pharmacokinetic (PBPK) approach to evaluate pharmacokinetics in patients with cancer.
Budha, NR; Cheeti, S; Dresser, MJ; Jin, JY; Rajan, S, 2013
)
0.39
"The pharmacokinetic effects of substrates or inhibitors of CYP3A4, P-gp and Bcrp (ABCG2) on rivaroxaban were studied in healthy volunteers."( Co-administration of rivaroxaban with drugs that share its elimination pathways: pharmacokinetic effects in healthy subjects.
Becka, M; Kubitza, D; Mueck, W, 2013
)
0.39
"To determine pharmacokinetic and pharmacodynamic properties of midazolam after IV and IM administration in alpacas."( Pharmacokinetics and pharmacodynamics of midazolam after intravenous and intramuscular administration in alpacas.
Aarnes, TK; Bednarski, RM; Bei, D; Chen, W; Fry, PR; Hubbell, JA; Lakritz, J; Lerche, P; Liu, Z, 2013
)
0.9
" Distribution half-life was 18."( Pharmacokinetics and pharmacodynamics of midazolam after intravenous and intramuscular administration in alpacas.
Aarnes, TK; Bednarski, RM; Bei, D; Chen, W; Fry, PR; Hubbell, JA; Lakritz, J; Lerche, P; Liu, Z, 2013
)
0.66
" Median distribution half-life was 24 min (range 6-42 min) and 39 min (range 33."( Pharmacokinetics of midazolam after intravenous administration to horses.
Aarnes, TK; Bednarski, RM; Hubbell, JA; Kelly, EM; Lakritz, J; Lerche, P; Liu, Z, 2013
)
0.71
" Population pharmacokinetic modeling with systematic covariate analysis was performed by use of NONMEM v6."( A novel maturation function for clearance of the cytochrome P450 3A substrate midazolam from preterm neonates to adults.
Burggraaf, J; Danhof, M; de Wildt, SN; Ince, I; Jacqz-Aigrain, E; Knibbe, CA; Peeters, MY; Tibboel, D; van den Anker, JN; Wang, C, 2013
)
0.62
" This function can be used to derive evidence-based doses for children, and to simulate exposure to midazolam and possibly other CYP3A substrates across the pediatric age range in population pharmacokinetic models or physiologically based pharmacokinetic models."( A novel maturation function for clearance of the cytochrome P450 3A substrate midazolam from preterm neonates to adults.
Burggraaf, J; Danhof, M; de Wildt, SN; Ince, I; Jacqz-Aigrain, E; Knibbe, CA; Peeters, MY; Tibboel, D; van den Anker, JN; Wang, C, 2013
)
0.83
" Physiologically based pharmacokinetic (PBPK) models have been used to evaluate treatment regimens resulting in maximal CYP3A inhibition by ketoconazole but have reached different conclusions."( Optimization of drug-drug interaction study design: comparison of minimal physiologically based pharmacokinetic models on prediction of CYP3A inhibition by ketoconazole.
Chien, JY; Hall, SD; Han, B; Mao, J, 2013
)
0.39
"Accurate predictions of cytochrome P450 (CYP) 3A-mediated drug-drug interactions (DDIs) account for dynamic changes of CYP3A activity at both major expression sites (liver and gut wall) by considering the full pharmacokinetic profile of the perpetrator and the substrate."( A semiphysiological population pharmacokinetic model for dynamic inhibition of liver and gut wall cytochrome P450 3A by voriconazole.
Frechen, S; Fuhr, U; Junge, L; Neuvonen, PJ; Olkkola, KT; Rokitta, D; Saari, TI; Suleiman, AA, 2013
)
0.39
" Therefore, a physiologically-based pharmacokinetic (PBPK) model for verapamil and its primary metabolite was developed and validated through the recovery of observed clinical plasma concentration data for both moieties and the reported interaction with midazolam, albeit a cytochrome P450 3A4-mediated DDI."( Application of permeability-limited physiologically-based pharmacokinetic models: part II - prediction of P-glycoprotein mediated drug-drug interactions with digoxin.
Barter, Z; Jamei, M; Neuhoff, S; Rostami-Hodjegan, A; Turner, DB; Yeo, KR, 2013
)
0.57
"This study assessed the safety, tolerability, and pharmacokinetic interaction between PA-824, a novel antitubercular nitroimidazo-oxazine, and midazolam, a CYP3A4 substrate, in 14 healthy adult male and female subjects."( Evaluation of pharmacokinetic interaction between PA-824 and midazolam in healthy adult subjects.
Egizi, E; Erondu, N; Everitt, D; Ginsberg, A; Pauli, E; Rouse, DJ; Severynse-Stevens, D; Winter, H, 2013
)
0.83
" Serial blood samples were collected over the course of the two studies and pharmacokinetic parameters were determined for all analytes."( Effect of netupitant, a highly selective NK₁ receptor antagonist, on the pharmacokinetics of midazolam, erythromycin, and dexamethasone.
Lanzarotti, C; Rossi, G, 2013
)
0.61
"Physiologically based pharmacokinetic models were developed using MATLAB Simulink® and PK-Sim®."( Investigation of an alternative generic model for predicting pharmacokinetic changes during physiological stress.
Cheung, B; Edginton, AN; Peng, HT, 2013
)
0.39
" A semi-physiologically based pharmacokinetic model (semi-PBPK) characterizing mechanism-based auto-inhibition was developed to predict the stereoselective pharmacokinetic profiles of verapamil and norverapamil following single or multiple oral doses."( A semi-physiologically-based pharmacokinetic model characterizing mechanism-based auto-inhibition to predict stereoselective pharmacokinetics of verapamil and its metabolite norverapamil in human.
Liu, L; Liu, X; Sai, Y; Wang, D; Wang, J; Xia, S; Xue, W, 2013
)
0.39
"A new approach for calculation of sample size in pediatric clinical pharmacokinetic studies was suggested based on desired precision for a pharmacokinetic parameter of interest."( Precision criteria to derive sample size when designing pediatric pharmacokinetic studies: which measure of variability should be used?
Aarons, L; Johnson, TN; Ogungbenro, K; Rostami-Hodjegan, A; Salem, F; Vajjah, P, 2014
)
0.4
"We aim to evaluate the influence of covariates, including cytochrome P450 3A (CYP3A) genetic polymorphisms, on the pharmacokinetics of midazolam (MDZ) in Asian cancer patients, using a population pharmacokinetic approach."( CYP3A5*3 and bilirubin predict midazolam population pharmacokinetics in Asian cancer patients.
Goh, BC; Hee, KH; Lee, LS; Sapari, NS; Seng, KY; Soon, GH; Soong, R, 2014
)
0.89
"The statistical identifiability of nonlinear pharmacokinetic (PK) models with the Michaelis-Menten (MM) kinetic equation is considered using a global optimization approach, which is particle swarm optimization (PSO)."( Statistical identifiability and convergence evaluation for nonlinear pharmacokinetic models with particle swarm optimization.
Kim, S; Li, L, 2014
)
0.4
" A population pharmacokinetic model using non-linear mixed-effects modeling software NONMEM was built, which included the phenotype tests as covariate."( Predictive value of CYP3A and ABCB1 phenotyping probes for the pharmacokinetics of sunitinib: the ClearSun study.
Balakrishnar, B; Bennink, RJ; Daali, Y; Eechoute, K; Gurney, H; Huitema, AD; Kam, BL; Kloth, JS; Klümpen, HJ; Mathijssen, RH; Samer, CF; Schellens, JH; Wong, M; Yu, H; Zwinderman, AH, 2014
)
0.4
"9% reduction in Cmax (120 and 180 mg kg(-1), respectively) compared with the control."( Effect of triacontanol on the pharmacokinetics of docetaxel in rats associated with induction of cytochrome P450 3A1/2.
Chen, X; Deng, S; Fan, A; Gao, W; Li, C; Li, N; Liu, Q; Wang, C; Wen, X; Zhang, Q; Zhang, W; Zhang, Y; Zhao, D; Zhao, J, 2014
)
0.4
" A physiologically based pharmacokinetic (PBPK) model was developed to project the dynamics and magnitude of CYP3A4 induction in vivo from in vitro data generated with primary human hepatocytes."( Physiologically based pharmacokinetic modeling of CYP3A4 induction by rifampicin in human: influence of time between substrate and inducer administration.
Baneyx, G; Iliadis, A; Lavé, T; Meille, C; Parrott, N, 2014
)
0.4
" The aims of this analysis were to develop population pharmacokinetic (PPK) models of AZD7325 and midazolam and to assess the induction effect of AZD7325 on CYP3A4 with midazolam as a substrate."( Population pharmacokinetic modelling to assess clinical drug-drug interaction between AZD7325 and midazolam.
Al-Huniti, N; Lu, Z; Sunzel, M; Xu, H; Zhou, D, 2014
)
0.84
" Population pharmacokinetic analysis was performed using nonlinear mixed effects modeling."( Population pharmacokinetic analysis of circadian rhythms in hepatic CYP3A activity using midazolam.
Di Gion, P; Frechen, S; Fuhr, U; Kerkweg, U; Kraus, D; Queckenberg, C; Rokitta, D; Suleiman, AA; Tomalik-Scharte, D, 2014
)
0.62
" The pharmacokinetic interaction between multiple oral doses of ridaforolimus and a single oral dose of midazolam was evaluated in an open-label, fixed-sequence study, in which cancer patients received a single oral dose of 2 mg midazolam followed by 5 consecutive daily single oral doses of 40 mg ridaforolimus with a single dose of 2 mg midazolam with the fifth ridaforolimus dose."( Lack of meaningful effect of ridaforolimus on the pharmacokinetics of midazolam in cancer patients: model prediction and clinical confirmation.
Agrawal, N; Breidinger, S; Lush, R; McCrea, J; Narasimhan, N; Orford, K; Palcza, J; Panebianco, D; Papadopoulos, KP; Patnaik, A; Sandhu, P; Stroh, M; Talaty, J; Tolcher, A; Trucksis, M; Wagner, JA, 2014
)
0.85
" A physiologically-based pharmacokinetic (PBPK) model was also built."( Prednisone has no effect on the pharmacokinetics of CYP3A4 metabolized drugs - midazolam and odanacatib.
Ballard, J; Evers, R; Gibson, CR; Hreniuk, D; Kassahun, K; Liu, C; Mahon, C; Marcantonio, EE; Mehta, A; Morris, D; Mostoller, K; Palamanda, J; Stoch, SA; Tang, C; Wagner, JA; Zajic, S, 2014
)
0.63
"This study evaluates the time-of-day effect on midazolam and 1-OH midazolam pharmacokinetics, and on the sedative pharmacodynamic response in rabbits."( The influence of the time of day on midazolam pharmacokinetics and pharmacodynamics in rabbits.
Bednarek, E; Bienert, A; Billert, H; Buda, K; Grześkowiak, E; Kaliszan, R; Kamińska, A; Kostrzewski, B; Płotek, W; Szczesny, D; Teżyk, A; Wiczling, P; Zaba, C, 2014
)
0.93
" The categorical pharmacodynamic data were described with a logistic model."( The influence of the time of day on midazolam pharmacokinetics and pharmacodynamics in rabbits.
Bednarek, E; Bienert, A; Billert, H; Buda, K; Grześkowiak, E; Kaliszan, R; Kamińska, A; Kostrzewski, B; Płotek, W; Szczesny, D; Teżyk, A; Wiczling, P; Zaba, C, 2014
)
0.68
"We did not find any time-of-day effects for the pharmacokinetic and pharmacodynamics parameters of midazolam."( The influence of the time of day on midazolam pharmacokinetics and pharmacodynamics in rabbits.
Bednarek, E; Bienert, A; Billert, H; Buda, K; Grześkowiak, E; Kaliszan, R; Kamińska, A; Kostrzewski, B; Płotek, W; Szczesny, D; Teżyk, A; Wiczling, P; Zaba, C, 2014
)
0.89
"To evaluate felodipine as a potential perpetrator of pharmacokinetic drug-drug interactions (PK-DDIs) involving cytochrome P450 (CYP) enzymes and P-glycoprotein (P-gp)."( Evaluation of felodipine as a potential perpetrator of pharmacokinetic drug-drug interactions.
Doogue, MP; Miners, JO; Polasek, TM; Rowland, A; Snyder, BD, 2014
)
0.4
" Vandetanib + digoxin increased digoxin area under the concentration-time curve from zero to the last quantifiable concentration (AUC0-last) and Cmax by 23 and 29 %, respectively, versus digoxin alone, with only a 9 % decrease in CLR."( Pharmacokinetic evaluations of the co-administrations of vandetanib and metformin, digoxin, midazolam, omeprazole or ranitidine.
Johansson, S; Leese, PT; Li, Y; Lisbon, E; Martin, P; Mathews, D; Oliver, S; Read, J; Steinberg, M, 2014
)
0.62
" Data from 12 healthy volunteers were available for a population pharmacokinetic analysis using NONMEM(®)."( Midazolam pharmacokinetics in morbidly obese patients following semi-simultaneous oral and intravenous administration: a comparison with healthy volunteers.
Brill, MJ; Burggraaf, J; Houwink, AP; Knibbe, CA; van Dongen, EP; van Ramshorst, B; van Rongen, A; Wiezer, RJ, 2014
)
1.85
" The objective of this work was to build a physiologically based pharmacokinetic (PBPK) model to assess MMAE-drug interactions for vc-MMAE ADCs."( Physiologically based pharmacokinetic modeling as a tool to predict drug interactions for antibody-drug conjugates.
Chen, Y; Girish, S; Hop, C; Jin, JY; Li, C; Lu, D; Mukadam, S; Samineni, D; Shen, BQ; Wong, H, 2015
)
0.42
" The model was developed using in silico and in vitro data and in vivo pharmacokinetic data from anti-CD22-vc-MMAE ADC."( Physiologically based pharmacokinetic modeling as a tool to predict drug interactions for antibody-drug conjugates.
Chen, Y; Girish, S; Hop, C; Jin, JY; Li, C; Lu, D; Mukadam, S; Samineni, D; Shen, BQ; Wong, H, 2015
)
0.42
"The pharmacokinetic profile of acMMAE and unconjugated MMAE following administration of anti-CD22-vc-MMAE was well described by simulations using the developed PBPK model."( Physiologically based pharmacokinetic modeling as a tool to predict drug interactions for antibody-drug conjugates.
Chen, Y; Girish, S; Hop, C; Jin, JY; Li, C; Lu, D; Mukadam, S; Samineni, D; Shen, BQ; Wong, H, 2015
)
0.42
"The aim of the study was to assess the magnitude of the CYP3A4 inhibitory effect of 2 dosing regimens of ketoconazole and the influence of the pharmacokinetic properties of the CYP3A4 substrate on the extent of the substrate exposure increase."( CYP3A4-based drug-drug interaction: CYP3A4 substrates' pharmacokinetic properties and ketoconazole dose regimen effect.
Boulenc, X; Donazzolo, Y; Hermabessière, S; Martin, V; Nicolas, O; Ollier, C; Zobouyan, I, 2016
)
0.43
" The present study investigated changes in the pharmacokinetic behavior of intravenously administered midazolam (MDZ), a probe for CYP3A, when rats were treated with menthol."( Change in pharmacokinetic behavior of intravenously administered midazolam due to increased CYP3A2 expression in rats treated with menthol.
Konishi, H; Nagai, K; Suzuki, S; Yamamura, A, 2015
)
0.87
"Doravirine is generally well tolerated in single doses up to 1,200 mg and multiple doses up to 750 mg once daily for up to 10 days, with a pharmacokinetic profile supportive of once-daily dosing."( Safety, tolerability and pharmacokinetics of doravirine, a novel HIV non-nucleoside reverse transcriptase inhibitor, after single and multiple doses in healthy subjects.
Ancona, JK; Anderson, MS; Butterton, JR; Cilissen, C; De Lepeleire, I; Dockendorf, MF; Gilmartin, J; Guo, Y; Liu, R; Tetteh, E; Van Bortel, L; Wagner, JA, 2015
)
0.42
" Blood samples for pharmacokinetic analysis were collected pre-dose and serially for 72 h post-dose."( Lisdexamfetamine Dimesylate Effects on the Pharmacokinetics of Cytochrome P450 Substrates in Healthy Adults in an Open-Label, Randomized, Crossover Study.
Corcoran, M; Ermer, J; Martin, P, 2015
)
0.42
" The area under the curve (AUC) and the half-life (t1/2) of intravenously administered MDZ were significantly increased, and the total clearance (CLtot) and the elimination rate constant at the terminal phase (ke) were significantly decreased without significant changes in the volume of distribution at a steady state (Vdss)."( Decreased elimination clearance of midazolam by doxorubicin through reductions in the metabolic activity of hepatic CYP3A in rats.
Kasahara, K; Kiyama, M; Konishi, H; Nagai, K; Yamamura, A; Yoshida, N, 2015
)
0.69
" Plasma concentrations of slowly eliminated caffeine and R-/S-warfarin and rapidly eliminated omeprazole and midazolam previously observed in cynomolgus monkeys were scaled to human oral biomonitoring equivalents using known species allometric scaling factors and in vitro metabolic clearance data with a simple physiologically based pharmacokinetic (PBPK) model."( Human plasma concentrations of cytochrome P450 probes extrapolated from pharmacokinetics in cynomolgus monkeys using physiologically based pharmacokinetic modeling.
Murayama, N; Shida, S; Shimizu, M; Uno, Y; Utoh, M; Yamazaki, H, 2015
)
0.63
" The aim of the current work was to develop a physiologically based pharmacokinetic (PBPK) model to predict quantitatively the magnitude of CYP3A4 mediated drug-drug interaction with midazolam as the substrate."( Physiologically based pharmacokinetic modeling to predict complex drug-drug interactions: a case study of AZD2327 and its metabolite, competitive and time-dependent CYP3A inhibitors.
Guo, J; Khanh, BH; Li, Y; Zhou, D, 2015
)
0.61
"Sixty-five tacrolimus- and 10 cyclosporine-treated renal transplant recipients underwent pharmacokinetic testing at day 7 and months 1, 3, 6 and 12 after transplantation, including 8-h area under the concentration-time curve (AUC) for tacrolimus or cyclosporine and assessment of CYP3A4 activity using oral and intravenous midazolam (MDZ) drug probes."( Progressive decline in tacrolimus clearance after renal transplantation is partially explained by decreasing CYP3A4 activity and increasing haematocrit.
de Jonge, H; de Loor, H; Kuypers, DR; Vanhove, T; Verbeke, K, 2015
)
0.59
" Midazolam concentrations were analyzed using population pharmacokinetic modeling."( The Pharmacokinetics of the CYP3A Substrate Midazolam in Morbidly Obese Patients Before and One Year After Bariatric Surgery.
Brill, MJ; Darwich, AS; Hazebroek, EJ; Knibbe, CA; Rostami-Hodjegan, A; van Dongen, EP; van Ramshorst, B; van Rongen, A, 2015
)
1.59
" Blood samples were collected for 12 h post dose to determine pharmacokinetic profiles."( Pharmacokinetics, pharmacodynamics, and safety of USL261, a midazolam formulation optimized for intranasal delivery, in a randomized study with healthy volunteers.
Bancke, LL; Dworak, HA; Gidal, BE; Halvorsen, MB; Rodvold, KA, 2015
)
0.66
"Increasing USL261 dose corresponded with increases in midazolam area under the concentration time curve (AUC) and maximum observed plasma concentration (Cmax ), with all doses demonstrating rapid median time to Cmax (Tmax ; 10-12 min)."( Pharmacokinetics, pharmacodynamics, and safety of USL261, a midazolam formulation optimized for intranasal delivery, in a randomized study with healthy volunteers.
Bancke, LL; Dworak, HA; Gidal, BE; Halvorsen, MB; Rodvold, KA, 2015
)
0.91
"Compared with intranasal delivery of a midazolam formulation intended for IV delivery, USL261, optimized for intranasal administration demonstrated improved bioavailability with similar pharmacodynamic effects."( Pharmacokinetics, pharmacodynamics, and safety of USL261, a midazolam formulation optimized for intranasal delivery, in a randomized study with healthy volunteers.
Bancke, LL; Dworak, HA; Gidal, BE; Halvorsen, MB; Rodvold, KA, 2015
)
0.93
"The physiologically based pharmacokinetic (PBPK) model for midazolam was developed using a SimCYP population-based simulator incorporating Chinese population demographic, physiological and enzyme data."( Evaluating a physiologically based pharmacokinetic model for predicting the pharmacokinetics of midazolam in Chinese after oral administration.
Chen, X; Hu, P; Jiang, J; Shi, J; Wang, HY, 2016
)
0.9
"The pharmacokinetics of cytochrome P450 probes in humans can be extrapolated from corresponding data in cynomolgus monkeys using simplified physiologically based pharmacokinetic (PBPK) modeling."( Human plasma concentrations of five cytochrome P450 probes extrapolated from pharmacokinetics in dogs and minipigs using physiologically based pharmacokinetic modeling.
Shida, S; Yamazaki, H, 2016
)
0.43
"Physiologically based pharmacokinetic (PBPK) modeling for itraconazole has been challenging due to highly variable in vitro d ata used for 'bottom-up' model building."( Development of a Physiologically Based Pharmacokinetic Model for Itraconazole Pharmacokinetics and Drug-Drug Interaction Prediction.
Budha, N; Chen, Y; Hop, CE; Jin, JY; Kenny, JR; Lu, T; Ma, F; Mao, J; Wong, H, 2016
)
0.43
" The key parameters that govern the pharmacokinetic profile, including non-linear clearance (i."( Development of a Physiologically Based Pharmacokinetic Model for Itraconazole Pharmacokinetics and Drug-Drug Interaction Prediction.
Budha, N; Chen, Y; Hop, CE; Jin, JY; Kenny, JR; Lu, T; Ma, F; Mao, J; Wong, H, 2016
)
0.43
"In a two-compartmental pharmacokinetic model, body weight was the most significant covariate for clearance and volume of distribution."( Inflammation and Organ Failure Severely Affect Midazolam Clearance in Critically Ill Children.
Brussee, JM; de Hoog, M; de Wildt, SN; Jerchel, IS; Knibbe, CA; Koch, BC; Mooij, MG; Tibboel, D; van Schaik, RH; Verlaat, CW; Vet, NJ, 2016
)
0.69
" The pharmacokinetic data of cytochrome P450 probes in humans can be extrapolated from corresponding data in cynomolgus monkeys, dogs and minipigs using simplified physiologically based pharmacokinetic (PBPK) modeling."( Human plasma concentrations of cytochrome P450 probe cocktails extrapolated from pharmacokinetics in mice transplanted with human hepatocytes and from pharmacokinetics in common marmosets using physiologically based pharmacokinetic modeling.
Kawano, M; Mitsui, M; Sasaki, E; Shimizu, M; Suemizu, H; Toda, A; Uehara, S; Uno, Y; Utoh, M; Yamazaki, H, 2016
)
0.43
" In this study, we developed a physiologically based pharmacokinetic (PBPK) model using SimCYP to predict the impact of elevated interleukin-6 (IL-6) levels on cytochrome P450 (CYP) enzymes and the treatment effect of an anti-IL-6 monoclonal antibody, sirukumab, in patients with rheumatoid arthritis (RA)."( Development of a Physiologically Based Pharmacokinetic Model to Predict Disease-Mediated Therapeutic Protein-Drug Interactions: Modulation of Multiple Cytochrome P450 Enzymes by Interleukin-6.
Jiang, X; Wang, W; Xu, Z; Zhou, H; Zhuang, Y, 2016
)
0.43
"This review gives an overview of how the pharmacokinetics in terminally ill patients may differ from the average population and discusses the effect of terminal illness on each of the four pharmacokinetic processes absorption, distribution, metabolism, and elimination."( Pharmacokinetic considerations and recommendations in palliative care, with focus on morphine, midazolam and haloperidol.
Baar, FP; de Winter, BC; Franken, LG; Koch, BC; Mathôt, RA; Tibboel, D; van Esch, HJ; van Gelder, T; van Zuylen, L, 2016
)
0.65
" Based on clearance of CYP isoform-specific substrates at the microsomal level (CLM), microsomal protein per gram of liver (MPPGL), liver weight, hepatic blood flow, hepatic clearance values (CLH) for 10 CYPs in HCC patients (n=102) were extrapolated using a predictive bottom-up pharmacokinetic model."( Changes in cytochrome P450s-mediated drug clearance in patients with hepatocellular carcinoma in vitro and in vivo: a bottom-up approach.
Fang, Y; Gao, J; Gao, N; He, XP; Jia, LJ; Jin, H; Qiao, HL; Tian, X; Wen, Q; Zhang, YF; Zhou, J, 2016
)
0.43
" The objectives of this study were to characterize the MDZ pharmacokinetics in critically ill patients and to describe the phenomenon of increasing daily dose by means of population pharmacokinetic analysis."( Semi-mechanistic autoinduction model of midazolam in critically ill patients: population pharmacokinetic analysis.
Aoyama, T; Aoyama, Y; Hayashi, H; Hirata, K; Matsumoto, Y; Yamamoto, Y; Yokota, H, 2016
)
0.7
" Population pharmacokinetic analysis was performed using the NONMEM software package."( Semi-mechanistic autoinduction model of midazolam in critically ill patients: population pharmacokinetic analysis.
Aoyama, T; Aoyama, Y; Hayashi, H; Hirata, K; Matsumoto, Y; Yamamoto, Y; Yokota, H, 2016
)
0.7
"The final population pharmacokinetic model was a one-compartment model estimated by incorporating a semi-mechanistic pharmacokinetic-enzyme turnover model for clearance, taking autoinduction into account."( Semi-mechanistic autoinduction model of midazolam in critically ill patients: population pharmacokinetic analysis.
Aoyama, T; Aoyama, Y; Hayashi, H; Hirata, K; Matsumoto, Y; Yamamoto, Y; Yokota, H, 2016
)
0.7
" Step-by-step dosage adjustment using this population pharmacokinetic model may be useful for establishing a MDZ dosage regimen in critically ill patients."( Semi-mechanistic autoinduction model of midazolam in critically ill patients: population pharmacokinetic analysis.
Aoyama, T; Aoyama, Y; Hayashi, H; Hirata, K; Matsumoto, Y; Yamamoto, Y; Yokota, H, 2016
)
0.7
" The objectives of the current study are to (1) develop a physiologically based pharmacokinetic (PBPK) model of palbociclib based on the in silico, in vitro, and in vivo pharmacokinetic data of palbociclib, (2) verify the PBPK model with clinical drug-drug interaction (DDI) results of palbociclib with strong CYP3A inhibitor (itraconazole), inducer (rifampin), and a sensitive CYP3A substrate (midazolam), and (3) predict the DDI risk of palbociclib with moderate/weak CYP3A inhibitors."( Physiologically Based Pharmacokinetic Modeling of Palbociclib.
Hoffman, J; Loi, CM; Wang, D; Yu, Y, 2017
)
0.62
" This finding also prompted a systematic review of available evidence on the pharmacokinetic alteration of midazolam by grapefruit juice."( Effect of Low-Furanocoumarin Hybrid Grapefruit Juice Consumption on Midazolam Pharmacokinetics.
Cancalon, P; Cooper-DeHoff, RM; de Oliveria, F; Frye, RF; Gmitter, FG; Handberg, EM; Kawaguchi-Suzuki, M; Kight, J; Nasiri-Kenari, N; Pepine, CJ; Shuster, J, 2017
)
0.9
"There were no significant correlations between the pharmacokinetic parameters of midazolam and urinary ratios of 6β-OHF/F."( Associations of the CYP3A5*3 and CYP3A4*1G polymorphisms with the pharmacokinetics of oral midazolam and the urinary 6β-hydroxycortisol/cortisol ratio as markers of CYP3A activity in healthy male Chinese.
Chan, SW; Chu, TT; Fok, BS; Hu, M; Lee, VH; Tomlinson, B; Xiao, Y; Yin, OQ, 2016
)
0.88
"There were no significant associations between midazolam pharmacokinetic parameters and urinary ratios of 6β-OHF/F and the two CYP3A polymorphisms were not associated with the urinary ratios of 6β-OHF/F or midazolam pharmacokinetic parameters."( Associations of the CYP3A5*3 and CYP3A4*1G polymorphisms with the pharmacokinetics of oral midazolam and the urinary 6β-hydroxycortisol/cortisol ratio as markers of CYP3A activity in healthy male Chinese.
Chan, SW; Chu, TT; Fok, BS; Hu, M; Lee, VH; Tomlinson, B; Xiao, Y; Yin, OQ, 2016
)
0.91
" To select a right dose in children, pharmacokinetic (PK) information is warranted."( Prediction of Clearance and Dose of Midazolam in Preterm and Term Neonates: A Comparative Study Between Allometric Scaling and Physiologically Based Pharmacokinetic Modeling.
Ahmad, T; Alam Khan, R; Mahmood, I; Mansoor, N; Sharib, SM,
)
0.41
"13230 AIM: When different models for weight and age are used in paediatric pharmacokinetic studies it is difficult to compare parameters between studies or perform model-based meta-analyses."( Scaling clearance in paediatric pharmacokinetics: All models are wrong, which are useful?
Barker, CI; Germovsek, E; Sharland, M; Standing, JF, 2017
)
0.46
"To elucidate the pharmacokinetic component to the tolerance, we administered midazolam (2 mg/kg) and morphine (10 mg/kg) alone or their combination daily to rats for 12 days followed by a pharmacokinetic study on day 13."( Pharmacokinetics cannot explain the increased effective dose requirement for morphine and midazolam in rats during their extended administration alone or in combination.
Alam, SM; Blobner, M; Greenblatt, DJ; Mao, J; Martyn, JA; Schaller, SJ; Zhao, Y, 2017
)
0.91
" Therefore, we developed a physiologically based pharmacokinetic (PBPK) model to estimate fetal drug exposure throughout pregnancy."( Development of a Novel Maternal-Fetal Physiologically Based Pharmacokinetic Model II: Verification of the model for passive placental permeability drugs.
Unadkat, JD; Zhang, Z, 2017
)
0.46
" To find clinically relevant parameters for dose individualization, we performed a pharmacokinetic study on midazolam, 1OH-midazolam (1-OH-M) and 1OH-midazolam-glucuronide (1-OH-MG) in terminally ill patients."( Hypoalbuminaemia and decreased midazolam clearance in terminally ill adult patients, an inflammatory effect?
Baar, FPM; de Winter, BCM; Franken, LG; Koch, BCP; Masman, AD; Mathot, RAA; Tibboel, D; van Gelder, T, 2017
)
0.95
"2), a population pharmacokinetic analysis was conducted with 192 samples from 45 terminally ill patients who received midazolam either orally or subcutaneously."( Hypoalbuminaemia and decreased midazolam clearance in terminally ill adult patients, an inflammatory effect?
Baar, FPM; de Winter, BCM; Franken, LG; Koch, BCP; Masman, AD; Mathot, RAA; Tibboel, D; van Gelder, T, 2017
)
0.95
"Whether the combined use of probe drugs for CYP3A4 and P-glycoprotein can clarify the relative contribution of these proteins to pharmacokinetic variability of a dual substrate like tacrolimus has never been assessed."( Fexofenadine, a Putative In Vivo P-glycoprotein Probe, Fails to Predict Clearance of the Substrate Tacrolimus in Renal Recipients.
Annaert, P; Bouillon, T; de Loor, H; Kuypers, D; Vanhove, T, 2017
)
0.46
"OBJECTIVE To determine the pharmacokinetic and pharmacodynamic effects of midazolam following IV and IM administration in sheep."( Pharmacokinetics and pharmacodynamics of midazolam following intravenous and intramuscular administration to sheep.
Cerullo, MN; Cox, SK; Doherty, TJ; Ebner, LS; Follette, C; Lizarraga, I; O, O; Scallan, EM; Simon, BT, 2017
)
0.95
" Full pharmacokinetic profiles were obtained on days 1 and 8 (midazolam and 1-hydroxymidazolam) and days 3 and 7 (delafloxacin)."( The Pharmacokinetics of the CYP3A Substrate Midazolam After Steady-state Dosing of Delafloxacin.
Cammarata, SK; Hoover, R; Lawrence, LE; Paulson, SK; Quintas, M; Wood-Horrall, RN, 2017
)
0.96
"The use of in vitro-in vivo extrapolation (IVIVE) techniques, mechanistically incorporated within physiologically based pharmacokinetic (PBPK) models, can harness in vitro drug data and enhance understanding of in vivo pharmacokinetics."( The Constraints, Construction, and Verification of a Strain-Specific Physiologically Based Pharmacokinetic Rat Model.
Harwood, MD; Jamei, M; Musther, H; Rostami-Hodjegan, A; Turner, DB; Yang, J, 2017
)
0.46
" Non-compartmental pharmacokinetic methods were used to calculate main pharmacokinetic parameters and absolute bioavailability."( A Two-way Randomized Cross-over Pharmacokinetic and Pharmacodynamic Study of an Innovative Oral Solution of Midazolam (ADV6209).
Burton, I; Granier, LA; Guittet, C; Manso, M; Marçon, F, 2017
)
0.67
" A 24-h pharmacokinetic profile was performed following midazolam administration, and bioequivalence criteria were investigated on an exploratory basis."( A pharmacokinetic drug-drug interaction study between selexipag and midazolam, a CYP3A4 substrate, in healthy male subjects.
Boehler, M; Bruderer, S; Dingemanse, J; Donazzolo, Y; Juif, PE, 2017
)
0.94
" The mean hepatic clearances determined by in silico fitting for individual pharmacokinetic models of warfarin and midazolam in the aged group were, respectively, 23% and 56% smaller than those for the young group."( Effects of aging and rifampicin pretreatment on the pharmacokinetics of human cytochrome P450 probes caffeine, warfarin, omeprazole, metoprolol and midazolam in common marmosets genotyped for cytochrome P450 2C19.
Inoue, T; Kusama, T; Mogi, M; Sasaki, E; Shimizu, M; Toda, A; Uehara, S; Uno, Y; Utoh, M; Yamazaki, H, 2018
)
0.89
"All pharmaceutical companies are required to assess pharmacokinetic drug-drug interactions (DDIs) of new chemical entities (NCEs) and mathematical prediction helps to select the best NCE candidate with regard to adverse effects resulting from a DDI before any costly clinical studies."( A quantitative systems pharmacology approach, incorporating a novel liver model, for predicting pharmacokinetic drug-drug interactions.
Cherkaoui-Rbati, MH; Littlewood, P; Paine, SW; Rauch, C, 2017
)
0.46
"Physiologically based pharmacokinetic modeling is considered a valuable tool for predicting pharmacokinetic changes in pregnancy to subsequently guide in-vivo pharmacokinetic trials in pregnant women."( A Physiologically Based Pharmacokinetic Model for Pregnant Women to Predict the Pharmacokinetics of Drugs Metabolized Via Several Enzymatic Pathways.
Coboeken, K; Dallmann, A; Eissing, T; Hempel, G; Ince, I, 2018
)
0.48
"Quantitative information on gestation-specific changes in enzyme activity available in the literature was incorporated in a pregnancy physiologically based pharmacokinetic model and the pharmacokinetics of eight drugs metabolized via one or multiple cytochrome P450 enzymes was predicted."( A Physiologically Based Pharmacokinetic Model for Pregnant Women to Predict the Pharmacokinetics of Drugs Metabolized Via Several Enzymatic Pathways.
Coboeken, K; Dallmann, A; Eissing, T; Hempel, G; Ince, I, 2018
)
0.48
"The pregnancy physiologically based pharmacokinetic model successfully predicted the pharmacokinetics of all tested drugs."( A Physiologically Based Pharmacokinetic Model for Pregnant Women to Predict the Pharmacokinetics of Drugs Metabolized Via Several Enzymatic Pathways.
Coboeken, K; Dallmann, A; Eissing, T; Hempel, G; Ince, I, 2018
)
0.48
"The presented pregnancy physiologically based pharmacokinetic model can quantitatively predict the pharmacokinetics of drugs that are metabolized via one or multiple cytochrome P450 enzymes by integrating prior knowledge of the pregnancy-related effect on these enzymes."( A Physiologically Based Pharmacokinetic Model for Pregnant Women to Predict the Pharmacokinetics of Drugs Metabolized Via Several Enzymatic Pathways.
Coboeken, K; Dallmann, A; Eissing, T; Hempel, G; Ince, I, 2018
)
0.48
" A previous pharmacokinetic (PK) study showed that variability between patients could be partly explained by renal function and inflammatory status."( Population pharmacodynamic modelling of midazolam induced sedation in terminally ill adult patients.
Baar, FPM; de Winter, BCM; Franken, LG; Koch, BCP; Masman, AD; Mathot, RAA; Tibboel, D; van Dijk, M; van Gelder, T, 2018
)
0.75
" There are no previous studies of validated anxiety scores with pharmacokinetic data to support optimal procedure timing."( Evaluating Clinical Effectiveness and Pharmacokinetic Profile of Atomized Intranasal Midazolam in Children Undergoing Laceration Repair.
Adelgais, K; Bourne, D; Brent, A; Brou, L; Galinkin, J; Mellion, SA; Wathen, J, 2017
)
0.68
"We describe the clinical and pharmacokinetic profile of atomized intranasal midazolam in children presenting for laceration repair."( Evaluating Clinical Effectiveness and Pharmacokinetic Profile of Atomized Intranasal Midazolam in Children Undergoing Laceration Repair.
Adelgais, K; Bourne, D; Brent, A; Brou, L; Galinkin, J; Mellion, SA; Wathen, J, 2017
)
0.91
" A simultaneous pharmacokinetic model of parent and active metabolites was initially developed by incorporating data from in vitro, preclinical, and clinical pharmacokinetic studies in healthy volunteers and in patients with AML or advSM."( Simultaneous Physiologically Based Pharmacokinetic (PBPK) Modeling of Parent and Active Metabolites to Investigate Complex CYP3A4 Drug-Drug Interaction Potential: A Case Example of Midostaurin.
Chun, DY; Dutreix, C; Einolf, HJ; Gu, H; He, H; Ouatas, T; Rebello, S; Wang, L, 2018
)
0.48
" There were no significant differences in the pharmacokinetic parameters of caffeine, omeprazole, metoprolol, chlorzoxazone, and midazolam between the SGI-pretreated and control groups."( Influence of Shenxiong Glucose Injection on the Activities of Six CYP Isozymes and Metabolism of Warfarin in Rats Assessed Using Probe Cocktail and Pharmacokinetic Approaches.
Gong, Z; Huang, J; Li, Y; Liu, C; Liu, T; Lu, Y; Pan, J; Sun, J; Wang, Y; Zheng, J; Zheng, L, 2017
)
0.66
"Plasma concentration data were collected from 37 paediatric patients and 12 healthy adults recruited in a single dose, open-label phase II pharmacokinetic study and in a single dose, randomised, open-label two-period crossover bioavailability study, respectively."( Population pharmacokinetic evaluation of ADV6209, an innovative oral solution of midazolam containing cyclodextrin.
Burton, I; Dupont, H; Granier, LA; Guittet, C; Jacqmin, P; Manso, MA; Marçon, F, 2018
)
0.71
" The population pharmacokinetic model indicated that 77% of the midazolam dose was absorbed within 30min after oral administration."( Population pharmacokinetic evaluation of ADV6209, an innovative oral solution of midazolam containing cyclodextrin.
Burton, I; Dupont, H; Granier, LA; Guittet, C; Jacqmin, P; Manso, MA; Marçon, F, 2018
)
0.95
" Blood samples were collected immediately before and at predetermined times for 8 hours after drug administration for determination of plasma midazolam concentration and pharmacokinetic analysis."( Pharmacokinetic evaluation of novel midazolam gel formulations following buccal administration to healthy dogs.
Aldawsari, MF; Arnold, RD; Babu, RJ; Lau, VW; Platt, SR, 2018
)
0.96
" In this study, its safety was evaluated from a pharmacokinetic point of view, based on daily ingestion of 5,7-DMF."( Effect of the active ingredient of Kaempferia parviflora, 5,7-dimethoxyflavone, on the pharmacokinetics of midazolam.
Aburada, M; Kashiwada, M; Kitaoka, S; Kobayashi, H; Koyama, Y; Nagai, T; Nakaishi, S; Ochiai, W; Sugiyama, K, 2018
)
0.69
" Pharmacokinetic parameters were calculated using non-compartmental model."( [Optimization of midazolam dosage and pharmacokinetics of CYP3A probe substrate in rats].
Bi, HC; Chen, X; Duan, WH; Huang, M; Qin, XL; Xue, XP, 2016
)
0.77
"To investigate influence of inflammation on metabolism and pharmacokinetics (PK) of midazolam (MDZ) and construct a semi-physiologically based pharmacokinetic (PBPK) model to predict PK in mice with inflammatory disease."( A Semi-Physiologically Based Pharmacokinetic Model Describing the Altered Metabolism of Midazolam Due to Inflammation in Mice.
Chang, W; Forrest, ML; Patel, N; Ruterbories, K; Varkhede, N, 2018
)
0.93
"Physiologically based pharmacokinetic (PBPK) modeling for itraconazole using a bottom-up approach is challenging, not only due to complex saturable pharmacokinetics (PK) and the presence of three metabolites exhibiting CYP3A4 inhibition, but also because of discrepancies in reported in vitro data."( Physiologically Based Pharmacokinetic Model of Itraconazole and Two of Its Metabolites to Improve the Predictions and the Mechanistic Understanding of CYP3A4 Drug-Drug Interactions.
Ericsson, H; Janzén, D; Kanebratt, KP; Lennernäs, H; Lundahl, A; Prieto Garcia, L, 2018
)
0.48
"The pharmacokinetic (PK) parameters of many drugs are altered as a consequence of the pathophysiological changes associated with critical illness."( Altered Pharmacokinetics in Prolonged Infusions of Sedatives and Analgesics Among Adult Critically Ill Patients: A Systematic Review.
Joynt, GM; Lee, A; Ling, L; Tse, AHW, 2018
)
0.48
" Three phase 1, open-label, drug-drug interaction studies were conducted to examine the pharmacokinetic interactions of orally administered rolapitant with midazolam, rolapitant with ketoconazole, and rolapitant with rifampin."( Pharmacokinetic Interactions of Rolapitant With Cytochrome P450 3A Substrates in Healthy Subjects.
Arora, S; Christensen, J; Hughes, L; Lu, S; Wang, J; Wang, X; Zhang, ZY, 2019
)
0.71
" inclusion/exclusion criteria, combination study design), we used human hepatocyte data and physiologically-based pharmacokinetic (PBPK) modelling to predict its CYP3A4-mediated DDI potential."( Physiologically-based pharmacokinetic modelling to predict oprozomib CYP3A drug-drug interaction potential in patients with advanced malignancies.
Cutler, RE; Gore, L; Harvey, RD; Mita, A; Ou, Y; Papadopoulos, KP; Pinchasik, DE; Tsimberidou, AM; Wang, Z; Xu, Y, 2019
)
0.51
" Body weight, age, hepatic and renal functions, and the UGT2B7 rs62298861 polymorphism are relevant predictors of midazolam pharmacokinetic variables."( Midazolam Dose Optimization in Critically Ill Pediatric Patients With Acute Respiratory Failure: A Population Pharmacokinetic-Pharmacogenomic Study.
Bradfield, J; Conrado, DJ; Curley, MAQ; Gastonguay, MR; Gastonguay, MS; Hakonarson, H; Moorthy, G; Prodell, J; Zane, NR; Zuppa, AF, 2019
)
2.17
"This work leveraged available knowledge on nonheritable and heritable factors affecting midazolam pharmacokinetic in pediatric subjects with primary respiratory failure requiring mechanical ventilation, providing the basis for a future implementation of an individual-based approach to sedation."( Midazolam Dose Optimization in Critically Ill Pediatric Patients With Acute Respiratory Failure: A Population Pharmacokinetic-Pharmacogenomic Study.
Bradfield, J; Conrado, DJ; Curley, MAQ; Gastonguay, MR; Gastonguay, MS; Hakonarson, H; Moorthy, G; Prodell, J; Zane, NR; Zuppa, AF, 2019
)
2.18
" The objective of this study was to develop and evaluate a physiologically based pharmacokinetic (PBPK) model for hyperforin (the constituent of SJW responsible for interactions), which has the potential to provide unique insights into SJW interactions and allow prediction of the likely extent of interactions with SJW compared to published interaction reports."( Physiologically Based Pharmacokinetic Modelling of Hyperforin to Predict Drug Interactions with St John's Wort.
Adiwidjaja, J; Boddy, AV; McLachlan, AJ, 2019
)
0.51
" We also examined the pharmacokinetic behavior of intravenously administered MDZ in rats treated with 5-FU (120 mg/kg, ip)."( Conflicting alterations in hepatic expression of CYP3A and enzyme kinetics in rats exposed to 5-fluorouracil: relevance to pharmacokinetics of midazolam.
Fujiike, M; Fukuno, S; Konishi, H; Nagai, K; Sasaki, Y, 2019
)
0.71
"A physiologically based pharmacokinetic (PBPK) model was used to simulate the impact of elevated levels of interleukin (IL)-6 on the exposure of several orally administered cytochrome P450 (CYP) probe substrates (caffeine, S-warfarin, omeprazole, dextromethorphan, midazolam, and simvastatin)."( Simulating the Impact of Elevated Levels of Interleukin-6 on the Pharmacokinetics of Various CYP450 Substrates in Patients with Neuromyelitis Optica or Neuromyelitis Optica Spectrum Disorders in Different Ethnic Populations.
Ducray, PS; Endo-Tsukude, C; Gardner, I; Gill, KL; Hatley, OJ; Machavaram, KK; Parrott, N; Terao, K, 2019
)
0.69
"Physiologically based pharmacokinetic (PBPK) modelling and simulation is a useful tool in predicting the PK profiles of a drug, assessing the effects of covariates such as demographics, ethnicity, genetic polymorphisms and disease status on the PK, and evaluating the potential of drug-drug interactions."( Development of a Korean-specific virtual population for physiologically based pharmacokinetic modelling and simulation.
Chung, JY; Hatley, O; Kim, Y; Lee, H; Lee, HA; Rhee, SJ; Yi, S; Yoon, S; Yu, KS, 2019
)
0.51
" Plasma alfaxalone concentrations were quantified by a liquid chromatography tandem-mass spectrometry method and analysed by non-compartmental pharmacokinetic analysis."( Clinical pharmacokinetics and pharmacodynamics of intravenous alfaxalone in young Thoroughbred horses premedicated with medetomidine and midazolam.
Aoki, M; Kushiro, A; Mae, N; Maeda, T; Minamijima, Y; Nagata, SI; Ohta, M; Wakuno, A; Yamazaki, Y, 2019
)
0.72
" Pharmacokinetic analyses were performed using non-linear mixed effects modelling; clinical effectiveness was defined as no use of additional anti-epileptic drugs."( Phenobarbital, Midazolam Pharmacokinetics, Effectiveness, and Drug-Drug Interaction in Asphyxiated Neonates Undergoing Therapeutic Hypothermia.
Cools, F; de Haan, TR; Dijk, PH; Dijkman, KP; Egberts, TCG; Favié, LMA; Groenendaal, F; Huitema, ADR; Nuytemans, DHGM; Rademaker, CMA; Rijken, M; Simons, SHP; van Bel, F; van den Broek, MPH; van der Lee, JH; van Heijst, A; van Straaten, HLM; Zecic, A; Zonnenberg, IA, 2019
)
0.87
" We conducted a retrospective analysis of two pharmacokinetic studies."( The Prediction of the Area under the Curve and Clearance of Midazolam from Single-Point Plasma Concentration and Urinary Excretion in Healthy Volunteers.
Inui, N; Kawakami, J; Miura, M; Namiki, N; Tanaka, S; Uchida, S; Watanabe, H, 2019
)
0.76
" Developing modelling and simulation tools, such as physiologically based pharmacokinetic (PBPK) models that incorporate developmental physiology and maturation of drug metabolism, can be used to predict drug exposure in this group of patients, and may help to optimize drug dose adjustment."( Preterm Physiologically Based Pharmacokinetic Model. Part II: Applications of the Model to Predict Drug Pharmacokinetics in the Preterm Population.
Abduljalil, K; Jamei, M; Johnson, TN; Pan, X; Pansari, A, 2020
)
0.56
"The aim of the present study was to develop a population pharmacokinetic model of midazolam, and to evaluate the influence of maturation process and other variability factors in critically ill children with severe acute bronchiolitis, who received a long-term intravenous infusion of midazolam."( Maturation of midazolam clearance in critically ill children with severe bronchiolitis: A population pharmacokinetic analysis.
Grabnar, I; Grosek, Š; Jovanović, M; Kos, MK; Miksić, M; Roškar, R, 2020
)
1.14
"The developed population pharmacokinetic model can contribute to the dosing optimisation of midazolam, especially in critically ill children as it includes the influence of size and maturation of clearance, which are important parameters for achieving the desired plasma concentrations of midazolam."( Maturation of midazolam clearance in critically ill children with severe bronchiolitis: A population pharmacokinetic analysis.
Grabnar, I; Grosek, Š; Jovanović, M; Kos, MK; Miksić, M; Roškar, R, 2020
)
1.14
" Plasma concentration-time data were fitted to pharmacokinetic models using non-linear mixed-effects modeling."( Midazolam Pharmacokinetics in Obese and Non-obese Children and Adolescents.
Burhenne, J; Christensen, HR; Dalhoff, K; Gade, C; Holm, JC; Holst, H; Johansen, MØ; Lund, TM; Mikus, G; Sonne, J; Sverrisdóttir, E, 2020
)
2
"The aim of the present study was to evaluate the safety, pharmacokinetic (PK) and pharmacodynamic (PD) properties of remimazolam besylate following single ascending dose (SAD) and continuous infusion in healthy Chinese volunteers."( Safety, pharmacokinetic and pharmacodynamic properties of single ascending dose and continuous infusion of remimazolam besylate in healthy Chinese volunteers.
Cui, YM; Li, LE; Liang, Y; Sheng, XY; Yang, XY; Ye, X; Zhao, X, 2020
)
0.56
"The half-life range of remimazolam was from 34."( Safety, pharmacokinetic and pharmacodynamic properties of single ascending dose and continuous infusion of remimazolam besylate in healthy Chinese volunteers.
Cui, YM; Li, LE; Liang, Y; Sheng, XY; Yang, XY; Ye, X; Zhao, X, 2020
)
0.56
"Prospective pharmacokinetic study."( Pharmacokinetics of midazolam in sevoflurane-anesthetized cats.
Cox, SK; Dholakia, U; Pypendop, BH; Seddighi, R; Sun, X, 2020
)
0.88
"The pharmacokinetic model was fitted to the data from five cats, as 1-hydroxymidazolam was not detected in one cat."( Pharmacokinetics of midazolam in sevoflurane-anesthetized cats.
Cox, SK; Dholakia, U; Pypendop, BH; Seddighi, R; Sun, X, 2020
)
1.11
" Thus, DDI prediction using simulated concentration-time profiles in each segment of the digestive tract was made by physiologically based pharmacokinetic (PBPK) modeling software GastroPlus."( Critical Impact of Drug-Drug Interactions via Intestinal CYP3A in the Risk Assessment of Weak Perpetrators Using Physiologically Based Pharmacokinetic Models.
Inoue, SI; Ishizuka, T; Nishiya, Y; Sugiyama, D; Watanabe, A; Watanabe, K; Watanabe, N; Yamada, M; Yamashita, S, 2020
)
0.56
" The primary objective was to determine the pharmacokinetic effects of lenvatinib on midazolam, and the secondary objective was to assess the safety of lenvatinib."( An Open-Label Phase 1 Study to Determine the Effect of Lenvatinib on the Pharmacokinetics of Midazolam, a CYP3A4 Substrate, in Patients with Advanced Solid Tumors.
Aluri, J; Dutcus, CE; He, C; Rance, C; Ren, M; Shumaker, R, 2020
)
1
" There was little change in the terminal elimination phase half-life of midazolam when administered with lenvatinib."( An Open-Label Phase 1 Study to Determine the Effect of Lenvatinib on the Pharmacokinetics of Midazolam, a CYP3A4 Substrate, in Patients with Advanced Solid Tumors.
Aluri, J; Dutcus, CE; He, C; Rance, C; Ren, M; Shumaker, R, 2020
)
1.01
" Our objective in this proof-of-concept study was to perform a pharmacokinetic (PK) bridging study from juvenile mice to neonates for drugs metabolized by CYP3A."( First dose in neonates: pharmacokinetic bridging study from juvenile mice to neonates for drugs metabolized by CYP3A.
Du, B; Hao, GX; Huang, X; Kan, M; Liu, XT; Su, LQ; Tang, BH; Wang, WQ; Ye, PP; Yu, F; Zhao, W; Zheng, Y; Zhou, Y, 2020
)
0.56
" A physiologically-based pharmacokinetic (PBPK) model was developed integrating in vitro, preclinical, and clinical data of HVs and patients with cancer."( Ribociclib Drug-Drug Interactions: Clinical Evaluations and Physiologically-Based Pharmacokinetic Modeling to Guide Drug Labeling.
Chakraborty, A; Dhuria, SV; Elmeliegy, M; He, H; Heimbach, T; Huth, F; Ji, Y; Miller, M; Samant, TS; Schiller, H; Umehara, K, 2020
)
0.56
" Pharmacokinetic samples were collected over 24 hours on days 1 and 8, then analyzed using liquid chromatography-tandem mass spectrometry."( The Effect of GS-548351 on the Pharmacokinetics of Midazolam Following Multiple Doses of ANS-6637 in Healthy Adults.
Aepfelbacher, J; Bunn, HT; George, JM; Kattakuzhy, S; Kottilil, S; Masur, H; Mathur, P; McLaughlin, M; Proschan, M; Rosenthal, E; Vijan, A, 2020
)
0.81
" Because it was suggested that DDIs mainly occur in the intestine, predictions using concentration-time profiles in each segment of the gastrointestinal tract were performed with GastroPlus, a physiologically based pharmacokinetic (PBPK) modeling software."( Drug-Drug Interaction Risk Assessment of Esaxerenone as a Perpetrator by In Vitro Studies and Static and Physiologically Based Pharmacokinetic Models.
Fischer, T; Inoue, SI; Ishizuka, T; Rozehnal, V; Sugiyama, D; Yamada, M, 2020
)
0.56
" Multiple models have been developed for midazolam, the typical probe substrate for CYP3A activity, but no population pharmacokinetic models have been developed for use with inhibition or induction."( Composite midazolam and 1'-OH midazolam population pharmacokinetic model for constitutive, inhibited and induced CYP3A activity.
Meid, AD; Mikus, G; Wiebe, ST, 2020
)
1.23
" We aimed to evaluate the performance of a clinical midazolam dose escalation pathway for the treatment of pediatric RSE that was designed based on a novel midazolam pharmacokinetic model."( Assessment of midazolam pharmacokinetics in the treatment of status epilepticus.
Abend, NS; Francoeur, C; Ichord, R; Topjian, AA; Welsh, SS; Zuppa, AF, 2020
)
1.17
"Prospective pharmacokinetic study of midazolam bolus and escalation of continuous midazolam infusion."( Assessment of midazolam pharmacokinetics in the treatment of status epilepticus.
Abend, NS; Francoeur, C; Ichord, R; Topjian, AA; Welsh, SS; Zuppa, AF, 2020
)
1.19
" Main study outcome measure was the accuracy of a pharmacokinetic model to predict serum midazolam concentrations."( Assessment of midazolam pharmacokinetics in the treatment of status epilepticus.
Abend, NS; Francoeur, C; Ichord, R; Topjian, AA; Welsh, SS; Zuppa, AF, 2020
)
1.14
" We therefore developed a novel pharmacokinetic midazolam model in children with RSE treated with continuous midazolam infusion."( Assessment of midazolam pharmacokinetics in the treatment of status epilepticus.
Abend, NS; Francoeur, C; Ichord, R; Topjian, AA; Welsh, SS; Zuppa, AF, 2020
)
1.17
" Plasma midazolam and metabolite concentrations were measured for population pharmacokinetic- and pharmacodynamic analysis using nonlinear mixed effects modeling (NONMEM) (Version VI; GloboMax LLC, Hanover, MD) software."( Sedation With Midazolam After Cardiac Surgery in Children With and Without Down Syndrome: A Pharmacokinetic-Pharmacodynamic Study.
Breatnach, CV; Goulooze, SC; Knibbe, CAJ; Mathôt, RAA; Peeters, MYM; Tibboel, D; Valkenburg, AJ; van Dijk, M, 2021
)
1.42
" Population pharmacokinetic and pharmacodynamics analysis revealed no statistically significant differences between the children with and without Down syndrome."( Sedation With Midazolam After Cardiac Surgery in Children With and Without Down Syndrome: A Pharmacokinetic-Pharmacodynamic Study.
Breatnach, CV; Goulooze, SC; Knibbe, CAJ; Mathôt, RAA; Peeters, MYM; Tibboel, D; Valkenburg, AJ; van Dijk, M, 2021
)
0.98
" This pharmacokinetic and pharmacodynamic analysis does not provide evidence for different dosing of midazolam in children with Down syndrome after cardiac surgery."( Sedation With Midazolam After Cardiac Surgery in Children With and Without Down Syndrome: A Pharmacokinetic-Pharmacodynamic Study.
Breatnach, CV; Goulooze, SC; Knibbe, CAJ; Mathôt, RAA; Peeters, MYM; Tibboel, D; Valkenburg, AJ; van Dijk, M, 2021
)
1.2
"In healthy volunteers, the probe drug method is widely practised to assess the pharmacokinetic mediated herb-drug interactions (HDI)."( Assessment of Herb-drug Interactions Based on the Pharmacokinetic Changes of Probe Drug, Midazolam.
Sabarathinam, S; Vijayakumar, TM, 2021
)
0.84
" For the first time, we developed a physiologically based pharmacokinetic (PBPK) model-based approach to assess CYP3A-mediated drug-drug interaction (DDI) risk for polatuzumab vedotin (Polivy), an anti-CD79b-vc-monomethyl auristatin E (MMAE) antibody-drug conjugate (ADC)."( Physiologically Based Pharmacokinetic Model-Informed Drug Development for Polatuzumab Vedotin: Label for Drug-Drug Interactions Without Dedicated Clinical Trials.
Chen, Y; Ding, H; Girish, S; Jin, J; Li, C; Lu, D; Ma, F; Mao, J; Miles, D; Samineni, D; Shi, R; Wright, M, 2020
)
0.56
" This review summarizes the pharmacokinetic (PK) and pharmacodynamic (PD) characteristics of MDZ nasal spray (MDZ-NS), which can be administered by non-health care providers in the outpatient, ambulatory setting."( Clinical pharmacokinetic and pharmacodynamic profile of midazolam nasal spray.
Bouw, MR; Chung, SS; Gidal, B; King, A; Tomasovic, J; Van Ess, PJ; Wheless, JW, 2021
)
0.87
"For decades, inflammation has been considered a cause of pharmacokinetic variability, mainly in relation to the inhibitory effect of pro-inflammatory cytokines on the expression level and activity of cytochrome P450 (CYP)."( Modeling Approach to Predict the Impact of Inflammation on the Pharmacokinetics of CYP2C19 and CYP3A4 Substrates.
Chenel, M; Gautier-Veyret, E; Payen, L; Simon, F; Stanke-Labesque, F; Tod, M; Truffot, A, 2021
)
0.62
"Changes in pharmacokinetic profiles and parameters induced by inflammation seem to be captured accurately by the models."( Modeling Approach to Predict the Impact of Inflammation on the Pharmacokinetics of CYP2C19 and CYP3A4 Substrates.
Chenel, M; Gautier-Veyret, E; Payen, L; Simon, F; Stanke-Labesque, F; Tod, M; Truffot, A, 2021
)
0.62
" Pharmacokinetic (PK) profile was also assessed."( A Phase 3 open-label study of the efficacy, safety and pharmacokinetics of buccally administered midazolam hydrochloride for the treatment of status epilepticus in pediatric Japanese subjects.
Benitez, A; Fournier, M; Kugler, AR; Takeda, S; Yoshinaga, H, 2021
)
0.84
"0 ng/mL, and mean time to peak concentration was 20."( A Phase 3 open-label study of the efficacy, safety and pharmacokinetics of buccally administered midazolam hydrochloride for the treatment of status epilepticus in pediatric Japanese subjects.
Benitez, A; Fournier, M; Kugler, AR; Takeda, S; Yoshinaga, H, 2021
)
0.84
"The efficacy, safety and pharmacokinetic profile of MHOS in pediatric Japanese subjects was consistent with that observed in non-Japanese populations."( A Phase 3 open-label study of the efficacy, safety and pharmacokinetics of buccally administered midazolam hydrochloride for the treatment of status epilepticus in pediatric Japanese subjects.
Benitez, A; Fournier, M; Kugler, AR; Takeda, S; Yoshinaga, H, 2021
)
0.84
" The objective of this study was to develop a framework for leveraging physiologically based pharmacokinetic (PBPK) modeling to predict CYP3A-mediated drug-drug interaction (DDI) potential in the pediatric population using solithromycin as a case study."( Leveraging Physiologically Based Pharmacokinetic Modeling and Experimental Data to Guide Dosing Modification of CYP3A-Mediated Drug-Drug Interactions in the Pediatric Population.
Carreño, FO; Cohen-Wolkowiez, M; Edginton, AN; Gonzalez, D; Salerno, SN, 2021
)
0.62
" Full pharmacokinetic profiles of midazolam and 1-hydroxymidazolam on days 0 and 14 and safety data were obtained."( Effects of Repeated Oral Administration of Esaxerenone on the Pharmacokinetics of Midazolam in Healthy Japanese Males.
Furuie, H; Igawa, Y; Ishizuka, H; Ishizuka, T; Kato, M; Kuroda, K; Nishikawa, Y; Okuda, Y; Shimizu, T; Toyama, K, 2021
)
1.13
" We used physiologically-based pharmacokinetic (PBPK) modeling to simulate the effect of inflammation on the pharmacokinetics of CYP3A metabolized drugs."( Physiologically Based Pharmacokinetic Modelling to Investigate the Impact of the Cytokine Storm on CYP3A Drug Pharmacokinetics in COVID-19 Patients.
Battegay, M; Marzolini, C; Sendi, P; Stader, F, 2022
)
0.72
"The aim of this work is the development of a mechanistic physiologically-based pharmacokinetic (PBPK) model using in vitro to in vivo extrapolation to conduct a drug-drug interaction (DDI) assessment of treosulfan against two cytochrome p450 (CYP) isoenzymes and P-glycoprotein (P-gp) substrates."( Evaluation of the drug-drug interaction potential of treosulfan using a physiologically-based pharmacokinetic modelling approach.
Balazki, P; Baumgart, J; Beelen, DW; Böhm, S; Hemmelmann, C; Hilger, RA; Martins, FS; Ring, A; Schaller, S, 2022
)
0.72
" However, considering the comprehensive treosulfan-based conditioning treatment schedule and the respective pharmacokinetic properties of the concomitantly used drugs (eg, half-life), the potential for interaction on all evaluated mechanisms would be low (AUCR < 1."( Evaluation of the drug-drug interaction potential of treosulfan using a physiologically-based pharmacokinetic modelling approach.
Balazki, P; Baumgart, J; Beelen, DW; Böhm, S; Hemmelmann, C; Hilger, RA; Martins, FS; Ring, A; Schaller, S, 2022
)
0.72
" In this study, a physiologically-based pharmacokinetic (PBPK) model was developed to assess CYPs mediated therapeutic protein drug interactions (TP-DIs) in patients with immune-mediated inflammatory diseases (IMIDs) with elevated systemic IL-6 levels when treated by anti-IL-6 therapies."( Utilization of physiologically-based pharmacokinetic model to assess disease-mediated therapeutic protein-disease-drug interaction in immune-mediated inflammatory diseases.
Chen, Y; Miao, X; Wang, L; Zhou, H; Zhou, W, 2022
)
0.72
" The aim of our study was to develop a physiologically based pharmacokinetic (PBPK) model to foresee the impact of elevated IL-6 levels in combination with drug interactions with esomeprazole on CYP3A and CYP2C19."( Prediction of cytochromes P450 3A and 2C19 modulation by both inflammation and drug interactions using physiologically based pharmacokinetics.
Daali, Y; Desmeules, JA; Lenoir, C; Niederer, A; Rollason, V; Samer, CF, 2022
)
0.72
" AUC and maximum plasma concentration of BAY 2433334 in plasma appeared dose proportional over 25-100 mg OD, with low-to-moderate variability in pharmacokinetic parameters."( Pharmacokinetics, pharmacodynamics and safety of BAY 2433334, a novel activated factor XI inhibitor, in healthy volunteers: A randomized phase 1 multiple-dose study.
Distler, J; Heckmann, M; Kanefendt, F; Koechel, A; Kubitza, D; Schwers, S, 2022
)
0.72
" This tutorial aims to provide a guideline and step-by-step tutorial on essential considerations when designing clinical pharmacokinetic studies and reporting results."( Tutorial: Statistical analysis and reporting of clinical pharmacokinetic studies.
Agergaard, K; Andersen, NE; Dunvald, AD; Iversen, DB; Järvinen, E; Kuhlmann, IB; Mortensen, C; Stage, TB; Svendsen, ALO, 2022
)
0.72
" Although some studies have explored the roles of gut microbiota and host Cyp450s in drug pharmacokinetics, few have explored their effects on pharmacokinetic variability, especially in disease states."( Gut microbiota and host Cyp450s co-contribute to pharmacokinetic variability in mice with non-alcoholic steatohepatitis: Effects vary from drug to drug.
Chen, LJ; Chen, XP; Chen, Y; Guo, J; Liou, YL; Tan, ZR; Xu, Y; Zhang, SX; Zhang, W; Zhou, HH, 2022
)
0.72
"In this study, we aim to investigate the effects of gut microbiota and host Cyp450s on pharmacokinetic variability in mice with non-alcoholic steatohepatitis (NASH), and to elucidate the contribution of gut microbiota and host Cyp450s to pharmacokinetic variability in this setting."( Gut microbiota and host Cyp450s co-contribute to pharmacokinetic variability in mice with non-alcoholic steatohepatitis: Effects vary from drug to drug.
Chen, LJ; Chen, XP; Chen, Y; Guo, J; Liou, YL; Tan, ZR; Xu, Y; Zhang, SX; Zhang, W; Zhou, HH, 2022
)
0.72
"The pharmacokinetic variability of mice with NASH was explored under intragastric and intravenous administrations of a cocktail mixture of omeprazole, phenacetin, midazolam, tolbutamide, chlorzoxazone, and metoprolol, after which the results were compared with those obtained from the control group."( Gut microbiota and host Cyp450s co-contribute to pharmacokinetic variability in mice with non-alcoholic steatohepatitis: Effects vary from drug to drug.
Chen, LJ; Chen, XP; Chen, Y; Guo, J; Liou, YL; Tan, ZR; Xu, Y; Zhang, SX; Zhang, W; Zhou, HH, 2022
)
0.92
" The pharmacokinetic variabilities of phenacetin, midazolam, omeprazole, and chlorzoxazone were mainly associated with decreased elimination activity in the gut microbiota."( Gut microbiota and host Cyp450s co-contribute to pharmacokinetic variability in mice with non-alcoholic steatohepatitis: Effects vary from drug to drug.
Chen, LJ; Chen, XP; Chen, Y; Guo, J; Liou, YL; Tan, ZR; Xu, Y; Zhang, SX; Zhang, W; Zhou, HH, 2022
)
0.97
"Gut microbiota and host Cyp450s co-contribute to the pharmacokinetic variability in mice with NASH, and the degree of contribution varies from drug to drug."( Gut microbiota and host Cyp450s co-contribute to pharmacokinetic variability in mice with non-alcoholic steatohepatitis: Effects vary from drug to drug.
Chen, LJ; Chen, XP; Chen, Y; Guo, J; Liou, YL; Tan, ZR; Xu, Y; Zhang, SX; Zhang, W; Zhou, HH, 2022
)
0.72
" Here, we investigate the pharmacokinetic drug-drug interaction potential of trilaciclib."( Pharmacokinetic Drug-Drug Interaction Studies Between Trilaciclib and Midazolam, Metformin, Rifampin, Itraconazole, and Topotecan in Healthy Volunteers and Patients with Extensive-Stage Small-Cell Lung Cancer.
Beelen, A; Curd, L; Goti, V; Horton, JK; Li, C; Sale, M; Tao, W, 2022
)
0.96
" Population pharmacokinetic modeling showed no significant effect of trilaciclib on topotecan clearance."( Pharmacokinetic Drug-Drug Interaction Studies Between Trilaciclib and Midazolam, Metformin, Rifampin, Itraconazole, and Topotecan in Healthy Volunteers and Patients with Extensive-Stage Small-Cell Lung Cancer.
Beelen, A; Curd, L; Goti, V; Horton, JK; Li, C; Sale, M; Tao, W, 2022
)
0.96
" Primary outcome measures were pharmacokinetic parameters of midazolam and 1-hydroxy-midazolam."( An Open-Label Study to Evaluate the Effect of Eluxadoline on the Single-Dose Pharmacokinetics of Midazolam in Healthy Participants.
Boinpally, R; Kaczynski, E; McGeeney, D; Weissman, D, 2022
)
1.18
" Pharmacokinetic modeling demonstrated a significant change in midazolam clearance with acute inflammation (measured using C-Reactive Protein), cardio-vascular status, and weight."( Inflammation and cardiovascular status impact midazolam pharmacokinetics in critically ill children: An observational, prospective, controlled study.
Austin, R; Mulla, H; Neupane, B; Pandya, H; Pandya, T; Rudge, J; Spooner, N, 2022
)
1.22
" The systems information gathered on intestine, liver and blood proteins and other physiological parameters was incorporated into a physiologically based pharmacokinetic (PBPK) platform to create a virtual population of CD patients, with a view for guiding dose adjustment in the absence of clinical data in CD."( Altered Bioavailability and Pharmacokinetics in Crohn's Disease: Capturing Systems Parameters for PBPK to Assist with Predicting the Fate of Orally Administered Drugs.
Alrubia, S; Barber, J; Chen, Y; Mao, J; Rostami-Hodjegan, A, 2022
)
0.72
" This study aimed to build a physiologically based pharmacokinetic (PBPK) model reflecting observed changes in physiological and molecular parameters relevant to drug disposition that are associated with MAFLD."( A Physiologically Based Pharmacokinetic Model to Predict the Impact of Metabolic Changes Associated with Metabolic Associated Fatty Liver Disease on Drug Exposure.
Newman, EM; Rowland, A, 2022
)
0.72
"One- and two-compartment in silico pharmacokinetic models of midazolam and pentobarbital."( Pharmacokinetic Modeling of Optimized Midazolam and Pentobarbital Dosing Used in Treatment Protocols of Refractory Status Epilepticus.
Akhondi-Asl, A; Au, CC; LaRovere, K; Luchette, M; Tasker, RC, 2023
)
1.42
"Our in silico pharmacokinetic modeling of standard midazolam and pentobarbital dosing protocols for RSE suggests potential variables to optimize in future clinical studies."( Pharmacokinetic Modeling of Optimized Midazolam and Pentobarbital Dosing Used in Treatment Protocols of Refractory Status Epilepticus.
Akhondi-Asl, A; Au, CC; LaRovere, K; Luchette, M; Tasker, RC, 2023
)
1.43
" For many ethical and logistic constrains, carrying out pharmacokinetic studies of pharmacological agents in neonatal population remains a challenging task and such data is therefore, insufficient."( Pharmacokinetics of Midazolam in preterm neonates with an insight in brain Tissue: A PBPK approach.
Ahmed, M; Czejka, M; Hassan, A; Hassan, S; Mansoor, N; Sharib, S, 2022
)
1.04
" We present a pharmacodynamic model for moderate sedation using midazolam, alfentanil and propofol."( Pharmacodynamic modeling of moderate sedation and rationale for dosing using midazolam, propofol and alfentanil.
Chang, WK; Kuo, IT; Liou, JY; Ting, CK; Tsou, MY, 2023
)
1.38
"Simplified physiologically based pharmacokinetic (PBPK) models using estimated tissue-to-unbound plasma partition coefficients (Kpus) were previously investigated by fitting them to in vivo pharmacokinetic (PK) data."( A "middle-out approach" for the prediction of human drug disposition from preclinical data using simplified physiologically based pharmacokinetic (PBPK) models.
Aarons, L; Gertz, M; Ogungbenro, K; Olivares-Morales, A; Yau, E, 2023
)
0.91
" Pharmacokinetic characteristics of probe drugs were subsequently assessed in a Phase I, open-label, single-sequence crossover study in healthy male participants."( Pharmacokinetic-Interactions of BI 425809, a Novel Glycine Transporter 1 Inhibitor, With Cytochrome P450 and P-Glycoprotein Substrates: Findings From In Vitro Analyses and an Open-Label, Single-Sequence Phase I Study.
Chan, T; Desch, M; Hohl, K; Ishiguro, N; Keller, S; Liesenfeld, KH; Müller, F; Schlecker, C; Wind, S; Wunderlich, G,
)
0.13
" With BI 425809, area under the plasma concentration curve from administration to the last measurement (AUC 0-tz ) and maximum plasma concentration ( Cmax ) for midazolam were lower than when administered alone."( Pharmacokinetic-Interactions of BI 425809, a Novel Glycine Transporter 1 Inhibitor, With Cytochrome P450 and P-Glycoprotein Substrates: Findings From In Vitro Analyses and an Open-Label, Single-Sequence Phase I Study.
Chan, T; Desch, M; Hohl, K; Ishiguro, N; Keller, S; Liesenfeld, KH; Müller, F; Schlecker, C; Wind, S; Wunderlich, G,
)
0.33
" Safety, pharmacokinetic, and pharmacodynamic assessments were conducted throughout the study."( Safety, Pharmacokinetics, and Pharmacodynamics of Midazolam Gel After Rectal Administration in Healthy Chinese Subjects.
Chen, J; Ding, S; Li, Y; Shao, F; Sun, X; Wang, L; Xie, L; Zhao, Y; Zheng, A; Zhou, C; Zhou, S; Zhu, B; Zhu, J, 2023
)
1.16
" This project used physiologically based pharmacokinetic (PBPK) modeling to assess the DDI potential of inhaled PUR1900, using midazolam as a "victim drug."( Evaluation of the Potential for Drug-Drug Interactions with Inhaled Itraconazole Using Physiologically Based Pharmacokinetic Modelling, Based on Phase 1 Clinical Data.
Bergagnini-Kolev, M; Curran, AK; Kane, K; Templeton, IE, 2023
)
1.12
" After cocktail alone or in combination with adavosertib administration, 24-h pharmacokinetic sampling occurred for probe substrates and their respective metabolites paraxanthine, 5-hydroxyomeprazole (5-HO), and 1'-hydroxymidazolam (1'-HM)."( Phase I study to assess the effect of adavosertib (AZD1775) on the pharmacokinetics of substrates of CYP1A2, CYP2C19, and CYP3A in patients with advanced solid tumors.
Ah-See, ML; Edenfield, WJ; Lewis, LD; Li, Y; Mugundu, GM; Nadeau, L; Någård, M; Ottesen, LH; Safran, HP; Strauss, J; Wise-Draper, T, 2023
)
1.1

Compound-Compound Interactions

The conscious sedation regimen of dexmedetomidine combined with midazolam monitored by BIS is considered to be safe and effective during bronchoscopy.

ExcerptReferenceRelevance
" Substitution of thiopentone by midazolam in combination with fentanyl abolished the adverse haemodynamic response and modified the increase in plasma catecholamine concentrations."( Catecholamine response to laryngoscopy and intubation. The influence of three different drug combinations commonly used for induction of anaesthesia.
Bjerre-Jepsen, K; Chraemmer-Jørgensen, B; Hertel, S; Høilund-Carlsen, PF; Strøm, J, 1992
)
0.57
" First, propofol infusion was compared to thiopentone combined with midazolam."( Total intravenous anaesthesia for direct laryngoscopy: propofol infusion compared to thiopentone combined with midazolam and methohexitone infusion.
Clausen, TG; Halck, S; Munksgaard, A; Sonne, NM; Valentin, N, 1992
)
0.73
"This study investigated antinociceptive effects of intrathecal morphine combined with intrathecal clonidine, noradrenaline, carbachol or midazolam in rats."( Antinociceptive and motor effects of intrathecal morphine combined with intrathecal clonidine, noradrenaline, carbachol or midazolam in rats.
Cmielewski, PL; Cousins, MJ; Gourlay, GK; Owen, H; Plummer, JL, 1992
)
0.69
"15 mg/kg) combined with Piritramid (0."( [Midazolam in combination with piritramid versus Thalamonal in premedication in ambulatory ENT interventions in childhood].
Bein, T; Heyde, G; Tremel, H, 1988
)
1.19
" The purpose of this study was to compare recovery of patients sedated with either midazolam or diazepam alone or in combination with fentanyl using the digit symbol substitution test (DSST) and Trieger test."( Recovery following sedation with midazolam or diazepam alone or in combination with fentanyl for outpatient surgery.
Anderson, JA; Ochs, MW; Tucker, MR; White, RP,
)
0.64
" This study compares the amnesia produced in patients sedated with midazolam or diazepam or in combination with fentanyl during oral surgery."( A comparison of amnesia in outpatients sedated with midazolam or diazepam alone or in combination with fentanyl during oral surgery.
Ochs, MW; Tucker, MR; White, RP, 1986
)
0.76
" doses of midazolam and diazepam in combination with meperidine on breathing pattern and thoracoabdominal motion were studied in eight healthy male volunteers."( Changes in breathing pattern and chest wall mechanics after benzodiazepines in combination with meperidine.
Berggren, L; Eriksson, I; Mollenholt, P, 1987
)
0.68
"Concerning the pharmacokinetic or pharmacodynamic interactions, the following is recommended: Use smaller doses of alfentanil when the latter is combined with propofol, because of a higher risk of ventilatory depression."( [Diprivan: drug interactions].
Steib, A, 1994
)
0.29
"03 mg/kg) combined with fentanyl (0."( Cardiac electrophysiologic effects of midazolam combined with fentanyl.
Kovoor, P; Lau, W; Ross, DL, 1993
)
0.56
"When establishing a rabbit model for cardiovascular research in our laboratory we have used midazolam in combination with fentanyl/fluanisone (MFF) and nitrous oxide as anaesthesia."( Midazolam in combination with fentanyl/fluanisone and nitrous oxide as anaesthesia in rabbits--cardiovascular parameters.
Fosse, RT; Hessevik, I; Hexeberg, E; Hexeberg, S, 1995
)
1.95
"Stress hormone response was investigated during midazolam/fentanyl/oxygen/air anesthesia combined with epidural anesthesia in six patients undergoing abdominal total hysterectomy (group MF)."( [Stress hormone response during midazolam/fentanyl anesthesia combined with epidural anesthesia for abdominal total hysterectomy].
Honda, N; Kitano, T; Miyakawa, H; Mizutani, A; Taniguchi, K; Yoshitake, S, 1996
)
0.83
"The optimal dose range of thiamylal, combined with midazolam, in the induction of anaesthesia was evaluated using haemodynamic variables."( Optimal dose of thiamylal in combination with midazolam for induction of anaesthesia.
Hanaoka, K; Nishiyama, T, 1996
)
0.8
"2 mg/kg), or a placebo in combination with 50% nitrous oxide/50% oxygen, or room air."( The effect of age on the behavioral responses of mice following diazepam and midazolam sedation in combination with nitrous oxide.
Condouris, G; Houpt, M; Press, SH, 1995
)
0.52
"Total intravenous anaesthesia (TIVA) using propofol, gamma-hydroxybutyrate (GHB) or midazolam in combination with sufentanil was investigated in 45 patients undergoing coronary artery bypass grafting (CABG)."( Total intravenous anaesthesia using propofol, gamma-hydroxybutyrate or midazolam in combination with sufentanil for patients undergoing coronary artery bypass surgery.
Grundmann, U; Janneck, U; Kleinschmidt, S; Kreienmeyer, J; Kulosa, R; Larsen, R, 1997
)
0.75
" The neurotoxic effect of midazolam, alone or combined with fentanyl, injected intrathecally repeatedly on 15 occasions over a period of 1 month, was studied in the same model."( An investigation of the possible neurotoxic effects of intrathecal midazolam combined with fentanyl in the rat.
Bahar, M; Chanimov, M; Cohen, ML; Grinshpoon, Y; Herbert, M; Kopolovic, U; Nass, D, 1998
)
0.84
"In this randomized, double-blinded study, we compared the onset and recovery characteristics of an investigational benzodiazepine, Ro 48-6791 (when administered alone or combined with meperidine), a midazolam-meperidine combination for sedation during gastrointestinal (GI) endoscopic procedures."( Comparison of the sedation and recovery profiles of Ro 48-6791, a new benzodiazepine, and midazolam in combination with meperidine for outpatient endoscopic procedures.
Gold, J; Gold, M; Tang, J; Wang, B; White, PF, 1999
)
0.71
" This study was to compare the analgesic and side effects of intravenous ketorolac with that of intravenous fentanyl, in combination with midazolam in ESWL."( Effects of intravenous ketorolac and fentanyl combined with midazolam on analgesia and side effects during extracorporeal shock wave lithotripsy.
Cherng, CH; Ho, ST; Wong, CS; Yang, CP, 2002
)
0.76
"Both intravenous ketorolac and fentanyl in combination with midazolam could provide good anesthesia for ESWL."( Effects of intravenous ketorolac and fentanyl combined with midazolam on analgesia and side effects during extracorporeal shock wave lithotripsy.
Cherng, CH; Ho, ST; Wong, CS; Yang, CP, 2002
)
0.8
"This study was performed to compare the effects of oral midazolam and oral diazepam, administered with intravenous (IV) meperidine, on pre-procedural, procedural, and post-procedural sedation and recovery in children undergoing diagnostic upper endoscopy."( A comparison of oral diazepam versus midazolam, administered with intravenous meperidine, as premedication to sedation for pediatric endoscopy.
Davis, J; Marquez, C; Martinez, JL; Medina, E; Merzel, D; Montano, N; Sutters, KA; Waite, S, 2002
)
0.83
" A target-controlled infusion of propofol was compared with patient-controlled propofol for sedation, combined with a small dose of midazolam to improve amnesia."( A comparison of target-controlled therapy with patient-controlled administration of propofol combined with midazolam for sedation during dental surgery.
Burns, R; McCrae, AF; Tiplady, B, 2003
)
0.74
"The purpose of this study was to investigate whether the use of a timed-release (TR) drug formulation can avoid unfavorable pharmacokinetic drug-drug interactions in vivo."( Timed-release formulation to avoid drug-drug interaction between diltiazem and midazolam.
Hayashi, M; Nakamura, K; Sako, K; Sawada, T; Yokohama, S; Yoshihara, K, 2003
)
0.55
" In this study we examined midazolam and clonidine for premedication in combination with target controlled infusion anaesthesia (TCI) in patients undergoing orthopaedic shoulder surgery and analysed the effects on the peri- and postoperative course."( [Comparison of premedication with clonidine and midazolam combined with TCI for orthopaedic shoulder surgery].
Dietrich, PJ; Grottke, O; Krause, TH; Müller, J; Wappler, F, 2003
)
0.87
"Premedication with the alpha(2)-adrenoceptor agonist clonidine is as good as with benzodiazepines in combination with TCI."( [Comparison of premedication with clonidine and midazolam combined with TCI for orthopaedic shoulder surgery].
Dietrich, PJ; Grottke, O; Krause, TH; Müller, J; Wappler, F, 2003
)
0.57
"Dexmedetomidine in combination with morphine PCA provided better analgesia for ESWL and was associated with higher patients' and urologist's satisfaction when compared with a tramadol/midazolam PCA combination."( Dexmedetomidine in combination with morphine PCA provides superior analgesia for shockwave lithotripsy.
Alhashemi, JA; Kaki, AM, 2004
)
0.51
" The aim of this study was to establish whether the use of a combination of intravenous midazolam with inhalation agents (nitrous oxide alone or in combination with sevoflurane) was any more likely to result in successful completion of treatment than midazolam alone."( A randomised controlled trial of paediatric conscious sedation for dental treatment using intravenous midazolam combined with inhaled nitrous oxide or nitrous oxide/sevoflurane.
Averley, PA; Bond, S; Girdler, NM; Steele, J; Steen, N, 2004
)
0.76
" The drug-drug interaction responsible for CYP3A enzyme(s) inhibition was observed when midazolam and inhibitors were co-administrated orally."( Model for the drug-drug interaction responsible for CYP3A enzyme inhibition. I: evaluation of cynomolgus monkeys as surrogates for humans.
Baba, T; Kanazu, T; Koike, M; Okamura, N; Yamaguchi, Y, 2004
)
0.55
" It was shown that the drug-drug interaction that occurs in vitro is also observed in vivo after oral administration of midazolam."( Model for the drug-drug interaction responsible for CYP3A enzyme inhibition. II: establishment and evaluation of dexamethasone-pretreated female rats.
Baba, T; Kanazu, T; Koike, M; Okamura, N; Yamaguchi, Y, 2004
)
0.53
"The complexity of in vitro kinetic phenomena observed for CYP3A4 substrates (homo- or heterotropic cooperativity) confounds the prediction of drug-drug interactions, and an evaluation of alternative and/or pragmatic approaches and substrates is needed."( CYP3A4 substrate selection and substitution in the prediction of potential drug-drug interactions.
Galetin, A; Hallifax, D; Houston, JB; Ito, K, 2005
)
0.33
" We hypothesized that regional analgesia combined with avoidance of narcotics administered to children scheduled for lower abdominal or urologic procedures may be associated with a lower incidence of POV."( Regional analgesia combined with avoidance of narcotics may reduce the incidence of postoperative vomiting in children.
Chuang, AZ; Farag, A; Govindaraj, R; Hanna, E; Khalil, SN, 2005
)
0.33
"We concluded that regional analgesia combined with the avoidance of narcotics administered to children scheduled for elective urologic or lower abdominal procedures, is associated with a lower incidence of POV and that age did not affect the incidence of POV."( Regional analgesia combined with avoidance of narcotics may reduce the incidence of postoperative vomiting in children.
Chuang, AZ; Farag, A; Govindaraj, R; Hanna, E; Khalil, SN, 2005
)
0.33
"In the current study, to understand the characteristics of dexamethasone (DEX)-treated female rats as an animal model for drug-drug interactions, a double-cannulation method was applied and separately assessed for the intestinal and hepatic first-pass metabolism of midazolam."( Assessment of the hepatic and intestinal first-pass metabolism of midazolam in a CYP3A drug-drug interaction model rats.
Baba, T; Kanazu, T; Koike, M; Okamura, N; Yamaguchi, Y, 2005
)
0.74
"Intrathecal midazolam acts synergically with other anesthetics to relieve surgical pain, and the drug combination may decrease complications attributable to each component drug."( Intrathecal midazolam combined with low-dose bupivacaine improves postoperative recovery in diabetic mellitus patients undergoing foot debridement.
Hong, CC; Hung, CP; Lu, HF; Shiau, JM; Tseng, CC; Wu, YW, 2005
)
1.09
"5 mg of hyperbaric bupivacaine; group 2 (M+M) received 5 mg of hyperbaric bupivacaine combined with 2 mg of midazolam intrathecally."( Intrathecal midazolam combined with low-dose bupivacaine improves postoperative recovery in diabetic mellitus patients undergoing foot debridement.
Hong, CC; Hung, CP; Lu, HF; Shiau, JM; Tseng, CC; Wu, YW, 2005
)
0.92
" Drug discrimination was used to examine the behavioral effects of L-838,417 and bretazenil, two low efficacy positive GABAA modulators that act at benzodiazepine sites, alone and in combination with benzodiazepines and a neuroactive steroid (alfaxolone)."( Differential behavioral effects of low efficacy positive GABAA modulators in combination with benzodiazepines and a neuroactive steroid in rhesus monkeys.
France, CP; McMahon, LR, 2006
)
0.33
" Our aim was to predict quantitatively the drug-drug interaction (DDI) potential of five macrolides from in vitro studies using testosterone as the CYP3A substrate, and to compare the predictions generated from human liver microsomal and recombinant CYP3A4 data."( Quantitative prediction of macrolide drug-drug interaction potential from in vitro studies using testosterone as the human cytochrome P4503A substrate.
Miners, JO; Polasek, TM, 2006
)
0.33
" Propofol in combination with opioids and/or benzodiazepines can be titrated to moderate sedation, which might be safer."( Propofol alone titrated to deep sedation versus propofol in combination with opioids and/or benzodiazepines and titrated to moderate sedation for colonoscopy.
Rex, DK; VanNatta, ME, 2006
)
0.33
"Propofol in combination with fentanyl and/or midazolam can be titrated to moderate levels of sedation without substantial loss of satisfaction and with shorter recovery times compared with propofol titrated to deep sedation throughout the procedure."( Propofol alone titrated to deep sedation versus propofol in combination with opioids and/or benzodiazepines and titrated to moderate sedation for colonoscopy.
Rex, DK; VanNatta, ME, 2006
)
0.59
"The most common clinical implication for the activation of the human pregnane X receptor (PXR) is the occurrence of drug-drug interactions mediated by up-regulated cytochromes P450 3A (CYP3A) isozymes."( The PREgnane X receptor gene-humanized mouse: a model for investigating drug-drug interactions mediated by cytochromes P450 3A.
Cheung, C; Feigenbaum, L; Gonzalez, FJ; Guo, GL; Idle, JR; Krausz, KW; Ma, X; Shah, Y, 2007
)
0.34
"To investigate the clinical efficacy of and complications arising from low-dose ketamine combined with fentanyl for intravenous postoperative analgesia in comparison with the exclusive use of fentanyl in elderly patients."( [Low-dose ketamine combined with fentanyl for intravenous postoperative analgesia in elderly patients].
Chen, YM; Liang, SW; Lin, CS, 2006
)
0.33
"For producing comparable postoperative analgesic effect, low-dose ketamine combined with fentanyl can markedly reduce fentanyl requirement in the elderly patients and lowers the incidences of nausea, vomiting and itching in comparison with the exclusive use of fentanyl."( [Low-dose ketamine combined with fentanyl for intravenous postoperative analgesia in elderly patients].
Chen, YM; Liang, SW; Lin, CS, 2006
)
0.33
"In drug-drug interaction (DDI) research, a two drug interaction is usually predicted by individual drug pharmacokinetics (PK)."( Drug-drug interaction prediction: a Bayesian meta-analysis approach.
Chin, R; Flockhart, DA; Hall, SD; Li, L; Lucksiri, A; Yu, M, 2007
)
0.34
" Metabolism-based inhibition of CYP3A might cause clinically significant drug-drug interactions (DDIs)."( Risk assessment for drug-drug interaction caused by metabolism-based inhibition of CYP3A using automated in vitro assay systems and its application in the early drug discovery process.
Nakamura, K; Okazaki, O; Okudaira, N; Sudo, K; Watanabe, A, 2007
)
0.34
"Forty-five minutes of preoperative warming combined with intraoperative skin-surface warming does not avoid but minimizes hypothermia caused by spinal anesthesia in patients with midazolam premedication."( Preoperative warming combined with intraoperative skin-surface warming does not avoid hypothermia caused by spinal anesthesia in patients with midazolam premedication.
Amorim, RB; Braz, JR; Braz, LG; Castiglia, YM; D'Angelo Vanni, SM; Ferrari, F; Ganem, EM; Rodrigues Júnior, GR, 2007
)
0.73
"To evaluate the quality of sedation and the effects of midazolam and diazepam alone or combined with clonidine on the heart rate (HR) and blood pressure (BP) of patients with suspected coronary artery disease."( Sedative and cardiovascular effects of midazolam and diazepam alone or combined with clonidine in patients undergoing hemodynamic studies for suspected coronary artery disease.
Carvalho, HG; Modolo, NS; Nascimento, Jdos S; Santos, KP; Silva, RC, 2007
)
0.86
"To compare the effects of fentanyl or remifentanil in combination with midazolam on hemodynamic parameters, pain, and satisfaction profile in cataract surgery."( Remifentanil versus fentanyl in combination with midazolam for retrobulbar block in cataract surgery.
Bahadir, M; Cok, OY; Ertan, A, 2008
)
0.83
"We examined hemodynamic responses during gastroscopy in healthy subjects and compared the changes with midazolam alone versus in combination with meperidine."( Comparison of the effects of intravenous midazolam alone and in combination with meperidine on hemodynamic and respiratory responses and on patient compliance during upper gastrointestinal endoscopy: a randomized, double-blind trial.
Demirtürk, L; Gürbüz, AK; Oncü, K; Ozel, AM; Yazgan, Y, 2008
)
0.83
" Intersubject variability in CYP3A activity (either inherent or from drug administration) alters the prediction of optimal midazolam sampling times; therefore, midazolam AUC is preferred for assessing CYP3A activity in drug-drug interaction studies."( Limitations of using a single postdose midazolam concentration to predict CYP3A-mediated drug interactions.
Alfaro, RM; Busse, KH; Davey, RT; Formentini, E; Penzak, SR; Robertson, SM, 2008
)
0.82
"Inhibition of cytochrome P450 (CYP) is a principal mechanism for metabolism-based drug-drug interactions (DDIs)."( Development of an in vitro drug-drug interaction assay to simultaneously monitor five cytochrome P450 isoforms and performance assessment using drug library compounds.
Burdette, D; Dunklee, MB; Fahmi, O; Heinle, L; Hyland, R; Lee, C; Miller, H; Smith, D; Thurston, A; Zientek, M,
)
0.13
"In drug-drug interaction (DDI) research, a two-drug interaction is usually predicted by individual drug pharmacokinetics (PK)."( A Bayesian meta-analysis on published sample mean and variance pharmacokinetic data with application to drug-drug interaction prediction.
Hall, S; Kim, S; Li, L; Wang, Z; Yu, M, 2008
)
0.35
"To compare results of population PK analyses obtained with a full empirical design (FD) and an optimal sparse design (MD) in a Drug-Drug Interaction (DDI) study aiming to evaluate the potential CYP3A4 inhibitory effect of a drug in development, SX, on a reference substrate, midazolam (MDZ)."( Drug-drug interaction predictions with PBPK models and optimal multiresponse sampling time designs: application to midazolam and a phase I compound. Part 2: clinical trial results.
Aarons, L; Bouzom, F; Cazade, F; Chenel, M; Mentré, F; Ogungbenro, K, 2008
)
0.73
"To determine the optimal sampling time design of a drug-drug interaction (DDI) study for the estimation of apparent clearances (CL/F) of two co-administered drugs (SX, a phase I compound, potentially a CYP3A4 inhibitor, and MDZ, a reference CYP3A4 substrate) without any in vivo data using physiologically based pharmacokinetic (PBPK) predictions, population PK modelling and multiresponse optimal design."( Drug-drug interaction predictions with PBPK models and optimal multiresponse sampling time designs: application to midazolam and a phase I compound. Part 1: comparison of uniresponse and multiresponse designs using PopDes.
Aarons, L; Bouzom, F; Chenel, M; Ogungbenro, K, 2008
)
0.56
" altered renal and hepatic function, catecholamine-related circulatory changes, altered drug volume of distribution, enteral versus parenteral feeding and morbid obesity, along with concomitant multiple drug regimens may account for the wide inter-individual variability in drug exposure and response in critically ill patients and for the high risk for drug-drug interactions to occur."( Mini-series: II. clinical aspects. clinically relevant CYP450-mediated drug interactions in the ICU.
de Hoon, J; Meersseman, W; Spriet, I; von Winckelmann, S; Willems, L; Wilmer, A, 2009
)
0.35
"This manuscript will cover a practical overview of clinically relevant CYP450-mediated drug-drug interactions."( Mini-series: II. clinical aspects. clinically relevant CYP450-mediated drug interactions in the ICU.
de Hoon, J; Meersseman, W; Spriet, I; von Winckelmann, S; Willems, L; Wilmer, A, 2009
)
0.35
"As a novel and effective approach, response surface model is used in the study of drug-drug interactions."( [Progress in the study of response surface modeling in investigation of drug-drug interaction in anesthetic drugs].
Bi, SS; Guan, Z; Lu, W; Yang, L; Zhang, LP; Zhou, TY, 2008
)
0.35
"Cytochrome P450 3A4 (CYP3A4) is the most important enzyme in drug metabolism and because it is the most frequent target for pharmacokinetic drug-drug interactions (DDIs) it is highly desirable to be able to predict CYP3A4-based DDIs from in vitro data."( Comparison of different algorithms for predicting clinical drug-drug interactions, based on the use of CYP3A4 in vitro data: predictions of compounds as precipitants of interaction.
Cook, J; Darekar, A; Dickins, M; Fahmi, OA; Guo, F; Hurst, S; Hyland, R; Obach, RS; Phipps, A; Plowchalk, D; Youdim, K, 2009
)
0.35
"To explore the application of propofol combined with midazolam intravenous anesthesia in pediatric upper gastrointestinal endoscopy."( [Propofol combined with midazolam intravenous sedation anesthesia in pediatric upper gastrointestinal endoscopy].
Ouyang, W; Shen, S; Tang, W; Wang, F; Wang, X; Xiao, D, 2009
)
0.91
"It is safe and effective to use propofol combined with midazolam intravenous sedation anesthesia in pediatric upper gastrointestinal endoscopy."( [Propofol combined with midazolam intravenous sedation anesthesia in pediatric upper gastrointestinal endoscopy].
Ouyang, W; Shen, S; Tang, W; Wang, F; Wang, X; Xiao, D, 2009
)
0.91
"Time-dependent inactivation (TDI) of human cytochromes P450 3A4 (CYP3A4) is a major cause of clinical drug-drug interactions (DDIs)."( Prediction of human drug-drug interactions from time-dependent inactivation of CYP3A4 in primary hepatocytes using a population-based simulator.
Chen, Y; Pan, Y; Shou, M; Skiles, GL; Xu, L, 2009
)
0.35
"To evaluate the antiemetic efficacy of dexamethasone combined with midazolam after middle ear surgery."( Antiemetic efficacy of dexamethasone combined with midazolam after middle ear surgery.
Baek, W; Jeon, YH; Jung, J; Kim, S; Ryu, T; Yeo, J, 2009
)
0.84
" The data suggest that L-theanine does not produce anxiolysis by modulation of the GABAA receptor; however, in combination with midazolam, a synergistic or additive effect was demonstrated by decreased anxiety and both fine and basic motor movements."( Anxiolytic effects of L-theanine--a component of green tea--when combined with midazolam, in the male Sprague-Dawley rat.
Adams, C; Ceremuga, TE; Heese, T; Jenkinson, J; Love, C; McCall, S; Milam, R; Perkins, L, 2009
)
0.79
"Model-based drug-drug interaction (DDI) is an important in-silico tool to assess the in vivo consequences of in vitro DDI."( Drug-drug interaction prediction assessment.
Hall, SD; Kim, S; Li, L; Qin, Z; Sara, QK; Wang, Z; Zhou, J, 2009
)
0.35
"Understanding the potential for cytochrome P450-mediated drug-drug interactions (DDIs) is a critical step in the drug discovery process."( Selection of alternative CYP3A4 probe substrates for clinical drug interaction studies using in vitro data and in vivo simulation.
Foti, RS; Rock, DA; Wahlstrom, JL; Wienkers, LC, 2010
)
0.36
"Nowadays, evaluation of potential risk of metabolic drug-drug interactions (mDDIs) is of high importance within the pharmaceutical industry, in order to improve safety and reduce the attrition rate of new drugs."( Predictions of metabolic drug-drug interactions using physiologically based modelling: Two cytochrome P450 3A4 substrates coadministered with ketoconazole or verapamil.
Blasco, H; Bouzom, F; Cazade, F; Chenel, M; Perdaems, N; Vinson, C; Whalley, S, 2010
)
0.36
"We tested the effects of intra-lateral septal infusions of neuropeptide Y (NPY) combined with systemic injections of topiramate in the DRL-72s paradigm and the elevated plus-maze test in male Wistar rats."( Antidepressant-like or anxiolytic-like actions of topiramate alone or co-administered with intra-lateral septal infusions of neuropeptide Y in male Wistar rats.
Jaramillo, MT; Molina-Hernández, M; Olivera-Lopez, JI; Téllez-Alcántara, NP, 2010
)
0.36
" The method is simple, rapid and rugged, and has been applied successfully to sample analysis in support of a drug-drug interaction study."( Simultaneous determination of tolbutamide, omeprazole, midazolam and dextromethorphan in human plasma by LC-MS/MS--a high throughput approach to evaluate drug-drug interactions.
Bertelsen, K; Guo, P; Han, F; Huang, MQ; Lin, ZJ; Weng, N; Zhang, W; Zhao, H, 2010
)
0.61
"Applying a comedication (COMD) covariate to apparent clearance (CL(app) = CL/F) is a common practice when using population pharmacokinetics (PopPK) to study metabolism-based drug-drug interactions (DDI)."( Bioavailability considerations in evaluating drug-drug interactions using the population pharmacokinetic approach.
Duan, JZ; Jackson, AJ; Zhao, P, 2011
)
0.37
"Ten common marmosets (Callithrix jacchus) and 10 black-tufted marmosets (Callithrix penicillata) were immobilized to compare the anesthetic effects of racemic ketamine and (S+) ketamine in combination with midazolam."( Comparison of racemic ketamine versus (S+) ketamine when combined with midazolam for anesthesia of Callithrix jacchus and Callithrix penicillata.
Cortopassi, SR; Furtado, MM; Intelizano, TR; Nunes, AL; Teixeira, RH, 2010
)
0.78
"Current assessment of drug-drug interaction (DDI) prediction success is based on whether predictions fall within a two-fold range of the observed data."( Critique of the two-fold measure of prediction success for ratios: application for the assessment of drug-drug interactions.
Aarons, L; Galetin, A; Guest, EJ; Houston, JB; Rostami-Hodjegan, A, 2011
)
0.37
" These results suggest modifications to drug-drug interaction (DDI) trial designs."( Rifampin's acute inhibitory and chronic inductive drug interactions: experimental and model-based approaches to drug-drug interaction trial design.
Cai, X; Chu, X; Ding, Y; Evers, R; Gibson, C; Reitman, ML; Roupe, K; Stoch, A; Stone, JA; Venkatasubramanian, R; Wagner, JA; Witter, R; Yabut, J; Zajic, S, 2011
)
0.37
"Aprepitant or its prodrug fosaprepitant, in combination with a corticosteroid and a 5-HT(3) receptor antagonist, are used to prevent chemotherapy-induced nausea and vomiting."( Pharmacokinetics of oral dexamethasone and midazolam when administered with single-dose intravenous 150 mg fosaprepitant in healthy adult subjects.
Caro, L; Jin, B; Marbury, TC; Murphy, G; Ngo, PL; Panebianco, D; Shadle, CR; Valentine, J, 2011
)
0.63
"Cryopreserved human hepatocytes suspended in human plasma (HHSHP) represent an integrated metabolic environment for predicting drug-drug interactions (DDIs)."( Prediction of CYP3A-mediated drug-drug interactions using human hepatocytes suspended in human plasma.
Hall, SD; Harrelson, JP; Mao, J; Mohutsky, MA; Wrighton, SA, 2011
)
0.37
"Conflicting drug-drug interaction (DDI) studies with the HIV protease inhibitors (PIs) suggest net induction or inhibition of intestinal or hepatic CYP3A."( Complex drug interactions of HIV protease inhibitors 1: inactivation, induction, and inhibition of cytochrome P450 3A by ritonavir or nelfinavir.
Collier, AC; Kharasch, ED; Kirby, BJ; Thummel, KE; Unadkat, JD; Whittington, D, 2011
)
0.37
"001), with the combination with propofol giving more favorable results."( Sedation, analgesia, and cardiorespiratory function in colonoscopy using midazolam combined with fentanyl or propofol.
Shen, SR; Tang, WL; Wang, F; Xiao, DH; Xu, CX, 2011
)
0.6
" The combination with fentanyl had a significantly lower effect on pulse rate and blood pressure."( Sedation, analgesia, and cardiorespiratory function in colonoscopy using midazolam combined with fentanyl or propofol.
Shen, SR; Tang, WL; Wang, F; Xiao, DH; Xu, CX, 2011
)
0.6
" Food and Drug Administration draft drug interaction guidance as CYP3A4 inducers for clinical drug-drug interaction (DDI) studies."( Simulation of clinical drug-drug interactions from hepatocyte CYP3A4 induction data and its potential utility in trial designs.
Hayashi, M; Shou, M; Skiles, GL; Xu, Y; Zhou, Y, 2011
)
0.37
" Despite raloxifene's in vitro bioactivation and TDI of CYP3A4, it is well tolerated in patients with no drug-drug interactions."( Use of a multistaged time-dependent inhibition assay to assess the impact of intestinal metabolism on drug-drug interaction potential.
Dalvie, D; Zientek, M, 2012
)
0.38
"Cryopreserved human hepatocytes suspended in human plasma (HHSHP) have previously provided accurate CYP3A drug-drug interaction (DDI) predictions from a single IC(50) that captures both reversible and time-dependent inhibition."( Predictions of cytochrome P450-mediated drug-drug interactions using cryopreserved human hepatocytes: comparison of plasma and protein-free media incubation conditions.
Hall, SD; Harrelson, JP; Mao, J; Mohutsky, MA; Wrighton, SA, 2012
)
0.38
"46) ng·mL-1 when used in combination with midazolam and topical lidocaine."( The optimal effect site concentration of remifentanil in combination with intravenous midazolam and topical lidocaine for awake fibreoptic nasotracheal intubation in patients undergoing cervical spine surgery.
Chang, CH; Kim, HS; Kwak, YL; Lee, JW; Shim, YH; Song, JW, 2012
)
0.87
" In the absence of in vitro TDI data, a PBPK model can be used to incorporate TDI mechanisms based on nonlinear PK data to predict clinical drug-drug interactions."( Predicting drug interaction potential with a physiologically based pharmacokinetic model: a case study of telithromycin, a time-dependent CYP3A inhibitor.
Berglund, EG; Huang, SM; Lesko, LJ; Reynolds, KS; Vieira, ML; Zhang, L; Zhao, P, 2012
)
0.38
"To investigate potential drug-drug interactions between clobazam and cytochrome P450 (CYP) isoenzyme substrates, inhibitors, and inducers."( Pharmacokinetic drug interactions between clobazam and drugs metabolized by cytochrome P450 isoenzymes.
Bekersky, I; Blum, RA; Tolbert, D; Walzer, M, 2012
)
0.38
"Two, prospective, open-label, single-center, drug-drug interaction (DDI) studies and a population pharmacokinetics analysis of seven multicenter phase II-III trials."( Pharmacokinetic drug interactions between clobazam and drugs metabolized by cytochrome P450 isoenzymes.
Bekersky, I; Blum, RA; Tolbert, D; Walzer, M, 2012
)
0.38
"Fifty-four healthy adult volunteers were enrolled in the two drug-drug interaction studies; 53 completed the studies."( Pharmacokinetic drug interactions between clobazam and drugs metabolized by cytochrome P450 isoenzymes.
Bekersky, I; Blum, RA; Tolbert, D; Walzer, M, 2012
)
0.38
"In the first drug-drug interaction study, 36 participants received a single oral dose of clobazam 10 mg on day 1, followed by either ketoconazole 400 mg once/day or omeprazole 40 mg once/day on days 17-22, with a single dose of clobazam 10 mg coadministered on day 22, to study the effects of CYP3A4 or CYP2C19 inhibition, respectively, on clobazam and its active metabolite N-desmethylclobazam (N-CLB)."( Pharmacokinetic drug interactions between clobazam and drugs metabolized by cytochrome P450 isoenzymes.
Bekersky, I; Blum, RA; Tolbert, D; Walzer, M, 2012
)
0.38
" In the second DDI study, no clinically significant drug-drug interactions were observed between clobazam 40 mg and the CYP probe substrates caffeine or tolbutamide."( Pharmacokinetic drug interactions between clobazam and drugs metabolized by cytochrome P450 isoenzymes.
Bekersky, I; Blum, RA; Tolbert, D; Walzer, M, 2012
)
0.38
"These findings suggest no clinically meaningful drug-drug interactions between clobazam and drugs metabolized by CYP3A4, CYP2C19, CYP1A2, or CYP2C9."( Pharmacokinetic drug interactions between clobazam and drugs metabolized by cytochrome P450 isoenzymes.
Bekersky, I; Blum, RA; Tolbert, D; Walzer, M, 2012
)
0.38
"The hepatic organic anion transporting polypeptides (OATPs) influence the pharmacokinetics of several drug classes and are involved in many clinical drug-drug interactions."( Classification of inhibitors of hepatic organic anion transporting polypeptides (OATPs): influence of protein expression on drug-drug interactions.
Artursson, P; Haglund, U; Karlgren, M; Kimoto, E; Lai, Y; Norinder, U; Vildhede, A; Wisniewski, JR, 2012
)
0.38
" These data suggest that GLT is unlikely to interact with drugs."( Evaluation of food-drug interaction of guava leaf tea.
Iwadate-Iwata, E; Kaneko, K; Kato, I; Onoue, M; Suzuki, K; Uchida, K, 2013
)
0.39
"The increase in cytochrome P450 (P450) enzyme activity noted upon exposure to therapeutics can elicit marked drug-drug interactions (DDIs) that may ultimately result in poor clinical outcome or adverse drug effects."( Utility of DPX2 cells for predicting CYP3A induction-mediated drug-drug interactions and associated structure-activity relationships.
Fahmi, OA; Hassanali, S; Lasker, JM; Ponce, E; Raucy, JL, 2012
)
0.38
" Here we summarize the clinical pharmacokinetics (PK), metabolism, and drug-drug interaction (DDI) profile of carfilzomib."( Clinical pharmacokinetics, metabolism, and drug-drug interaction of carfilzomib.
Alsina, M; Badros, A; Bomba, D; Fang, Y; Infante, JR; Kirk, C; Li, J; Papadopoulos, K; Wang, Z; Wong, A; Woo, T; Yang, J, 2013
)
0.39
" While grapefruit juice has been extensively studied with respect to its drug-drug interaction potential, numerous other fruit juices such as cranberry juice, orange juice, grape juice, pineapple juice and pomegranate juice have also been investigated for its potential to show drug-drug interaction of any clinical relevance."( Is pomegranate juice a potential perpetrator of clinical drug-drug interactions? Review of the in vitro, preclinical and clinical evidence.
Srinivas, NR, 2013
)
0.39
"Digoxin is the recommended substrate for assessment of P-glycoprotein (P-gp)-mediated drug-drug interactions (DDIs) in vivo."( Application of permeability-limited physiologically-based pharmacokinetic models: part II - prediction of P-glycoprotein mediated drug-drug interactions with digoxin.
Barter, Z; Jamei, M; Neuhoff, S; Rostami-Hodjegan, A; Turner, DB; Yeo, KR, 2013
)
0.39
" Due to the difference in the IC50 values for CYP3A4 and CYP3A5, nonconcordant expression of CYP3A4 and CYP3A5 protein can significantly affect the observed magnitude of CYP3A-mediated drug-drug interactions in humans."( Effect of CYP3A5 expression on the inhibition of CYP3A-catalyzed drug metabolism: impact on modeling CYP3A-mediated drug-drug interactions.
Chang, SY; Grubb, MF; Isoherranen, N; Peng, CC; Rodrigues, AD; Shirasaka, Y; Thummel, KE, 2013
)
0.39
" This study evaluated the CYP3A-mediated drug-drug interaction potential of brentuximab vedotin and the excretion of MMAE."( CYP3A-mediated drug-drug interaction potential and excretion of brentuximab vedotin, an antibody-drug conjugate, in patients with CD30-positive hematologic malignancies.
Alley, SC; Chen, R; Cooper, M; Gopal, AK; Goy, A; Grove, LE; Han, TH; Lynch, CM; Matous, JV; O'Connor, OA; Ramchandren, R, 2013
)
0.39
" Here, we address the clinical relevance of CYP3A4-related drug-drug interactions with midostaurin as either a "victim" or "perpetrator."( Investigation into CYP3A4-mediated drug-drug interactions on midostaurin in healthy volunteers.
Dutreix, C; Lorenzo, S; Munarini, F; Roesel, J; Wang, Y, 2013
)
0.39
" Drug-drug interactions involving voclosporin and CYP3A substrates are not expected."( Cytochrome P450 3A and P-glycoprotein drug-drug interactions with voclosporin.
Aspeslet, LJ; Foster, RT; Freitag, DG; Huizinga, RB; Larouche, R; Ling, SY; Mayo, PR, 2014
)
0.4
" This observed discrepancy between in vitro risk assessment and in vivo drug-drug interaction (DDI) profile was rationalized by time-varying dynamic pharmacokinetic models that incorporated circulating concentrations of fluoxetine and norfluoxetine enantiomers, mutual inhibitor-inhibitor interactions, and CYP3A4 induction."( Fluoxetine- and norfluoxetine-mediated complex drug-drug interactions: in vitro to in vivo correlation of effects on CYP2D6, CYP2C19, and CYP3A4.
Davis, C; Foti, RS; Isoherranen, N; Kunze, KL; Lutz, JD; Sager, JE, 2014
)
0.4
" Potential drug-drug interactions need to be considered."( Midazolam and drug-drug interactions in dental conscious sedation.
Broderick, D; Clarke, M; Stassen, L,
)
1.57
"To evaluate felodipine as a potential perpetrator of pharmacokinetic drug-drug interactions (PK-DDIs) involving cytochrome P450 (CYP) enzymes and P-glycoprotein (P-gp)."( Evaluation of felodipine as a potential perpetrator of pharmacokinetic drug-drug interactions.
Doogue, MP; Miners, JO; Polasek, TM; Rowland, A; Snyder, BD, 2014
)
0.4
"Pigeons were sedated by INS MID alone at a dose of 5 mg kg(-1) (group MID, n = 6) or in combination with INS DXM at a dose 80 μg kg(-1) (group MID-DXM, n = 6)."( A preliminary trial of the sedation induced by intranasal administration of midazolam alone or in combination with dexmedetomidine and reversal by atipamezole for a short-term immobilization in pigeons.
Bilek, J; Hornak, S; Hromada, R; Ledecky, V; Liptak, T; Mazensky, D; Petrovic, V, 2015
)
0.65
" Based on these results, a series of clinical drug-drug interaction (DDI) studies were conducted to evaluate the effect of ivacaftor on sensitive substrates of CYP2C8 (rosiglitazone), CYP3A (midazolam), CYP2D6 (desipramine), and P-gp (digoxin)."( Clinical drug-drug interaction assessment of ivacaftor as a potential inhibitor of cytochrome P450 and P-glycoprotein.
Chavan, AB; Dubey, N; Gilmartin, GS; Higgins, M; Li, C; Luo, X; Mahnke, L; Robertson, SM, 2015
)
0.61
" Therefore, evaluating the drug-drug interaction (DDI) potential associated with MMAE is important in the clinical development of ADCs."( Physiologically based pharmacokinetic modeling as a tool to predict drug interactions for antibody-drug conjugates.
Chen, Y; Girish, S; Hop, C; Jin, JY; Li, C; Lu, D; Mukadam, S; Samineni, D; Shen, BQ; Wong, H, 2015
)
0.42
"Botanical medicines are frequently used in combination with therapeutic drugs, imposing a risk for harmful botanical-drug interactions (BDIs)."( An ex vivo approach to botanical-drug interactions: a proof of concept study.
Gurley, BJ; Markowitz, JS; Munoz, J; Wang, X; Zhu, HJ, 2015
)
0.42
"The regulatory prohibition of ketoconazole as a CYP3A index inhibitor in drug-drug interaction (DDI) studies has compelled consideration of alternative inhibitors."( Ritonavir is the best alternative to ketoconazole as an index inhibitor of cytochrome P450-3A in drug-drug interaction studies.
Greenblatt, DJ; Harmatz, JS, 2015
)
0.42
" The aim of this study was to evaluate the clinical effects of dexmedetomidine combined with midazolam in postoperative intensive care following pediatric cardiac surgery."( Dexmedetomidine in combination with midazolam after pediatric cardiac surgery.
Hasegawa, T; Maruo, A; Matsuhisa, H; Matsushima, S; Noda, R; Oshima, Y; Tanaka, A, 2015
)
0.91
"Since drug-drug interaction (DDI) can affect organic anion-transporting polypeptide (OATP) and cause clinical events, prediction of such DDI is important in early clinical development."( Dehydroepiandrosterone sulfate, a useful endogenous probe for evaluation of drug-drug interaction on hepatic organic anion transporting polypeptide (OATP) in cynomolgus monkeys.
Tamai, I; Watanabe, M; Watanabe, T; Yabuki, M, 2015
)
0.42
" The aim of the current work was to develop a physiologically based pharmacokinetic (PBPK) model to predict quantitatively the magnitude of CYP3A4 mediated drug-drug interaction with midazolam as the substrate."( Physiologically based pharmacokinetic modeling to predict complex drug-drug interactions: a case study of AZD2327 and its metabolite, competitive and time-dependent CYP3A inhibitors.
Guo, J; Khanh, BH; Li, Y; Zhou, D, 2015
)
0.61
" CETP inhibitors are likely to be utilized as 'add-on' therapy to statins in patients receiving concomitant medications, so the potential for evacetrapib to cause clinically important drug-drug interactions (DDIs) with cytochromes P450 (CYP) was evaluated."( CYP-mediated drug-drug interactions with evacetrapib, an investigational CETP inhibitor: in vitro prediction and clinical outcome.
Cannady, EA; Friedrich, S; Krueger, KA; Nicholls, SJ; Rehmel, JR; Suico, JG; Wang, MD, 2015
)
0.42
" This work investigated if CAB was a substrate for efflux transporters, the potential for CAB to interact with drug-metabolizing enzymes and transporters to cause clinical drug interactions, and the effect of CAB on the pharmacokinetics of midazolam, a CYP3A4 probe substrate, in humans."( Drug interaction profile of the HIV integrase inhibitor cabotegravir: assessment from in vitro studies and a clinical investigation with midazolam.
Bowers, GD; Ford, SL; Gould, EP; Humphreys, JE; Polli, JW; Reese, MJ; Webster, LO, 2016
)
0.82
" Under-prediction of pharmacokinetics and drug-drug interactions (DDIs) following multiple doses of itraconazole has limited the use of PBPK model simulation to aid an itraconazole clinical DDI study design."( Development of a Physiologically Based Pharmacokinetic Model for Itraconazole Pharmacokinetics and Drug-Drug Interaction Prediction.
Budha, N; Chen, Y; Hop, CE; Jin, JY; Kenny, JR; Lu, T; Ma, F; Mao, J; Wong, H, 2016
)
0.43
" As RA patients might be treated with multiple medications simultaneously, possible drug-drug interactions of filgotinib with cytochrome P450 enzymes and with key drug transporters were evaluated in vitro and in clinical studies."( Clinical Confirmation that the Selective JAK1 Inhibitor Filgotinib (GLPG0634) has a Low Liability for Drug-drug Interactions.
Desrivot, J; Harrison, P; Namour, F; Tasset, C; Van der Aa, A; van't Klooster, G, 2016
)
0.43
"In vitro, filgotinib and its active metabolite at clinically relevant concentrations did not interact with cytochrome P450 enzymes and uridine 5'-diphospho-glucuronosyltransferases, and did not inhibit key drug transporters."( Clinical Confirmation that the Selective JAK1 Inhibitor Filgotinib (GLPG0634) has a Low Liability for Drug-drug Interactions.
Desrivot, J; Harrison, P; Namour, F; Tasset, C; Van der Aa, A; van't Klooster, G, 2016
)
0.43
"The aim of the present study is to compare the success rate and complications of caudal epidural bupivacaine alone or in combination with intravenous (IV) midazolam and ketamine in awake infants undergoing lower abdominal surgery."( The success rate and complications of awake caudal epidural bupivacaine alone or in combination with intravenous midazolam and ketamine in pre-term infants.
Azarfarin, R; Mashhoori, M; Seyedhejazi, M; Shekhzadeh, D; Taghizadieh, N,
)
0.54
"The objectives of this study were to determine: (1) the sedative effects of dexmedetomidine in combination with methadone, midazolam, or both, and (2) the propofol dose required to achieve endotracheal intubation in healthy dogs."( Comparison of sedation scores and propofol induction doses in dogs after intramuscular administration of dexmedetomidine alone or in combination with methadone, midazolam, or methadone plus midazolam.
Bustamante, R; Canfrán, S; Cediel, R; de Segura, IA; González, P; Re, M, 2016
)
0.84
" To further validate this cocktail, in this study, we have verified whether probe drugs contained in the latter cause mutual drug-drug interactions."( Evaluation of Mutual Drug-Drug Interaction within Geneva Cocktail for Cytochrome P450 Phenotyping using Innovative Dried Blood Sampling Method.
Bosilkovska, M; Daali, Y; Déglon, J; Desmeules, J; Samer, C; Thomas, A; Walder, B, 2016
)
0.43
" Even though ketamine alone and in combination with midazolam or dexmedetomidine are frequently used in laboratory animals, the side-effects of such protocols are not well known."( Ketamine alone or combined with midazolam or dexmedetomidine does not affect anxiety-like behaviours and memory in adult Wistar rats.
Antunes, L; Magalhães, A; Melo, P; Pereira, M; Summavielle, T; Valentim, A; Venâncio, C, 2017
)
0.99
"Quantitative assessment of potential drug-drug interactions (DDIs) is one of the major focuses in drug development."( Characterization of Long-Lasting Oatp Inhibition by Typical Inhibitor Cyclosporine A and In Vitro-In Vivo Discrepancy in Its Drug Interaction Potential in Rats.
Kato, Y; Kogi, T; Masuo, Y; Nakamichi, N; Taguchi, T, 2016
)
0.43
" We present results from 3 fixed-sequence studies evaluating drug-drug interactions for alectinib through CYP3A."( Clinical Drug-Drug Interactions Through Cytochrome P450 3A (CYP3A) for the Selective ALK Inhibitor Alectinib.
Bogman, K; Bordogna, W; Cleary, Y; Dall, G; De Petris, L; Guerini, E; Martin-Facklam, M; Morcos, PN; Phipps, A; Viteri, S; Yu, L, 2017
)
0.46
"To determine the intubation dose and select physiologic effects of alfaxalone alone or in combination with midazolam or ketamine in dogs."( Alfaxalone alone or combined with midazolam or ketamine in dogs: intubation dose and select physiologic effects.
Muñoz, KA; Robertson, SA; Wilson, DV, 2017
)
0.95
" Serum glucose and insulin concentrations were not influenced by administration of alfaxalone alone or when administered with midazolam or ketamine."( Alfaxalone alone or combined with midazolam or ketamine in dogs: intubation dose and select physiologic effects.
Muñoz, KA; Robertson, SA; Wilson, DV, 2017
)
0.94
"This phase 1, open-label, crossover study sought to evaluate drug-drug interactions between tivantinib and cytochrome P450 (CYP) substrates and tivantinib and P-glycoprotein."( Evaluation of the pharmacokinetic drug interaction potential of tivantinib (ARQ 197) using cocktail probes in patients with advanced solid tumours.
Gajee, R; Papadopoulos, KP; Puzanov, I; Strickler, JH; Tachibana, M; Wang, Y; Zahir, H, 2018
)
0.48
"The data suggest that tivantinib 360 mg twice daily has either a minimal or no effect on the pharmacokinetics of probe drugs for CYP1A2, CYP2C9, CYP2C19 and CYP3A4 substrates, and decreases the systemic exposure of P-glycoprotein substrates when administered with tivantinib."( Evaluation of the pharmacokinetic drug interaction potential of tivantinib (ARQ 197) using cocktail probes in patients with advanced solid tumours.
Gajee, R; Papadopoulos, KP; Puzanov, I; Strickler, JH; Tachibana, M; Wang, Y; Zahir, H, 2018
)
0.48
"All pharmaceutical companies are required to assess pharmacokinetic drug-drug interactions (DDIs) of new chemical entities (NCEs) and mathematical prediction helps to select the best NCE candidate with regard to adverse effects resulting from a DDI before any costly clinical studies."( A quantitative systems pharmacology approach, incorporating a novel liver model, for predicting pharmacokinetic drug-drug interactions.
Cherkaoui-Rbati, MH; Littlewood, P; Paine, SW; Rauch, C, 2017
)
0.46
" Based on a previous clinical drug-drug interaction study with ketoconazole (KTZ), the contribution of CYP3A4 in vivo was estimated to be ∼40%."( Physiologically Based Pharmacokinetic Model Predictions of Panobinostat (LBH589) as a Victim and Perpetrator of Drug-Drug Interactions.
Chun, DY; Einolf, HJ; Gu, H; He, H; Lin, W; Mangold, JB; Wang, L; Won, CS, 2017
)
0.46
" In vitro and clinical drug-drug interaction (DDI) studies indicated that midostaurin and its metabolites are substrates, reversible and time-dependent inhibitors, and inducers of CYP3A4."( Simultaneous Physiologically Based Pharmacokinetic (PBPK) Modeling of Parent and Active Metabolites to Investigate Complex CYP3A4 Drug-Drug Interaction Potential: A Case Example of Midostaurin.
Chun, DY; Dutreix, C; Einolf, HJ; Gu, H; He, H; Ouatas, T; Rebello, S; Wang, L, 2018
)
0.48
"To evaluate the capacity for modafinil to be a perpetrator of metabolic drug-drug interactions by altering cytochrome P450 activity following a single dose and dosing to steady state."( Evaluation of modafinil as a perpetrator of metabolic drug-drug interactions using a model informed cocktail reaction phenotyping trial protocol.
Mangoni, AA; Rowland, A; Sorich, MJ; van Dyk, M; Warncken, D, 2018
)
0.48
"These data support consideration of the risk of clinically relevant metabolic drug-drug interactions perpetrated by modafinil when this drug is co-administered with drugs that are primarily cleared by CYP2C19 (single modafinil dose or steady state modafinil dosing) or CYP3A4 (steady state modafinil dosing only) catalysed metabolic pathways."( Evaluation of modafinil as a perpetrator of metabolic drug-drug interactions using a model informed cocktail reaction phenotyping trial protocol.
Mangoni, AA; Rowland, A; Sorich, MJ; van Dyk, M; Warncken, D, 2018
)
0.48
"Ritonavir is one of several ketoconazole alternatives used to evaluate strong CYP3A4 inhibition potential in clinical drug-drug interaction (DDI) studies."( Verification of a physiologically based pharmacokinetic model of ritonavir to estimate drug-drug interaction potential of CYP3A4 substrates.
He, H; Heimbach, T; Huth, F; Umehara, KI; Won, CS, 2018
)
0.48
" The aim of our study was to test the effects of dexmedetomidine in combination with opioids and benzodiazepines compared to benzodiazepine-opioids alone."( Use of low-dose dexmedetomidine in combination with opioids and midazolam in pediatric cardiac surgical patients: randomized controlled trial.
Benegni, S; Cogo, P; Garisto, C; Pezzella, C; Ricci, Z; Tofani, L, 2018
)
0.72
"Low dose of dexmedetomidine in combination with morphine and midazolam was safe in a high-risk cohort of CHD children after cardiac surgery and reduced the onset of withdrawal symptoms."( Use of low-dose dexmedetomidine in combination with opioids and midazolam in pediatric cardiac surgical patients: randomized controlled trial.
Benegni, S; Cogo, P; Garisto, C; Pezzella, C; Ricci, Z; Tofani, L, 2018
)
0.96
" The intraday and interday precision and accuracy of the assays were within acceptable ranges, and the assays were successfully applied to support a study where a microdose cocktail was dosed to healthy human subjects for simultaneous assessment of clinical drug-drug interactions mediated by major drug transporters and CYP3A."( Microdosing Cocktail Assay Development for Drug-Drug Interaction Studies.
Bateman, KP; Chavez-Eng, CM; Goykhman, D; Lutz, RW, 2018
)
0.48
" These results were used to inform the US prescribing information in the absence of clinical drug-drug interaction studies."( PBPK Modeling Strategy for Predicting Complex Drug Interactions of Letermovir as a Perpetrator in Support of Product Labeling.
Chen, D; Cho, CR; Hartmann, G; Menzel, K; Wang, YH, 2019
)
0.51
" The overall objective of this study is to provide a comprehensive mechanistic PBPK model for itraconazole in order to increase the confidence in its drug-drug interaction (DDI) predictions."( Physiologically Based Pharmacokinetic Model of Itraconazole and Two of Its Metabolites to Improve the Predictions and the Mechanistic Understanding of CYP3A4 Drug-Drug Interactions.
Ericsson, H; Janzén, D; Kanebratt, KP; Lennernäs, H; Lundahl, A; Prieto Garcia, L, 2018
)
0.48
"The aim of this study was to investigate the sedative effects of medetomidine in combination with midazolam or butorphanol for routine imaging procedures in dogs."( Randomised clinical trial comparing clinically relevant sedation outcome measures in dogs after intramuscular administration of medetomidine in combination with midazolam or butorphanol for routine diagnostic imaging procedures.
Le Chevallier, D; Murrell, JC; Slingsby, L, 2018
)
0.89
"Introduction: Drug-drug interactions occur more frequently in intensive care units than in other services."( Characterization of potential drug-drug interactions in patients hospitalized in the intensive care unit of a tertiary hospital in Bogotá
Bustamante, C; Hernández, M; Tribiño, G, 2018
)
0.48
" This unusual property elicits uncertainty regarding the optimal approach for predicting its drug-drug interaction (DDI) risk."( Physiologically-based pharmacokinetic modelling to predict oprozomib CYP3A drug-drug interaction potential in patients with advanced malignancies.
Cutler, RE; Gore, L; Harvey, RD; Mita, A; Ou, Y; Papadopoulos, KP; Pinchasik, DE; Tsimberidou, AM; Wang, Z; Xu, Y, 2019
)
0.51
" Administration of midazolam in combination with medetomidine resulted in 71% of dogs displaying paradoxical behaviours (p < 0."( Use of midazolam in combination with medetomidine for premedication in healthy dogs.
Le Chevallier, D; Murrell, J; Slingsby, L, 2019
)
1.3
" This drug combination IV is not recommended for premedication in healthy dogs."( Use of midazolam in combination with medetomidine for premedication in healthy dogs.
Le Chevallier, D; Murrell, J; Slingsby, L, 2019
)
0.97
" This study confirmed that the Inje cocktail approach was able to detect relevant drug-drug interactions impacting further development of ASP8477 and future therapeutic use."( A Cocktail Interaction Study Evaluating the Drug-Drug Interaction Potential of the Perpetrator Drug ASP8477 at Multiple Ascending Dose Levels.
Collins, C; Ernault, E; Fuhr, R; Gangaram-Panday, S; Passier, P; Treijtel, N; van Bruijnsvoort, M, 2019
)
0.51
"We verified a physiologically-based pharmacokinetic (PBPK) model to predict cytochrome P450 3A4/5-mediated drug-drug interactions (DDIs)."( Quantitative Prediction of CYP3A4- and CYP3A5-Mediated Drug Interactions.
Dickinson, GL; Guo, Y; Hall, SD; Hilligoss, JK; Lucksiri, A; Vuppalanchi, RK, 2020
)
0.56
" Accordingly, the drug-drug interaction (DDI) potential of darolutamide was investigated in both nonclinical and clinical studies."( Drug-Drug Interaction Potential of Darolutamide: In Vitro and Clinical Studies.
Bairlein, M; Denner, K; Fricke, R; Gieschen, H; Graudenz, K; Korjamo, T; Koskinen, M; Prien, O; von Bühler, CJ; Wilkinson, G; Zurth, C, 2019
)
0.51
"To evaluate the sedative and cardiorespiratory effects of IM administration of alfaxalone and butorphanol combined with acepromazine, midazolam, or dexmedetomidine in dogs."( Sedative and cardiorespiratory effects of intramuscular administration of alfaxalone and butorphanol combined with acepromazine, midazolam, or dexmedetomidine in dogs.
Aarnes, TK; Bednarski, RM; Cremer, J; Lerche, P; Murdock, MA; Riccó Pereira, CH, 2020
)
0.97
"4 mg/kg] combined with acepromazine [0."( Sedative and cardiorespiratory effects of intramuscular administration of alfaxalone and butorphanol combined with acepromazine, midazolam, or dexmedetomidine in dogs.
Aarnes, TK; Bednarski, RM; Cremer, J; Lerche, P; Murdock, MA; Riccó Pereira, CH, 2020
)
0.76
"The objective of this study was to compare intravenous (IV) xylazine and detomidine as sedatives in combination with midazolam and ketamine for induction of anaesthesia in horses undergoing field castration."( Comparison of xylazine and detomidine in combination with midazolam/ketamine for field castration in Quarter Horses.
Bass, L; Damone, J; Mama, K; Rao, S; Smith, MC, 2020
)
1.01
"A great deal of effort has been being made to improve the accuracy of the prediction of drug-drug interactions (DDIs)."( Critical Impact of Drug-Drug Interactions via Intestinal CYP3A in the Risk Assessment of Weak Perpetrators Using Physiologically Based Pharmacokinetic Models.
Inoue, SI; Ishizuka, T; Nishiya, Y; Sugiyama, D; Watanabe, A; Watanabe, K; Watanabe, N; Yamada, M; Yamashita, S, 2020
)
0.56
" An integrated in silico, in vitro, and clinical approach including a clinical drug interaction study as well as a bespoke physiologically based pharmacokinetic (PBPK) model was used to assess the drug-drug interaction (DDI) risk."( Drug Interactions for Low-Dose Inhaled Nemiralisib: A Case Study Integrating Modeling, In Vitro, and Clinical Investigations.
Cahn, AP; Georgiou, A; Harrell, AW; Hessel, EM; Marotti, M; Patel, A; Riddell, K; Taskar, KS; Taylor, M; Tracey, H; Wilson, R, 2020
)
0.56
"Administration of finerenone 20 mg once daily confers no risk of clinically relevant drug-drug interactions with substrates of cytochrome P450 enzymes."( Results from Drug-Drug Interaction Studies In Vitro and In Vivo Investigating the Effect of Finerenone on the Pharmacokinetics of Comedications.
Bairlein, M; Gerisch, M; Heinig, R; Loewen, S; Nagelschmitz, J, 2020
)
0.56
"Midazolam alone or in combination with sufentanil improved the general indicators along with long duration of sedative analgesia, reduced serum TNF-α, and IL-1β secretion and few adverse reactions."( Effects of midazolam combined with sufentanil on injury and expression of HMGB1 and NF-κB in rats with pancreatitis.
Liu, Y; Liu, YY; Zhou, H; Zhu, ZH, 2020
)
2.39
"Midazolam combined with sufentanil can inhibit the expression of HMGB1 and NF-κB, inhibit inflammation, thereby improving the sedative and analgesic effects, protecting pancreatic tissue, and reducing acute pancreatitis injury."( Effects of midazolam combined with sufentanil on injury and expression of HMGB1 and NF-κB in rats with pancreatitis.
Liu, Y; Liu, YY; Zhou, H; Zhu, ZH, 2020
)
2.39
" The probe cocktail was generally well-tolerated when administered in combination with guselkumab in patients with psoriasis."( Evaluating Potential Disease-Mediated Protein-Drug Interactions in Patients With Moderate-to-Severe Plaque Psoriasis Receiving Subcutaneous Guselkumab.
Chen, D; Piantone, A; Sharma, A; Shu, C; Xu, Y; Xu, Z; Zhou, H; Zhu, Y; Zhuang, Y, 2020
)
0.56
"We aimed to incorporate a pharmacologically inactive midazolam microdose into early clinical studies for the assessment of CYP3A drug-drug interaction liability."( Midazolam microdosing applied in early clinical development for drug-drug interaction assessment.
Goettel, M; Herich, L; Huennemeyer, A; Jambrecina, A; Kadus, W; Mikus, G; Schlieker, L; Schultz, A; Vinisko, R; Wiebe, ST, 2021
)
2.31
"Midazolam microdosing incorporated into early clinical studies is a feasible tool for reducing dedicated drug-drug interaction studies, meaning reduced subject burden."( Midazolam microdosing applied in early clinical development for drug-drug interaction assessment.
Goettel, M; Herich, L; Huennemeyer, A; Jambrecina, A; Kadus, W; Mikus, G; Schlieker, L; Schultz, A; Vinisko, R; Wiebe, ST, 2021
)
3.51
"Ribociclib is approved in combination with endocrine therapy as initial endocrine-based therapy for HR-positive and HER2-negative advanced breast cancer."( Ribociclib Drug-Drug Interactions: Clinical Evaluations and Physiologically-Based Pharmacokinetic Modeling to Guide Drug Labeling.
Chakraborty, A; Dhuria, SV; Elmeliegy, M; He, H; Heimbach, T; Huth, F; Ji, Y; Miller, M; Samant, TS; Schiller, H; Umehara, K, 2020
)
0.56
" Here, the drug-drug interaction (DDI) potential of esaxerenone was evaluated in vitro, and its impact in clinical practice was estimated."( Drug-Drug Interaction Risk Assessment of Esaxerenone as a Perpetrator by In Vitro Studies and Static and Physiologically Based Pharmacokinetic Models.
Fischer, T; Inoue, SI; Ishizuka, T; Rozehnal, V; Sugiyama, D; Yamada, M, 2020
)
0.56
" The aim of this study was to better understand the drug-drug interaction (DDI) potential of CYP3A and P-gp inhibitors."( PBPK modeling of CYP3A and P-gp substrates to predict drug-drug interactions in patients undergoing Roux-en-Y gastric bypass surgery.
Chan, LN; Chen, KF; Lin, YS, 2020
)
0.56
" For drugs that are not clinically significant transporter substrates, it is expected that drug-drug interactions would not result in any changes in volume of distribution."( Volume of Distribution is Unaffected by Metabolic Drug-Drug Interactions.
Benet, LZ; Huang, CH; Sodhi, JK, 2021
)
0.62
"An evaluation of this hypothesis proceeded via an extensive analysis of published intravenous metabolic drug-drug interactions, based on clinically recommended index substrates and inhibitors of major cytochrome P450 (CYP) isoforms."( Volume of Distribution is Unaffected by Metabolic Drug-Drug Interactions.
Benet, LZ; Huang, CH; Sodhi, JK, 2021
)
0.62
"Age-related comorbidities and consequently polypharmacy are highly prevalent in the elderly, resulting in an increased risk for drug-drug interactions (DDIs)."( Clinical Data Combined With Modeling and Simulation Indicate Unchanged Drug-Drug Interaction Magnitudes in the Elderly.
Battegay, M; Courlet, P; Decosterd, LA; Kinvig, H; Marzolini, C; Penny, MA; Siccardi, M; Stader, F, 2021
)
0.62
" Since drug-drug interactions can cause serious adverse effects and impede overall curative effects, evidence regarding the risk associated with drug-drug interactions between Hb-V and such simultaneously administered drugs is needed."( Assessing cytochrome P450-based drug-drug interactions with hemoglobin-vesicles, an artificial red blood cell preparation, in healthy rats.
Ohtsuki, S; Otagiri, M; Sakai, H; Taguchi, K; Tokuno, M; Yamasaki, K, 2020
)
0.56
"This study aimed to investigate the sedative effect of dexmedetomidine combined with midazolam nasal drops before a pediatric craniocerebral magnetic resonance imaging (MRI)."( Observation of the Sedative Effect of Dexmedetomidine Combined With Midazolam Nasal Drops Before a Pediatric Craniocerebral MRI.
He, L; Lai, Y; Li, SJ; Wu, ZF; Zhang, YP, 2020
)
1.02
"Eighty children who needed an MRI examination were enrolled in the present study and randomly divided into 2 groups: the observation group (dexmedetomidine combined with midazolam nasal drops) and the control group."( Observation of the Sedative Effect of Dexmedetomidine Combined With Midazolam Nasal Drops Before a Pediatric Craniocerebral MRI.
He, L; Lai, Y; Li, SJ; Wu, ZF; Zhang, YP, 2020
)
0.99
"To characterize the clinical relevance of in vitro drug-drug interaction findings with apararenone (MT-3995), the effects of apararenone on the sensitive substrates of cytochrome P450 3A4 (midazolam) and 2C9 (warfarin), and P-glycoprotein (digoxin), were assessed through a series of studies conducted in healthy volunteers."( Drug-Drug Interactions of the Nonsteroidal Mineralocorticoid Receptor Antagonist Apararenone With Midazolam, Warfarin, and Digoxin: A Phase 1 Studies in Healthy Volunteers.
Kawaguchi, A; Nakamura, T; Shimizu, H, 2020
)
0.97
"The findings from this analysis of data from healthy volunteers suggest minimal risk for potential drug-drug interactions between apararenone and other drugs that are likely to be used concurrently in patients."( Drug-Drug Interactions of the Nonsteroidal Mineralocorticoid Receptor Antagonist Apararenone With Midazolam, Warfarin, and Digoxin: A Phase 1 Studies in Healthy Volunteers.
Kawaguchi, A; Nakamura, T; Shimizu, H, 2020
)
0.78
" For the first time, we developed a physiologically based pharmacokinetic (PBPK) model-based approach to assess CYP3A-mediated drug-drug interaction (DDI) risk for polatuzumab vedotin (Polivy), an anti-CD79b-vc-monomethyl auristatin E (MMAE) antibody-drug conjugate (ADC)."( Physiologically Based Pharmacokinetic Model-Informed Drug Development for Polatuzumab Vedotin: Label for Drug-Drug Interactions Without Dedicated Clinical Trials.
Chen, Y; Ding, H; Girish, S; Jin, J; Li, C; Lu, D; Ma, F; Mao, J; Miles, D; Samineni, D; Shi, R; Wright, M, 2020
)
0.56
" The validity of a cocktail study for use as a quantitative drug-drug interactions (DDIs) assessment was evaluated."( Verification of a cocktail approach for quantitative drug-drug interaction assessment: a comparative analysis between the results of a single drug and a cocktail drug.
Hakamata, A; Inui, N; Kamiya, C; Katayama, N; Kawakami, J; Miura, M; Namiki, N; Odagiri, K; Tanaka, S; Uchida, S; Watanabe, H, 2021
)
0.62
" The study investigated the drug-drug interaction (DDI) potential of ceritinib when coadministered with midazolam and warfarin as probe substrates for CYP3A and CYP2C9 activity, respectively."( Effect of ceritinib on the pharmacokinetics of coadministered CYP3A and 2C9 substrates: a phase I, multicenter, drug-drug interaction study in patients with ALK + advanced tumors.
de Braud, F; De Castro Carpeño, J; de Miguel Luken, MJ; Hurtado, FK; Lau, YY; Mau-Sorensen, M; McCulloch, T; Scott, J; Wang, D, 2021
)
0.84
" A single dose of a cocktail consisting of midazolam and warfarin was administered with and without concomitant administration of ceritinib."( Effect of ceritinib on the pharmacokinetics of coadministered CYP3A and 2C9 substrates: a phase I, multicenter, drug-drug interaction study in patients with ALK + advanced tumors.
de Braud, F; De Castro Carpeño, J; de Miguel Luken, MJ; Hurtado, FK; Lau, YY; Mau-Sorensen, M; McCulloch, T; Scott, J; Wang, D, 2021
)
0.88
" This study aimed to investigate the safety and efficacy of dexmedetomidine combined with midazolam for undergoing conscious sedation during bronchoscopy."( Dexmedetomidine combined with midazolam infusion guided by bispectral index during bronchoscopy.
Dai, P; Dong, D; Guan, S; He, Q; Qiu, H; Wang, X; Xu, Q; Xu, X; Zhang, Q; Zhang, S; Zhou, J, 2021
)
1.13
" Patients were randomized into DEX group (dexmedetomidine combined with midazolam) and FEN group (fentanyl combined with midazolam)."( Dexmedetomidine combined with midazolam infusion guided by bispectral index during bronchoscopy.
Dai, P; Dong, D; Guan, S; He, Q; Qiu, H; Wang, X; Xu, Q; Xu, X; Zhang, Q; Zhang, S; Zhou, J, 2021
)
1.14
"The conscious sedation regimen of dexmedetomidine combined with midazolam monitored by BIS is considered to be safe and effective during bronchoscopy."( Dexmedetomidine combined with midazolam infusion guided by bispectral index during bronchoscopy.
Dai, P; Dong, D; Guan, S; He, Q; Qiu, H; Wang, X; Xu, Q; Xu, X; Zhang, Q; Zhang, S; Zhou, J, 2021
)
1.15
"We developed an efficient and sensitive probe for drug-drug interactions mediated by human CYP3A4 by using midazolam (MDZ) as a probe substrate."( Midazolam as a Probe for Drug-Drug Interactions Mediated by CYP3A4: Homotropic Allosteric Mechanism of Site-Specific Hydroxylation.
Camp, T; Denisov, IG; Grinkova, YV; McLean, MA; Sligar, SG, 2021
)
2.28
" The purpose of this study was to identify the factors and procedure time associated with the use of intravenous sedation with propofol alone or propofol combined with midazolam in dental patients with special needs."( A comparative study of propofol alone and propofol combined with midazolam for dental treatments in special needs patients.
Chen, SL; Chong, SY; Huang, MS; Huang, TS; Lin, IH; Tsai, HH; Wang, PY, 2021
)
1.05
" The objective of this study was to develop a framework for leveraging physiologically based pharmacokinetic (PBPK) modeling to predict CYP3A-mediated drug-drug interaction (DDI) potential in the pediatric population using solithromycin as a case study."( Leveraging Physiologically Based Pharmacokinetic Modeling and Experimental Data to Guide Dosing Modification of CYP3A-Mediated Drug-Drug Interactions in the Pediatric Population.
Carreño, FO; Cohen-Wolkowiez, M; Edginton, AN; Gonzalez, D; Salerno, SN, 2021
)
0.62
"We investigated savolitinib pharmacokinetics (PK) when administered alone or in combination with rifampicin, itraconazole or famotidine, and investigated midazolam PK when administered with or without savolitinib in healthy males."( Clinical evaluation of the potential drug-drug interactions of savolitinib: Interaction with rifampicin, itraconazole, famotidine or midazolam.
Burke, W; Cantarini, M; Frewer, P; Goldwater, R; Han, D; Hara, I; Li, Y; Ren, S; Scarfe, G; Schalkwijk, S; Vishwanathan, K, 2022
)
1.12
" While many pediatric patients receive risdiplam, a drug-drug interaction (DDI) study in pediatric patients with SMA was not feasible."( Model-Based Drug-Drug Interaction Extrapolation Strategy From Adults to Children: Risdiplam in Pediatric Patients With Spinal Muscular Atrophy.
Aarons, L; Cleary, Y; Galetin, A; Gertz, M; Grimsey, P; Günther, A; Heinig, K; Kletzl, H; Ogungbenro, K, 2021
)
0.62
" RNAi therapeutics, such as givosiran, have a low liability for drug-drug interactions (DDIs) because they are not metabolized by cytochrome 450 (CYP) enzymes, and do not directly inhibit or induce CYP enzymes in the liver."( A Drug-Drug Interaction Study Evaluating the Effect of Givosiran, a Small Interfering Ribonucleic Acid, on Cytochrome P450 Activity in the Liver.
Agarwal, S; Clausen, VA; Harper, P; Najafian, N; Robbie, GJ; Sardh, E; Simon, AR; Vassiliou, D, 2021
)
0.62
"The aim of this work is the development of a mechanistic physiologically-based pharmacokinetic (PBPK) model using in vitro to in vivo extrapolation to conduct a drug-drug interaction (DDI) assessment of treosulfan against two cytochrome p450 (CYP) isoenzymes and P-glycoprotein (P-gp) substrates."( Evaluation of the drug-drug interaction potential of treosulfan using a physiologically-based pharmacokinetic modelling approach.
Balazki, P; Baumgart, J; Beelen, DW; Böhm, S; Hemmelmann, C; Hilger, RA; Martins, FS; Ring, A; Schaller, S, 2022
)
0.72
"To best promote drug tolerability and efficacy in the clinic, data from drug-drug interaction (DDI) evaluations and subsequent translation of the results to DDI prevention and/or management strategies must be incorporated into the US Food and Drug Administration (FDA) product labeling in a consistent manner because differences in language might result in varied interpretations."( Analysis of Drug-Drug Interaction Labeling Language and Clinical Recommendations for Newly Approved Drugs Evaluated With Digoxin, Midazolam, and S-Warfarin.
Henderson, LM; Ragueneau-Majlessi, I; Steinbronn, CE; Yeung, CK; Yu, J, 2021
)
0.83
"Xenobiotics can interact with cytochromes P450 (CYPs), resulting in drug-drug interactions, but CYPs can also contribute to drug-disease interactions, especially in the case of inflammation, which downregulates CYP activities through pretranscriptional and posttranscriptional mechanisms."( Prediction of cytochromes P450 3A and 2C19 modulation by both inflammation and drug interactions using physiologically based pharmacokinetics.
Daali, Y; Desmeules, JA; Lenoir, C; Niederer, A; Rollason, V; Samer, CF, 2022
)
0.72
"Human cytochrome P450 CYP3A4 is involved in the processing of more than 35% of current pharmaceuticals and therefore is responsible for multiple drug-drug interactions (DDI)."( Midazolam as a Probe for Heterotropic Drug-Drug Interactions Mediated by CYP3A4.
Camp, T; Denisov, IG; Grinkova, YV; McLean, MA; Sligar, SG, 2022
)
2.16
" Here, we investigate the pharmacokinetic drug-drug interaction potential of trilaciclib."( Pharmacokinetic Drug-Drug Interaction Studies Between Trilaciclib and Midazolam, Metformin, Rifampin, Itraconazole, and Topotecan in Healthy Volunteers and Patients with Extensive-Stage Small-Cell Lung Cancer.
Beelen, A; Curd, L; Goti, V; Horton, JK; Li, C; Sale, M; Tao, W, 2022
)
0.96
"Overall, the drug-drug interaction and safety profiles of trilaciclib in these studies support its continued use in patients with extensive-stage small-cell lung cancer."( Pharmacokinetic Drug-Drug Interaction Studies Between Trilaciclib and Midazolam, Metformin, Rifampin, Itraconazole, and Topotecan in Healthy Volunteers and Patients with Extensive-Stage Small-Cell Lung Cancer.
Beelen, A; Curd, L; Goti, V; Horton, JK; Li, C; Sale, M; Tao, W, 2022
)
0.96
" Understanding potential drug-drug interactions (DDIs) informs proper dosing when co-administering tucatinib with other therapies."( Evaluation of Safety and Clinically Relevant Drug-Drug Interactions with Tucatinib in Healthy Volunteers.
Abdulrasool, LI; Endres, CJ; Lee, A; Mayor, JG; Rustia, EL; Sun, H; Topletz-Erickson, A; Walker, L, 2022
)
0.72
" It is metabolized via cytochrome P450 (CYP) 3A, but little is known about the drug-drug interactions of JNJ-56136379 when combined with drugs that inhibit or are metabolized by CYP3A."( Drug-Drug Interactions With the Hepatitis B Virus Capsid Assembly Modulator JNJ-56136379 (Bersacapavir).
Biermer, M; Biewenga, J; Hillewaert, V; Kakuda, TN; Nangosyah, J; Palmer, M; Rasschaert, F; Snoeys, J; Talloen, W; Vandenbossche, J; Yogaratnam, J, 2022
)
0.72
"To evaluate the effects of IM and IV administration of alfaxalone alone and in combination with medetomidine, midazolam, or both on key stress-related neurohormonal and metabolic changes in isoflurane-anesthetized cats undergoing ovariohysterectomy or castration."( A randomized clinical trial on effects of alfaxalone combined with medetomidine and midazolam in preventing stress-related neurohormonal and metabolic responses of isoflurane-anesthetized cats undergoing surgery.
Hikasa, Y; Kamohara, H; Kamohara, T, 2022
)
1.16
"Compared with baseline concentrations, plasma adrenaline and noradrenaline concentrations decreased during anesthesia in cats premedicated with alfaxalone alone and in combination with medetomidine."( A randomized clinical trial on effects of alfaxalone combined with medetomidine and midazolam in preventing stress-related neurohormonal and metabolic responses of isoflurane-anesthetized cats undergoing surgery.
Hikasa, Y; Kamohara, H; Kamohara, T, 2022
)
0.95
"The US Food and Drug Administration (FDA) guidance has recommended several model-based predictions to determine potential drug-drug interactions (DDIs) mediated by cytochrome P450 (CYP) induction."( Beyond the Michaelis-Menten: Accurate Prediction of Drug Interactions Through Cytochrome P450 3A4 Induction.
Chae, JW; Kim, JK; Kim, SK; Song, YM; Tran, QT; Vu, NT; Yun, HY, 2023
)
0.91
" A phase 1 drug-drug interaction study was conducted to evaluate the effect of multiple-dose administration of brigatinib on the single-dose pharmacokinetics of midazolam, a sensitive cytochrome P450 3A substrate."( A Phase 1 Drug-Drug Interaction Study Between Brigatinib and the CYP3A Substrate Midazolam in Patients With ALK-Positive or ROS1-Positive Solid Tumors.
D'Arcangelo, M; Felip, E; Garrido, P; Gupta, N; Hanley, MJ; Vranceanu, F; Ye, M; Zhu, J, 2023
)
1.33
"To evaluate the adverse effects and particularly the anesthetic effect of low-dose etomidate combined with oxycodone and midazolam in endoscopic injection sclerotherapy."( Application of low-dose etomidate combined with oxycodone and midazolam in endoscopic injection sclerotherapy.
Cao, Y; Hao, S; Quan, Z; Yao, J; Zhou, C, 2023
)
1.36
"Low-dose etomidate combined with oxycodone and midazolam for endoscopic injection sclerotherapy could reduce the incidence of hypoxia without increasing the incidence of complications."( Application of low-dose etomidate combined with oxycodone and midazolam in endoscopic injection sclerotherapy.
Cao, Y; Hao, S; Quan, Z; Yao, J; Zhou, C, 2023
)
1.41
" Based on nonclinical in vitro characterization of gepotidacin metabolism, two phase I studies were conducted in healthy participants to investigate clinical drug-drug interactions (DDIs)."( Clinical assessment of gepotidacin (GSK2140944) as a victim and perpetrator of drug-drug interactions via CYP3A metabolism and transporters.
Barth, A; Brimhall, DB; Dumont, EF; Nguyen, D; Perry, CR; Shabbir, S; Srinivasan, M; Swift, B; Thomas, S; Zamek-Gliszczynski, MJ, 2023
)
0.91
" A tiered approach was applied to understand the CYP3A victim and perpetrator drug-drug interaction (DDI) potential for vonoprazan."( Tiered approach to evaluate the CYP3A victim and perpetrator drug-drug interaction potential for vonoprazan using PBPK modeling and clinical data to inform labeling.
Jones, HM; Leifke, E; Michon, I; Mulford, DJ; Ramsden, D; Scarpignato, C; Smith, N; Zhang, L, 2023
)
0.91
" Phase I studies investigated the drug-drug interactions of futibatinib with itraconazole (a dual P-gp and strong CYP3A inhibitor), rifampin (a dual P-gp and strong CYP3A inducer), or midazolam (a sensitive CYP3A substrate) in healthy adult participants."( Evaluation of the Cytochrome P450 3A and P-glycoprotein Drug-Drug Interaction Potential of Futibatinib.
Benhadji, KA; Gao, L; He, Y; Hunt, A; Mina, M; Sonnichsen, D; Takenaka, T; Yamamiya, I, 2023
)
1.1
"Management of drug-drug interactions (DDIs) for ensitrelvir, a novel 3-chymotrypsin-like protease inhibitor of SARS-CoV-2 infection is crucial."( Evaluation of the Drug-Drug Interaction Potential of Ensitrelvir Fumaric Acid with Cytochrome P450 3A Substrates in Healthy Japanese Adults.
Fukuhara, T; Kubota, R; Kuwata, A; Matsuo, Y; Matsuzaki, T; Shimizu, R; Sonoyama, T, 2023
)
0.91
" Either dexamethasone, prednisolone, or midazolam was administered alone (Day - 2) or in combination with ensitrelvir (Day 5) in each of the cohorts."( Evaluation of the Drug-Drug Interaction Potential of Ensitrelvir Fumaric Acid with Cytochrome P450 3A Substrates in Healthy Japanese Adults.
Fukuhara, T; Kubota, R; Kuwata, A; Matsuo, Y; Matsuzaki, T; Shimizu, R; Sonoyama, T, 2023
)
1.18
"To test the effectiveness of low-dose midazolam combined with verbal sedation during TEE."( Efficacy of Low Doses of Midazolam in Combination with Verbal Sedation during Transesophageal Echocardiography.
Haitov, Z; Leitman, M; Pilcha, I; Tyomkin, V, 2023
)
1.48
" All patients received local pharyngeal anesthesia and low doses of midazolam combined with verbal sedation."( Efficacy of Low Doses of Midazolam in Combination with Verbal Sedation during Transesophageal Echocardiography.
Haitov, Z; Leitman, M; Pilcha, I; Tyomkin, V, 2023
)
1.45
" In 6% of the patients, low dose midazolam in combination with verbal sedation was insufficient and propofol was administrated."( Efficacy of Low Doses of Midazolam in Combination with Verbal Sedation during Transesophageal Echocardiography.
Haitov, Z; Leitman, M; Pilcha, I; Tyomkin, V, 2023
)
1.49
"In most patients, TEE can be conducted easily using low-dose midazolam combined with verbal sedation."( Efficacy of Low Doses of Midazolam in Combination with Verbal Sedation during Transesophageal Echocardiography.
Haitov, Z; Leitman, M; Pilcha, I; Tyomkin, V, 2023
)
1.46
"To observe the efficacy and safety of intranasal dexmedetomidine combined with midazolam in cranial magnetic resonance imaging of children."( Clinical Analysis of Intranasal Dexmedetomidine Combined With Midazolam in Pediatric Cranial Magnetic Resonance Examinations.
He, L; Li, SJ; Ming, L; Shen, KF; Wu, ZF; Zhang, YP, 2023
)
1.38
" For children aged 2-6 years with dental anxiety who require dental surgery, anesthesiologists may consider using midazolam oral solution combined with esketamine nasal drops for noninvasive sedation after a preoperative anxiety scale evaluation."( Intranasal esketamine combined with oral midazolam provides adequate sedation for outpatient pediatric dental procedures: a prospective cohort study.
Chen, S; Chen, Z; Liao, J; Ran, H; Wang, J; Yu, C; Zeng, J; Zhao, N, 2023
)
1.39
"Itraconazole is a potent inhibitor of cytochrome P450 3A4 (CYP3A4), associated with numerous drug-drug interactions (DDI)."( Evaluation of the Potential for Drug-Drug Interactions with Inhaled Itraconazole Using Physiologically Based Pharmacokinetic Modelling, Based on Phase 1 Clinical Data.
Bergagnini-Kolev, M; Curran, AK; Kane, K; Templeton, IE, 2023
)
0.91
" The trial also examined how palovarotene might interact with other treatments that are broken down by the body in the same way as palovarotene."( The Pharmacokinetic Profile of Palovarotene: An Open-Label Phase I Trial Investigating the Effect of Food and Potential for Drug-Drug Interaction in Healthy Participants.
Dube, L; Le Quan Sang, KH; Marino, R; Ogier, J, 2023
)
0.91

Bioavailability

Saquinavir increased the bioavailability of oral midazolam from 41% to 90%. The mean (+sd) time to peak absorption rate was also shorter.

ExcerptReferenceRelevance
" The results are consistent with an estimated mean bioavailability of 55%."( Pharmacokinetics of midazolam in children: comparative study of intranasal and intravenous administration.
Delaunay, L; Murat, I; Olive, G; Pons, G; Rey, E; Richard, MO; Saint-Maurice, C, 1991
)
0.6
" The absolute bioavailability of intramuscular midazolam was calculated in 11 patients as 87 +/- 18%."( A comparative pharmacokinetic study of intravenous and intramuscular midazolam in patients with epilepsy.
Bell, DM; Cromarty, J; Dhillon, S; Oxley, JR; Patsalos, PN; Richards, G; Sander, JW,
)
0.62
" This finding is in keeping with pharmacokinetics showing a tmax of intranasal midazolam of 11 minutes and a bioavailability of 51% in children (10)."( [Intranasal premedication of young children using midazolam (Dormicum). Clinical experience].
Bünz, R; Gossler, M, 1991
)
0.76
"The purpose of this investigation was to compare the rate of absorption and clearance time of midazolam (Versed) when administered by the submucosal (SM) route), and the intramuscular (IM) route in ten healthy adult volunteers, ranging in age from 25 to 35 years."( Absorption and elimination of midazolam by submucosal and intramuscular routes.
Alfonzo-Echeverri, E; George, W; Troutman, KC,
)
0.64
" With a bioavailability of 92% (IV), 82-91% (IM) and 50-52% "per os", the CNS effects of MDZ are similar in all three ways."( [Midazolam in anesthesiology].
Arroyo, JL; García-Pedrajas, F,
)
1.04
" Significant changes in the Cmax, tmax, and AUC parameters for both midazolam and its metabolite were seen when midazolam was ingested one hour after a meal: There was a delayed and reduced rate of absorption as well as a small reduction in the extent of absorption."( Influence of food on midazolam absorption.
Bornemann, LD; Chen, SS; Crews, T; Patel, IH; Twardak, S, 1986
)
0.83
" After both oral and parenteral administration, midazolam has a fast absorption rate and is rapidly excreted, with a half-life of only about 2 hours."( Midazolam: the first water-soluble benzodiazepine. Pharmacology, pharmacokinetics and efficacy in insomnia and anesthesia.
Kanto, JH,
)
1.83
" The rectal bioavailability was 40-65% (mean 52%) and the terminal half-life was 114-305 min (mean 161 min)."( Pharmacokinetics of midazolam and alpha-hydroxy-midazolam following rectal and intravenous administration.
Clausen, TG; Crevoisier, C; Dixon, JS; Hansen, PB; Larsen, F; Rasmussen, SN; Wolff, J, 1988
)
0.6
"The extent of bioavailability of midazolam following sublingual and oral administration were evaluated."( Relative bioavailability of midazolam following sublingual versus oral administration in healthy volunteers.
Fujii, J; Inotsume, N; Nakano, M, 1988
)
0.85
" We conclude that: midazolam kinetics are characterized by rapid absorption, but incomplete bioavailability and rapid elimination, midazolam intravenously may lower blood pressure significantly, and the level of consciousness correlates poorly with the degree of memory impairment."( Midazolam: kinetics and effects on memory, sensorium, and haemodynamics.
Chouinard, G; East, S; Kreeft, JH; Langlois, S; Ogilvie, RI; Ross-Chouinard, A, 1987
)
2.04
" The mean absolute bioavailability is 91% for the hydrochloride and 82% for the lactate."( [Relation between the clinical effect and the pharmacokinetics of midazolam following i.m. and i.v. administration/2nd comm.: Pharmacokinetical aspects (author's transl)].
Crevoisier, C; Eckert, M; Heizmann, P; Thurneysen, DJ; Ziegler, WH, 1981
)
0.5
" Administration of the H2-receptor blocker significantly increased bioavailability of the benzodiazepine and resulted in higher plasma levels for the first 6 h after taking midazolam."( Ranitidine influences the uptake of oral midazolam.
Collier, PS; Dundee, JW; Elwood, RJ; Hildebrand, PJ, 1983
)
0.73
"The pharmacokinetic behaviour and the bioavailability of midazolam were investigated in six volunteers after intravenous (0."( Pharmacokinetics and bioavailability of midazolam in man.
Eckert, M; Heizmann, P; Ziegler, WH, 1983
)
0.78
" Temazepam bioavailability after oral administration is unchanged after either H2 receptor antagonist, or after the emulsion antacid."( The influence of H2 receptor antagonists on the plasma concentrations of midazolam and temazepam.
Collier, PS; Dundee, JW; Elliott, P; Elwood, RJ, 1984
)
0.5
"7% unbound), or oral bioavailability (38% vs."( Effect of age, gender, and obesity on midazolam kinetics.
Abernethy, DR; Greenblatt, DJ; Harmatz, JS; Limjuco, RA; Locniskar, A; Shader, RI, 1984
)
0.54
"024) than during part B(710+/-241 ml/min), bioavailability did not change (range 37 to 44%)."( Physiologic and temporal variation in hepatic elimination of midazolam.
Klotz, U; Ziegler, G, 1982
)
0.51
"Pretreatment with grapefruit juice is associated with increased bioavailability and changes in the pharmacodynamics of midazolam that may be clinically important, particularly in patients with other causes for increased midazolam bioavailability such as advanced age, cirrhosis of the liver, and administration of other inhibitors of cytochrome P450."( Interaction between grapefruit juice and midazolam in humans.
Ha, HR; Krähenbühl, S; Kupferschmidt, HH; Meier, PJ; Ziegler, WH, 1995
)
0.77
" The switch to oral agents must take into consideration the differences in potency, half-life, and oral bioavailability between the agents."( Outpatient therapy of iatrogenic drug dependency following prolonged sedation in the pediatric intensive care unit.
Deshpande, JK; Gregory, DF; Tobias, JD, 1994
)
0.29
" The metabolic acidosis associated with the seizures may have caused hypotension by direct cardiotoxicity, an increase in bioavailability of tricyclic antidepressant because of changes in protein binding, an alteration of the effects of tricyclic antidepressant on cardiac membrane sodium channels, or a combination of these mechanisms."( Recurrent hypotension immediately after seizures in nortriptyline overdose.
Bell, A; Gaynor, B; Lipper, B, 1994
)
0.29
"Studies in humans in vivo have demonstrated that substances found in grapefruit juice may increase the bioavailability of dihydropyridine derivatives as a result of the inhibition of liver enzyme activities by flavonoids found in grapefruit."( In vitro inhibition of midazolam and quinidine metabolism by flavonoids.
Chen, J; Follath, F; Freiburghaus, AU; Ha, HR; Leuenberger, PM, 1995
)
0.6
" Despite complete oral absorption, measured oral bioavailability was on average about 50% less than that predicted on the assumption that only the liver contributed to first-pass metabolism."( Oral first-pass elimination of midazolam involves both gastrointestinal and hepatic CYP3A-mediated metabolism.
Kunze, KL; O'Shea, D; Paine, MF; Perkins, JD; Shen, DD; Thummel, KE; Wilkinson, GR, 1996
)
0.58
" The mean (+sd) time to peak absorption rate was also shorter for midazolam (9 +/- 2 vs 13."( Comparative absorption kinetics of intramuscular midazolam and diazepam.
Dyck, JB; Hung, OR; Shafer, SL; Stanski, DR; Varvel, J, 1996
)
0.79
" The mean absolute bioavailability was route-dependent: 39."( Pharmacokinetics and bioavailability of midazolam after intravenous, subcutaneous, intraperitoneal and oral administration under a chronic food-limited regimen: relating DRL performance to pharmacokinetics.
Lau, CE; Ma, F; Smith, C; Wang, Y, 1996
)
0.56
"After oral administration, the bioavailability and clearance of midazolam were not affected by sauna bathing, nor was there a significant difference in alpha-hydroxy midazolam plasma concentration or the alpha-hydroxy midazolam/midazolam AUC-ratio between the sessions."( Effects of heat exposure in a Finnish sauna on the pharmacokinetics and metabolism of midazolam.
Idänpään-Heikkilä, JJ; Olkkola, KT; Seppälä, T; Vanakoski, J, 1996
)
0.76
"Some drugs demonstrate a significantly greater (up to 3-fold) mean oral bioavailability on coadministration with grapefruit juice."( Drug interactions with grapefruit juice.
Ameer, B; Weintraub, RA, 1997
)
0.3
" Collectively, these results demonstrate that the upper small intestine serves as the major site for intestinal CYP3A-mediated first-pass metabolism and provides a rationale for interindividual differences in oral bioavailability for some CYP3A substrates."( Characterization of interintestinal and intraintestinal variations in human CYP3A-dependent metabolism.
Fisher, JM; Khalighi, M; Kunze, KL; Marsh, CL; Paine, MF; Perkins, JD; Shen, DD; Thummel, KE, 1997
)
0.3
"The aim of this study was to determine the bioavailability and absorption kinetics of midazolam given as an intranasal (i."( Pharmacokinetics of midazolam given as an intranasal spray to adult surgical patients.
Björkman, S; Idvall, J; Rigemar, G, 1997
)
0.84
" This gave a mean midazolam bioavailability of 74."( Midazolam pharmacokinetics following intravenous and buccal administration.
Alincic, S; Schwagmeier, R; Striebel, HW, 1998
)
2.08
"The pharmacokinetic data presented in this study demonstrate a high bioavailability and reliable plasma concentrations following buccal midazolam."( Midazolam pharmacokinetics following intravenous and buccal administration.
Alincic, S; Schwagmeier, R; Striebel, HW, 1998
)
1.95
"Delayed absorption and low rectal bioavailability may explain these data."( An approach for dose finding of drugs in infants: sedation by midazolam studied using the continual reassessment method.
Chevret, S; D'Athis, P; Fabre, E; Olive, G; Piechaud, JF; Pons, G; Rey, E; Vauzelle-Kervoedan, F, 1998
)
0.54
" Concomitant intake of rifampicin (600 mg/die) induced especially the presystemic (prehepatic) metabolism of verapamil so that oral bioavailability approached zero and PD effects almost diminished."( Effect of age on pharmacokinetics and pharmacodynamics in man.
Klotz, U, 1998
)
0.3
" Co-administered ketoconazole (2 micromol) significantly increased the bioavailability to 53% and 7%, respectively, in these rats."( Dose-dependent intestinal and hepatic first-pass metabolism of midazolam, a cytochrome P450 3A substrate with differently modulated enzyme activity in rats.
Higashikawa, F; Kaneda, T; Kato, A; Murakami, T; Takano, M, 1999
)
0.54
" The absolute bioavailability was close to 100%."( Pharmacokinetics of midazolam: comparison of sublingual and intravenous routes in rabbit.
Barthélémy, C; Brunet, C; Cazin, JC; Cazin, M; Chatelier, D; Dine, T; Gressier, B; Luyckx, M; Odou, P; Robert, H,
)
0.45
"Saquinavir increased the bioavailability of oral midazolam from 41% to 90% (P < ."( Effect of saquinavir on the pharmacokinetics and pharmacodynamics of oral and intravenous midazolam.
Ahonen, J; Neuvonen, PJ; Olkkola, KT; Palkama, VJ, 1999
)
0.78
"To determine the intestinal and hepatic contribution to the bioavailability of midazolam with use of the CYP3A inhibitor ketoconazole."( Differentiation of intestinal and hepatic cytochrome P450 3A activity with use of midazolam as an in vivo probe: effect of ketoconazole.
Greenblatt, DJ; Tsunoda, SM; Velez, RL; von Moltke, LL, 1999
)
0.76
" Total bioavailability increased from 25% to 80% (P < ."( Differentiation of intestinal and hepatic cytochrome P450 3A activity with use of midazolam as an in vivo probe: effect of ketoconazole.
Greenblatt, DJ; Tsunoda, SM; Velez, RL; von Moltke, LL, 1999
)
0.53
" The significance of the intestinal first pass effect for the bioavailability of the three model drugs, midazolam, cyclosporin and digoxin, has been reviewed."( [Drug metabolism in the small intestine--the significance for biological availability].
Andersen, VC; Sonne, J, 2000
)
0.52
"The quantitative structure-bioavailability relationship of 232 structurally diverse drugs was studied to evaluate the feasibility of constructing a predictive model for the human oral bioavailability of prospective new medicinal agents."( QSAR model for drug human oral bioavailability.
Topliss, JG; Yoshida, F, 2000
)
0.31
"The oral bioavailability of midazolam was about equally determined by intestinal and hepatic extraction with CYP3A activity at the former site exhibiting greater variability."( CYP3A activity in African American and European American men: population differences and functional effect of the CYP3A4*1B5'-promoter region polymorphism.
Hall, JM; Stein, CM; Wandel, C; Wilkinson, GR; Witte, JS; Wood, AJ, 2000
)
0.6
"Effective cyclosporine therapy is confounded by large interindividual differences in oral bioavailability and a narrow therapeutic window."( Can oral midazolam predict oral cyclosporine disposition?
Davis, CL; Marsh, CL; Paine, MF; Raisys, VA; Shen, DD; Thummel, KE, 2000
)
0.72
" The possibility also existed for inhibition of intestinal and hepatic CYP3A4 by RG 12525 to reduce "first-pass" metabolism and increase absolute bioavailability of CYP3A4 substrates orally coadministered."( Lack of correlation between in vitro inhibition of CYP3A-mediated metabolism by a PPAR-gamma agonist and its effect on the clinical pharmacokinetics of midazolam, an in vivo probe of CYP3A activity.
Fayer, JL; Kirkesseli, S; Luo, Y; Sidhu, R; Stevens, JC; Zannikos, PN, 2001
)
0.51
" Absolute oral bioavailability and its associated gastrointestinal and hepatic extraction ratios also showed no statistically significant interracial differences."( CYP3A activity in European American and Japanese men using midazolam as an in vivo probe.
Asoh, M; Kobayashi, S; Mizorogi, Y; Nakura, H; Shirai, H; Tateishi, T; Thummel, KE; Watanabe, M; Wilkinson, GR, 2001
)
0.55
" This results in increased blood plasma levels of midazolam of 56% and increased midazolam bioavailability of 35%."( Oral midazolam-grapefruit juice drug interaction.
Goho, C,
)
0.9
"It has been suggested that cytochrome P450 3A4 (CYP3A4) and MDR1 P-glycoprotein (P-gp) act synergistically to limit the bioavailability of orally administered agents."( Comparative studies to determine the selective inhibitors for P-glycoprotein and cytochrome P4503A4.
Achira, M; Ito, K; Sugiyama, Y; Suzuki, H, 1999
)
0.3
" Eligible study patients were enrolled into one of three study arms: Arm I (midazolam/metabolite pharmacokinetic evaluation after oral administration of a syrup formulation), Arm II (the absolute bioavailability of midazolam syrup), and Arm III (midazolam and metabolite pharmacokinetics after IV administration)."( The single-dose pharmacokinetics of midazolam and its primary metabolite in pediatric patients after oral and intravenous administration.
Akbari, B; Blumer, JL; Kearns, GL; Khoo, KC; Pou, S; Reed, MD; Rodarte, A, 2001
)
0.82
" The absolute bioavailability of midazolam in the nasal formulation was determined to be 64 +/- 19% (mean +/- standard deviation)."( Intranasal administration of midazolam in a cyclodextrin based formulation: bioavailability and clinical evaluation in humans.
Fjalldal, O; Gudmundsdottir, H; Loftsson, T; Masson, M; Sigurjonsdottir, JF; Stefansson, E, 2001
)
0.88
" Rapid uptake and high bioavailability were demonstrated."( Pharmacokinetics and pharmacodynamics of midazolam administered as a concentrated intranasal spray. A study in healthy volunteers.
Brekelmans, GJ; de Haan, GJ; Edelbroek, PM; Jonker, DM; Knoester, PD; Van Der Hoeven, RT; Vermeij, TA, 2002
)
0.58
"Grapefruit juice inhibits CYP3A4 in the intestinal wall leading to a reduced intestinal first pass metabolism and thereby an increased oral bioavailability of certain drugs."( Intestinal first pass metabolism of midazolam in liver cirrhosis --effect of grapefruit juice.
Andersen, V; Larsen, NE; Larsen, S; Pedersen, N; Sonne, J, 2002
)
0.59
" The objective of the present study was to determine the absolute bioavailability of subcutaneous midazolam and its pharmacokinetics in young, healthy, male volunteers."( Absolute bioavailability of midazolam after subcutaneous administration to healthy volunteers.
Dostert, P; Homery, MC; Marquet, P; Montestruc, F; Pecking, M; Wodey, E, 2002
)
0.83
"This study has shown that subcutaneous midazolam has excellent bioavailability and that administration of midazolam by this route could be preferable when the intravenous route is inappropriate."( Absolute bioavailability of midazolam after subcutaneous administration to healthy volunteers.
Dostert, P; Homery, MC; Marquet, P; Montestruc, F; Pecking, M; Wodey, E, 2002
)
0.88
"There were no significant differences in bioavailability (0."( Application of semisimultaneous midazolam administration for hepatic and intestinal cytochrome P450 3A phenotyping.
Amico, JA; Chaves-Gnecco, D; Frye, RF; Kroboth, PD; Lee, JI; Wilson, JW, 2002
)
0.6
"Consumption of typical quantities of grapefruit juice (GFJ) increases the oral bioavailability of several CYP3A4 substrates without affecting their elimination, consistent with selective inhibition of intestinal but not hepatic CYP3A4."( Exposure-dependent inhibition of intestinal and hepatic CYP3A4 in vivo by grapefruit juice.
Burke, JP; Dorval, EP; Gillen, LP; Greenberg, HE; Hauck, WW; Pequignot, E; Veronese, ML; Waldman, SA, 2003
)
0.32
" No change in the absorption rate or extraction ratio (ER) for midazolam was observed when P-gp was inhibited with GG918."( CYP3A4-transfected Caco-2 cells as a tool for understanding biochemical absorption barriers: studies with sirolimus and midazolam.
Benet, LZ; Christians, U; Cummins, CL; Jacobsen, W, 2004
)
0.77
" In conclusion, in individuals with moderate alcohol consumption, there was no alteration in the hepatic CYP3A activity, but the reduced midazolam oral bioavailability suggests that moderate alcohol consumption may cause intestinal CYP3A induction."( Activity of CYP2E1 and CYP3A enzymes in adults with moderate alcohol consumption: a comparison with nonalcoholics.
Chalasani, N; Gorski, JC; Hall, SD; Kolwankar, D; Liangpunsakul, S; Pinto, A, 2005
)
0.53
" When ketoconazole was given orally to the animals, in conjunction with midazolam, the extraction ratio in the liver decreased from 93% to 77% in the control rats, and the bioavailability of midazolam increased to 23%."( Assessment of the hepatic and intestinal first-pass metabolism of midazolam in a CYP3A drug-drug interaction model rats.
Baba, T; Kanazu, T; Koike, M; Okamura, N; Yamaguchi, Y, 2005
)
0.8
" The bioavailability of oral midazolam was increased from 31% to 84% (P < ."( Effect of voriconazole on the pharmacokinetics and pharmacodynamics of intravenous and oral midazolam.
Laine, K; Leino, K; Neuvonen, PJ; Olkkola, KT; Saari, TI; Valtonen, M, 2006
)
0.85
"On the basis of in vitro studies indicating that ursodeoxycholic acid (UDCA) is a cytochrome P450 (CYP) 3A4 inducer and a pregnane X receptor activator and because the pregnane X receptor is a transcriptional regulator of multidrug resistance 1 (MDR1)/P-glycoprotein (P-gp), we postulated that UDCA might decrease the bioavailability of CYP3A4 and P-gp probe drugs in humans."( Effects of ursodeoxycholic acid on P-glycoprotein and cytochrome P450 3A4-dependent pharmacokinetics in humans.
Becquemont, L; Burk, O; Drescher, S; Eichelbaum, M; Fromm, MF; Glaeser, H; Heinkele, G; Hitzl, M; Hofmann, U; Murdter, TE; Schaefer, C; Simon, N; Verstuyft, C, 2006
)
0.33
"The bioavailability (F) of midazolam in cynomolgus monkeys (0."( Marked species differences in the bioavailability of midazolam in cynomolgus monkeys and humans.
Akabane, T; Sakuda, S; Teramura, T, 2006
)
0.88
"Absolute bioavailability studies in humans are not routinely performed as part of the drug registration process."( The use of isotopes in the determination of absolute bioavailability of drugs in humans.
Garner, RC; Lappin, G; Rowland, M, 2006
)
0.33
" Apparently bidirectional delivery did not increase systemic bioavailability of midazolam."( Intranasal midazolam: a comparison of two delivery devices in human volunteers.
Dale, O; Djupesland, PG; Hjorth Tønnesen, H; Holand, T; Kaasa, S; Klepstad, P; Loftsson, T; Nilsen, T, 2006
)
0.95
"Oral bioavailability of some drugs is substantially lower in cynomolgus monkeys than in various other species, including humans."( Asymmetric intestinal first-pass metabolism causes minimal oral bioavailability of midazolam in cynomolgus monkey.
Amano, N; Fujita, H; Kato, Y; Kimura, Y; Kubo, Y; Nishimura, T; Ono, M; Tsuji, A, 2007
)
0.56
" Human oral bioavailability is an important pharmacokinetic property, which is directly related to the amount of drug available in the systemic circulation to exert pharmacological and therapeutic effects."( Hologram QSAR model for the prediction of human oral bioavailability.
Andricopulo, AD; Moda, TL; Montanari, CA, 2007
)
0.34
" In addition, the effects of DHA on in vitro midazolam metabolism in rat intestinal microsomes and on midazolam bioavailability in rats were examined."( Inhibitory effect of docosahexaenoic acid (DHA) on the intestinal metabolism of midazolam: in vitro and in vivo studies in rats.
Hirunpanich, V; Murakoso, K; Sato, H, 2008
)
0.83
" Hence, it was speculated that quercetin may influence the bioavailability of pioglitazone, which could be particularly crucial, as any increment in its plasma levels may raise safety concerns."( Quercetin pretreatment increases the bioavailability of pioglitazone in rats: involvement of CYP3A inhibition.
Bansod, KU; Dixit, PV; Kumar, V; Umathe, SN; Wanjari, MM, 2008
)
0.35
"The data support an alteration in bioavailability due to an AMD070-mediated inhibition of presystemic metabolism, though an intestinal P-glycoprotein effect could also be contributing."( Pharmacokinetic effect of AMD070, an Oral CXCR4 antagonist, on CYP3A4 and CYP2D6 substrates midazolam and dextromethorphan in healthy volunteers.
Becker, S; Calandra, GB; Chee, P; Everts, S; Hendrix, CW; MacFarland, RT; Nyunt, MM; Scarborough, R, 2008
)
0.57
" Comparative bioavailability of midazolam, estimated by the ratio (nebulized:nasal) of area under the 60 min plasma concentration curve, was 1:2."( Plasma concentrations and sedation scores after nebulized and intranasal midazolam in healthy volunteers.
Berry, D; McCormick, AS; Thomas, PW; Thomas, VL, 2008
)
0.86
"The presence of cytochrome P450 enzymes in the small bowel results in the reduced bioavailability of several drugs."( Intestinal metabolism and transport of drugs in children: the effects of age and disease.
Johnson, TN; Thomson, M, 2008
)
0.35
" Therefore, RH40 might be used to prepare drug formulations in pharmaceutical industry and would increase the bioavailability of some drugs transformed by CYP3As and further lead to significant clinical pharmacologic effects."( [Effect of polyoxyl ether analogous surfactants on the activity of cytochromes P450 3A in rats in vivo].
Cao, L; Li, G; Qiu, J; Ren, XH; Si, LQ; Yao, J, 2008
)
0.35
" The study has shown that a single administration of UDCA in rats induces significant hepatic CYP3A activity and increases significantly the oral bioavailability of midazolam."( Effect of ursodeoxycholic acid on the pharmacokinetics of midazolam and CYP3A in the liver and intestine of rats.
Ito, Y; Kurosawa, S; Uchida, S; Yamada, S, 2009
)
0.79
" Women had higher weight-corrected systemic and oral clearance than men, but dose-adjusted AUC and bioavailability differences were not observed between sexes."( Association of genotypes of the CYP3A cluster with midazolam disposition in vivo.
Gorski, CJ; Hall, SD; Jin, Y; Kim, S; Li, L; Marunde, RL; Miao, J; Quinney, S; Radovich, M, 2009
)
0.6
"SchE can markedly increase the oral bioavailability of midazolam in healthy volunteers."( Effects of Schisandra sphenanthera extract on the pharmacokinetics of midazolam in healthy volunteers.
Li, Q; Wu, XC; Xin, HW; Xiong, L; Yu, AR, 2009
)
0.83
"Oral bioavailability (F) is a product of fraction absorbed (Fa), fraction escaping gut-wall elimination (Fg), and fraction escaping hepatic elimination (Fh)."( Physicochemical space for optimum oral bioavailability: contribution of human intestinal absorption and first-pass elimination.
Chang, G; El-Kattan, A; Miller, HR; Obach, RS; Rotter, C; Steyn, SJ; Troutman, MD; Varma, MV, 2010
)
0.36
" The following pharmacokinetic parameters were included for the analysis: MDZ oral and systemic clearance, area under the concentration-time curve (AUC) of oral and intravenous MDZ, MDZ oral bioavailability (F), and MDZ gastrointestinal extraction (E(G))."( Sex-dependent differences in cytochrome P450 3A activity as assessed by midazolam disposition in humans: a meta-analysis.
Hu, ZY; Zhao, YS, 2010
)
0.59
"Intestinal first-pass metabolism may contribute to low oral drug bioavailability and drug-drug interactions, particularly for CYP3A substrates."( Prediction of human intestinal first-pass metabolism of 25 CYP3A substrates from in vitro clearance and permeability data.
Galetin, A; Gertz, M; Harrison, A; Houston, JB, 2010
)
0.36
" Rhei Rhizoma extract (100 microg/ml) significantly suppressed the CYP3A-mediated 6beta-hydroxylation of testosterone in hepatic microsomes, and increased the extent of bioavailability of midazolam, a typical CYP3A substrate, in rats."( Interaction of Rhei Rhizoma extract with cytochrome P450 3A and efflux transporters in rats.
Akashi, H; Kida, M; Mori, M; Mori, N; Murakami, T; Yokooji, T; Yoshihara, S, 2010
)
0.55
"Mean bioavailability of midazolam after nasal administration ranged from 76 +/- 12% to 92 +/- 15%."( Pharmacokinetics and pharmacodynamics of nasally delivered midazolam.
Briellmann, TA; Drewe, J; Dussy, FE; Fröhlich, J; Haschke, M; Hofmann, S; Imanidis, G; Krähenbühl, S; Surber, C; Suter, K; Witschi, R, 2010
)
0.91
" In vivo experiments conducted in rabbits further confirmed that in situ nasal gels provided better bioavailability of midazolam than the gels prepared from synthetic mucoadhesive polymers."( Development and characterization of mucoadhesive in situ nasal gel of midazolam prepared with Ficus carica mucilage.
Bandyopadhyay, AK; Basu, S, 2010
)
0.8
" Collectively, these results obtained from the present study demonstrated that P123 and F127 were capable of inhibiting the intestinal P-gp activity, but had little or no effect on intestinal cytochrome P450 3A activity, indicating that P123 and F127 can potentially be used as pharmaceutical ingredients to improve the oral bioavailability of coadministered P-gp substrates via P-gp efflux pump inhibition."( Effect of pluronic P123 and F127 block copolymer on P-glycoprotein transport and CYP3A metabolism.
Guan, Y; Huang, J; Li, G; Qiu, J; Si, L; Xu, J; Zuo, L, 2011
)
0.37
" The bioavailability of IN midazolam was 82%."( Pharmacokinetics and tolerability of nasal versus intravenous midazolam in healthy Dutch volunteers: a single-dose, randomized-sequence, open-label, 2-period crossover pilot study.
de Krom, MC; Fiddelers, AA; Marcus, MA; Neef, C; Theunissen, HM; van der Kuy, PH; Veldhorst-Janssen, NM, 2011
)
0.91
" Midazolam displayed rapid sublingual absorption (mean t(max) ≤30min from the liquid formulations and 60 min from the solid formulation) with high absolute bioavailability (>68%) from all evaluated formulations."( The effect of hydroxypropyl-beta-cyclodextrin and sucrose on the sublingual absorption of midazolam in rabbits.
Jarho, P; Järvinen, K; Kaartama, R; Kokki, H; Lehtonen, M; Ranta, VP; Savolainen, J; Toljamo, K; Turunen, E, 2012
)
1.51
" Mean bioavailability of midazolam was 70."( Bioavailability of a novel midazolam gel after intranasal administration in dogs.
Eagleson, JS; Freeman, AC; Kent, M; Nghiem, PP; Platt, SR; Strong, DL; White, CA; Zheng, B, 2012
)
0.98
" AUC and oral bioavailability trended higher October through March compared to April through September."( Intestinal CYP3A4 and midazolam disposition in vivo associate with VDR polymorphisms and show seasonal variation.
Chande, N; Cheng, C; Fan, Y; Gregor, JC; Hall, SD; Kim, RB; Lamba, JK; Qi, A; Schuetz, EG; Thirumaran, RK; Thummel, KE; Urquhart, BL, 2012
)
0.69
" The oromucosal administration of the drug avoids first-pass hepatic metabolism; as a result, it has a higher bioavailability than oral midazolam."( Oromucosal midazolam: a review of its use in pediatric patients with prolonged acute convulsive seizures.
Garnock-Jones, KP, 2012
)
0.97
" The time-course of drug-drug interactions due to clarithromycin will vary with the relative contribution of intestinal and hepatic CYP3A to the clearance and bioavailability of a victim substrate."( Rate of onset of inhibition of gut-wall and hepatic CYP3A by clarithromycin.
Chalasani, N; Gorski, JC; Hall, SD; Hamman, MA; Malireddy, SR; Quinney, SK; Vuppalanchi, R, 2013
)
0.39
"  Ritonavir dramatically increases the bioavailability of a variety of concurrently administered drugs by inhibition of metabolic enzymes and drug transporters."( Analysis of the pharmacokinetic boosting effects of ritonavir on oral bioavailability of drugs in mice.
Banba, H; Takayama, K; Takeda-Morishita, M; Tomaru, A, 2013
)
0.39
" The absolute oral bioavailability of these compounds was lower than 12%."( Development of oseltamivir phosphonate congeners as anti-influenza agents.
Chen, CA; Chen, CL; Cheng, TJ; Cheng, YS; Fang, JM; Hsieh, WC; Hu, OY; Huang, PW; Jan, JT; Lin, WH; Shie, JJ; Tarbet, EB; Wang, SY; Weinheimer, S; Wong, CH, 2012
)
0.38
" However, maximum plasma concentration, half-life, area under the curve, and oral bioavailability were not different."( Pharmacokinetic and pharmacodynamic alterations in the Roux-en-Y gastric bypass recipients.
Chalasani, N; Hall, SD; Jones, DR; Mattar, S; Tandra, S; Vuppalanchi, R, 2013
)
0.39
"4 min with a bioavailability of 50 ± 16%."( The pharmacokinetics of midazolam after intravenous, intramuscular, and rectal administration in healthy dogs.
Messenger, KM; Muñana, KR; Nettifee-Osborne, JA; Papich, MG; Schwartz, M, 2013
)
0.7
" The number of times DEX-P was administered was not a significant factor in the induction of either hepatic or intestinal CYP3A; however, administration of DEX-P multiple times markedly decreased the bioavailability of DEX-P by self-induction of CYP3A."( Time-dependent changes in hepatic and intestinal induction of cytochrome P450 3A after administration of dexamethasone to rats.
Honjo, T; Iwanaga, K; Kakemi, M; Miyazaki, M, 2013
)
0.39
" Bioavailability of midazolam after IM administration was 92%."( Pharmacokinetics and pharmacodynamics of midazolam after intravenous and intramuscular administration in alpacas.
Aarnes, TK; Bednarski, RM; Bei, D; Chen, W; Fry, PR; Hubbell, JA; Lakritz, J; Lerche, P; Liu, Z, 2013
)
0.98
"Midazolam was well absorbed after IM administration, had a short duration of action, and induced moderate levels of sedation in alpacas."( Pharmacokinetics and pharmacodynamics of midazolam after intravenous and intramuscular administration in alpacas.
Aarnes, TK; Bednarski, RM; Bei, D; Chen, W; Fry, PR; Hubbell, JA; Lakritz, J; Lerche, P; Liu, Z, 2013
)
2.1
" These results suggested that 3-day treatment of Sch B could increase concentration and oral bioavailability of drug metabolized by CYP3A."( In vivo effect of Schisandrin B on cytochrome P450 enzyme activity.
Li, WL; Wu, XC; Xin, HW; Yu, AR, 2013
)
0.39
" The systematic underprediction also applies to CYP3A substrates with high bioavailability and long half-lives."( Optimization of drug-drug interaction study design: comparison of minimal physiologically based pharmacokinetic models on prediction of CYP3A inhibition by ketoconazole.
Chien, JY; Hall, SD; Han, B; Mao, J, 2013
)
0.39
"Recently, a new type of interaction has been reported in which fruit juices diminish oral drug bioavailability through inhibition of organic anion-transporting polypeptide (OATP)."( Comparison of inhibitory duration of grapefruit juice on organic anion-transporting polypeptide and cytochrome P450 3A4.
Inui, N; Miyakawa, S; Namiki, N; Takeuchi, K; Tanaka, S; Uchida, S; Watanabe, H, 2013
)
0.39
" Hepatic and intestinal biotransformation of 1α,25(OH)2D3 and modifiers of metabolic capacity could be important determinants of bioavailability in serum and tissues."( Ginsenoside-mediated blockade of 1α,25-dihydroxyvitamin D3 inactivation in human liver and intestine in vitro.
Adomat, H; Chin, MY; Deb, S; Guns, ES, 2014
)
0.4
"Anti-POR siRNA can be used to significantly reduce hepatic metabolism by various CYPs as well as greatly increase the bioavailability of high clearance compounds following an oral dose, thus enabling it to be used as a tool to increase drug exposure in vivo."( siRNA-mediated knockdown of P450 oxidoreductase in rats: a tool to reduce metabolism by CYPs and increase exposure of high clearance compounds.
Brown, D; Burke, RS; Carr, BA; Deshmukh, SV; DiMuzio, J; DiPietro, MA; Eisenhandler, R; Fauty, SE; Gibson, C; Gindy, ME; Hamilton, KA; Hochman, JH; Knemeyer, I; Koeplinger, KA; Kwon, HW; Lifsted, TQ; Menzel, K; Patel, M; Prueksaritanont, T; Pudvah, N; Rearden, P; Rudd, DJ; Seitzer, J; Somasuntharam, I; Strapps, WR; Thompson, CD, 2014
)
0.4
" As CYP3A activity may influence both clearance and oral bioavailability in a distinct manner, in this study the pharmacokinetics of the CYP3A substrate midazolam were evaluated after semi-simultaneous oral and intravenous administration in morbidly obese patients, and compared with healthy volunteers."( Midazolam pharmacokinetics in morbidly obese patients following semi-simultaneous oral and intravenous administration: a comparison with healthy volunteers.
Brill, MJ; Burggraaf, J; Houwink, AP; Knibbe, CA; van Dongen, EP; van Ramshorst, B; van Rongen, A; Wiezer, RJ, 2014
)
2.04
"36 (4 %) L/min], while oral bioavailability was 60 % (13 %) in morbidly obese patients versus 28 % (7 %) in healthy volunteers (P < 0."( Midazolam pharmacokinetics in morbidly obese patients following semi-simultaneous oral and intravenous administration: a comparison with healthy volunteers.
Brill, MJ; Burggraaf, J; Houwink, AP; Knibbe, CA; van Dongen, EP; van Ramshorst, B; van Rongen, A; Wiezer, RJ, 2014
)
1.85
"In morbidly obese patients, systemic clearance of midazolam is unchanged, while oral bioavailability is increased."( Midazolam pharmacokinetics in morbidly obese patients following semi-simultaneous oral and intravenous administration: a comparison with healthy volunteers.
Brill, MJ; Burggraaf, J; Houwink, AP; Knibbe, CA; van Dongen, EP; van Ramshorst, B; van Rongen, A; Wiezer, RJ, 2014
)
2.1
"The relative contribution of hepatic compared with intestinal oxidative metabolism is a crucial factor in drug oral bioavailability and therapeutic efficacy."( Application of a novel regulatable Cre recombinase system to define the role of liver and gut metabolism in drug oral bioavailability.
Gilbert, I; Henderson, CJ; McLaren, AW; McLaughlin, LA; Osuna-Cabello, M; Taylor, M; Wolf, CR, 2015
)
0.42
" Oral bioavailability of a midazolam microdose was 23."( Midazolam microdose to determine systemic and pre-systemic metabolic CYP3A activity in humans.
Burhenne, J; Carls, A; Haefeli, WE; Hohmann, N; Kocheise, F; Mikus, G, 2015
)
2.16
" The pharmacokinetics of four different dosages (iv 5, 10mg/kg and ig 15, 30mg/kg) revealed that XL184 was eliminated slowly, the t1/2 was longer than 10h and the absolute bioavailability was 25."( Pharmacokinetics and tissue distribution model of cabozantinib in rat determined by UPLC-MS/MS.
Chen, H; Hu, L; Lin, F; Ma, J; Wang, S; Wang, X; Wen, C; Zhang, Q, 2015
)
0.42
" After treatment with morroniside, the activity, mRNA and protein expression of CYP3A were significantly induced and the absorbance and bioavailability of midazolam in rats were reduced."( Induction of CYP3A by morroniside in rats.
Li, J; Wang, X; Xiong, S; Zhang, W; Zhang, Z, 2015
)
0.61
" Bioavailability of midazolam was 4% in marmosets, presumably because of contribution of marmoset P450 3A4 expressed in small intestine and liver, with a high catalytic efficiency for midazolam 1'-hydroxylation as evident in the recombinant system."( Simultaneous pharmacokinetics evaluation of human cytochrome P450 probes, caffeine, warfarin, omeprazole, metoprolol and midazolam, in common marmosets (Callithrix jacchus).
Inoue, T; Sasaki, E; Shimizu, M; Toda, A; Uehara, S; Uno, Y; Utoh, M; Yamazaki, H, 2016
)
0.97
"01)], while oral bioavailability was unchanged (0."( The Pharmacokinetics of the CYP3A Substrate Midazolam in Morbidly Obese Patients Before and One Year After Bariatric Surgery.
Brill, MJ; Darwich, AS; Hazebroek, EJ; Knibbe, CA; Rostami-Hodjegan, A; van Dongen, EP; van Ramshorst, B; van Rongen, A, 2015
)
0.68
" Although MTT was found to be faster, oral bioavailability remained unchanged, which considering the increased systemic clearance implies an increase in the fraction escaping intestinal first pass metabolism."( The Pharmacokinetics of the CYP3A Substrate Midazolam in Morbidly Obese Patients Before and One Year After Bariatric Surgery.
Brill, MJ; Darwich, AS; Hazebroek, EJ; Knibbe, CA; Rostami-Hodjegan, A; van Dongen, EP; van Ramshorst, B; van Rongen, A, 2015
)
0.68
"Compared with intranasal delivery of a midazolam formulation intended for IV delivery, USL261, optimized for intranasal administration demonstrated improved bioavailability with similar pharmacodynamic effects."( Pharmacokinetics, pharmacodynamics, and safety of USL261, a midazolam formulation optimized for intranasal delivery, in a randomized study with healthy volunteers.
Bancke, LL; Dworak, HA; Gidal, BE; Halvorsen, MB; Rodvold, KA, 2015
)
0.93
" Studies have demonstrated that a mean bioavailability (F) of more than 73% can be achieved with IN-administered midazolam."( The Use of Intranasal Midazolam in a Special Care Dentistry Department: Technique and Cases.
Drysdale, D, 2015
)
0.94
" The MDZ-pro/A oryzae protease system showed greater than 25-fold increase in absorption rate of MDZ across MDCKII-wt monolayers, compared to saturated MDZ."( Chirally Pure Prodrugs and Their Converting Enzymes Lead to High Supersaturation and Rapid Transcellular Permeation of Benzodiazepines.
Cheryala, N; Cloyd, JC; Georg, GI; Kapoor, M; Rautiola, D; Siegel, RA, 2016
)
0.43
"Short-term fasting can alter drug exposure but it is unknown whether this is an effect of altered oral bioavailability and/or systemic clearance."( Effect of Short-Term Fasting on Systemic Cytochrome P450-Mediated Drug Metabolism in Healthy Subjects: A Randomized, Controlled, Crossover Study Using a Cocktail Approach.
Achterbergh, R; Lammers, LA; Mathôt, RAA; Romijn, JA; van Schaik, RHN, 2017
)
0.46
"The objective of this study was to assess the bioavailability and the sedative effect of a single-dose administration of an innovative oral solution of midazolam containing γ-cyclodextrins (ADV6209)."( A Two-way Randomized Cross-over Pharmacokinetic and Pharmacodynamic Study of an Innovative Oral Solution of Midazolam (ADV6209).
Burton, I; Granier, LA; Guittet, C; Manso, M; Marçon, F, 2017
)
0.87
"A bioavailability study with a standard two-sequences, two-periods, and crossover design was conducted."( A Two-way Randomized Cross-over Pharmacokinetic and Pharmacodynamic Study of an Innovative Oral Solution of Midazolam (ADV6209).
Burton, I; Granier, LA; Guittet, C; Manso, M; Marçon, F, 2017
)
0.67
" ADV6209 had a bioavailability of 39."( A Two-way Randomized Cross-over Pharmacokinetic and Pharmacodynamic Study of an Innovative Oral Solution of Midazolam (ADV6209).
Burton, I; Granier, LA; Guittet, C; Manso, M; Marçon, F, 2017
)
0.67
"Cyclodextrins have little impact on midazolam oral bioavailability and the pharmacokinetics parameters of midazolam formulation ADV6209 are close to those reported previously."( A Two-way Randomized Cross-over Pharmacokinetic and Pharmacodynamic Study of an Innovative Oral Solution of Midazolam (ADV6209).
Burton, I; Granier, LA; Guittet, C; Manso, M; Marçon, F, 2017
)
0.94
"Plasma concentration data were collected from 37 paediatric patients and 12 healthy adults recruited in a single dose, open-label phase II pharmacokinetic study and in a single dose, randomised, open-label two-period crossover bioavailability study, respectively."( Population pharmacokinetic evaluation of ADV6209, an innovative oral solution of midazolam containing cyclodextrin.
Burton, I; Dupont, H; Granier, LA; Guittet, C; Jacqmin, P; Manso, MA; Marçon, F, 2018
)
0.71
" Oral area under the plasma concentration-time curve (AUC) and bioavailability of well known BCRP (sulfasalazine and rosuvastatin), P-glycoprotein (fexofenadine, aliskiren, and talinolol), and CYP3A (midazolam) substrates were investigated in the presence and absence of inhibitors."( Curcumin as an In Vivo Selective Intestinal Breast Cancer Resistance Protein Inhibitor in Cynomolgus Monkeys.
Abe, K; Ando, O; Imaoka, T; Karibe, T, 2018
)
0.67
" The use of MAD even gives as better bioavailability of drugs."( Intranasal drug administration for procedural sedation in children admitted to pediatric Emergency Room.
Chiaretti, A; Fabrizio, GC; Fantacci, C; Ferrara, P; Franceschi, F, 2018
)
0.48
" This results in a highly variable and high total oral bioavailability of 92."( First-Pass CYP3A-Mediated Metabolism of Midazolam in the Gut Wall and Liver in Preterm Neonates.
Brill, MJE; Brussee, JM; de Roos, B; de Wildt, SN; Knibbe, CAJ; Krekels, EHJ; Rostami-Hodjegan, A; van den Anker, JN; Yu, H, 2018
)
0.75
" In the model, consisting of physiological compartments representing the gastro-intestinal tract and liver,intrinsic intestinal and hepatic clearances were estimated to derive values for bioavailability and plasma clearance."( Characterization of Intestinal and Hepatic CYP3A-Mediated Metabolism of Midazolam in Children Using a Physiological Population Pharmacokinetic Modelling Approach.
Barrett, JS; Brill, MJE; Brussee, JM; de Wildt, SN; Knibbe, CAJ; Krekels, EHJ; Palić, S; Rostami-Hodjegan, A; Yu, H, 2018
)
0.71
" When expressed per gram of organ, intrinsic clearance increases with increasing body weight in the gut wall, but decreases in the liver, indicating that CYP3A-mediated intrinsic clearance and local bioavailability in the gut wall and liver do not change with age in parallel."( Characterization of Intestinal and Hepatic CYP3A-Mediated Metabolism of Midazolam in Children Using a Physiological Population Pharmacokinetic Modelling Approach.
Barrett, JS; Brill, MJE; Brussee, JM; de Wildt, SN; Knibbe, CAJ; Krekels, EHJ; Palić, S; Rostami-Hodjegan, A; Yu, H, 2018
)
0.71
"Accurately discriminating changes in clearance (CL) from changes in bioavailability (F) following an oral drug-drug interaction is difficult without carrying out an intravenous interaction study."( A Simple Methodology to Differentiate Changes in Bioavailability From Changes in Clearance Following Oral Dosing of Metabolized Drugs.
Benet, LZ; Sodhi, JK, 2020
)
0.56
" In drug discovery research, using human IECs to evaluate membrane permeability and metabolic stability can offer very useful information when exploring for drug candidate compounds that have good bioavailability and when trying to predict the fraction absorbed and intestinal availability in humans."( Generation of intestinal organoids derived from human pluripotent stem cells for drug testing.
Kawachi, T; Kume, S; Miwa, H; Takahashi, K; Yoshida, S, 2020
)
0.56
" The simulations suggest that for highly soluble drugs, such as verapamil, the predicted bioavailability was comparable pre- and post-RYGBS."( PBPK modeling of CYP3A and P-gp substrates to predict drug-drug interactions in patients undergoing Roux-en-Y gastric bypass surgery.
Chan, LN; Chen, KF; Lin, YS, 2020
)
0.56
"It is concluded that midazolam shows a good response in all clinical studies because of its lesser half-life and bioavailability when compared with other probe drugs."( A Short Exploration of Selected Sensitive CYP3A4 Substrates (Probe Drug).
Sabarathinam, S; Vijayakumar, TM, 2021
)
0.94
" Apparent oral clearance and relative bioavailability for caffeine and S-warfarin were not significantly different between the subject populations."( Therapeutic Protein Drug Interaction Potential in Subjects With Psoriasis: An Assessment Based on Population Pharmacokinetic Analyses of Sensitive Cytochrome P450 Probe Substrates.
Mohamed, MF; Othman, AA; Sathe, AG, 2021
)
0.62
" We therefore tested in a single-center, open-label clinical trial with 12 healthy volunteers the absolute bioavailability of 10 μg of midazolam after buccal administration in relation to buccal exposure time."( Absolute Bioavailability of Microdosed Midazolam After Buccal Administration Is Dependent on Buccal Exposure Time.
Blank, A; Burhenne, J; Grass, J; Haefeli, WE; Mikus, G; Rose, P, 2021
)
1.09
" Patients were followed for 2 years, with four pharmacokinetic investigations using semisimultaneous oral and intravenous dosing to determine changes in midazolam absolute bioavailability and clearance, within and between groups."( Short- and long-term effects of body weight loss following calorie restriction and gastric bypass on CYP3A-activity - a non-randomized three-armed controlled trial.
Andersson, S; Andersson, TB; Angeles, PC; Artursson, P; Åsberg, A; Christensen, H; Hjelmesaeth, J; Hole, K; Jansson-Löfmark, R; Johnson, LK; Karlsson, C; Krogstad, V; Kvitne, KE; Robertsen, I; Sandbu, R; Skovlund, E; Wegler, C; Wollmann, BM, 2022
)
0.92
" Accordingly, the bioavailability of midazolam was increased by about 3 times, thus enhancing its pharmacological effect."( Involvement of the Parathyroid Hormone-Related Protein on Changes in the CYP3A Expression in Cancer Cachexia.
Chikamatsu, M; Fujita, I; Ichimizu, S; Ikegami, K; Imafuku, T; Kobayashi, K; Maeda, H; Maruyama, T; Tanaka, R; Watanabe, H; Yamada, K, 2021
)
0.89
" 4βOHC concentrations correlated weakly with midazolam absolute bioavailability (ρ =  - 0."( Correlations between 4β-hydroxycholesterol and hepatic and intestinal CYP3A4: protein expression, microsomal ex vivo activity, and in vivo activity in patients with a wide body weight range.
Andersson, S; Andersson, TB; Artursson, P; Åsberg, A; Christensen, H; Eide Kvitne, K; Hertel, JK; Hjelmesæth, J; Hole, K; Jansson-Löfmark, R; Johnson, LK; Karlsson, C; Krogstad, V; Molden, E; Robertsen, I; Sandbu, R; Skovlund, E; Wegler, C; Wollmann, BM, 2022
)
0.98
" The changes to the integrity of the intestine and its drug metabolising enzymes and transporters (DMETs) can alter the oral bioavailability of drugs."( Altered Bioavailability and Pharmacokinetics in Crohn's Disease: Capturing Systems Parameters for PBPK to Assist with Predicting the Fate of Orally Administered Drugs.
Alrubia, S; Barber, J; Chen, Y; Mao, J; Rostami-Hodjegan, A, 2022
)
0.72
" We investigated the bioavailability of the two midazolam doses with ODF swallowed immediately (ODF-IS) or delayed after 2 min (ODF-DS) by comparing their pharmacokinetics with intravenous and oral midazolam solution in 12 healthy volunteers."( Oral bioavailability of microdoses and therapeutic doses of midazolam as a 2-dimensionally printed orodispersible film in healthy volunteers.
Blank, A; Breithaupt, MH; Burhenne, J; Czock, D; Dachtler, M; Eggenreich, K; Foerster, KI; Haefeli, WE; Hoppe-Tichy, T; Huber, G; Koerner, E; Krohmer, E; Mikus, G; Taylor, L; Venkatesh, R, 2022
)
1.22
"This trial demonstrates the tolerability and unchanged bioavailability of midazolam printed on ODF over a 100-fold dose range, proving the suitability of ODF for dose individualization."( Oral bioavailability of microdoses and therapeutic doses of midazolam as a 2-dimensionally printed orodispersible film in healthy volunteers.
Blank, A; Breithaupt, MH; Burhenne, J; Czock, D; Dachtler, M; Eggenreich, K; Foerster, KI; Haefeli, WE; Hoppe-Tichy, T; Huber, G; Koerner, E; Krohmer, E; Mikus, G; Taylor, L; Venkatesh, R, 2022
)
1.19
" Off-label benzodiazepines, such as orally disintegrating lorazepam and intranasal use of an intravenous (IV) formulation of midazolam via nasal atomizer, are less well characterized regarding bioavailability and tolerability compared with approved agents."( Rescue Treatments for Seizure Clusters.
Gidal, BE; Kotloski, RJ, 2022
)
0.93
", catheter obstruction and embolism), and enhancing in vivo bioavailability and efficacy."( Effective loading of incompatible drugs into nanosized vesicles: a strategy to allow concurrent administration of furosemide and midazolam in simulated clinical settings.
El Gazayerly, ON; El-Badry, M; Elsabahy, M; Fathi, HA; Yousry, C, 2023
)
1.12
"It was found that about 75% of the dose was left in the portal blood with different oral administration doses, while the bioavailability in the liver was 37."( Dose-dependent pharmacokinetics of midazolam in rats: influence of hepatic first-pass metabolism.
Diao, Z; Li, R; Liu, Z; Peng, Y; Sun, J; Wang, G; Wang, Q; Xie, L, 2023
)
1.19
" We have previously shown substantial intraindividual variability in midazolam absolute bioavailability and clearance in patients with obesity before and after weight loss induced by gastric bypass or a strict diet."( Intraindividual Variability in Absolute Bioavailability and Clearance of Midazolam in Healthy Individuals.
Åsberg, A; Drevland, OM; Haugli, N; Kvitne, KE; Robertsen, I; Skadberg, E; Zaré, HK, 2023
)
1.38
"At baseline, mean absolute bioavailability and clearance were 46 ± 18% and 31 ± 10 L/h, respectively."( Intraindividual Variability in Absolute Bioavailability and Clearance of Midazolam in Healthy Individuals.
Åsberg, A; Drevland, OM; Haugli, N; Kvitne, KE; Robertsen, I; Skadberg, E; Zaré, HK, 2023
)
1.14
"On average, intraindividual variability in absolute bioavailability and clearance of midazolam was low to moderate; however, especially absolute bioavailability showed considerable variability in a relatively large proportion of the individuals."( Intraindividual Variability in Absolute Bioavailability and Clearance of Midazolam in Healthy Individuals.
Åsberg, A; Drevland, OM; Haugli, N; Kvitne, KE; Robertsen, I; Skadberg, E; Zaré, HK, 2023
)
1.37
"Intranasal bioavailability was high and sedation onset was rapid, with maximum sedative effects after 32 min."( Development of a pharmacokinetic and pharmacodynamic model for intranasal administration of midazolam in older adults: a single-site two-period crossover study.
Absalom, A; Barends, C; Colin, P; den Daas, I; Driesens, M; Visser, A, 2023
)
1.13
" The objective of this study was to evaluate the safety, pharmacokinetics, pharmacodynamics, and absolute bioavailability of midazolam rectal gel in healthy Chinese subjects."( Safety, Pharmacokinetics, and Pharmacodynamics of Midazolam Gel After Rectal Administration in Healthy Chinese Subjects.
Chen, J; Ding, S; Li, Y; Shao, F; Sun, X; Wang, L; Xie, L; Zhao, Y; Zheng, A; Zhou, C; Zhou, S; Zhu, B; Zhu, J, 2023
)
1.37
"Midazolam rectal gel may be a feasible alternative with a high level of acceptance in pediatric sedation and enhanced bioavailability compared to an oral formulation."( Safety, Pharmacokinetics, and Pharmacodynamics of Midazolam Gel After Rectal Administration in Healthy Chinese Subjects.
Chen, J; Ding, S; Li, Y; Shao, F; Sun, X; Wang, L; Xie, L; Zhao, Y; Zheng, A; Zhou, C; Zhou, S; Zhu, B; Zhu, J, 2023
)
2.61

Dosage Studied

No dosing regimen has been established for the initial treatment of pediatric status epilepticus with intravenous midazolam. Diazepam (30 micro M) caused a downward shift in the dose-response curve to extracellular Ca(2+) for shortening, with no concomitant effect on peak intracellular Ca('2+) transient. A reduced dosage of midazlam to patients with advanced cirrhosis of the liver is recommended.

ExcerptRelevanceReference
" The cost per dosage was 2:1 greater with midazolam."( [Diazepam versus midazolam as pre-endoscopic medication].
Córdova Villalobos, JA; Hernández Ortiz, TM; Ramírez Barba, EJ; Rojas Hernández, R,
)
0.74
" Rats were administered midazolam, dexmedetomidine, or a combination of midazolam and dexmedetomidine intravenously to derive three dose-response curves for loss of righting reflex (LRR)."( Synergistic interaction between alpha 2-adrenergic agonists and benzodiazepines in rats.
Maze, M; Reid, K; Salonen, M, 1992
)
0.59
" Quantal dose-response curves were determined in 400 female patients for the drugs individually and in combination."( Hypnotic and anaesthetic interactions between midazolam, propofol and alfentanil.
Chui, PT; Plummer, JL; Short, TG, 1992
)
0.54
" Using a cumulative dosing procedure, PTZ substituted for PTZ, and MDZ, chlordiazepoxide and diazepam (DZP) substituted for MDZ, in a dose-dependent manner."( Tolerance, cross-tolerance and withdrawal in rats made dependent on diazepam.
Boone, MS; Emmett-Oglesby, MW; Pugh, SL, 1992
)
0.28
" Dosage adjustments must be considered in the elderly, individuals with medical disorders, and patients taking multiple medications."( Antianxiety/sedative drugs. The benzodiazepines.
Giacalone, VF, 1992
)
0.28
" Addition of morphine caused a left shift in the dose-response curves of all the non-opioid drugs, indicating at least some degree of additive effects."( Antinociceptive and motor effects of intrathecal morphine combined with intrathecal clonidine, noradrenaline, carbachol or midazolam in rats.
Cmielewski, PL; Cousins, MJ; Gourlay, GK; Owen, H; Plummer, JL, 1992
)
0.49
" Although the propofol dosage requirements to maintain comparable levels of sedation were similar in both groups, midazolam decreased patients' recall of intraoperative events (e."( Midazolam in combination with propofol for sedation during local anesthesia.
Ghouri, AF; Taylor, E; White, PF,
)
1.78
" With the little therapeutic use observed with the given premedication, a more widespread application of the substance in this dosage cannot be recommended, particularly when taking into account the possibility of complications and the loss of the patients's fitness to drive for the next twelve hours."( [The question of oral sedation using midazolam in outpatient dental surgery].
Dietrich, U; Fischer, W; Wahlmann, UW, 1992
)
0.56
" Amnesic effect correlated more with the dose than the dosage determined by body weight."( [The effect of age and gender on the effect of midazolam as intramuscular premedicant].
Tabuchi, Y, 1992
)
0.54
" Despite a significant decrease in heart rate and respiratory rate, cardiac output, blood gases, and pH remained within normal ranges at all dosage levels."( Sedative and cardiovascular effects of midazolam in swine.
Smith, AC; Spinale, FG; Swindle, MM; Zellner, JL, 1991
)
0.55
" Using end-points of "hypnosis" (loss of response to verbal command) and "anaesthesia" (loss of response to a 5-s transcutaneous tetanic stimulus), we determined dose-response curves for propofol and midazolam alone and in combination."( Propofol and midazolam act synergistically in combination.
Chui, PT; Short, TG, 1991
)
0.84
"The effect of midazolam on the induction dose-response curve for alfentanil was studied in non-premedicated ASA physical status I or II patients."( Sedation in the ICU.
Kissin, I; Vinik, HR, 1991
)
0.64
" Plasma concentrations for each hypnotic after dosing were measured by electron-capture gas-liquid chromatography."( Intranasal absorption of flurazepam, midazolam, and triazolam in dogs.
Amidon, GL; Goldberg, A; Lui, CY, 1991
)
0.55
"03-3 mg/kg did not produce changes in the midazolam dose-response curve for either unpunished or punished responding."( NMDA antagonists: lack of antipunishment effect in squirrel monkeys.
Balster, RL; Jortani, SA; Mansbach, RS; Willetts, J, 1991
)
0.55
"The influence of dosage time of midazolam on its pharmacokinetics and effects on the central nervous system were investigated in six healthy volunteers, with pharmacokinetic-pharmacodynamic modeling."( The influence of dosage time of midazolam on its pharmacokinetics and effects in humans.
Danhof, M; Dingemanse, J; Horsten, GP; Koopmans, R; van Boxtel, CJ, 1991
)
0.85
"Perioperative antiarrhythmic therapy with lidocaine (bolus dosage 100 mg followed by infusion of 200 mg/h) was performed in 24 patients; 12 of them simultaneously received an intravenous injection of 10 mg midazolam with the bolus of lidocaine (group I: with midazolam; group II: without midazolam)."( [Is the plasma protein binding of lidocaine modified by the simultaneous administration of midazolam?].
Bachmann-M, B; Biscoping, J; Hempelmann, G; Schürg, R, 1991
)
0.69
"Inability to open eyes on command was used as an end point of anesthesia and the dose-response curves were determined using a probit procedure."( Midazolam potentiates thiopental sodium anesthetic induction in patients.
Bradley, EL; Kissin, I; Vinik, HR,
)
1.57
" In nine dogs anesthetized with fentanyl and midazolam, halothane dose-response curves (0."( Effects of cardiopulmonary bypass and cardioplegia on regional and global cardiac actions of halothane in dogs.
Hu, WC; Leone, BJ; McRae, RL; Smith, LR; Spahn, DR, 1991
)
0.54
"Twenty-four patients in a paediatric intensive care unit mostly undergoing cardiac surgery, received a midazolam dosage between 50-400 micrograms/kg per hour as a continuous intravenous infusion partly in combination with fentanyl [0,5-2,5 micrograms/kg per hour] for analgesia and sedation."( Clinical experience with continuous intravenous sedation using midazolam and fentanyl in the paediatric intensive care unit.
Hartwig, S; Roth, B; Theisohn, M, 1991
)
0.74
" Dose-response curves for thiopentone and midazolam individually and in combination were determined using the two end-points in 300 unpremedicated patients."( Hypnotic and anaesthetic action of thiopentone and midazolam alone and in combination.
Galletly, DC; Plummer, JL; Short, TG, 1991
)
0.8
" In each patient the dosage of the drugs was adjusted to obtain the optimum responses during induction and maintenance."( [Propofol for induction and maintenance of anesthesia during heart surgery. Results of pharmacological studies in man].
Haverich, A; Kirchner, E; Lübbe, N; Schaps, D; Seitz, W, 1991
)
0.28
" During the course of the study, mean catecholamine dosage increased significantly in the fentanyl group from 12."( [The use of ketamine and midazolam for analgesia and sedation in ventilated patients subject to obligatory treatment with catecholamines].
Adams, HA; Biscoping, J; Claussen, E; Gebhardt, B; Hempelmann, G, 1991
)
0.58
" For each drug, a dose-response curve was determined before (prechronic) and two weeks after (postchronic) discontinuation of chronic administration."( Behavioral effects of chronic buspirone administration in the pigeon: comparison to midazolam.
Nader, MA, 1991
)
0.51
" On this basis, dosage recommendations for midazolam in total intravenous anaesthesia techniques are possible, aiming at hypnotic plasma concentrations of at least 250 ng."( Anaesthesia techniques for midazolam and flumazenil--an overview.
Kulka, PJ; Lauven, PM, 1990
)
0.84
" An inactive dose of intrathecally-administered midazolam (20 micrograms) produced a leftward shift in the dose-response curve for intrathecally administered morphine, in the thermal antinociceptive tests."( Interaction of midazolam and morphine in the spinal cord of the rat.
Sabbe, MB; Stevens, CW; Yaksh, TL; Yanez, A, 1990
)
0.89
" Flumazenil (Ro 15-1788) administration caused a parallel shift to the right of the dose-response curve for midazolam spinal analgesia."( On the mechanism by which midazolam causes spinally mediated analgesia.
Edwards, M; Gent, JP; Goodchild, CS; Serrao, JM, 1990
)
0.79
" Furthermore, total drug dosage requirements were measured and compared."( [Infusion or repetitive bolus injection? A clinical study of midazolam/fentanyl and diazepam/fentanyl combination anesthesia in neurosurgical operations].
Luger, TJ; Mair, P; Morawetz, R; Mutz, N; Stroschneider, E, 1990
)
0.52
" The purpose of the present paper is to review the pharmacokinetics of midazolam in this category of patients, and to examine what kind of practical information and dosing recommendation can be derived."( Postoperative sedation with midazolam in heart surgery patients: pharmacokinetic considerations.
Maitre, PO, 1990
)
0.81
" A lower dosage of each substance is necessary to maintain a better state of analgosedation."( [Analgesia and sedation in neurosurgical intensive care patients].
Brandt, L; el Gindi, M; Hundt, F, 1990
)
0.28
" Meticulous surgical technique combined with local anesthesia and some form of intravenous sedation in minimal therapeutic dosage will provide satisfactory conditions to perform surgical arthroscopy of the knee."( Arthroscopic surgery of the knee under local anesthesia.
Bruce, R; Conahan, TJ; Kitz, DS; Torg, JS; Yacobucci, GN, 1990
)
0.28
" The pharmacology and mechanisms of action, use of the medications for endoscopic procedures, dosing schedules, and monitoring are addressed."( Review of current research on midazolam and diazepam for endoscopic premedication.
Aker, J, 1990
)
0.57
" Dosing regimens should be based on pharmacokinetic data derived from patients whose severity of disease is comparable to that of the patients to be treated."( Pharmacokinetics of antibiotics in critically ill patients.
van Dalen, R; Vree, TB, 1990
)
0.28
" Careful dosing and titration to the desired clinical effects is mandatory."( Midazolam use in the emergency department.
Borron, SW; Chudnofsky, CR; Dronen, SC; Wright, MB; Wright, SW, 1990
)
1.72
"The induction dose-response of midazolam was compared with the dose-response of its combination with fentanyl and with that of fentanyl alone in three groups of 60 unpremedicated, ASA physical status I or II women undergoing minor gynaecological surgery."( Midazolam acts synergistically with fentanyl for induction of anaesthesia.
abd-el-Khalim, H; Ben-Shlomo, I; Ezry, J; Tverskoy, M; Zohar, S, 1990
)
2.01
"Monitoring with pulse oximetry, careful dosage and use of an ultra-slow technique in the administration of this potent drug for dental cases indicates that a continuous oxygen supplement would not appear necessary routinely."( Intravenous sedation in general dental practice--why oximetry?
Read-Ward, G, 1990
)
0.28
"The effects of alfentanil on the midazolam dose-response curve for hypnosis was studied with response to the verbal command as an end point in 95 patients."( Alfentanil potentiates midazolam-induced unconsciousness in subanalgesic doses.
Bradley, EL; Castillo, R; Kissin, I; Vinik, HR, 1990
)
0.87
" Dose-response curves were determined with a probit procedure."( Sedative and hypnotic midazolam-morphine interactions in rats.
Bradley, EL; Brown, PT; Kissin, I, 1990
)
0.59
"0 mg/kg dosage induced moderate sedation at 15 and 20 minutes; sedation was adequate for positioning the geese."( Determination of a sedative dose and influence of midazolam on cardiopulmonary function in Canada geese.
Dyson, DH; Honeyman, VL; Valliant, AE; Valverde, A, 1990
)
0.53
" using a specific monoclonal antibody, varied during a dosing interval between 175 and 600 ng ml-1."( Is cyclosporin A an inhibitor of drug metabolism?
Klotz, U; Li, G; Meinshausen, J; Treiber, G; Werringloer, J; Wolf, J, 1990
)
0.28
"The effect of midazolam on the induction dose-response curve for alfentanil was studied in nonpremedicated ASA physical status I or II patients."( Midazolam-alfentanil synergism for anesthetic induction in patients.
Bradley, EL; Kissin, I; Vinik, HR, 1989
)
2.08
" The two patients with coma of unknown origin demonstrated no clinical response to flumazenil at a dosage of 2 mg."( [The efficacy of the benzodiazepine antagonist flumazenil (Ro 15-1788) based on the EEG of mechanically ventilated intensive care patients].
Kulka, PJ; Lauven, PM; Rommelsheim, K; Schwilden, H, 1989
)
0.28
" A phase-response curve and a dose-response curve were measured to determine the effects of a single intraperitoneal injection of midazolam on the circadian clock of hamsters free-running in constant light."( Midazolam, a short-acting benzodiazepine, resets the circadian clock of the hamster.
Turek, FW; Wee, BE, 1989
)
1.92
" Dosage requirements for anesthetic agents are shown."( Fentanyl-midazolam-flumazenil anesthesia for induced abortion.
Garamvölgyi, G; Hamar, O; Kálmán, A, 1989
)
0.69
" The dose-response curve of the GABA-evoked catecholamine release was shifted to the left by midazolam without affecting the maximal response to GABA."( Benzodiazepines facilitate the stimulatory action of gamma-aminobutyric acid (GABA) on basal and veratridine-evoked catecholamine release from cultured bovine adrenal chromaffin cells.
Dohi, T; Kitayama, S; Morita, K; Tsujimoto, A,
)
0.35
" However, on a pharmacokinetic basis a reduced dosage of midazolam to patients with advanced cirrhosis of the liver is recommended."( Pharmacokinetics of midazolam following intravenous and oral administration in patients with chronic liver disease and in healthy subjects.
Crevoisier, C; Himberg, JJ; Pentikäinen, PJ; Välisalmi, L, 1989
)
0.85
"The acute effects of two doses of orally administered midazolam (Dormicum, 10 and 30 mg) which as a putative anaesthetic premedicant is clinically expected to provide valid effects already after acute dosing on sedation parameters, were evaluated vs placebo within a randomized double-blind 3-period crossover design in 12 healthy male volunteers."( Acute effects of two dosages of orally administered midazolam on psychomotor performance in healthy volunteers.
Klausnitzer, W; Schaffler, K, 1989
)
0.78
" The peak concentration is directly proportional to the dosage of midazolam and the relation between the two is linear."( [The pharmacokinetics of midazolam following intramuscular administration].
Asskali, F; Behne, M; Förster, H; Janshon, G, 1989
)
0.82
"The induction dose-response of midazolam was compared with the dose-response of its combination with methohexitone sodium and with that of methohexitone alone."( Midazolam acts synergistically with methohexitone for induction of anaesthesia.
Ben-Shlomo, I; Ezry, J; Finger, J; Fleyshman, G; Tverskoy, M, 1989
)
2.01
"The effect of thiopental on the induction dose-response curve for midazolam was studied in nonpremedicated ASA physical status I and II patients."( Midazolam-thiopental anesthetic interaction in patients.
Bradley, EL; Fleyshman, G; Kissin, I; Tverskoy, M, 1988
)
1.95
" The dose-response curves for midazolam, morphine, and their combination (each in a group of 30 patients) were determined by probit procedure and compared with isobolographic and algebraic (fractional) analyses."( Midazolam-morphine sedative interaction in patients.
Bradley, EL; Ezry, J; Fleyshman, G; Kissin, I; Tverskoy, M, 1989
)
2.01
" The cardio-stimulatory effect of laryngoscopy and tracheal intubation was not prevented by either of the benzodiazepines and morphine in the dosage used."( Haemodynamic changes during induction of anaesthesia with midazolam and diazepam (Valium) in patients undergoing coronary artery bypass surgery.
Carson, IW; Clarke, RS; Dundee, JW; Kawar, P; Lyons, SM, 1985
)
0.51
" Midazolam 5 mg kg-1 caused a shift to the left of the cumulative dose-response curves of vecuronium."( Interaction of midazolam with two non-depolarizing neuromuscular blocking drugs in the rat in vivo sciatic nerve-tibialis anterior muscle preparation.
Booij, LH; Crul, JF; Driessen, JJ; van Egmond, J; Vree, TB, 1985
)
1.53
" In contrast, the steady-state midazolam concentration after ranitidine dosing (61."( Effect of single doses of cimetidine and ranitidine on the steady-state plasma levels of midazolam.
Arvela, P; Klotz, U; Rosenkranz, B, 1985
)
0.78
" We conclude that midazolam is a new intravenous induction agent for use in the elderly, but careful titration of the dosage according to the response of the patient is required."( Midazolam as an intravenous induction agent in the elderly: a clinical and pharmacokinetic study.
Aaltonen, L; Himberg, JJ; Hovi-Viander, M; Kanto, J, 1986
)
2.05
" Using an appropriate dosage of intrathecal midazolam selective blockade of spasticity of the hind legs may be demonstrated with integrated EMG."( [Spasticity treatment with spinal morphine or midazolam. In vitro experiments, animal studies and clinical studies on compatibility and effectiveness].
Boldt, J; Börner, U; Gerlach, H; Hempelmann, G; Hild, P; Müller, H; Oehler, KU; Zierski, J, 1986
)
0.79
" Midazolam (greater than 10(-6) M) reliably potentiated GABA responses with a parallel shift to the left of the dose-response curve."( Electrophysiological studies in cultured mouse CNS neurones of the actions of an agonist and an inverse agonist at the benzodiazepine receptor.
Jensen, MS; Lambert, JD, 1986
)
1.18
" We concluded that there are no major differences between the three drugs in the dosage used."( Diazepam, flunitrazepam and midazolam for elective endoscopy--a comparative study.
Badran, I; Hunjul, N; Sbeih, Z; Takrouri, MS; Toukan, A, 1988
)
0.57
" In different groups of rats trained to discriminate nicotine or midazolam separately from saline, neither drug appreciably altered the dose-response curve for the other, suggesting a minimal role for pharmacological interactions when effects of mixtures were assessed."( Discriminative stimulus effects of a nicotine-midazolam mixture in rats.
Norris, EA; Rauch, RJ; Stolerman, IP, 1987
)
0.77
" The Before Group was affected, and although complete tolerance to work-rate decrements developed rapidly to chronic dosing (3."( Midazolam and discriminative motor control: chronic administration, withdrawal and modulation by the antagonist Ro 15-1788.
Falk, JL; Lau, CE; Tang, M, 1988
)
1.72
"5 mg/kg) allowed for a significant reduction in the mean dosage of midazolam required to produce satisfactory sedation when compared with trials where midazolam was used alone."( New intravenous sedative combinations in oral surgery: a comparative study of nalbuphine or pentazocine with midazolam.
Hook, PC; Lavery, KM, 1988
)
0.72
" However, the slope of midazolam's dose-response curve for sedation appeared to be steeper (i."( Comparison of midazolam and diazepam for sedation during plastic surgery.
Mathes, SA; Vasconez, LO; Way, WL; Wender, LA; White, PF, 1988
)
0.95
" An oral dosage form is under investigation in the United States."( Use of midazolam hydrochloride in anesthesia.
Khanderia, U; Pandit, SK, 1987
)
0.73
" This situation demonstrates the difficulties of assessing the level of sedation as well as the dosage requirements in this type of patient."( Detection of overdosage of sedation in a patient with renal failure by the absence of lower oesophageal motility.
Sinclair, ME; Suter, PM, 1988
)
0.27
" We tested the dosage of drugs needed in relation to the length of treatment, the size of the stone and the overall energy output of the lithotriptor."( [Extracorporeal shockwave lithotripsy in sedation-analgesia].
Berger, M; Brandstetter, A; Chowanetz, E; Gasser, G; Mossig, H; Schmidt, P, 1988
)
0.27
" The dosage of anesthetic agents was calculated according to body weight."( [Combined midazolam-ketamine anesthesia in traumatologic interventions. Patterns of endocrine reactions].
Bornscheuer, A; Hamkens, A; Lübbe, N; Seitz, W, 1988
)
0.68
" Irrespective of the dosage sleep was almost exclusively increased at the expense of NREM sleep."( Short-term sleep laboratory evaluation of midazolam in chronic insomniacs. Preliminary results.
Alterwain, P; Altier, H; Debellis, J; Monti, D; Monti, JM; Pellejero, T, 1987
)
0.54
" Using this dosage regime, midazolam caused significantly greater impairment in psychomotor function in both cirrhotic and non cirrhotic subjects, and the time taken for recovery of normal function was also significantly prolonged."( Sedation for gastroscopy: a comparative study of midazolam and Diazemuls in patients with and without cirrhosis.
Hamdy, NA; Kennedy, HJ; Nicholl, J; Triger, DR, 1986
)
0.82
" It is concluded that intrathecal midazolam in the dosage used interrupts somatic nociceptive afferent pathways but not abdominal visceral nociceptive afferent pathways."( The effects of intrathecal midazolam on sympathetic nervous system reflexes in man--a pilot study.
Goodchild, CS; Noble, J, 1987
)
0.85
" The dosage of a drug given in a continuous infusion is based upon knowledge of its clearance and of the function of concentration and effect."( [Continuous Midazolam infusion for sedation of respirator patients].
Asskali, F; Behne, M; Förster, H; Steuer, A, 1987
)
0.65
" Antipyrine pharmacokinetics were studied immediately before midazolam administration was started, after the dosage schedule had been completed and one week after dosing had been discontinued."( The effect of midazolam (Hypnovel) administration on antipyrine pharmacokinetics in humans.
Alderson, J; Allen, JG; Galloway, DB; Hallett, C, 1987
)
0.87
" Dose-response curves were then established, before, immediately after and 4 weeks after the daily administration of midazolam (3."( Investigation of the development of tolerance to the actions of zolpidem and midazolam.
Sanger, DJ; Zivkovic, B, 1987
)
0.71
"0 mg/kg) from saline, and then generalization tests were conducted using a cumulative dosing procedure."( Discriminative stimulus properties of buspirone in the pigeon.
Barrett, JE; Mansbach, RS, 1987
)
0.27
" There have been at least ten studies comparing diazepam with midazolam for upper gastrointestinal endoscopy but many have involved relatively small numbers and none have adequately addressed the question of dosage in the elderly."( Intravenous midazolam for upper gastrointestinal endoscopy: a study of 800 consecutive cases relating dose to age and sex of patient.
Bell, GD; Logan, RF; Morden, A; Reeve, PA; Spickett, GP, 1987
)
0.89
" Midazolam (10(-7)-10(-5) M) potentiated responses to all three agonists to a similar extent with a shift to the left of the dose-response curve."( Modulation of the responses to the GABA-mimetics, THIP and piperidine-4-sulphonic acid, by agents which interact with benzodiazepine receptors. An electrophysiological study on cultured mouse neurones.
Jensen, MS; Lambert, JD, 1984
)
1.18
" There was no dose-response effect for effectiveness with either initial or continued drug administration."( Midazolam: dose-response studies of effectiveness and rebound insomnia.
Bixler, EO; Goff, PJ; Kales, A; Soldatos, CR; Vela-Bueno, A, 1983
)
1.71
" Factors which had a statistically significant influence on the dosage requirement were (a) sex, 30."( Hypnotic efficacy of midazolam in pre-surgical patients: a dose-finding study.
Du Cailar, J; Holzer, J; Jullien, Y; Passeron, D, 1983
)
0.58
"Three different dosage studies were carried out with midazolam in 47 institutionalized geriatric patients (17 males: mean age 82."( Midazolam dosage studies in institutionalized geriatric patients.
Beck, H; Holzer, J; Salom, M, 1983
)
1.96
" Such differences may be very important clinically because pharmacokinetic data will help to optimize drug therapy with respect to the choice of the proper drug and drug preparation, as well as with the choice of a proper dose and dosage regimen."( Pharmacokinetics of benzodiazepines: metabolic pathways and plasma level profiles.
Breimer, DD; Jochemsen, R, 1984
)
0.27
" The EEG is a proven parameter with regard to dosage determination and as objective means to find sleep-inducing quantities of drugs."( Modern trends in the investigation of new hypnotics in anaesthesia.
Doenicke, A, 1984
)
0.27
" Midazolam elimination half-life (t1/2) after iv dosage was significantly prolonged in elderly (aged 60-74 yr) versus young (24-33 yr) males (5."( Effect of age, gender, and obesity on midazolam kinetics.
Abernethy, DR; Greenblatt, DJ; Harmatz, JS; Limjuco, RA; Locniskar, A; Shader, RI, 1984
)
1.45
" Dose-response curves for pancuronium, duration of blockade, and adequacy of relaxation for tracheal intubation did not differ between patients receiving midazolam (N = 10) or thiopental (N = 10)."( Comparison of thiopental and midazolam on the neuromuscular responses to succinylcholine or pancuronium in humans.
Cronnelly, R; Miller, RD; Morris, RB, 1983
)
0.76
" Dosage rules based on pharmacokinetic principles, for repeated administration and infusion are outlined for the induction, maintenance and termination of anaesthesia."( [Principles of clinical pharmacokinetics in anaesthesiology (author's transl)].
Lauven, PM; Schüttler, J; Schwilden, H; Stoeckel, H, 1982
)
0.26
"After oral dosing of 10 mg 8-chloro-6-(2-fluorophenyl)-1-methyl-4H-imidazo[1,5-a][1,4] benzodiazepine (midazolam, Ro 21-3981, Dormicum) labelled with 14C (25 microCi) to 4 human volunteers, the total radioactivity is mainly excreted via the kidneys."( Excretion and metabolism of 14C-midazolam in humans following oral dosing.
Heizmann, P; Ziegler, WH, 1981
)
0.76
"Sex differences, and the influence of drug dosage and additional upper airway obstruction were studied in midazolam-induced breathing patterns and sedation in 30 healthy volunteers (8 males and 22 females)."( Differences in midazolam-induced breathing patterns in healthy volunteers.
Haji, A; Ito, Y; Masuda, A; Shakunaga, K; Shibuya, N; Wakasugi, M, 1995
)
0.86
" The control group and the test groups were comparable with regard to biological data, duration of operation, applied dosage of local anaesthetics and actual anxiety before operation."( [Analgesia-sedation for maxillo-facial surgery with midazolam-pentazocine and miazolam-ketamine. Clinical double-blind study of anxiety, analgesia, sedation and amnesia].
Daubländer, M; Dick, W; Lipp, M; Sebastian, M, 1995
)
0.54
"High doses of MDZ are effective for treating refractory status epilepticus; optimal dosage and duration of treatment remains to be determined."( [Use of intravenous midazolam in status epilepticus in children].
Daoud, P; Desguerre, I; Lemerle, J; Moutard, ML; Rodriguez, D, 1995
)
0.61
" Subjects performed three practice tests before dosing to account for any effects caused by familiarization ("learning curve") with the testing procedure."( Simultaneous modeling of the pharmacokinetics and pharmacodynamics of midazolam and diazepam.
Choma, N; Crews, T; DeFeo, TM; Limjuco, R; Milla, G; Mould, DR; Patel, IH; Reele, S, 1995
)
0.53
" The dose-response relationship when midazolam is administered was studied using this jet injector."( Preanesthetic medication of children with midazolam using the Biojector jet injector.
Greenberg, RS; Maxwell, LG; Yaster, M; Zahurak, M, 1995
)
0.83
"The dosage of sedatives required for sedation was studied in patients who underwent total abdominal histerectomy under epidural anesthesia using patient-controlled sedation (PCS) and in those with anesthesiologist-controlled sedation (ACS)."( [The dosage of sedative was reduced by patient-controlled sedation during epidural anesthesia].
Tsunoda, K, 1995
)
0.29
" The midazolam infusion allowed for continuation of the morphine dosage and also permitted further dosage escalation."( Continuous midazolam infusion for the management of morphine-induced myoclonus.
Adams, VR; Chavez, CM; Duncan, MH; Holdsworth, MT; Vaughan, LJ, 1995
)
1.19
" If further dosage increase of morphine are necessary in this setting, increases in the midazolam infusion also may be required."( Continuous midazolam infusion for the management of morphine-induced myoclonus.
Adams, VR; Chavez, CM; Duncan, MH; Holdsworth, MT; Vaughan, LJ, 1995
)
0.9
" This synergism varies considerably according to the different drugs, the different endpoints of anaesthesia and the differently combined dosage of both agents."( [The art of reasonable combining drugs in anesthesia].
Glass, PS, 1994
)
0.29
" At the spinal level, the dose-response curves for peak effect and area under the curve for morphine were shifted to the left (indicating potentiation) by a submaximal dose of intrathecal (i."( The spinal potentiating effect and the supraspinal inhibitory effect of midazolam on opioid-induced analgesia in rats.
Hayashi, T; Hill, HF; Luger, TJ; Weiss, CG, 1995
)
0.52
" In the first, dose-response experiments (n = 59) demonstrated a dose-dependent suppression of the noxiously evoked activity of spinal WDR neurons after midazolam administration."( Intravenous midazolam suppresses noxiously evoked activity of spinal wide dynamic range neurons in cats.
Hanaoka, K; Ide, Y; Nagase, M; Sekiyama, H; Sumida, T; Tagami, M, 1995
)
0.87
" The thiopental requirements were determined by titration; the midazolam requirements were determined from dose-response curves obtained with bolus injections of predetermined doses of the drug."( Subarachnoid bupivacaine blockade decreases midazolam and thiopental hypnotic requirements.
Finger, J; Kissin, I; Shagal, M; Tverskoy, M,
)
0.63
" When a benzodiazepine is combined with a narcotic, the narcotic should be given first and the dosage of the sedative adjusted."( Sedation and monitoring in gastrointestinal endoscopy.
Nagengast, FM, 1993
)
0.29
" The dosage requirement with PCS was higher than that found with INS or BIVS."( Comparison between intranasal and intravenous midazolam sedation (with or without patient control) in a dental phobia clinic.
Davidson, E; Kaufman, E; Magora, F; Sheinkman, Z, 1994
)
0.55
"The purpose of this study was to examine the anaesthetic requirement of intrathecal midazolam in a dose-response fashion in isoflurane-anaesthetized, tracheostomized rats, and to evaluate the apnoeic threshold after each intrathecal midazolam dose."( Intrathecal midazolam reduces isoflurane MAC and increases the apnoeic threshold in rats.
Forster, A; Jorge-Costa, M; Morel, DR; Pizzolato, GP; Schwieger, IM, 1994
)
0.89
" The author calls the attention to the importance of the observance of the dosage and administration of the drug which may prevent the development of a great number of side-effects."( Placebo-controlled clinical trial of Dormicum 15-mg tablet.
Köves, P, 1993
)
0.29
" We were unable to identify any differences between the two groups with respect to narcotic, benzodiazepine dosage or usage of inhalational agents."( Recall of intraoperative events after general anaesthesia and cardiopulmonary bypass.
Devitt, JH; Harrington, EM; McLean, RF; Phillips, AA, 1993
)
0.29
" Thirty-two subjects completed this randomized, double-blind, placebo-controlled study investigating the dose-response relationship and duration of flumazenil's effects on ventilatory depression and hypnosis induced by a continuous midazolam infusion."( The effects of large-dose flumazenil on midazolam-induced ventilatory depression.
Flögel, CM; Ritter, JW; Wada, DR; Ward, DS, 1993
)
0.74
" Cumulative dose-response curves for chlordiazepoxide were obtained before and during chronic chlordiazepoxide administration and during chronic saline administration."( Tolerance to the behavioral effects of chlordiazepoxide: pharmacological and biochemical selectivity.
Alastra, AJ; Cohen, C; Goldberg, SR; Marley, RJ; Sannerud, CA; Serdikoff, SL, 1993
)
0.29
"Quantal dose-response curves were determined in 170 female patients for the drugs, individually and in combination."( Hypnotic and anesthetic interactions between ketamine and midazolam in female patients.
Hong, W; Hui, TW; Short, TG, 1993
)
0.53
" Dose-response curves for the three drugs given separately and in combination were determined with a probit procedure and the ED50 values were compared with an isobolographic analysis."( Triple anesthetic combination: propofol-midazolam-alfentanil.
Bradley, EL; Kissin, I; Vinik, HR, 1994
)
0.56
" The dose-response curves for each group were determined by a logistic regression procedure while isobolographic analysis compared the actions of both agents separately and together."( [Synergism of midazolam and propofol in the induction of anesthesia].
Caba, F; Echevarría, M; Guerrero, JA; Morales, R; Rodríguez, R,
)
0.49
" Continuous application is considered to be more effective concerning basic anxiety, cumulative dosage and to avoid volume overload in infants and young children, following cardiac surgery; overdosage was not observed."( [Analgosedation with fentanyl/midazolam after correction of congenital heart defects].
Hund, F; Huth, R; Michel-Behnke, I; Oelert, H; Rothes, A; Schmidt, FX; Schranz, D; Wippermann, CF,
)
0.42
" We conclude that in this patient population: (1) both P and M achieved optimal sedation in a large fraction of patients when administered by specified dosing protocols; (2) P had a faster, more reliable, wake-up time; (3) assessments of time-to-awaken were objective and reproducible; (4) time to sedation was not significantly different; (5) V O2 decreased similarly with both."( Sedation of critically ill patients during mechanical ventilation. A comparison of propofol and midazolam.
Hall, JB; Kress, JP; Lavoie, A; O'Connor, MF; Olson, D; Pohlman, AS; Toledano, A, 1996
)
0.51
" Optimal length was determined, a dose-response curve to acetylcholine was established, and the 50% effective dose (ED50) of acetylcholine was calculated."( Direct relaxant effects of intravenous anesthetics on airway smooth muscle.
Bosnjak, ZJ; Cheng, EY; Coon, RL; Kampine, JP; Mazzeo, AJ, 1996
)
0.29
" The dosage based on experimental studies."( [Clinical investigations of an i.m. combination anesthesia with fentanylclimazolam/xylazine and postoperative i.v. antagonism with naloxone/sarmazenil/yohimbine in guinea pigs].
Brill, T; Erhardt, W; Henke, J; Lendl, C; Matis, U; Otto, K; Roberts, U, 1996
)
0.29
" The mean dosage was 10."( Midazolam intravenous conscious sedation in oral surgery. A retrospective study of 372 cases.
Runes, J; Ström, C, 1996
)
1.74
" Dose-response determinations then showed that the devaluation procedure had indeed attenuated the response to midazolam, whereas the previously overshadowed response to nicotine was restored."( Reversal of overshadowing in a drug mixture discrimination in rats.
Stolerman, IP; White, JA, 1996
)
0.51
" Midazolam dose-response curves were obtained by probit analysis."( Effect of epidural bupivacaine block on midazolam hypnotic requirements.
Finger, J; Fleyshman, G; Kissin, I; Shifrin, V; Tverskoy, M,
)
1.31
"We determined the dose-response curves and effective doses of propofol for insertion of the laryngeal mask airway (LMA) in 50 unpremedicated children and in 60 children premedicated with midazolam, aged 3-12 yr."( Dose of propofol for laryngeal mask airway insertion in children: effect of premedication with midazolam.
Baker, RD; Martlew, RA; Meakin, G; Sharples, A; Wadsworth, R, 1996
)
0.7
" In the first study, 30 birds were randomly assigned to receive midazolam at a dosage of 2, 4, or 6 mg/kg of body weight (10 birds/dosage)."( Evaluation of sedation in quail induced by use of midazolam and reversed by use of flumazenil.
Day, TK; Roge, CK, 1996
)
0.79
" Anesthetic requirements, circulatory variables, interventions, and isoproterenol dose-response curves (pre- and postoperatively) were determined."( Clonidine for major vascular surgery in hypertensive patients: a double-blind, controlled, randomized study.
Bayon, MC; Boucaud, C; Bouilloc, X; Brudon, JR; Butin, E; Danays, T; Frehring, B; Ghignone, M; Levron, JC; Petit, P; Quintin, L; Tassan, H; Tissot, S; Viale, JP, 1996
)
0.29
" route, for studying midazolam dose-response relations."( Pharmacokinetics and bioavailability of midazolam after intravenous, subcutaneous, intraperitoneal and oral administration under a chronic food-limited regimen: relating DRL performance to pharmacokinetics.
Lau, CE; Ma, F; Smith, C; Wang, Y, 1996
)
0.88
" This suggests that dosage of midazolam in Vietnamese should be based on total bodyweight."( Pharmacokinetics of midazolam in Vietnamese subjects.
Balson, KR; Elliott, SL; McAlindon, ME; Morgan, DJ; Richmond, BH; Yeomans, ND, 1996
)
0.91
"1 and 10 micro M of propofol significantly blocked the high-K evoked DA release, although the dosage of larger than 50 micro M of propofol potentiated DA release."( [Effects of midazolam and propofol on dopamine release from rat striatal slice using a fast-cyclic voltammetry system].
Hotta, O; Isshiki, A, 1997
)
0.68
" Dosage requirements to reach the initial sedation end points of slurred speech and ptosis of eyelids vary widely from one patient to another."( Multidrug intravenous sedation: determinants of the sedative dose of midazolam.
Finder, RL; Jackson, DL; Moore, PA, 1997
)
0.53
"An assessment of physical, cardiovascular, behavioral, and pharmacologic factors that might predict midazolam dosage requirements for the initial sedation titration was carried out with data collected from a large controlled clinical trial of fentanyl, midazolam, and methohexital sedation for third molar surgery."( Multidrug intravenous sedation: determinants of the sedative dose of midazolam.
Finder, RL; Jackson, DL; Moore, PA, 1997
)
0.75
" Dose-response curves for M and P were obtained under these conditions and also when every 30th peck during the FI was punished by shock."( Punishment alters the discriminative stimulus effects of midazolam.
Barrett, JE; Roden, MM; Tatham, TA, 1997
)
0.54
" The dosage needed to initiate and maintain sedation must be adjusted to body weight, degree of sedation desired, and concomitant medications, as well as to underlying health and cardiovascular status."( Sedation with intravenous midazolam in the pediatric intensive care unit.
Notterman, DA, 1997
)
0.6
"Diazepam in a dosage of 11."( Midazolam versus diazepam in lipid emulsion as conscious sedation for colonoscopy with or without reversal of sedation with flumazenil.
Gevers, AM; Hendrickx, A; Macken, E; Rutgeerts, P, 1998
)
1.74
" Single-drug therapy with propofol and inadequate benzodiazepine dosing were linked to patient recall."( Patient recall of therapeutic paralysis in a surgical critical care unit.
Hammond, JS; Palmeri, BA; Sweeney, JB; Wagner, BK; Zavotsky, KE,
)
0.13
" Adequate dosing with benzodiazepines and narcotics is warranted to prevent recall and discomfort."( Patient recall of therapeutic paralysis in a surgical critical care unit.
Hammond, JS; Palmeri, BA; Sweeney, JB; Wagner, BK; Zavotsky, KE,
)
0.13
" In three groups, propofol, fentanyl and midazolam were administered intravenously in incremental doses to construct dose-response curves for the depressant effects of each one on PNA."( Synergistic interaction between the effects of propofol and midazolam with fentanyl on phrenic nerve activity in rabbits.
Chakrabarti, MK; Ma, D; Sapsed-Byrne, SM; Whitwam, JG, 1998
)
0.81
"05) difference in the urinary excretion of 1'-hydroxymidazolam after intravenous and oral dosing on day 1 or day 8, indicating that the oral dose was completely absorbed into the gut wall."( The contribution of intestinal and hepatic CYP3A to the interaction between midazolam and clarithromycin.
Gorski, JC; Haehner-Daniels, BD; Hall, SD; Hamman, MA; Jones, DR; O'Mara, EM, 1998
)
0.78
" A sedation score > or =4 (six-point scale) 30 to 60 min after dosing was rated as a success."( An approach for dose finding of drugs in infants: sedation by midazolam studied using the continual reassessment method.
Chevret, S; D'Athis, P; Fabre, E; Olive, G; Piechaud, JF; Pons, G; Rey, E; Vauzelle-Kervoedan, F, 1998
)
0.54
" Next, the drug discrimination dose-response curves were redetermined."( A history of postponing shock does not appear to alter the discriminative stimulus effects of cocaine.
Hasling, TA; Tatham, TA, 1998
)
0.3
" A suboptimal dosing regimen may lead to relative overdosing, which could result in delayed extubation and increased cost."( Population pharmacodynamics of midazolam administered by target controlled infusion in SICU patients after CABG surgery.
Donner, A; Geller, E; Ramsay, J; Shafer, SL; Sladen, R; Somma, J; Zomorodi, K, 1998
)
0.59
" Consideration of menstrual cycle variability in the metabolism of CYP3A4 substrates does not appear indicated in the dosing or design of clinical trials."( Menstrual cycle variability in midazolam pharmacokinetics.
Cox, K; Kharasch, ED; Lentz, G; Mautz, D; Senn, T, 1999
)
0.59
"To evaluate methodology for in vivo interaction studies of benzodiazepines (BZs) and ketoconazole (KCZ) in animal models, this study assessed the pharmacokinetics and electroencephalographic (EEG) effect of KCZ, and suitable dosage regimens of KCZ to maintain sufficiently high KCZ concentrations to inhibit metabolism of BZs in rats."( Pharmacokinetics and electroencephalographic effects of ketoconazole in the rat.
Durol, AL; Greenblatt, DJ; Kotegawa, T; Laurijssens, BE, 1999
)
0.3
" Under basolateral sink conditions and low apical MDZ dosing concentration (1-8 microM), the first-pass extraction ratio was found to be approximately 15%."( First-pass midazolam metabolism catalyzed by 1alpha,25-dihydroxy vitamin D3-modified Caco-2 cell monolayers.
Calamia, JC; Fisher, JM; Kunze, KL; Schmiedlin-Ren, P; Shen, DD; Thummel, KE; Watkins, PB; Wrighton, SA, 1999
)
0.69
" The results indicated that a simple dosing regimen based on weight was unable to give the same depth of anaesthesia in individual rats."( On-line analysis of middle latency auditory evoked potentials (MLAEP) for monitoring depth of anaesthesia in laboratory rats.
Henneberg, SW; Jensen, EW; Nygaard, M, 1998
)
0.3
" With RRA dosage, however, AUCs were greater than those obtained by HPLC dosage (174%)."( Pharmacokinetics of midazolam: comparison of sublingual and intravenous routes in rabbit.
Barthélémy, C; Brunet, C; Cazin, JC; Cazin, M; Chatelier, D; Dine, T; Gressier, B; Luyckx, M; Odou, P; Robert, H,
)
0.45
" A cumulative dosing procedure was used to test discriminative stimulus effects of ethanol (0."( The influence of menstrual cycle phase on sensitivity to ethanol-like discriminative stimulus effects of GABA(A)-positive modulators.
Azarov, AV; Grant, KA; Green, KL; Purdy, RH; Szeliga, KT, 1999
)
0.3
" Midazolam dosage was adjusted to induce a light sleep state to control agitation and involuntary motor activity."( Continuous intravenous midazolam infusion for Centruroides exilicauda scorpion envenomation.
Berg, RA; Conroy, C; Gibly, R; McNally, J; Walter, FG; Williams, M, 1999
)
1.52
" Given a compound out of the group of benzodiazepines as an example this paper represents todays methods of integrated pharmacokinetic-pharmacodynamic modelling as well as the special computer aided strategies of drug dosing as powerful tools in the anaesthetic drug development process."( [Pharmacokinetic-pharmacodynamic modeling in phase II of drug development. A comparative study with young and old volunteers with benzdiazepine as an example].
Albrecht, S; Hering, W; Ihmsen, H; Schüttler, J; Schwilden, H, 1999
)
0.3
" All three benzodiazepines were susceptible to drug interactions, but oral dosing of midazolam and triazolam resulted in greater alterations in the pharmacokinetic parameters than alprazolam due to their larger presystemic extraction."( Pharmacokinetic and pharmacodynamic consequences of metabolism-based drug interactions with alprazolam, midazolam, and triazolam.
Balian, JD; Flockhart, DA; Yuan, R, 1999
)
0.74
"0 micrograms kg-1, the dosage was adjusted to the patients needs (0."( No reduction in the sufentanil requirement of elderly patients undergoing ventilatory support in the medical intensive care unit.
Frass, M; Freye, E; Hammerschmidt, V; Hofbauer, R; Kofler, J; Kordova, H; Staudinger, T; Tesinsky, P; Vrastiolova, M, 1999
)
0.3
" For LRP and DF, premedication was associated with significant, non-parallel increases in the slope of the thiopental dose-response curves, resulting in marked potency ratio changes from ED50 to ED95 (LRP +31%, DF +29%)."( Midazolam premedication and thiopental induction of anaesthesia: interactions at multiple end-points.
Bissonnette, B; Decosterd, LA; Despland, PA; Ravussin, PA; Wilder-Smith, OH, 1999
)
1.75
" These results may help to explain observed clinical phenomena and raise important issues regarding drug dosing in ECMO patients."( In vitro evaluation of sedative drug losses during extracorporeal membrane oxygenation.
Burke, MD; Firmin, RK; Killer, H; Lawson, G; Mulla, H; Upton, DU; von Anrep, C, 2000
)
0.31
" Supplemental dosing was administered to children who were judged inadequately sedated 30 minutes after the initial medication."( Chloral hydrate versus midazolam for sedation of children for neuroimaging: a randomized clinical trial.
D'Agostino, J; Terndrup, TE, 2000
)
0.62
"Heterogeneity in CYP3A activity contributes to interpatient differences in cyclosporine dosage requirements after liver transplantation."( Prediction of cyclosporine clearance in liver transplant recipients by the use of midazolam as a cytochrome P450 3A probe.
Bannon, P; De Maeght, S; L'Ecuyer, L; Villeneuve, JP, 2000
)
0.53
" Continued study of costs, side effects, and appropriate dosing strategies of all sedative agents is needed to answer questions not sufficiently addressed in the current literature."( Sedation in the intensive care unit.
Hilton, A; Knudsen, N; Reves, JG; Young, C, 2000
)
0.31
" A second dose-effect determination demonstrated that rats chronically dosed with DZ or MZ pre-session displayed more contingent tolerance to alterations in peak force than rats that had received 36 drug injections postsession, where there was no opportunity to practice the force-discrimination response while under the drug state."( Behavioral tolerance to the force differentiation effects of diazepam and midazolam in rats.
Bowen, SE; Fowler, SC; Kallman, MJ; Stanford, JA, 2000
)
0.54
"Results of previous studies of rectal ketamine as a pediatric premedication are clouded because of lack of dose-response relation, inappropriate time of assessing sedative effects, and previous administration or coadministration of benzodiazepines."( Reevaluation of rectal ketamine premedication in children: comparison with rectal midazolam.
Nishikawa, T; Saito, A; Sato, M; Tanaka, M, 2000
)
0.53
" Dose-response determinations of ethanol, pentobarbital, midazolam, muscimol and morphine were made under the training condition of 30 min pretreatment interval."( Characterization of the discriminative stimulus effects of GABA(A) receptor ligands in Macaca fascicularis monkeys under different ethanol training conditions.
Azarov, A; Grant, KA; Green-Jordan, K; Szeliga, KT; Waters, CA, 2000
)
0.55
" These data demonstrate that multiple dosing of simvastatin, at the highest recommended clinical dose, does not significantly alter the in vivo hepatic or intestinal CYP3A4/5 activity as measured by the commonly used EBT and oral midazolam probes."( Simvastatin does not affect CYP3A activity, quantified by the erythromycin breath test and oral midazolam pharmacokinetics, in healthy male subjects.
Brucker, MJ; Gagliano, K; Gillen, L; Greenberg, HE; McLoughlin, D; Prueksaritanont, T; Rogers, JD; Vega, JM; Waldman, SA; Wong, PH, 2000
)
0.71
" Nevertheless, a major number of therapeutic failures were detected with 2% propofol because of the need for dosage increase."( Midazolam and 2% propofol in long-term sedation of traumatized critically ill patients: efficacy and safety comparison.
Alted Lopez, E; Peinado Rodriguez, J; Sa Borges, M; Sanchez-Izquierdo Riera, JA; Sandiumenge Camps, A; Toral Vazquez, D, 2000
)
1.75
" Dose-response studies of S(+)-ketamine for rectal premedication in pediatric anesthesia may be warranted."( S(+)-ketamine for rectal premedication in children.
Erlacher, W; Freitag, H; Greher, M; Höchtl, A; Marhofer, P; Semsroth, M, 2001
)
0.31
"Midazolam dosage varied between 5 and 14 mg."( A sedation technique for implant and periodontal surgery.
Boyle, CA; Craig, DC; Fleming, GJ; Palmer, P, 2000
)
1.75
" The pharmacokinetics of oral midazolam, a probe for intestinal and hepatic CYP3A activity, was not influenced by either the low (100 mg qd for 4 days) or high (600 mg qd for4 days) RG 12525 dosing regimen despite the resulting total plasma concentrations of inhibitor that were well above in vitro Ki values."( Lack of correlation between in vitro inhibition of CYP3A-mediated metabolism by a PPAR-gamma agonist and its effect on the clinical pharmacokinetics of midazolam, an in vivo probe of CYP3A activity.
Fayer, JL; Kirkesseli, S; Luo, Y; Sidhu, R; Stevens, JC; Zannikos, PN, 2001
)
0.8
" Fentanyl dosing strategies, with or without midazolam, do not prevent a hormonal or metabolic stress response in infants undergoing cardiac surgery."( Stress response in infants undergoing cardiac surgery: a randomized study of fentanyl bolus, fentanyl infusion, and fentanyl-midazolam infusion.
Casta, A; Chakravorti, S; Davis, PJ; Gruber, EM; Hansen, DD; Hickey, PR; Laussen, PC; McGowan, FX; Odegard, KC; Reid, R; Zimmerman, AA; Zurakowski, D, 2001
)
0.78
" To maintain comfort, drugs were required at doses substantially above standard dosing schemes."( Management of background pain and anxiety in critically burned children requiring protracted mechanical ventilation.
Querzoli, E; Sheridan, R; Stoddard, F,
)
0.13
"001) but times from dosing to discharge (medians 105 and 110 minutes) were similar."( Sedation for children requiring wound repair: a randomised controlled double blind comparison of oral midazolam and oral ketamine.
Kendall, JM; Younge, PA, 2001
)
0.53
" Patients weighing >50 kg and patients with traumatic brain injury (TBI) were evaluated separately to determine differences between north and south with regard to midazolam dosing and incidence of hypotension."( The use of midazolam for prehospital rapid-sequence intubation may be associated with a dose-related increase in hypotension.
Davis, DP; Kimbro, TA; Vilke, GM,
)
0.72
"The inhibition potential of drugs towards five major human hepatic cytochrome P450 (CYP) isozymes (CYP2A6, 3A4, 2C9, 2D6, and 2E1) was investigated via cassette dosing of the five probe substrates (coumarin, midazolam, tolbutamide, dextromethorphan, and chlorzoxazone) in human liver microsomes using a 96-well plate format."( High-throughput cytochrome P450 (CYP) inhibition screening via a cassette probe-dosing strategy. VI. Simultaneous evaluation of inhibition potential of drugs on human hepatic isozymes CYP2A6, 3A4, 2C9, 2D6 and 2E1.
Bu, HZ; Knuth, K; Magis, L; Teitelbaum, P, 2001
)
0.5
" We studied the dose-response characteristics of midazolam for reducing the diaphragmatic contractility in dogs."( Dose-response characteristics of midazolam for reducing diaphragmatic contractility.
Fujii, Y; Hoshi, T; Toyooka, H; Uemura, A, 2001
)
0.85
" The marked interpatient variability in pharmacokinetics explains in part, the substantial variation in dosage requirements of midazolam to produce sedation in critically ill pediatric patients."( Pharmacokinetics of midazolam in critically ill pediatric patients.
Anglin, D; Jones, PR; McMorrow, J; Nahara, MC; Rosenberg, R,
)
0.66
"Patient-controlled sedation (PCS) allows the patient to titrate the dosage of sedative drugs according to need."( Patient-controlled sedation with propofol for colonoscopy.
Kong, CF; Ng, JM; Nyam, D, 2001
)
0.31
" They were compared through a simulation study under six situations that could represent the underlying unknown dose-response (either toxicity or failure) relationship, in terms of sample size, probability of correct selection and bias of the response probability associated to the MTD (or MED)."( The continual reassessment method: comparison of Bayesian stopping rules for dose-ranging studies.
Chevret, S; Zohar, S, 2001
)
0.31
" Tolbutamide (CYP2C9), caffeine (CYP1A2), dextromethorphan (CYP2D6), oral midazolam (intestinal wall and hepatic CYP3A), and intravenous midazolam (hepatic CYP3A) were administered before, with short-term St John's wort dosing (900 mg), and after 2 weeks of intake (300 mg 3 times a day) to determine CYP activities."( The effects of St John's wort (Hypericum perforatum) on human cytochrome P450 activity.
Gorski, JC; Hall, SD; Hamman, MA; Huang, SM; Lesko, LJ; Wang, Z, 2001
)
0.54
" A study evaluating time-dependent alterations in the PK profile of TAM showed no change in apparent oral clearance (Cl(app)) during two weeks of chronic dosing with TAM."( Molecular and pharmacokinetic evaluation of rat hepatic and gastrointestinal cytochrome p450 induction by tamoxifen.
Cotreau, MM; Greenblatt, DJ; Harmatz, JS; von Moltke, LL, 2001
)
0.31
" The 2 h plasma concentration ratios from studies 1 and 2 were combined and a pooled analysis performed to compare ratios within each study (to determine the change in ratio when MDZ was dosed with and without chlorzoxazone) and between studies (to determine the consistency of the ratios when MDZ was given either as part of the two six drug cocktails or when given alone and as part of the five drug cocktail)."( An interaction between the cytochrome P450 probe substrates chlorzoxazone (CYP2E1) and midazolam (CYP3A).
Dickins, M; Gibson, A; Palmer, JL; Pleasance, S; Scott, RJ, 2001
)
0.53
" The A UC ratios of alpha-hydroxymidazolam to midazolam after IV dosing were similar across all age groups and were smaller than corresponding values following oral administration."( The single-dose pharmacokinetics of midazolam and its primary metabolite in pediatric patients after oral and intravenous administration.
Akbari, B; Blumer, JL; Kearns, GL; Khoo, KC; Pou, S; Reed, MD; Rodarte, A, 2001
)
0.87
"According to midazolam pharmacokinetic and pharmacodynamic variability, an individual dosage adjustment is essential for long-term sedation."( [Sedation induced by midazolam in intensive care: pharmacologic and pharmacokinetic aspects].
Bastien, O; Bolon, M; Boulieu, R; Flamens, C; Paulus, S, 2002
)
1
"The dosage of thiopental was 50 mg per kg for infants under 6 months of age, 35 mg per kg between six and 12 months, and 25 mg per kg for older children."( Efficacy and safety of rectal thiopental, intramuscular cocktail and rectal midazolam for sedation in children undergoing neuroimaging.
Alp, H; Altinkaynak, S; Güler, I; Orbak, Z, 2002
)
0.54
" It is also safe and effective at the dosage studied in children undergoing MRI."( Efficacy and safety of rectal thiopental, intramuscular cocktail and rectal midazolam for sedation in children undergoing neuroimaging.
Alp, H; Altinkaynak, S; Güler, I; Orbak, Z, 2002
)
0.54
"The time of induction and the propofol dosage in group M (2."( [Effects of midazolam premedication on induction doses of propofol and hemodynamic changes during tumor patient induction].
Lin, WQ; Tan, HY; Wang, J; Xu, MX; Zeng, WA, 2002
)
0.69
" Diazepam (30 micro M), but not midazolam (10 micro M), caused a downward shift in the dose-response curve to extracellular Ca(2+) for shortening, with no concomitant effect on peak intracellular Ca(2+) transient."( The differential effects of midazolam and diazepam on intracellular Ca2+ transients and contraction in adult rat ventricular myocytes.
Damron, DS; Kanaya, N; Murray, PA, 2002
)
0.89
" However, the situations suggest that we should carefully check the dosage and review the correct procedures, even when using a drug that is considered to be familiar with most practitioners."( Accidental overdose of midazolam as intramuscular premedication.
Hanaoka, K; Nishiyama, T, 2002
)
0.63
"Midazolam and metabolites were dosed in plasma and ultratiltration liquid by chromatography."( [Use of midazolam in postoperative sedation of patients with multiple organ failure treated with hemodiafiltration. Clinical study and pharmacokinetics].
Bastien, O; Bolon, M; Boulieu, R; Flamens, C; Lehot, JJ, 2002
)
2.19
" Plasma midazolam concentrations were obtained before dosing and at 5, 30, 60, 120, 240, 300, and 360 minutes after dosing and were assayed by liquid chromatography-tandem mass spectrometry."( Flumazenil reduces midazolam-induced cognitive impairment without altering pharmacokinetics.
Bertino, JS; Jones, CL; Morrison, AL; Nafziger, AN; Rocci, ML; Rogers, JF, 2002
)
1.08
" The cumulation dosage of propofol, sedative effect, variation of BP and SaO2 were observed in all patient."( [Associated sedation of propofol and midazolam in small dosage and gastroscopy].
Jiang, XW; Liu, SJ; Tang, WL, 2001
)
0.58
"The cumulative dosage of propofol in the experimental group was lower than that in the control group [(73."( [Associated sedation of propofol and midazolam in small dosage and gastroscopy].
Jiang, XW; Liu, SJ; Tang, WL, 2001
)
0.58
"In such a rapid operation of gastroscopy, the dosage of propofol in the experimental group is obviously less than that in the control group, while it does not affect the effect of sedation, the diagnose and cure time in gastroscopy room, and has more security and less cost."( [Associated sedation of propofol and midazolam in small dosage and gastroscopy].
Jiang, XW; Liu, SJ; Tang, WL, 2001
)
0.58
" We concluded that within this dosage midazolam does not have any antioxidant effect in reperfused rat kidneys following ischemia."( Is midazolam effective as an antioxidant in preventing reperfusion injury in rat kidney?
Aslan, R; Erol, A; Erol, U; Gurdal, M; Konukoğlu, D; Onmus, H, 2002
)
1.21
"6 mg/kg) was dose-related, but the dose-response relationship was not dependent upon the presence of midazolam."( Nicotine trace discrimination in rats with midazolam as a mediating stimulus.
Mariathasan, EA; Stolerman, IP, 2003
)
0.8
" After repeated NN703 dosing (day 9), NN703 levels reached steady state, and midazolam AUC further increased to 93% relative to baseline (P=0."( A clinical study investigating the pharmacokinetic interaction between NN703 (tabimorelin), a potential inhibitor of CYP3A4 activity, and midazolam, a CYP3A4 substrate.
Christiansen, T; Ilondo, MM; Olsen, AK; Rasmussen, MH; Schulz, R; Taub, ME; Thomsen, MS; Zdravkovic, M, 2003
)
0.75
" In this study, pretreatment with a small dosage of etomidate or midazolam was compared with placebo for the prevention of myoclonic muscle movements."( Midazolam pretreatment reduces etomidate-induced myoclonic movements.
Fritz, HG; Hueter, L; Schwarzkopf, KR; Simon, M, 2003
)
2
"3 mg/kg), and to compare the accuracy of the dosing of midazolam for ED RSI with the accuracy of dosing of other agents."( Underdosing of midazolam in emergency endotracheal intubation.
Barton, ED; Chiang, V; Sagarin, MJ; Sakles, JC; Vissers, RJ; Walls, RM, 2003
)
0.92
" More than half (56%) of the children, and nearly all (92%) of the adults, received dosages lower than the minimum recommended dosage (0."( Underdosing of midazolam in emergency endotracheal intubation.
Barton, ED; Chiang, V; Sagarin, MJ; Sakles, JC; Vissers, RJ; Walls, RM, 2003
)
0.67
"Underdosing of midazolam during ED RSI is frequent, and appears to be related to incorrect dosage selection, rather than to a deliberate intention to reduce the dose used."( Underdosing of midazolam in emergency endotracheal intubation.
Barton, ED; Chiang, V; Sagarin, MJ; Sakles, JC; Vissers, RJ; Walls, RM, 2003
)
1.02
" This software seems to be appropriate for providing significant help to the clinician for midazolam dosage adjustment, according to midazolam concentrations and clinical sedation."( Evaluation of the estimation of midazolam concentrations and pharmacokinetic parameters in intensive care patients using a bayesian pharmacokinetic software (PKS) according to sparse sampling approach.
Bastien, O; Bolon, M; Boulieu, R; Flamens, C; Paulus, S; Salord, F, 2003
)
0.82
" Group 1--bolus dosing of a 20% solution of gamma oxy-oil acid (GOOA), 75-100 mg/kg; group 2--bolus dosing of a 1% solution of thiopental sodium (5-7 mg/kg); and group 3--micro-flow introduction of dormycum (0."( [Central hemodynamics during therapeutic sedation in children under artificial pulmonary ventilation].
Nikitin, VV; Ostreĭkov, IF; Petrova, ZhI; Shtatnov, MK; Tarasov, SV,
)
0.13
"5 mg kg(-1) at 15 min after induction of anaesthesia directly followed by a maintenance dosage of 50 microg kg(-1) min(-1), while the control group received saline (i."( Effects of intravenous lidocaine on isoflurane concentration, physiological parameters, metabolic parameters and stress-related hormones in horses undergoing surgery.
Dzikiti, TB; Hellebrekers, LJ; van Dijk, P, 2003
)
0.32
" 3 Our data, together with the results of the audit, would suggest many endoscopists are employing unnecessarily large and at times potentially dangerous doses of intravenous sedation in elderly patients and that the vast majority of upper gastrointestinal endoscopies can be performed successfully, without topical pharyngeal anaesthesia, using a bolus injection techniquewith a reduced dosage of sedative agent."( Small bolus injections of intravenous midazolam for upper gastrointestinal endoscopy: a study of 788 consecutive cases.
Bell, GD; Jones, JG; Morden, AE; Quine, MA; Smith, MR; Spencer, GM, 1993
)
0.56
"05 mg/kg over a 30-minute period) and oral doses of midazolam (3-8 mg of a stable isotope, (15)N(3)-midazolam) before and after 7 days of rifampin dosing (600 mg once daily in the evening)."( The effect of age, sex, and rifampin administration on intestinal and hepatic cytochrome P450 3A activity.
Ambrosius, WT; Bruce, MA; Gorski, JC; Haehner-Daniels, B; Hall, SD; Hamman, MA; Vannaprasaht, S, 2003
)
0.57
" The incidental finding of greater M7 formation after basolateral compared with apical dosing could not be explained by differences in saquinavir cell content."( Contributions of CYP3A4, P-glycoprotein, and serum protein binding to the intestinal first-pass extraction of saquinavir.
Mouly, SJ; Paine, MF; Watkins, PB, 2004
)
0.32
" However, problems concerning the role of sedation in diagnostic upper endoscopy are a matter for debate as little is known about dosage and timing."( Intravenous midazolam sedation in pediatric diagnostic upper digestive endoscopy. A prospective study in a general hospital.
Mulder, CJ; Verhage, J; Willekens, FL, 2003
)
0.7
" Dosing of the analgesics and sedatives was based on a neonatal sedation score for ventilated infants."( Endogenous distress in ventilated full-term newborns with acute respiratory failure.
Aretz, S; Licht, C; Roth, B, 2004
)
0.32
" There was no difference in blood pressure and blood glucose concentrations following the cocktail and dosing of the individual probes."( Pharmacokinetic and pharmacodynamic assessment of a five-probe metabolic cocktail for CYPs 1A2, 3A4, 2C9, 2D6 and 2E1.
Aherne, Z; Blakey, GE; Lockton, JA; Norwood, P; Perrett, J; Plume, J; Russell, M, 2004
)
0.32
"The five probe drugs when coadministered, in this dosing regimen, demonstrated no evidence of either a metabolic or pharmacodynamic interaction that might confound the conclusions drawn during a cocktail study."( Pharmacokinetic and pharmacodynamic assessment of a five-probe metabolic cocktail for CYPs 1A2, 3A4, 2C9, 2D6 and 2E1.
Aherne, Z; Blakey, GE; Lockton, JA; Norwood, P; Perrett, J; Plume, J; Russell, M, 2004
)
0.32
" Because metabolism of some chemotherapeutic agents may involve CYP3A4, the potential inductive effect of the CINV dosing regimen of aprepitant on this metabolic pathway was evaluated using intravenous midazolam, a sensitive probe substrate of CYP3A4."( Evaluation of potential inductive effects of aprepitant on cytochrome P450 3A4 and 2C9 activity.
Blum, RA; Bradstreet, TE; Evans, JK; Gargano, C; Lee, Y; Majumdar, AK; Petty, KJ; Shadle, CR, 2004
)
0.51
" Deramciclane had no effect on alcohol consumption in either acute or repeated dosing study."( Comparison of deramciclane to benzodiazepine agonists in behavioural activity of mice and in alcohol drinking of alcohol-preferring rats.
Honkanen, A; Ingman, K; Korpi, ER; Sallinen, J, 2004
)
0.32
" The mean dosage for midazolam was 18."( Use of sedation to relieve refractory symptoms in dying patients.
Blitz-Lindeque, J; Bridge, D; Cameron, D, 2004
)
0.64
" Regular evaluation of the effect of these drugs and subsequent adaptation of dosage are more important than the choice of specific analgesics and hypnotics."( Analgesia and sedation in critically ill patients.
Tramèr, MR; Walder, B, 2004
)
0.32
" It seems that the 5 mg dosage works better than the lower one."( Supplementing epidural lidocaine with midazolam: effect on sensorymotor block level.
Islami, M; Sajedi, P, 2004
)
0.59
" However, a great variability of the drug effect between patients could be demonstrated, which, as a consequence, may complicate the development of dosing strategies based on midazolam plasma concentrations to better control sedation in critically ill patients."( Midazolam therapeutic drug monitoring in intensive care sedation: a 5-year survey.
Bremer, F; Reulbach, U; Schüttler, J; Schwilden, H, 2004
)
1.96
"The purpose of the case study was to investigate the effect from the bolus dosing of midazolam and ketamine on the autonomic hemostasis in patients with ischemic heart disease (IHD) with the prevalence of the activity of sympathetic or parasympathetic parts in the autonomic nervous system."( [Effect of intravenous hypnotics on autonomic response in patients with ischemic heart disease].
Aksel'rod, BA; Babalian, GV; Shmyrin, MM,
)
0.36
" In 20 of the 21 patients midazolam dosing could be effectively titrated to the desired level of sedation, assessed by the COMFORT scale."( Pharmacodynamics of midazolam in pediatric intensive care patients.
de Hoog, M; de Wildt, SN; Joosten, KF; van den Anker, JN; van Dijk, M; Vinks, AA, 2005
)
0.95
" CYP3A4 is the primary enzyme responsible for CYP-mediated metabolism of QTP in clinical therapy dosage in vivo."( Metabolic mechanism of quetiapine in vivo with clinical therapeutic dose.
Cheng, ZN; Li, HD; Li, KY; Li, X, 2005
)
0.33
" The maximum serum concentration after oral midazolam dosing was significantly different between the 2 groups."( Activity of CYP2E1 and CYP3A enzymes in adults with moderate alcohol consumption: a comparison with nonalcoholics.
Chalasani, N; Gorski, JC; Hall, SD; Kolwankar, D; Liangpunsakul, S; Pinto, A, 2005
)
0.59
" Sedation dosage was standardized for each patient based on age, gender and weight from a previously published dosing nomogram."( The effect of moderate sedation on exocrine pancreas function in normal healthy subjects: a prospective, randomized, cross-over trial using the synthetic porcine secretin stimulated Endoscopic Pancreatic Function Test (ePFT).
Conwell, DL; Dumot, J; Fein, S; O'laughlin, C; Purich, E; Trolli, P; Vanlente, F; Vargo, J; Zuccaro, G, 2005
)
0.33
" Younger children required a higher dosage (p=0."( Use of midazolam and ketamine as sedation for children undergoing minor operative procedures.
Chan, GC; Cheuk, DK; Ha, SY; Lau, YL; Lee, TL; Ma, E; Wong, WH, 2005
)
0.78
" A trend was noted for midazolam to prolong recovery times as the dosage increased."( Melatonin vs. midazolam premedication in children: a double-blind, placebo-controlled study.
Albassam, A; Aldammas, F; Alotibi, W; Naguib, M; Riad, W; Samarkandi, A; Thalaj, A, 2005
)
1
" However, various dosing regimens when used alone or in combination have variable efficacy and side effect profile."( Comparative evaluation of midazolam and ketamine with midazolam alone as oral premedication.
Chari, P; Ghai, B; Grandhe, RP; Kumar, A, 2005
)
0.63
"Because the rates at which therapeutics are cleared from the body can affect their effectiveness, knowing and accounting for the variables that contribute to drug clearance is of utmost importance when designing a drug dosage regimen for patients."( CYP3A probes can quantitatively predict the in vivo kinetics of other CYP3A substrates and can accurately assess CYP3A induction and inhibition.
Kharasch, ED; Thummel, KE; Watkins, PB, 2005
)
0.33
" The dosage of lamotrigine was increased and the patient received clonazepam intravenously, but a new seizure quickly occurred."( [Epileptic seizures during childbirth in a patient with idiopathic generalised epilepsy].
Bloem, BR; Renier, WO; Voermans, NC; Zwarts, MJ, 2005
)
0.33
" We undertook this study to assess the sedative drug doses administered during bronchoscopy in lung transplant recipients and to assess if there is a change in the dosage requirements over time following lung transplantation."( Sedative drug requirements during bronchoscopy are higher in cystic fibrosis after lung transplantation.
Aboyoun, C; Chhajed, PN; Chhajed, TP; Glanville, AR; Harrison, GA; Leuppi, JD; Malouf, MA; Tamm, M, 2005
)
0.33
"To determine the clinical sedative effect and dosage of intranasal midazolam in refraction and fundus examination of children with strabismus."( Evaluation of intranasal midazolam in refraction and fundus examination of young children with strabismus.
Altintas, O; Caglar, Y; Demirci, G; Karabas, VL; Onur, I,
)
0.67
" Dose-response curves to benzodiazepines on peak [Ca2+]i and shortening were not affected by pretreatment with Bay K 8644 (0."( Effects of L-type Ca2+ channel modulation on direct myocardial effects of diazepam and midazolam in adult rat ventricular myocytes.
Damron, DS; Kanaya, N; Murray, PA, 2006
)
0.56
"Correct dosing of drugs in neonates, infants and children is hampered by a general lack of knowledge about drug disposition in this population."( Prediction of cytochrome p450-mediated hepatic drug clearance in neonates, infants and children : how accurate are available scaling methods?
Björkman, S, 2006
)
0.33
" Blood samples were collected during each day of midazolam dosing to determine plasma midazolam concentrations."( Duration of pleconaril effect on cytochrome P450 3A activity in healthy adults using the oral biomarker midazolam.
Bertino, JS; Liu, S; Ma, JD; Nafziger, AN; Rhodes, G, 2006
)
0.8
" The model improves the accuracy of predicting the inhibitory effect of increasing KTZ dosing on MDZ PK by incorporating a saturable KTZ efflux from the site of enzyme inhibition in the liver."( Stochastic prediction of CYP3A-mediated inhibition of midazolam clearance by ketoconazole.
Chien, JY; Ernest, CS; Gorski, JC; Hall, SD; Lucksiri, A; Wrighton, SA, 2006
)
0.58
" Two groups had seven days of repeated dosing with either midazolam 100 microg/kg/day (repeat midazolam group) or 10 microg/kg/day neostigmine (repeat neostigmine group)."( The neurotoxic effects of intrathecal midazolam and neostigmine in rabbits.
Demirel, E; Dolgun, H; Egemen, N; Kahilogullari, G; Kecik, Y; Sargon, ME; Ugur, HC, 2006
)
0.85
" This makes precise dosing difficult to achieve clinically, which may compromise safe therapy."( Ketoconazole renders poor CYP3A phenotype status with midazolam as probe drug.
Fan, L; Goh, BC; Lee, HS; Lee, SC; Ong, AB; Soo, R; Sukri, N; Tham, LS; Wang, L; Yong, WP, 2006
)
0.58
"Marked interindividual variation in drug disposition and toxicity pose an ongoing challenge to chemotherapy dosage individualization."( Predictors of vinorelbine pharmacokinetics and pharmacodynamics in patients with cancer.
Ackland, SP; Balleine, RL; Blair, EY; Clarke, CL; Collins, M; Evans, S; Farlow, D; Garg, MB; Gurney, H; Hoskins, JM; Mann, GJ; McLachlan, AJ; Rivory, LP; Wong, M, 2006
)
0.33
" Although higher exposure to gefitinib occurs in individuals who are poor CYP2D6 metabolisers, genotyping prior to initiation of therapy and dosage adjustment are not warranted."( Exploring the relationship between expression of cytochrome P450 enzymes and gefitinib pharmacokinetics.
Cantarini, MV; Fuhr, R; Holt, A; Swaisland, HC, 2006
)
0.33
" However, it provides a valuable aid to decision-making with regard to first-time dosing in children and study design."( Prediction of the clearance of eleven drugs and associated variability in neonates, infants and children.
Johnson, TN; Rostami-Hodjegan, A; Tucker, GT, 2006
)
0.33
"A comparison of clearance and peak and systemic exposure to midazolam following administration of roflumilast indicated no effect of roflumilast dosed to steady state on the pharmacokinetics of midazolam."( Lack of a pharmacokinetic interaction between steady-state roflumilast and single-dose midazolam in healthy subjects.
Blume, H; Erb, KA; Hermann, R; Knoerzer, D; Lahu, G; Nassr, N; Reutter, F; Schug, B; von Richter, O; Zech, K, 2007
)
0.8
" Twenty-four hours after ischemia, five rats in each group were killed by injecting the above dosage of ketamine or ketamine-midazolam intraperitoneally and infarct size was measured."( Effects of ketamine-midazolam anesthesia on the expression of NMDA and AMPA receptor subunit in the peri-infarction of rat brain.
Liu, Y; Qiu, SD; Tian, YF; Wang, Y; Zhang, PB; Zhang, YL, 2006
)
0.86
" The midazolam cohort had an increased use of nonintravenous route for initial dosing (65% vs."( Midazolam and diazepam for pediatric seizures in the prehospital setting.
Frederick, C; Warden, CR,
)
2.09
"Variable interindividual expression of cytochrome P450 3A presents a challenge in dosing drugs."( Drug-metabolizing enzyme inhibition by ketoconazole does not reduce interindividual variability of CYP3A activity as measured by oral midazolam.
Bertino, JS; Chen, M; Nafziger, AN, 2006
)
0.54
" Reduction of the barbiturate dosage resulted in clinical and subclinical partial seizures appearing repetitively in clusters."( Acute encephalitis with refractory, repetitive partial seizures: case reports of this unusual post-encephalitic epilepsy.
Inoue, T; Maegaki, Y; Nanba, Y; Ogura, K; Ohno, K; Okamoto, R; Saito, Y; Takahashi, Y; Togawa, M, 2007
)
0.34
" CYP2C9 probe (tolbutamide, 125 mg) and CYP3A4 probe (midazolam, 8 mg) were orally administered to 10 male healthy volunteers before and after GBE intake (360 mg/d) for 28 days, and they received 75 g glucose after the dosing of tolbutamide."( Effects of Ginkgo biloba extract on pharmacokinetics and pharmacodynamics of tolbutamide and midazolam in healthy volunteers.
Li, XD; Maruyama, S; Ohashi, K; Ohmori, Y; Oki, T; Uchida, S; Umegaki, K; Watanabe, H; Yamada, H; Yamada, S, 2006
)
0.8
" A noninvasive dosing line was placed in the duodenum by use of endoscopy, and 50% dextrose (3 ml/kg) was administered."( Comparison of three anesthetic protocols for intraduodenal drug administration using endoscopy in rhesus monkeys (Macaca mulatta).
Authier, S; Breault, C; Chaurand, F; Legaspi, M; Troncy, E, 2006
)
0.33
"The total analgesic dosage and PCA dosage in the two groups were similar (P>0."( [Low-dose ketamine combined with fentanyl for intravenous postoperative analgesia in elderly patients].
Chen, YM; Liang, SW; Lin, CS, 2006
)
0.33
" Midazolam was administered by a titration dosage to achieve a sedation score of three (M group)."( Amnesia for electric dental pulp stimulation and picture recall test under different levels of propofol or midazolam sedation.
Ichinohe, T; Kaneko, Y; Matsuki, Y, 2007
)
1.46
" The dental records were examined using a standard pro forma sheet and data collected for: age, previous behaviour using the Frankl [1962] scale, units of work planned and achieved using the modified index of O'Sullivan and Curzon [1991], midazolam dosage and treatment outcome."( Effectiveness of oral midazolam for paediatric dental care: a retrospective study in two specialist centres.
Day, PF; Hibbert, SA; Paterson, SA; Power, AM, 2006
)
0.83
" The median dosage used for sedation was 5 mg midazolam (range 2-5 mg) and 160 mg propofol (range 70-320 mg)."( The effect of sedation on the quality of upper gastrointestinal endoscopy: an investigator-blinded, randomized study comparing propofol with midazolam.
Bajbouj, M; Burzin, M; Frankenberger, U; Kassem, AM; Meining, A; Prinz, C; Reichenberger, J; Sander, R; Schmid, RM; Semmler, V, 2007
)
0.8
" As yet, standardized dosing regimens for individual patients do not exist."( Endoscopist administered sedation during ERCP: impact of chronic narcotic/benzodiazepine use and predictive risk of reversal agent utilization.
Baron, TH; Gleeson, FC; Papachristou, DJ; Papachristou, GI; Petersen, BT, 2007
)
0.34
" Within 2 days the children age 1-4 years received the maximum midazolam dosage (0."( Age is of influence on midazolam requirements in a paediatric intensive care unit.
de Gast-Bakker, DA; Plötz, FB; Sibarani-Ponsen, R; Swart, EL; van der Werff, SD, 2007
)
0.89
" These results might suggest that CYP2D and 3A substrates should be prescribed for male and female cats using different dosage regimen."( Characterization of cytochrome P450-mediated drug metabolism in cats.
Regmi, NL; Sanda, S; Sasaki, K; Shah, SS; Shimoda, M, 2007
)
0.34
" In addition to increased clinical attention, future research efforts are essential to delineate precise dosing guidelines and mechanisms of the effect of hypothermia on drug disposition and response."( Effects of hypothermia on drug disposition, metabolism, and response: A focus of hypothermia-mediated alterations on the cytochrome P450 enzyme system.
Kochanek, PM; Poloyac, SM; Tortorici, MA, 2007
)
0.34
" Dosage C in contrast had fewer side effects but less favourable cardiovascular results and a longer recovery period."( A comparative clinical study of three different dosages of intramuscular midazolam-medetomidine-ketamine immobilization in cats.
Busch, R; Ebner, J; Erhardt, W; Henke, J; Wehr, U, 2007
)
0.57
"Fixed dosing was found to be feasible, without increased variability of clearance or neutrophil toxicity compared to BSA-based dosing."( A phase I study of docetaxel with ketoconazole modulation in patients with advanced cancers.
Goh, BC; Lee, HS; Lee, SC; Soo, R; Sukri, N; Tham, LS; Wang, LZ; Wong, CI; Yong, WP, 2008
)
0.35
"Group M: mean dosage of pethidine and midazolam 88."( Midazolam and pethidine versus propofol and fentanyl patient controlled sedation/analgesia for upper gastrointestinal tract ultrasound endoscopy: a prospective randomized controlled trial.
Agostoni, M; Arcidiacono, PG; Fanti, L; Gemma, M; Strini, G; Testoni, PA; Torri, G, 2007
)
2.05
" The addition of flumazenil showed no significant difference to atipamezole alone, but subcutaneous administration of atipamezole alone was not sufficient in the dosage used to show an advantage compared to non-reversed cats."( Partial antagonization of midazolam-medetomidine-ketamine in cats--atipamezole versus combined atipamezole and flumazenil.
Baumgartner, C; Ebner, J; Erhardt, W; Henke, J; Wehr, U, 2007
)
0.64
" Seven healthy volunteers were dosed with carbamazepine over 16 consecutive days."( Pharmacodynamics of carbamazepine-mediated induction of CYP3A4, CYP1A2, and Pgp as assessed by probe substrates midazolam, caffeine, and digoxin.
Cederberg, J; Dahl, ML; Karlsson, MO; Magnusson, MO; Sandström, R, 2008
)
0.56
"The primary objective of the present study was to compare the dosage of intravenous propofol required in patients being sedated with propofol alone (group P) with the dosage of propofol required in patients who also received an oral dose of midazolam (group M + P) for endoscopic retrograde cholangiopancreatography (ERCP) procedures."( Deep sedation for endoscopic retrograde cholangiopancreatography: intravenous propofol alone versus intravenous propofol with oral midazolam premedication.
Chlouverakis, G; Manolaraki, MM; Paspatis, GA; Theodoropoulou, A; Vardas, E, 2008
)
0.73
"Our data suggest that synergistic sedation with an oral dose of midazolam combined with intravenous propofol can provide a significant benefit, with a reduction in the dosage of propofol required and in patient anxiety levels before ERCP."( Deep sedation for endoscopic retrograde cholangiopancreatography: intravenous propofol alone versus intravenous propofol with oral midazolam premedication.
Chlouverakis, G; Manolaraki, MM; Paspatis, GA; Theodoropoulou, A; Vardas, E, 2008
)
0.79
" The dosage of anesthetic medications administered was also recorded for each patient."( Metoclopramide does not influence the frequency of propofol-induced spontaneous movements.
Ahmed, SA; Herazo, L; Iyer, C; Joshi, GP; Lenkovsky, F; Markin, V; Robertson, BD; Ross, L, 2007
)
0.34
" Dosage adjustments may be required for drugs that are substrates of CYP3A4 (e."( Interaction profile of armodafinil with medications metabolized by cytochrome P450 enzymes 1A2, 3A4 and 2C19 in healthy subjects.
Darwish, M; Hellriegel, ET; Kirby, M; Robertson, P, 2008
)
0.35
"To determine the safety, effectiveness, and dosing of dexmedetomidine in intensive care infants and children who require sedation, and the rationale for patient selection."( Use of dexmedetomidine in the pediatric intensive care unit.
Buck, ML; Willson, DF, 2008
)
0.35
" Our study suggests that the clinical dosage of UDCA could not affect both hepatic and intestinal CYP3A activities and that the drug interaction between UDCA and substrates for CYP3A is unlikely in humans."( Effects of ursodeoxycholic acid on the pharmacokinetics and pharmacodynamics of intravenous and oral midazolam in healthy volunteers.
Inui, N; Luo, J; Misaka, S; Ohashi, K; Takeuchi, K; Uchida, S; Watanabe, H; Yamada, S; Yan, D; Yang, Y, 2008
)
0.56
" Demographic data, time in ED, and dosage of each medication given were abstracted."( Inadequate provision of postintubation anxiolysis and analgesia in the ED.
Bonomo, JB; Butler, AS; Lindsell, CJ; Venkat, A, 2008
)
0.35
" These findings suggest that differential affinities for solute carriers should be considered when selecting an appropriate phenotypic probe to allow tailored dosing of pharmaceuticals that are CYP3A4 substrates."( Influence of solute carriers on the pharmacokinetics of CYP3A4 probes.
Baker, SD; Franke, RM; Mathijssen, RH; Schuetz, EG; Sparreboom, A, 2008
)
0.35
"The significant interindividual and intraindividual variability in the blood concentrations of the most commonly used calcineurin inhibitors such as tacrolimus and cyclosporine makes the exact dosing of these agents in transplant recipients very challenging."( Altered first-pass effects in a liver transplant recipient explained intraindividual variation in calcineurin inhibitor concentrations: a case report.
Chalasani, NP; Gorski, JC; Hall, SD; Malireddy, SR; Pinto, AG, 2008
)
0.35
"A liver transplant recipient, who had previously presented with tacrolimus toxicity on his usual dosing regimen and intolerant to standard doses of cyclosporine, was selected to undergo the study."( Altered first-pass effects in a liver transplant recipient explained intraindividual variation in calcineurin inhibitor concentrations: a case report.
Chalasani, NP; Gorski, JC; Hall, SD; Malireddy, SR; Pinto, AG, 2008
)
0.35
" Longer duration of use and high dosing are risk factors for development of withdrawal symptoms in children."( Withdrawal symptoms in critically ill children after long-term administration of sedatives and/or analgesics: a first evaluation.
de Hoog, M; Gamel, C; Ista, E; Tibboel, D; van Dijk, M, 2008
)
0.35
" Although IM and buccal administration of MDZ may be more practical in peripheral healthcare facilities, the efficacy appears to be poorer at the dose used, and a different dosage regimen might improve the efficacy."( Pharmacokinetics and clinical efficacy of midazolam in children with severe malaria and convulsions.
Edwards, G; Kokwaro, GO; Muchohi, SN; Newton, CR; Ogutu, BR; Ward, SA, 2008
)
0.61
"Combination of midazolam and propofol can not only ensure anterograde amnesia in critical patients, reduce drug dosage and adverse reactions, but also can help reduce the hospital expenses."( [Effects of combination of midazolam and propofol on anterograde amnesia in critical patients].
Dai, TJ; Li, JQ; Li, L; Li, MQ; Liu, J; Lu, F; Mo, X; Xu, JY; Xu, YJ; Zhang, Z, 2008
)
1
" Blood samples were collected predose and at selected time points up to 24 hours after dosing with midazolam for measurement of midazolam pharmacokinetic parameters."( Cinacalcet does not affect the activity of cytochrome P450 3A enzymes, a metabolic pathway for common immunosuppressive agents : a randomized, open-label, crossover, single-centre study in healthy volunteers.
Emery, M; Padhi, D; Salfi, M, 2008
)
0.56
" Dosage adjustments based on these covariates are, therefore, necessary."( Effects of age and gender on intravenous midazolam premedication: a randomized double-blind study.
Chen, PY; Chia, YY; Hsu, MC; Shaw, FZ; Sun, GC, 2008
)
0.61
"A higher dosage of midazolam is required for loss of response to verbal stimulation during unilateral spinal anesthesia than during bilateral spinal anesthesia."( Midazolam dose for loss of response to verbal stimulation during the unilateral or bilateral spinal anesthesia.
Jeon, YT; Kim, YC; Kim, YH; Oh, AY; Yun, MJ, 2009
)
2.12
"The case is reported of a female patient with attack-like neuropathic pain following lower arm injury with repeated respiratory depression and unconsciousness even after several administrations of sufficiently dosed analgetics for suppression of the attacks."( [Life-threatening respiratory depression after pain therapy].
Gläser, M; Kohlhaas, K; Maier, C; Tegenthoff, M, 2008
)
0.35
"One study in sedated patients demonstrated a reduction in pain score but not midazolam dosage when warm water infusion was used to manage colonic spasm."( Pilot feasibility study of the method of water infusion without air insufflation in sedated colonoscopy.
Leung, FW; Leung, JW; Mann, S; Salera, R; Toomsen, L, 2009
)
0.58
" As compared with 4% lidocaine, however, 2% lidocaine requires a smaller dosage and results in lower plasma concentrations."( Spray-as-you-go airway topical anesthesia in patients with a difficult airway: a randomized, double-blind comparison of 2% and 4% lidocaine.
Guo, XL; He, N; Liao, X; Liu, HP; Xu, XZ; Xu, YC; Xue, FS; Yang, QY; Zhang, YM, 2009
)
0.35
" Here we preliminarily demonstrate the model's utility to predict midazolam pharmacokinetics following intravenous bolus dosing in women undergoing Caesarian section."( Physiologically based pharmacokinetic model of midazolam disposition during pregnancy.
Andrew, MA; Hebert, MF; Vicini, P, 2008
)
0.84
" Therefore, patients with advanced cirrhosis may have greater drug exposure following oral dosing as a result of both impaired liver function and decreased intestinal CYP3A expression and activity."( Reduced duodenal cytochrome P450 3A protein expression and catalytic activity in patients with cirrhosis.
Blough, DK; Hashizume, T; Lin, YS; Mathisen, TL; McConn, DJ; Shuhart, MC; Taylor, SL; Thummel, KE; Xu, Y, 2009
)
0.35
" An electroencephalographic burst-suppression should be targeted for about 24 hour, before progressive weaning of the dosage under EEG monitoring."( [Drug treatment of refractory status epilepticus].
Rossetti, AO; Santoli, F, 2009
)
0.35
" However, midazolam given in the designated dosage did not offer any modulatory effects on hemodynamic responses, multiple organic dysfunction and survival rate in rats with endotoxemia."( Effects of midazolam on organ dysfunction in rats with endotoxemia induced by lipopolysaccharide.
Ho, ST; Liaw, WJ; Tsao, CM; Wu, CC, 2009
)
1.15
" Further studies should address the optimization of dosing and lock out setting."( Remifentanil vs. meperidine for patient-controlled analgesia during colonoscopy: a randomized double-blind trial.
Agostoni, M; Alberto, TP; Antonio, F; Facciorusso, A; Fanti, L; Gambino, G; Gemma, M; Giorgio, T; Giulia, G; Guslandi, M; Marco, G; Mario, G; Massimo, A; Testoni, PA; Torri, G, 2009
)
0.35
" Optimal INM dosing strategies for uncooperative children undergoing TTE are largely unknown, including second-dose INM strategies, introduced to maximize the potential for successful sedation and minimize risk."( Minimal sedation second dose strategy with intranasal midazolam in an outpatient pediatric echocardiographic setting.
DeGroff, CG; Lazol, JP, 2009
)
0.6
"The influence of increasing the dosage of ketamine on anaesthesia induced by a combination of ketamine, xylazine and midazolam in pigs was determined by assessing the onset of action (OAN), duration of analgesia (DAN), anaesthesia time (ANT), and recovery time (RCT) in 10 growing pigs (Mean weight: 18."( Increasing ketamine dose enhances the anaesthetic properties of ketamine-xylazine-midazolam combinations in growing pigs.
Adeleye, OE; Ajadi, RA; Makinde, AF; Smith, OF, 2008
)
0.78
", 5-min pretreatment) shifted the ethanol, PB, and midazolam dose-response functions rightward in a vast majority of monkeys tested (15/15, 16/17, and 11/12, respectively)."( Antagonism of the ethanol-like discriminative stimulus effects of ethanol, pentobarbital, and midazolam in cynomolgus monkeys reveals involvement of specific GABA(A) receptor subtypes.
Grant, KA; Helms, CM; Rogers, LS, 2009
)
0.82
" Anticonvulsant effective doses (ED(50)) were determined using an up-down dosing procedure over successive animals."( Protection against sarin-induced seizures in rats by direct brain microinjection of scopolamine, midazolam or MK-801.
McDonough, JH; Shih, TM; Skovira, JW, 2010
)
0.58
" The present study has shown that the pharmacokinetics of midazolam at relatively low doses are linear for both intravenous and oral dosing regimens."( Pharmacokinetics and pharmacodynamics of low doses of midazolam administered intravenously and orally to healthy volunteers.
Imai, H; Inui, N; Misaka, S; Nishio, S; Ohashi, K; Uchida, S; Watanabe, H; Yamada, S, 2010
)
0.85
" Therefore, we tested the dose-response direct cardiac effects of clinically available induction agents in an isolated septic rat heart model."( Cardiac effects of induction agents in the septic rat heart.
Busse, H; Graf, BM; Lunz, D; Sinner, B; Zausig, YA; Zink, W, 2009
)
0.35
" He had received therapeutic dosing of phenobarbital and midazolam up to 5 hours prior to a brain death examination."( A 10-month-old infant with reversible findings of brain death.
deCaen, AR; Duff, J; Joffe, AR; Kolski, H, 2009
)
0.6
"5-mg/kg dosing regimen was well tolerated and effective for sedation during colonoscopy and was associated with higher rates of sedation success, memory retention, and physician satisfaction than the fospropofol 2-mg/kg dose."( A randomized, double-blind, phase 3 study of fospropofol disodium for sedation during colonoscopy.
Cattau, E; Cohen, LB; Goetsch, A; Kline, JM; Rex, DK; Shah, A; Weber, JR,
)
0.13
"Transcutaneous PCO(2 )(PtcCO(2)), oxygen saturation, patients' tolerance, time after FB until recovery and application of drug dosage were assessed in patients receiving either midazolam with alfentanil (n = 15) or midazolam alone (n = 15) for sedation for FB."( Sedation during flexible bronchoscopy in patients with pre-existing respiratory failure: Midazolam versus Midazolam plus Alfentanil.
Dreher, M; Ekkernkamp, E; Kabitz, HJ; Storre, JH; Windisch, W, 2010
)
0.78
" Single-dose escalation from 50 to 400 mg resulted in a 164-fold increase in GS-9350 exposure, whereas multiple-dose escalation in the dosage range of 50-300 mg resulted in a 47-fold increase in exposure."( Pharmacokinetics and pharmacodynamics of GS-9350: a novel pharmacokinetic enhancer without anti-HIV activity.
German, P; Hui, J; Jain, A; Kearney, BP; Mathias, AA; Murray, BP; Warren, D; Wei, L; West, S, 2010
)
0.36
" No significant difference in the AUC after oral dosing of MDZ was noted between sexes."( Sex-dependent differences in cytochrome P450 3A activity as assessed by midazolam disposition in humans: a meta-analysis.
Hu, ZY; Zhao, YS, 2010
)
0.59
" Main outcomes recorded were dosage of lidocaine administered and amount of conscious sedation (midazolam and fentanyl) administered for pain management."( A review of physician anaesthesia prescribing practices in an abortion clinic in British Columbia.
Fitzsimmons, BP; Hodgson, ZG; MacKay-Dunn, MH; Mo, D, 2010
)
0.58
" AKI unpredictably affects the pharmacokinetics and pharmacodynamics of drugs and dosing in patients with AKI is largely based on data from chronic kidney disease patients, but how appropriately is unknown."( Using drug probes to monitor hepatic drug metabolism in critically ill patients: midazolam, a flawed but useful tool for clinical investigation of CYP3A activity?
Kirwan, C; MacPhee, I; Philips, B, 2010
)
0.59
"The dose-response relationship of intrathecal midazolam was not evaluated in our study, so further study should be conducted with different doses of intrathecal midazolam for management of PHN."( Efficacy of intrathecal midazolam with or without epidural methylprednisolone for management of post-herpetic neuralgia involving lumbosacral dermatomes.
Dureja, GP; Jamal, A; Khan, M; Tahseen, M; Usmani, H,
)
0.7
" General anaesthesia was effective in 100% of cases with a dosage of propofol, ranging between 20 mg to a maximum of 80 mg, after 5 mg of midazolam was administered."( General anaesthesia for external electrical cardioversion of atrial fibrillation: experience of an exclusively cardiological procedural management.
Angheben, C; Bergamini, C; Cicoira, M; Lanza, D; Morani, G; Pozzani, L; Tomasi, L; Vassanelli, C, 2010
)
0.56
" Moreover, the association of midazolam and a very small dosage of propofol, given their synergic action, is effective and safe in inducing anaesthesia."( General anaesthesia for external electrical cardioversion of atrial fibrillation: experience of an exclusively cardiological procedural management.
Angheben, C; Bergamini, C; Cicoira, M; Lanza, D; Morani, G; Pozzani, L; Tomasi, L; Vassanelli, C, 2010
)
0.65
" The dosage range of midazolam in this study fits the recommendations of the Dutch national guideline on palliative sedation, although international studies show smaller dosage ranges."( The practice of continuous palliative sedation in elderly patients: a nationwide explorative study among Dutch nursing home physicians.
Hasselaar, JG; Koopmans, RT; Krijnsen, PJ; Van Deijck, RH; Verhagen, SC; Vissers, KC, 2010
)
0.68
" The most common diazepam dosage was 10 mg every 6 hours, and individual doses ranged from 5 to 30 mg."( Diazepam as a component of goal-directed sedation in critically ill trauma patients.
Birrer, KL; Cheatham, ML; Dasta, JF; Gesin, G; Kane-Gill, SL; Kolnik, LJ, 2011
)
0.37
"Based on this limited sample, the use of diazepam as a component of goal-directed therapy appears safe and effective in providing adequate sedation in critically ill trauma patients using an average dosage of 40 mg/d."( Diazepam as a component of goal-directed sedation in critically ill trauma patients.
Birrer, KL; Cheatham, ML; Dasta, JF; Gesin, G; Kane-Gill, SL; Kolnik, LJ, 2011
)
0.37
" Rifampin's effect on the AUC(0-3 h) of digoxin was biphasic: the AUC(0-3 h) increased with concomitant dosing of the two drugs but decreased when digoxin was administered after rifampin."( Rifampin's acute inhibitory and chronic inductive drug interactions: experimental and model-based approaches to drug-drug interaction trial design.
Cai, X; Chu, X; Ding, Y; Evers, R; Gibson, C; Reitman, ML; Roupe, K; Stoch, A; Stone, JA; Venkatasubramanian, R; Wagner, JA; Witter, R; Yabut, J; Zajic, S, 2011
)
0.37
" The data suggest that dosing diltiazem XR for 2 days predicts the change in midazolam AUC as reliably as 5 days of XR dosing and 2 days of CR dosing."( Effect of different durations and formulations of diltiazem on the single-dose pharmacokinetics of midazolam: how long do we go?
Bergman, AJ; Chodakewitz, J; Fraser, IP; Friedman, EJ; Larson, PJ; Li, CC; Stoch, SA; Wagner, JA; Wang, YH, 2011
)
0.81
" The dosage of the drugs was unknown."( Distribution of metoprolol, tramadol, and midazolam in human autopsy material.
Arenz, N; Goltz, L; Kirch, W; Oertel, R; Pietsch, J; Zeitz, SG, 2011
)
0.63
" To optimize the dose regimens of these inducers for use in DDI studies, their effect at various doses and dosing durations on the area under the curve (AUC) of multiple probe substrates was simulated using a population-based simulator."( Simulation of clinical drug-drug interactions from hepatocyte CYP3A4 induction data and its potential utility in trial designs.
Hayashi, M; Shou, M; Skiles, GL; Xu, Y; Zhou, Y, 2011
)
0.37
"7 mg and dosage ranged from 2 to 10 mg."( Effectiveness and acceptability of intravenous sedation in child and adolescent dental patients: report of a case series at King's College Hospital, London.
Lourenço-Matharu, L; Roberts, GJ, 2011
)
0.37
" Since midazolam is frequently used in neonates for sedation during various examinations, future investigations on the selection of appropriate drugs and dosage for sedation in neonates, including the usage of midazolam, are necessary."( [Paroxysmal automatic movements mimicking neonatal seizures induced by midazolam].
Arakaki, Y; Ishizaki, Y; Mimaki, N; Ohtsuka, Y; Watabe, S, 2011
)
1.06
"Sedative effect of dexmedetomidine is satisfactory for patients undergoing MV after operation, with the property of easier arousal, lower delirium rate, and it helps to shorten the duration of MV with reduction the dosage of fentanyl by 50%."( [Comparison of sedative effect of dexmedetomidine and midazolam for post-operative patients undergoing mechanical ventilation in surgical intensive care unit].
Huang, QQ; Li, SH; Lin, L; Wan, LJ; Yue, JX, 2011
)
0.62
"67) ketamine, respectively within the recommended dosage guidelines."( Ketamine and midazolam sedation for pediatric gastrointestinal endoscopy in the Arab world.
Abdelhadi, R; Gilger, MA; Hayajneh, WA; Miqdady, MI, 2011
)
0.74
" By applying elements of time-series analysis within both frequentist and Bayesian frameworks, the authors evaluate differences in shift-based dosing of medication in a medical ICU."( Bayesian time-series analysis of a repeated-measures poisson outcome with excess zeroes.
Araujo, KL; Murphy, TE; Pisani, MA; Van Ness, PH, 2011
)
0.37
"Midazolam sedation poses a significant dilemma in paediatric dentistry, which is to find out the optimal dosing with minimal undesirable adverse events."( Optimising the dose of oral midazolam sedation for dental procedures in children: a prospective, randomised, and controlled study.
Abu Ras, Z; Cherni, N; Darawshi, G; Gaitini, LA; Kharouba, J; Parisinos, CA; Smidt, A; Somri, M, 2012
)
2.12
" A dose-response study on midazolam in the elevated plus maze test was carried out in adulthood (experiment 1) in order to screen GABAA-benzodiazepine function alterations."( Effects of early postnatal allopregnanolone administration on elevated plus maze anxiety scores in adult male Wistar rats.
Darbra, S; Pallarès, M, 2012
)
0.68
"2 µm after 10 mg daily dosing to steady-state."( A clinical study to assess CYP1A2 and CYP3A4 induction by AZD7325, a selective GABA(A) receptor modulator - an in vitro and in vivo comparison.
Desai, D; Grimm, SW; Lin, J; Ribadeneira, MD; Smith, MA; Sunzel, M; Zhou, D, 2012
)
0.38
" Midazolam pharmacokinetics were assessed over 24 h following single dose 2 mg administration prior to administering tofacitinib and after twice daily dosing of tofacitinib 30 mg for 6 days."( Lack of effect of tofacitinib (CP-690,550) on the pharmacokinetics of the CYP3A4 substrate midazolam in healthy volunteers: confirmation of in vitro data.
Alvey, C; Dowty, ME; Fahmi, OA; Gupta, P; Krishnaswami, S; Riese, RJ; Walsky, RL; Wang, R, 2012
)
1.51
" We report on modeling of the data and simulations of dosage regimens for future study."( A placebo- and midazolam-controlled phase I single ascending-dose study evaluating the safety, pharmacokinetics, and pharmacodynamics of remimazolam (CNS 7056): Part II. Population pharmacokinetic and pharmacodynamic modeling and simulation.
Borkett, KM; Kilpatrick, GJ; Tilbrook, GS; Wiltshire, HR, 2012
)
0.73
" Population pharmacokinetic and pharmacodynamic modeling of the data was undertaken and the parameters obtained were used for Monte-Carlo simulations of alternative dosing regimens."( A placebo- and midazolam-controlled phase I single ascending-dose study evaluating the safety, pharmacokinetics, and pharmacodynamics of remimazolam (CNS 7056): Part II. Population pharmacokinetic and pharmacodynamic modeling and simulation.
Borkett, KM; Kilpatrick, GJ; Tilbrook, GS; Wiltshire, HR, 2012
)
0.73
" No covariate effects considered to be clinically relevant were observed, suggesting that dosing by body weight may offer no advantage over fixed doses in terms of consistency of exposure to remimazolam within the weight range studied (65-90 kg)."( A placebo- and midazolam-controlled phase I single ascending-dose study evaluating the safety, pharmacokinetics, and pharmacodynamics of remimazolam (CNS 7056): Part II. Population pharmacokinetic and pharmacodynamic modeling and simulation.
Borkett, KM; Kilpatrick, GJ; Tilbrook, GS; Wiltshire, HR, 2012
)
0.73
" The pharmacokinetics of midazolam in different dosage forms was investigated in rabbits (dose 1mg/rabbit) after intravenous administration of midazolam solution and after sublingual administration of midazolam solution, midazolam/HP-β-CD/sucrose solution or midazolam/HP-β-CD/sucrose powder."( The effect of hydroxypropyl-beta-cyclodextrin and sucrose on the sublingual absorption of midazolam in rabbits.
Jarho, P; Järvinen, K; Kaartama, R; Kokki, H; Lehtonen, M; Ranta, VP; Savolainen, J; Toljamo, K; Turunen, E, 2012
)
0.9
"92) mg with a dosage rate being (0."( [Clinical evaluation of midazolam intravenous sedation under bispectral index monitoring on romoval of anterior supernumerary teeth in children].
Cui, NH; Ding, B; Guan, M; Liu, Y; Wang, EB; Zhang, W, 2012
)
0.69
" We recommend calling the patients in the OR suite one hour prior and the dosage being prescribed by the primary anaesthetist in order to keep this standardized."( Audit on preoperative midazolam and level of sedation.
Muhammad, S; Siddiqui, S, 2011
)
0.68
" Atomised intranasal midazolam spray ensures accurate drug dosage and better patient acceptability, with rapid onset of action and virtually complete absorption."( Atomised intranasal midazolam spray as premedication in pediatric patients: comparison between two doses of 0.2 and 0.3 mg/kg.
Baldwa, NM; Dave, NM; Garasia, MB; Padvi, AV, 2012
)
1.02
" Trials were grouped into placebo-controlled, dosage and head-to-head comparisons."( Sedation of children undergoing dental treatment.
Ashley, PF; Furness, S; Lourenço-Matharu, L, 2012
)
0.38
" Concomitant use of drugs metabolized by CYP2D6 may require dosage adjustment."( Pharmacokinetic drug interactions between clobazam and drugs metabolized by cytochrome P450 isoenzymes.
Bekersky, I; Blum, RA; Tolbert, D; Walzer, M, 2012
)
0.38
" However, dosing regimens in children are based upon rather empirical extrapolations from the dosing regimens in adults."( Growing up with midazolam in the neonatal and pediatric intensive care.
Plötz, FB; Slort, PR; Swart, EL, 2012
)
0.72
" Healthy subjects were co-administered (1) single dose midazolam, a prototypical CYP3A4 substrate, followed by 14 days of lersivirine twice daily with single dose midazolam on the final day of lersivirine dosing or (2) 10 days of once-daily (QD) lersivirine and QD oral contraceptives (OCs; ethinylestradiol and levonorgestrel), substrates for CYP3A4, UGT2B7, and/or P-glycoprotein."( The effect of lersivirine, a next-generation NNRTI, on the pharmacokinetics of midazolam and oral contraceptives in healthy subjects.
Chong, CL; Davis, J; Langdon, G; Layton, G; Ndongo, MN; Vourvahis, M, 2012
)
0.85
" Risk factor and midazolam dosage data were collected from medical records."( The association between nurse-administered midazolam following cardiac surgery and incident delirium: an observational study.
Fernandes, C; Galdas, PM; Gallaher, J; Jillings, C; Manning, D; Ratner, PA; Taipale, PG, 2012
)
0.98
" Almost all of the dosages of midazolam (85-87%) were given before the first indication of delirium; that is, most of the patients had received their entire dosage before the first signs of delirium were detected."( The association between nurse-administered midazolam following cardiac surgery and incident delirium: an observational study.
Fernandes, C; Galdas, PM; Gallaher, J; Jillings, C; Manning, D; Ratner, PA; Taipale, PG, 2012
)
0.93
" No significant differences were seen between groups concerning FOB duration, procedures, lidocaine dosage and complications."( Sedation with midazolam in flexible bronchoscopy: a prospective study.
Alves, D; Coelho, F; Cunha, J; Fernandes, G; Hespanhol, V; Magalhães, A; Mota, PC; Rolo, R,
)
0.49
" This may have important implications for dosing of midazolam and other CYP3A drug substrates in critically ill children."( Critical illness is a major determinant of midazolam clearance in children aged 1 month to 17 years.
Danhof, M; de Wildt, SN; Ince, I; Knibbe, CA; Murry, DJ; Peeters, MY; Tibboel, D, 2012
)
0.89
" For each drug treatment in each brain area, anticonvulsant ED₅₀ values were calculated using an up-down dosing procedure over successive animals."( Neuropharmacological specificity of brain structures involved in soman-induced seizures.
McDonough, JH; Shih, TM; Skovira, JW, 2012
)
0.38
" In the multiple-ascending-dose part, subjects were dosed with midazolam on days -2, 2, and 12 to investigate interactions with CYP3A4."( Clinical pharmacology of single- and multiple-ascending doses of ACT-178882, a new direct renin inhibitor, and its pharmacokinetic interaction with food and midazolam.
Binkert, C; Dingemanse, J; Nicolas, L, 2013
)
0.83
" Since the efficacy and safety data of midazolam used in children, excluding low-birth-weight infants and newborns, for "sedation under artificial respiration in intensive care units" were quite limited, a post-marketing survey was carried out to confirm the validity of the established dosage and administration."( [Safety and efficacy of midazolam in children under mechanical ventilation in the intensive care unit].
Lee, T; Miyasaka, K; Sogabe, K; Sou, M, 2012
)
0.96
") and efficacy issue were manifest in the patients treated with the dosage and administration method established at the approval of the drug."( [Safety and efficacy of midazolam in children under mechanical ventilation in the intensive care unit].
Lee, T; Miyasaka, K; Sogabe, K; Sou, M, 2012
)
0.69
" Micro/small dosing is useful for examining the mechanism of drug interactions without safety concern."( Mechanisms of pharmacokinetic enhancement between ritonavir and saquinavir; micro/small dosing tests using midazolam (CYP3A4), fexofenadine (p-glycoprotein), and pravastatin (OATP1B1) as probe drugs.
Ando, Y; Deguchi, M; Hirota, T; Ieiri, I; Irie, S; Izumi, N; Kanda, E; Kimura, M; Kotani, N; Kusuhara, H; Maeda, K; Matsuguma, K; Matsuki, S; Morishita, M; Okuzono, T; Sugiyama, Y; Tsunemitsu, S; Yamane, N, 2013
)
0.6
" Based on dosage equivalency conversion, equal doses of fentanyl and meperidine were used."( Impact of fentanyl in lieu of meperidine on endoscopy unit efficiency: a prospective comparative study in patients undergoing EGD.
Crowell, MD; Dzeletovic, I; Gurudu, SR; Harris, LA; Harrison, ME; Heigh, RI; Leighton, JA; Pasha, SF; Ramirez, FC; Yows, CR, 2013
)
0.39
" The dosage of propofol recommended in these guidelines is, however, based on one single study."( [Palliative sedation in a man with oral cancer; the Royal Dutch Medical Association guidelines not always sufficient].
Broekhoff, FJ; Dompeling, EC; Smelt, WL; Vos-Westerman, JH; Wulffraat, ET, 2013
)
0.39
" Adequate symptom control was only achieved when propofol was administered in a high dosage of 150 mg/h and levomepromazine administration was reinitiated."( [Palliative sedation in a man with oral cancer; the Royal Dutch Medical Association guidelines not always sufficient].
Broekhoff, FJ; Dompeling, EC; Smelt, WL; Vos-Westerman, JH; Wulffraat, ET, 2013
)
0.39
" Pharmacokinetics (PK) and biotransformation of MDZ were investigated following dosing to Cyp2c KO and wild type mice before and after TAO treatment."( Drug-drug interactions and metabolism in cytochrome P450 2C knockout mice: application to troleandomycin and midazolam.
Gallagher, R; Grimsley, A; Hutchison, M; Pickup, K; Samuelsson, K; Wilson, ID, 2013
)
0.6
" The drug dosage in combination group was decreased significantly compared with propofol group and midazolam group (total dosage of propofol: 25."( [Comparison of sedative effects of propofol and midazolam on emergency critical patients on mechanical ventilation].
Hong, GL; Lu, ZQ; Qiu, QM; Wu, B; Xu, AY; Zhao, GJ, 2013
)
0.86
" Recorded data included patient signalment, sedation score, propofol dosage and any adverse reactions."( A dose titration study into the effects of diazepam or midazolam on the propofol dose requirements for induction of general anaesthesia in client owned dogs, premedicated with methadone and acepromazine.
Borer-Weir, K; Robinson, R, 2013
)
0.64
"A total of 54 patients infected with hepatitis C virus genotype 1 received an oral drug cocktail (2 mg midazolam, 10 mg warfarin and 10 mg vitamin K) before and after 14 days of dosing with either danoprevir/r or placebo plus low-dose ritonavir (placebo/r)."( A randomised study of the effect of danoprevir/ritonavir or ritonavir on substrates of cytochrome P450 (CYP) 3A and 2C9 in chronic hepatitis C patients using a drug cocktail.
Brennan, BJ; Chang, L; Giraudon, M; Kulkarni, R; Morcos, PN; Shulman, N; Smith, PF; Tran, JQ, 2013
)
0.6
" A comparator population was established by replacement of the placebo group with a retrospective cohort and preservation of criteria for inclusion, exclusion, dosing and endpoint assessment."( Effectiveness of Centruroides scorpion antivenom compared to historical controls.
Alagón, A; Berg, M; Boyer, LV; Carbajal, Y; Chase, PB; de Jesus-Hernandez, T; Mallie, J; Olvera, F; Osnaya, N; Theodorou, AA, 2013
)
0.39
" Additionally, propofol dosage and overall rate of adverse events in group Cs were lower than those in group Cc."( Stepwise sedation for elderly patients with mild/moderate COPD during upper gastrointestinal endoscopy.
Cao, K; Chen, X; Guo, Q; Jia, Y; Liu, XM; Shen, SR; Tong, LL; Wang, F; Wang, XY; Xiao, DH; Xu, CX; Zou, HF, 2013
)
0.39
" Additional bolus/es was/were administered in the dosage similar to induction dose in case of inadequate sedation."( A double blind randomized trial of ketofol versus propofol for endodontic treatment of anxious pediatric patients.
Gauba, K; Goyal, A; Jain, K; Kapur, A; Mittal, N, 2013
)
0.39
" There are often patients who desire extensive liposuction on approximately 30% of total body surface area, which means the lidocaine total dose might be over the dosing recommendation."( Safe extensive tumescent liposuction with segmental infiltration of lower concentration lidocaine under monitored anesthesia care.
Cao, WG; Jiang, ZH; Li, SL; Liu, LN; Wang, G, 2015
)
0.42
"Co-administration of probe substrates midazolam, pioglitazone, omeprazole, and rosuvastatin following repeat dosing of vercirnon 500 mg BID demonstrated vercirnon had no clinically significant effect on CYP3A4, CYP2C8, CYP2C19 enzyme activity or BCRP or OATP1B1 transporter activity."( Effects of vercirnon on the activity of CYP3A4, CYP2C19 and CYP2C8 enzymes and BCRP and OATP1B1 transporters using probe substrates.
Cargill, A; Haberer, LJ; McCarthy, L; McSherry, I, 2014
)
0.67
" Maximum dosage was 11 mg (average 8 ± 2 mg)."( Electrical cardioversion of atrial fibrillation: evaluation of sedation safety with midazolam by means of EtCO₂ and IPI algorithm analysis.
Mantovan, R; Sabbatani, P, 2013
)
0.61
" Each patient's demographic and clinical characteristics, the need for ventilatory support, the use and dosage of medications, the number of nursing staff per bed, the time elapsed from admission to the intensive care unit until the effective start of enteral feeding, and the causes for nonadministration were recorded."( Nurse to bed ratio and nutrition support in critically ill patients.
Azevedo, LC; Bafi, AT; Castro, I; Freitas, FG; Honda, CK; Machado, FR; Mazza, BF; Nascente, AP; Stanich, P, 2013
)
0.39
" Conclusion Achievement of daily calorie goals was inadequate, and the main factors associated with this failure were the use and dosage of midazolam and the number of nurses available."( Nurse to bed ratio and nutrition support in critically ill patients.
Azevedo, LC; Bafi, AT; Castro, I; Freitas, FG; Honda, CK; Machado, FR; Mazza, BF; Nascente, AP; Stanich, P, 2013
)
0.59
" The need for alternative dosage form options for patients unable to take tablets and shortages of other forms of the drug have led compounding pharmacies to seek alternatives, mainly solutions and suspensions."( Stability of midazolam in syrspend SF and syrspend SF cherry.
Geiger, CM; Sorenson, B; Whaley, PA,
)
0.5
" Hepatic clearance of docetaxel was enhanced in vitro and in vivo at dosage of 120 and 180 mg kg(-1), and CYP3A activity was up-regulated by measuring the formation rate of 1-hydroxymidazolam."( Effect of triacontanol on the pharmacokinetics of docetaxel in rats associated with induction of cytochrome P450 3A1/2.
Chen, X; Deng, S; Fan, A; Gao, W; Li, C; Li, N; Liu, Q; Wang, C; Wen, X; Zhang, Q; Zhang, W; Zhang, Y; Zhao, D; Zhao, J, 2014
)
0.59
" Despite heterogeneity between trials, clonidine premedication in an adequate dosage (4 µg/kg) was likely to have a beneficial effect on postoperative pain in children."( Clonidine premedication for postoperative analgesia in children.
Cyna, AM; Knight, N; Lambert, P; Middleton, P, 2014
)
0.4
"6 for the three dosing groups (10, 20 and 100 mg)."( Quinine compared to 4β-hydroxycholesterol and midazolam as markers for CYP3A induction by rifampicin.
Andersson, TB; Bäckström, T; Bertilsson, L; Björkhem-Bergman, L; Bredberg, E; Diczfalusy, U; Nylén, H; Rönquist-Nii, Y, 2014
)
0.66
" The mean midazolam dosage administered was 1 ± 0."( [Prehospital analgesia performed by paramedics: quality in processes and effects under medical supervision].
Gaier, G; Häske, D; Niederberger, C; Schempf, B, 2014
)
0.8
" Simulations were performed to predict dosing regimens to account for the induction of CYP3A4."( Population pharmacokinetic modelling to assess clinical drug-drug interaction between AZD7325 and midazolam.
Al-Huniti, N; Lu, Z; Sunzel, M; Xu, H; Zhou, D, 2014
)
0.62
" The model could provide basis for the rational dosing of AZD7325 in clinical practice."( Population pharmacokinetic modelling to assess clinical drug-drug interaction between AZD7325 and midazolam.
Al-Huniti, N; Lu, Z; Sunzel, M; Xu, H; Zhou, D, 2014
)
0.62
" For both experiments, cumulative morphine anti-nociceptive dose-response (ED50) was tested and hyperactive behaviors such as jumping and scratching were recorded."( Midazolam exacerbates morphine tolerance and morphine-induced hyperactive behaviors in young rats with burn injury.
Chen, L; Mao, J; Martyn, JA; Song, L; Wang, S; Zuo, Y, 2014
)
1.85
"We designed a prospective, non-randomized, single-arm study (UMIN trial number 000003971) using patient questionnaires and vital sign monitoring to assess the efficacy and safety of a standardized midazolam dosing protocol based on gender and age for use during bronchoscopy."( Prospective analysis of efficacy and safety of an individualized-midazolam-dosing protocol for sedation during prolonged bronchoscopy.
Hasegawa, Y; Hashimoto, I; Hashimoto, N; Imai, N; Imaizumi, K; Ito, S; Kondo, M; Ogawa, T; Sato, M; Shimokata, T; Shindo, Y; Uozu, S, 2014
)
0.83
"The midazolam dosing protocol examined in this study was safe and effective."( Prospective analysis of efficacy and safety of an individualized-midazolam-dosing protocol for sedation during prolonged bronchoscopy.
Hasegawa, Y; Hashimoto, I; Hashimoto, N; Imai, N; Imaizumi, K; Ito, S; Kondo, M; Ogawa, T; Sato, M; Shimokata, T; Shindo, Y; Uozu, S, 2014
)
1.2
" The dosage of propofol needed for induction, consumption during maintenance and recovery time were recorded."( Impact of malnutrition on propofol consumption and recovery time among patients undergoing laparoscopic gastrointestinal surgery.
Bu, H; Fan, Y; Gao, F; Manyande, A; Tian, X; Tian, Y; Xiang, Y; Yang, H, 2014
)
0.4
"The present results indicate that the dosage and recovery time of propofol does change in malnourished individuals."( Impact of malnutrition on propofol consumption and recovery time among patients undergoing laparoscopic gastrointestinal surgery.
Bu, H; Fan, Y; Gao, F; Manyande, A; Tian, X; Tian, Y; Xiang, Y; Yang, H, 2014
)
0.4
" We surveyed choice of sedative agent and dosage on the basis of accompanying diseases or conditions in patients receiving treatment at the Department of Dental Anesthesiology, Tokyo Dental College Chiba Hospital between 2010 and 2011."( Survey on choice of intravenous sedative agent at department of dental anesthesiology, Tokyo Dental College Chiba Hospital between 2010 and 2011.
Ichinohe, T; Kasahara, M; Matsuki, Y; Matsuura, N; Okamura, T; Shiozaki, K, 2014
)
0.4
" Secondly, we examined how different dosage and optimum injection timing of ATI affected mice recovery from anesthesia."( Anesthetic effects of a three-drugs mixture--comparison of administrative routes and antagonistic effects of atipamezole in mice.
Kirihara, Y; Kobayashi, Y; Kurosaki, K; Saito, Y; Takechi, M; Takeuchi, T, 2015
)
0.42
" We discuss on a clinical case requiring an exceptionally high dosage of midazolam-up to 160 mg iv daily-to achieve palliative sedation."( Palliative sedation for status epilepticus in a patient with progressive multifocal leukoencephalopathy.
Cancelli, F; Dubra, A; Zulian, GB, 2014
)
0.63
"The aim of the study was to assess the magnitude of the CYP3A4 inhibitory effect of 2 dosing regimens of ketoconazole and the influence of the pharmacokinetic properties of the CYP3A4 substrate on the extent of the substrate exposure increase."( CYP3A4-based drug-drug interaction: CYP3A4 substrates' pharmacokinetic properties and ketoconazole dose regimen effect.
Boulenc, X; Donazzolo, Y; Hermabessière, S; Martin, V; Nicolas, O; Ollier, C; Zobouyan, I, 2016
)
0.43
"5 in the area under the plasma concentration-time curve during the dosing interval (AUC0-24 h), Cmax and trough plasma concentration (C24 h)."( Safety, tolerability and pharmacokinetics of doravirine, a novel HIV non-nucleoside reverse transcriptase inhibitor, after single and multiple doses in healthy subjects.
Ancona, JK; Anderson, MS; Butterton, JR; Cilissen, C; De Lepeleire, I; Dockendorf, MF; Gilmartin, J; Guo, Y; Liu, R; Tetteh, E; Van Bortel, L; Wagner, JA, 2015
)
0.42
" Additional studies are needed to evaluate the dosing schemes and long-term outcomes of dexmedetomidine premedication in pediatric anesthesia."( Premedication with dexmedetomidine in pediatric patients: a systematic review and meta-analysis.
Ji, FH; Li, J; Peng, K; Wu, SR, 2014
)
0.4
"The objective was to evaluate the anticonvulsant effectiveness and hemodynamic safety of midazolam in hypothermic newborns and to provide dosing guidance."( Anticonvulsant effectiveness and hemodynamic safety of midazolam in full-term infants treated with hypothermia.
de Vries, LS; Egberts, T; Groenendaal, F; Huitema, AD; Rademaker, K; Toet, MC; van den Broek, MP; van Straaten, HL, 2015
)
0.89
" An abnormal liver function test likely gives the clinician a hint about dosage adjustment."( Serum alanine transaminase total bilirubin concentrations predict CYP3A activity as measured by midazolam and 1'-hydroxylation.
He, R; Li, Y; Ruan, J, 2015
)
0.64
" Clinically fentanyl dosage adjustments may become necessary when ketoconazole or other strong CYP3A inhibitors are given simultaneously."( Pharmacokinetic interaction of intravenous fentanyl with ketoconazole.
Haefeli, WE; König, SK; Mahlke, NS; Mikus, G; Skopp, G; Ziesenitz, VC, 2015
)
0.42
" Patient signalment, sedation score, propofol dosage and adverse reactions were recorded."( The effects of diazepam or midazolam on the dose of propofol required to induce anaesthesia in cats.
Borer-Weir, K; Robinson, R, 2015
)
0.71
" Except for benzodiazepines, which were dosed higher in women than men, equal doses of sedation were given to female and male patients."( Practice patterns of sedation for colonoscopy.
Childers, RE; Sonnenberg, A; Williams, JL, 2015
)
0.42
" Data extracted included information about study design, country of origin, number of participants and demographic details, type of surgery, type of anaesthesia, intervention and dosing regimen, preoperative anxiety outcome measures and postoperative anxiety outcome measures."( Melatonin for pre- and postoperative anxiety in adults.
Gögenur, I; Halladin, NL; Hansen, MV; Møller, AM; Rosenberg, J, 2015
)
0.42
"51 μg/mL after 150 mg daily dosing to steady state."( Effect of multiple intravenous doses of lanicemine (AZD6765) on the pharmacokinetics of midazolam in healthy subjects.
Agbo, F; Bui, KH; Guo, J; Zhou, D, 2015
)
0.64
" RAUC values were not significantly related to inhibitor dosage or to duration of inhibitor pre-exposure prior to administration of MDZ."( Ritonavir is the best alternative to ketoconazole as an index inhibitor of cytochrome P450-3A in drug-drug interaction studies.
Greenblatt, DJ; Harmatz, JS, 2015
)
0.42
" After 2 weeks' exposure to DM at low dosage (5 mg/kg), biochemical parameters of hepatic functions were measured, histology and CYP450 expressed in liver was detected."( Effect of Dimethoate on the Activity of Hepatic CYP450 Based on Pharmacokinetics of Probe Drugs.
Hu, L; Lin, F; Tang, M; Zheng, Y; Zhuang, Z, 2015
)
0.42
"A low dosage of DM could induce the activity of CYP2D1 in liver and increase the metabolism of metoprolol when exposed for 2 weeks."( Effect of Dimethoate on the Activity of Hepatic CYP450 Based on Pharmacokinetics of Probe Drugs.
Hu, L; Lin, F; Tang, M; Zheng, Y; Zhuang, Z, 2015
)
0.42
"45-fold, respectively, after multiple dosing of AZD2327, indicating no or low risk for clinically relevant drug-drug interactions (DDI)."( Physiologically based pharmacokinetic modeling to predict complex drug-drug interactions: a case study of AZD2327 and its metabolite, competitive and time-dependent CYP3A inhibitors.
Guo, J; Khanh, BH; Li, Y; Zhou, D, 2015
)
0.42
"Midazolam causes a hormetic dose-response relationship in human neuroblastoma cells."( Pretreatment but not subsequent coincubation with midazolam reduces the cytotoxicity of temozolomide in neuroblastoma cells.
Bauer, I; Braun, S; Pannen, B; Werdehausen, R, 2015
)
2.11
"Rhesus monkeys (n=4) were trained under a progressive-ratio schedule of intravenous midazolam delivery and dose-response functions were determined for triazolam, in the absence and presence of flumazenil (non-selective antagonist), βCCT and 3-PBC (α1GABAA-preferring antagonists), and XLi-093 (α5GABAA-selective antagonist)."( Antagonism of triazolam self-administration in rhesus monkeys responding under a progressive-ratio schedule: In vivo apparent pA2 analysis.
Cook, JM; Fischer, BD; Namjoshi, OA; Platt, DM; Rallapalli, SK; Rowlett, JK, 2016
)
0.66
"Flumazenil, βCCT and 3-PBC shifted the dose-response functions for triazolam to the right in a surmountable fashion, whereas XLi-093 was ineffective."( Antagonism of triazolam self-administration in rhesus monkeys responding under a progressive-ratio schedule: In vivo apparent pA2 analysis.
Cook, JM; Fischer, BD; Namjoshi, OA; Platt, DM; Rallapalli, SK; Rowlett, JK, 2016
)
0.43
" Compared with the alcohol and control groups, the opioid group used a statistically higher mean medication dosage to achieve sedation."( Chronic Opioid Users Are More Difficult to Sedate than Alcoholics and Controls.
Clayton, S; Gill, J; Patel, R; Quintero, E, 2015
)
0.42
"Bolus dosing of fentanyl and midazolam fails to reduce the intracranial hypertension burden when administered for episodic intracranial hypertension."( Fentanyl and Midazolam Are Ineffective in Reducing Episodic Intracranial Hypertension in Severe Pediatric Traumatic Brain Injury.
Doctor, A; Kharasch, ED; Leonard, JR; Pineda, JA; Wallendorf, MJ; Welch, TP, 2016
)
1.09
" To improve the quality of life of these patients, more knowledge and more pharmacokinetic/pharmacodynamics studies in terminally ill patients are needed to develop individualised dosing guidelines."( Pharmacokinetic considerations and recommendations in palliative care, with focus on morphine, midazolam and haloperidol.
Baar, FP; de Winter, BC; Franken, LG; Koch, BC; Mathôt, RA; Tibboel, D; van Esch, HJ; van Gelder, T; van Zuylen, L, 2016
)
0.65
" Generally, maintenance doses depend upon drug clearance, so individual dosage regimens should be customized for HCC patients based on the condition of patients."( Changes in cytochrome P450s-mediated drug clearance in patients with hepatocellular carcinoma in vitro and in vivo: a bottom-up approach.
Fang, Y; Gao, J; Gao, N; He, XP; Jia, LJ; Jin, H; Qiao, HL; Tian, X; Wen, Q; Zhang, YF; Zhou, J, 2016
)
0.43
" The impact of obesity-related alterations on drug metabolism and its consequences for drug dosing remains largely unknown in both children and adults."( The CYTONOX trial.
Christensen, HR; Dalhoff, KP; Gade, C; Holm, JC; Holst, H; Mikus, G, 2016
)
0.43
" The results are expected to be used in the future as a basis for drug dosing recommendations in obese children."( The CYTONOX trial.
Christensen, HR; Dalhoff, KP; Gade, C; Holm, JC; Holst, H; Mikus, G, 2016
)
0.43
"The dosage of remifentanil used in observation group was (98."( [The influence of the sedation based on remifentanil analgesia on the occurrence of delirium in critically ill patients].
An, Y; Feng, Y; Liu, D; Lyu, J, 2015
)
0.42
" Step-by-step dosage adjustment using this population pharmacokinetic model may be useful for establishing a MDZ dosage regimen in critically ill patients."( Semi-mechanistic autoinduction model of midazolam in critically ill patients: population pharmacokinetic analysis.
Aoyama, T; Aoyama, Y; Hayashi, H; Hirata, K; Matsumoto, Y; Yamamoto, Y; Yokota, H, 2016
)
0.7
"Preoperatively, 95% of the patients received morphine versus 100% postoperatively, with a median dosage of 10."( Infants Operated on for Necrotizing Enterocolitis: Towards Evidence-Based Pain Guidelines.
Keyzer-Dekker, CM; Knibbe, CA; Meesters, NJ; Simons, SH; Tibboel, D; van Dijk, M, 2016
)
0.43
" Dosing regimens have been studied but most require fixed dosing intervals."( A Response Surface Model Exploration of Dosing Strategies in Gastrointestinal Endoscopies Using Midazolam and Opioids.
Hou, MC; Liou, JY; Ting, CK; Tsou, MY, 2016
)
0.65
" An electroencephalographic endpoint was used in over half of the patients; higher midazolam dosing was used with a burst suppression endpoint."( Refractory Status Epilepticus in Children: Intention to Treat With Continuous Infusions of Midazolam and Pentobarbital.
Abend, NS; Arya, R; Brenton, JN; Carpenter, JL; Chapman, KE; Gaillard, WD; Glauser, TA; Goldstein, J; Goodkin, HP; Helseth, AR; Jackson, MC; Kapur, K; Loddenkemper, T; Mikati, MA; Peariso, K; Sánchez Fernández, I; Tasker, RC; Wainwright, MS; Wilfong, AA; Williams, K, 2016
)
0.88
" Multiple pairwise comparisons were conducted using Welch t tests for continuous variables to determine whether dosing was different for the older groups vs the younger group; separate analyses were performed within and across ASA-PS class."( Does intravenous induction dosing among patients undergoing gastrointestinal surgical procedures follow current recommendations: a study of contemporary practice.
Akhtar, S; Burg, MM; Dai, F; Heng, J; Liu, J; Schonberger, RB, 2016
)
0.43
"No significant decrease in dosing between age groups was observed for fentanyl and midazolam."( Does intravenous induction dosing among patients undergoing gastrointestinal surgical procedures follow current recommendations: a study of contemporary practice.
Akhtar, S; Burg, MM; Dai, F; Heng, J; Liu, J; Schonberger, RB, 2016
)
0.66
"Weight-adjusted anesthetic induction dosing, age-associated differences in dosing by ASA-PS (American Society of Anesthesiology-Physical Status), and hemodynamic outcomes between younger (18-64 years, n = 537) and older (≥65 years, n = 231) female patients were analyzed."( A Retrospective Observational Study of Anesthetic Induction Dosing Practices in Female Elderly Surgical Patients: Are We Overdosing Older Patients?
Akhtar, S; Burg, MM; Dai, F; Heng, J; Schonberger, RB, 2016
)
0.43
" The dosage of midazolam was determined using the Dixon up-down method."( Effective Dosage of Midazolam to Erase the Memory of Vascular Pain During Propofol Administration.
Boku, A; Hanamoto, H; Inoue, M; Kudo, C; Niwa, H; Oyamaguchi, A; Sugimura, M,
)
0.81
" Sedative and analgesic dosing was not clinically significantly higher in obese patients than in non-obese patients."( Sedation for Bronchoscopy and Complications in Obese Patients.
Bellinger, CR; Chatterjee, AB; Haponik, E; Khan, I, 2016
)
0.43
" Recently, enzalutamide was approved for treatment of metastatic prostate cancer and is often dosed as a combination in clinical practice."( Application of a "Fit for Purpose" PBPK Model to Investigate the CYP3A4 Induction Potential of Enzalutamide.
Hoffmann, M; Kumar, G; Narayanan, R; Surapaneni, S, 2016
)
0.43
"A "fit for purpose" PBPK model of enzalutamide was developed to illustrate the CYP3A4 induction potential, understand the kinetics of de-induction of CYP3A4 following cessation of enzalutamide dosing and guide dose-selection of a co-administered CYP3A substrate."( Application of a "Fit for Purpose" PBPK Model to Investigate the CYP3A4 Induction Potential of Enzalutamide.
Hoffmann, M; Kumar, G; Narayanan, R; Surapaneni, S, 2016
)
0.43
"Bispectral index was used for quantifying the depth of sedation, and total dosage of the propofol was used for sedative requirements."( Effects of music on sedation depth and sedative use during pediatric dental procedures.
Araz, C; Cehreli, SB; Kayhan, Z; Ozkalayci, O; Tirali, RE, 2016
)
0.43
"In addition, the data were also gathered on the dosage of ephedrine and atropine were used, as well as the intraoperative awareness in the patients who were followed up on the first day after the operation."( [Impact of dexmedetomidine-sevoflurane anesthesia on intraoperative wake-up test in children patients undergoing scoliosis surgery].
An, HX; Quan, LX; Wang, DX, 2016
)
0.43
" Current guidelines for refractory status epilepticus (RSE) recommend initiating a continuous intravenous (CIV) anesthetic over bolus dosing with a different AED."( Continuous Infusion Antiepileptic Medications for Refractory Status Epilepticus: A Review for Nurses.
Jones, GM; Marler, J; Samarin, M; Wiss, AL,
)
0.13
"The impact of different single oral doses of ketoconazole (KTZ) (100, 200 and 400 mg) and of staggering its dosage (400 mg at -12, -2, 0, 2 and 4 h), with respect to the administration of a single 5 mg oral dose of midazolam (MDZ) on the extent of inhibition of the metabolism of the latter, was evaluated in healthy subjects in two separate studies."( The absorption kinetics of ketoconazole plays a major role in explaining the reported variability in the level of interaction with midazolam: Interplay between formulation and inhibition of gut wall and liver metabolism.
Crewe, HK; Liu, B; Ozdemir, M; Rostami-Hodjegan, A; Rowland Yeo, K; Tucker, G, 2017
)
0.85
"Our aim was to describe the effect of dosing and genetic factors on sufentanil- and midazolam-induced analgosedation and withdrawal syndrome (WS) in pediatric population."( Sufentanil and midazolam dosing and pharmacogenetic factors in pediatric analgosedation and withdrawal syndrome.
Hronová, K; Pokorná, P; Posch, L; Slanař, O, 2016
)
1.01
" Overall, our m-f-PBPK model well predicted the maternal and fetal exposure to the two verification drugs, theophylline and zidovudine, at term, across a range of dosing regimens, with nearly all observed MP and UV plasma drug concentrations falling within the 90% prediction interval [i."( Development of a Novel Maternal-Fetal Physiologically Based Pharmacokinetic Model II: Verification of the model for passive placental permeability drugs.
Unadkat, JD; Zhang, Z, 2017
)
0.46
"Our study indicates albumin levels and eGFR as relevant clinical parameters to optimize midazolam dosing in terminally ill patients."( Hypoalbuminaemia and decreased midazolam clearance in terminally ill adult patients, an inflammatory effect?
Baar, FPM; de Winter, BCM; Franken, LG; Koch, BCP; Masman, AD; Mathot, RAA; Tibboel, D; van Gelder, T, 2017
)
0.96
" Patient satisfaction increased with an increasing dosage of propofol up until 4 mg/kg/hr, reaching a peak of 78."( Optimal and safe standard doses of midazolam and propofol to achieve patient and doctor satisfaction with dental treatment: A prospective cohort study.
Gotoh, K; Iijima, T; Masuda, R; Nishimura, A; Nonaka, M; Oka, S, 2017
)
0.73
" Such respiratory monitoring data provide the opportunity for individualizing dosing and adjustment of clinical interventions, especially important in elderly patients."( Quantification of respiratory depression during pre-operative administration of midazolam using a non-invasive respiratory volume monitor.
Brayanov, JB; Gonzalez Castro, LN; Mehta, JH; Mullen, GJ, 2017
)
0.68
"In a retrospective study of patients undergoing colonoscopy, we found that compared with titrated administration of sedative, bolus dosing improves endoscopy unit efficiency and safety and decreases the amount of sedative required."( Bolus Administration of Fentanyl and Midazolam for Colonoscopy Increases Endoscopy Unit Efficiency and Safety Compared With Titrated Sedation.
Boyd, A; Finn, RT; Gellad, ZF; Lin, L, 2017
)
0.73
" This is especially important in the case of pediatric patients, and dose-response relationships require studies using pharmacokinetic-pharmacodynamic modeling."( A highly sensitive method for the simultaneous UHPLC-MS/MS analysis of clonidine, morphine, midazolam and their metabolites in blood plasma using HFIP as the eluent additive.
Aro, R; Herodes, K; Kipper, K; Lutsar, I; Metsvaht, T; Standing, JF; Veigure, R, 2017
)
0.68
" The current dosing strategy of cabazitaxel is based on body surface area (BSA)."( Towards better dose individualisation: metabolic phenotyping to predict cabazitaxel pharmacokinetics in men with prostate cancer.
Bloemendal, HJ; Janssen, A; Mathijssen, RHJ; Ter Heine, R; van der Vlist, A; Verkleij, CPM, 2017
)
0.46
"Ten patients with metastatic castration-resistant prostate cancer, who received cabazitaxel dosed on BSA as a part of routine palliative care, were enrolled in this study."( Towards better dose individualisation: metabolic phenotyping to predict cabazitaxel pharmacokinetics in men with prostate cancer.
Bloemendal, HJ; Janssen, A; Mathijssen, RHJ; Ter Heine, R; van der Vlist, A; Verkleij, CPM, 2017
)
0.46
" In particular, we compared the occurrence of complications and the dosage of administered sedative drugs between the groups."( Analogosedation during flexible bronchoscopy using a combination of midazolam, propofol and fentanyl - A retrospective analysis.
Cornelissen, CG; Dreher, M; Krüger, S; Müller, T; Thümmel, K, 2017
)
0.69
" The dosage of midazolam was lower in the MFP compared to the MF or MP group (MFP vs."( Analogosedation during flexible bronchoscopy using a combination of midazolam, propofol and fentanyl - A retrospective analysis.
Cornelissen, CG; Dreher, M; Krüger, S; Müller, T; Thümmel, K, 2017
)
1.04
"In summary we were able to demonstrate that triple sedation can safely be administered during flexible bronchoscopy and is associated with a reduced dosage of midazolam and propofol."( Analogosedation during flexible bronchoscopy using a combination of midazolam, propofol and fentanyl - A retrospective analysis.
Cornelissen, CG; Dreher, M; Krüger, S; Müller, T; Thümmel, K, 2017
)
0.89
" Additional studies are recommended that examine the anxiolytic and antidepressant effects of curcumin through alternate dosing regimens, modulation of other subunits on the GABAA receptor, and interactions with other central nervous system neurotransmitter systems."( Investigation of the Anxiolytic and Antidepressant Effects of Curcumin, a Compound From Turmeric (Curcuma longa), in the Adult Male Sprague-Dawley Rat.
Ceremuga, TE; Golder, J; Helmrick, K; Keller, B; Kelley, J; Kufahl, Z; Padrón, G; Philippe, F,
)
0.13
"Balanced anesthesia allows for a reduced dosage of each component, while inducing general anesthesia of sufficient depth with potentially fewer side effects."( Premedication with fentanyl-midazolam improves sevoflurane anesthesia for surgical intervention in laboratory mice.
Arras, M; Cesarovic, N; Jirkof, P; Lipiski, M, 2017
)
0.75
" The results from these studies were incorporated into the Food and Drug Administration-approved product label, providing guidance for panobinostat dosing recommendations when it is combined with other drugs."( Physiologically Based Pharmacokinetic Model Predictions of Panobinostat (LBH589) as a Victim and Perpetrator of Drug-Drug Interactions.
Chun, DY; Einolf, HJ; Gu, H; He, H; Lin, W; Mangold, JB; Wang, L; Won, CS, 2017
)
0.46
"Pain was not better controlled with the addition of continuous infusions of morphine and midazolam when compared with intermittent dosing only."( Intermittent Versus Continuous and Intermittent Medications for Pain and Sedation After Pediatric Cardiothoracic Surgery; A Randomized Controlled Trial.
Brady, CM; Lefaiver, CA; Penk, JS; Steffensen, CM; Wittmayer, K, 2018
)
0.7
" Our aim was to evaluate a previously developed population pharmacokinetic model both in critically ill children and other populations, in order to allow the model to be used to guide dosing in clinical practice."( Predicting CYP3A-mediated midazolam metabolism in critically ill neonates, infants, children and adults with inflammation and organ failure.
Brussee, JM; de Hoog, M; de Wildt, SN; Jacqz-Aigrain, E; Knibbe, CAJ; Krekels, EHJ; Swart, EL; Tibboel, D; Valkenburg, AJ; van den Anker, JN; van Gerven, JMA; Vet, NJ, 2018
)
0.78
"The recently published pharmacokinetic model for midazolam, quantifying the influence of maturation, inflammation and organ failure in children, yields unbiased clearance predictions and can therefore be used for dosing instructions in term neonates, children and adults with varying levels of critical illness, including healthy adults, but not for extrapolation to preterm neonates."( Predicting CYP3A-mediated midazolam metabolism in critically ill neonates, infants, children and adults with inflammation and organ failure.
Brussee, JM; de Hoog, M; de Wildt, SN; Jacqz-Aigrain, E; Knibbe, CAJ; Krekels, EHJ; Swart, EL; Tibboel, D; Valkenburg, AJ; van den Anker, JN; van Gerven, JMA; Vet, NJ, 2018
)
1.04
"2 observed ratio) after daily dosing of midostaurin for 4 days."( Simultaneous Physiologically Based Pharmacokinetic (PBPK) Modeling of Parent and Active Metabolites to Investigate Complex CYP3A4 Drug-Drug Interaction Potential: A Case Example of Midostaurin.
Chun, DY; Dutreix, C; Einolf, HJ; Gu, H; He, H; Ouatas, T; Rebello, S; Wang, L, 2018
)
0.48
"To evaluate the capacity for modafinil to be a perpetrator of metabolic drug-drug interactions by altering cytochrome P450 activity following a single dose and dosing to steady state."( Evaluation of modafinil as a perpetrator of metabolic drug-drug interactions using a model informed cocktail reaction phenotyping trial protocol.
Mangoni, AA; Rowland, A; Sorich, MJ; van Dyk, M; Warncken, D, 2018
)
0.48
"These data support consideration of the risk of clinically relevant metabolic drug-drug interactions perpetrated by modafinil when this drug is co-administered with drugs that are primarily cleared by CYP2C19 (single modafinil dose or steady state modafinil dosing) or CYP3A4 (steady state modafinil dosing only) catalysed metabolic pathways."( Evaluation of modafinil as a perpetrator of metabolic drug-drug interactions using a model informed cocktail reaction phenotyping trial protocol.
Mangoni, AA; Rowland, A; Sorich, MJ; van Dyk, M; Warncken, D, 2018
)
0.48
" For both active substances, the dosage necessary to reach sufficient deep analgosedation was significantly higher for patients under 24 months of age."( Bone marrow aspirations in oncological patients: experience from an in-house standard in paediatrics.
Foell, J; Graeber, S; Lieser, U; Sauer, H, 2019
)
0.51
" However, a high dosage is related to hemodynamic abnormalities such as hypotension and bradycardia."( Effects of remifentanil with or without midazolam pretreatment on the 95% effective dose of propofol for loss of consciousness during induction: A randomized, clinical trial.
Han, DW; Kim, NY; Ko, SH; Koh, JC; Park, J; You, AH, 2017
)
0.72
" A dose-response trial was conducted whereby 10, 30, and 50 mg/kg alfaxalone was administered subcutaneously (SC) to 10 Bengalese finches ( Lonchura domestica) in a randomized complete crossover study design."( ALFAXALONE ANESTHESIA IN THE BENGALESE FINCH ( LONCHURA DOMESTICA).
Bertelsen, MF; Nielsen, JB; Perrin, KL; Thomsen, AF, 2017
)
0.46
"Sedation during flexible bronchoscopy is desirable, but the drugs and the dosage protocols that are used vary."( Comparison of midazolam with fentanyl-midazolam combination during flexible bronchoscopy: A randomized, double-blind, placebo-controlled study.
Chogtu, B; Magazine, R; Prabhudev, AM,
)
0.49
"To increase knowledge about the CYP3A enzyme and the impact of drug interactions on its activity to improve dosing in palliative care patients."( In Vivo CYP3A Activity in Palliative Care Patients: Study Protocol for a Single Arm Prospective Trial.
Bardenheuer, HJ; Burhenne, J; Geist, MJP; Mikus, G, 2018
)
0.48
" The trial is based on reliable and established methods aiming to provide improved dosing regimens and thus optimize pharmacological therapies in this specialty."( In Vivo CYP3A Activity in Palliative Care Patients: Study Protocol for a Single Arm Prospective Trial.
Bardenheuer, HJ; Burhenne, J; Geist, MJP; Mikus, G, 2018
)
0.48
"The objective was to compare the safety and efficacy of an algorithm for abortion intravenous sedation dosing (AAID) to standard dosing during first-trimester surgical abortion."( A randomized comparison of intravenous sedation using a dosing algorithm compared to standard care during first-trimester surgical abortion.
Braaten, KP; Fortin, J; Goldberg, AB; Maurer, R; Urman, RD, 2018
)
0.48
"This was a randomized, single-blinded, controlled trial in which women undergoing first-trimester surgical abortion received fentanyl and midazolam dosed per either an algorithm or clinic standard."( A randomized comparison of intravenous sedation using a dosing algorithm compared to standard care during first-trimester surgical abortion.
Braaten, KP; Fortin, J; Goldberg, AB; Maurer, R; Urman, RD, 2018
)
0.68
" Patients who failed to achieve adequate sedation in any arm were rescued with midazolam dosed at the investigator's discretion."( A phase III study evaluating the efficacy and safety of remimazolam (CNS 7056) compared with placebo and midazolam in patients undergoing colonoscopy.
Barish, CF; Bernstein, D; Bhandari, R; Cash, BD; DeMicco, MP; Desta, T; Etzkorn, K; Pruitt, R; Quirk, D; Rex, DK; Schaeffer, C; Sullivan, S; Tiongco, F, 2018
)
0.92
"The study was conducted to evaluate the pharmacokinetics of midazolam (MDZ) under different oral dosages in rats, and determine the optimum oral dosage of MDZ, a CYP3 A probe substrate in vivo."( [Optimization of midazolam dosage and pharmacokinetics of CYP3A probe substrate in rats].
Bi, HC; Chen, X; Duan, WH; Huang, M; Qin, XL; Xue, XP, 2016
)
1.02
" Performance of the model was validated using prespecified acceptance criteria against different dosing regimens, formulations for 29 PK, and DDI studies with midazolam and other CYP3A4 substrates."( Physiologically Based Pharmacokinetic Model of Itraconazole and Two of Its Metabolites to Improve the Predictions and the Mechanistic Understanding of CYP3A4 Drug-Drug Interactions.
Ericsson, H; Janzén, D; Kanebratt, KP; Lennernäs, H; Lundahl, A; Prieto Garcia, L, 2018
)
0.68
"We show that PCS is non-inferior to RCS in terms of dosage given and degree of sedation."( Randomized and controlled study comparing patient controlled and radiologist controlled intra-procedural conscious sedation, using midazolam and fentanyl, for patients undergoing insertion of a central venous line.
Clements, W; Goh, GS; Joseph, T; Kavnoudias, H; Koukounaras, J; Sneddon, D; Snow, T, 2018
)
0.69
" The significance of these results is that CYP3A4 is the drug-metabolizing enzyme of greatest clinical importance and variability in CYP3A4 activity is poorly described by existing precision dosing strategies."( Plasma extracellular nanovesicle (exosome)-derived biomarkers for drug metabolism pathways: a novel approach to characterize variability in drug exposure.
Mackenzie, PI; Marshall, JC; Meech, R; Rodrigues, AD; Rowland, A; Ruanglertboon, W; Sorich, MJ; van Dyk, M; Wijayakumara, D; Wood, LS, 2019
)
0.51
"5 K: the standard dosage of ketamine (0."( [Evaluation of Anesthesia Method to Minimize Intraoperative Body Movement and Respiratory Depression for Dilatation and Curettage A Retrospective Study].
Kitamura, J; Yamaguchi, S, 2016
)
0.43
" Midazolam was administered at a dosage of 5 mg to all patients, while propofol was administered at a dosage ranging from 20 to 80 mg (25."( Safety and efficacy of a cardiologist-only approach to deep sedation for electrical cardioversion.
Bolzan, B; Borio, G; Morani, G; Ribichini, FL, 2019
)
1.42
"No dosing regimen has been established for the initial treatment of pediatric status epilepticus with intravenous midazolam."( Efficacy, safety, and pharmacokinetics of intravenous midazolam in Japanese children with status epilepticus.
Fukuyama, T; Hamano, SI; Miki, M; Osawa, M; Sugai, K; Tabata, T, 2019
)
0.97
" Sedative medication dosing and observed adverse events were similar to those reported previously in children without ASD."( Procedural sedation in children with autism spectrum disorders in the emergency department.
Brown, JJ; Farooqi, A; Gray, JM; Kannikeswaran, N; Roback, MG; Sethuraman, U, 2019
)
0.51
" Vital signs before and after dosing were not significantly different."( Intranasal midazolam and fentanyl for procedural sedation and analgesia in infants in the neonatal intensive care unit.
Bidegain, M; Cotten, CM; Fisher, K; Goldberg, RN; Greenberg, RG; Hornik, CD; Ku, LC; Simmons, C; Smith, PB, 2019
)
0.9
" Studies were grouped into placebo-controlled, dosage and head-to-head comparisons."( Sedation of children undergoing dental treatment.
Ashley, PF; Chaudhary, M; Lourenço-Matharu, L, 2018
)
0.48
"A literature review was conducted, and studies were included if involving adults, receiving Midazolam, alone or in combination, whatever the route, dosage or indication and if they reported adverse events related to the use of Midazolam."( Tolerability of Midazolam to treat acute agitation in elderly demented patients: A systematic review.
Bloch, F; Boutalha, S; Defouilloy, C; Dubaele, JM; Karoui, I, 2019
)
1.08
" Rats were chronically dosed with respectively clomipramine, citalopram, or midazolam."( Distribution of clomipramine, citalopram, midazolam, and metabolites in skeletal tissue after chronic dosing in rats.
Cuypers, E; Somers, T; Vandenbosch, M, 2019
)
1.01
" Response to noxious stimuli was absent in 2 of the rabbits given dexmedetomidine only, 4 of those given alfaxalone with dexmedetomidine, and all 6 of the animals dosed with alfaxalone, butorphanol, and dexmedetomidine; this last group displayed the longest absence of a toe-pinch response (57 ± 3 min)."( Intramuscular Administration of Alfaxalone Alone and in Combination for Sedation and Anesthesia of Rabbits (
Bradley, MP; Doerning, CM; Lester, PA; Nowland, MH, 2019
)
0.51
" Dosing of major CYP3A substrate drugs needs to be reduced in palliative patients with haematological diseases, otherwise escalation of debilitating symptoms due to drug interactions might occur."( Decreased Cytochrome P450 3A activity in palliative patients with haematological diseases: Potential impact on supportive drug therapies.
Bardenheuer, H; Burhenne, J; Egerer, G; Geist, MJP; Mikus, G; Siller, N, 2019
)
0.51
"In a selected population of pediatric patients, buccal dexmedetomidine with or without midazolam provides adequate sedation for most MRI studies with few adverse effects, but given a failure rate of almost 20%, modifications to buccal dexmedetomidine dosing should be investigated."( Safety and Efficacy of Buccal Dexmedetomidine for MRI Sedation in School-Aged Children.
Boriosi, JP; Eickhoff, JC; Hollman, GA, 2019
)
0.74
"In order to improve drug dosing in end-of-life care and to avoid drug interactions, cytochrome P450 3A activity was determined in patients of a palliative care unit under real-life clinical conditions."( Alteration of drug-metabolizing enzyme activity in palliative care patients: Microdosed assessment of cytochrome P450 3A.
Bardenheuer, H; Burhenne, J; Geist, M; Mikus, G, 2019
)
0.51
" Secondarily, dosing of opioids and benzodiazepines was examined."( The Effectiveness of α2 Agonists As Sedatives in Pediatric Critical Care: A Propensity Score-Matched Cohort Study.
Breatnach, CV; Cousins, G; Dawkins, I; Doherty, DR; Gallagher, PJ; Hayden, JC; Healy, M; Leacy, FP, 2019
)
0.51
" Recently, a new dosing advice for midazolam for sedation on intensive care units has been included in the label (0."( Recently Registered Midazolam Doses for Preterm Neonates Do Not Lead to Equal Exposure: A Population Pharmacokinetic Model.
Andriessen, P; Beggah, F; de Wildt, S; Flint, RB; Knibbe, CAJ; Koch, BCP; Liem, KD; Reiss, I; Simons, SHP; van den Anker, JN; Völler, S; Zimmermann, LJI, 2019
)
1.11
" However, the preparation of microdosed dosage forms remains a challenge."( Microdosed midazolam for the determination of cytochrome P450 3A activity: Development and clinical evaluation of a buccal film.
Burhenne, J; Haefeli, WE; Haschke, M; Hayasi, N; Huwyler, J; Inada, H; Kiene, K; Krähenbühl, S; Mikus, G; Schmid, Y; Sünderhauf, C; Uchitomi, R, 2019
)
0.9
" Midazolam, caffeine, and TMU concentrations were assessed at baseline and following dosing of rifampicin (300 mg daily) for 7 days."( Identification of the caffeine to trimethyluric acid ratio as a dietary biomarker to characterise variability in cytochrome P450 3A activity.
Hopkins, A; Marshall, JC; Miners, JO; Rowland, A; Sorich, MJ; van Dyk, M; Wood, LS, 2019
)
1.42
" Predictors of poorer neurocognitive function were midazolam dosage >3 mg (P<0."( Comparison of the Effects of Midazolam/Fentanyl, Midazolam/Propofol, and Midazolam/Fentanyl/Propofol on Cognitive Function After Gastrointestinal Endoscopy.
Riordan, S; Seck, V; Thompson, R; Wong, S, 2019
)
1.06
" Medication dosing generally followed standard dosing guidelines with very few exceptions."( Seizure Rescue Medication Use among US Pediatric Epilepsy Providers: A Survey of the Pediatric Epilepsy Research Consortium.
Payne, E; Wallace, A; Wirrell, E, 2019
)
0.51
" To assess maximal hepatic CYP3A4 induction, oral rifampin (600 mg daily) should be dosed for > 10 days."( Guidance for Rifampin and Midazolam Dosing Protocols To Study Intestinal and Hepatic Cytochrome P450 (CYP) 3A4 Induction and De-induction.
Kapetas, AJ; Rodrigues, AD; Rowland, A; Sorich, MJ, 2019
)
0.81
" Results Fifty studies (3704 participants) were included and grouped into placebo-controlled, dosage and head-to-head comparisons."( Conscious sedation in children: the need to strengthen the evidence base remains.
Rolland, SL; Stamp, AJ; Vernazza, CR; Wilson, KE, 2019
)
0.51
"To assess pharmacokinetics and clinical anti-epileptic effectiveness of phenobarbital and midazolam in asphyxiated neonates and to develop dosing guidelines."( Phenobarbital, Midazolam Pharmacokinetics, Effectiveness, and Drug-Drug Interaction in Asphyxiated Neonates Undergoing Therapeutic Hypothermia.
Cools, F; de Haan, TR; Dijk, PH; Dijkman, KP; Egberts, TCG; Favié, LMA; Groenendaal, F; Huitema, ADR; Nuytemans, DHGM; Rademaker, CMA; Rijken, M; Simons, SHP; van Bel, F; van den Broek, MPH; van der Lee, JH; van Heijst, A; van Straaten, HLM; Zecic, A; Zonnenberg, IA, 2019
)
1.09
" These data are important for informing adult and pediatric dosing recommendations for NA-induced seizures."( Evaluation of first-line anticonvulsants to treat nerve agent-induced seizures and prevent neuropathology in adult and pediatric rats.
Ardinger, C; Dunn, E; Haines, K; Lee-Stubbs, R; Matson, L; McCarren, H; McDonough, J; Miller-Smith, S; Whitten, K, 2019
)
0.51
" A dose-response profile was noted for anxiolytic effects, dissociative side effects, and changes in blood pressure and heart rate after ketamine dosing."( Effects of ketamine in patients with treatment-refractory generalized anxiety and social anxiety disorders: Exploratory double-blind psychoactive-controlled replication study.
Broughton, L; Glue, P; Le Nedelec, M; McNaughton, N; Medlicott, NJ; Neehoff, S; Sabadel, A; Shadli, S, 2020
)
0.56
" The range of oral midazolam doses providing effective sedation in the different pediatric age subsets was analyzed in order to assess optimum dosing strategies."( Efficacy of oral midazolam for minimal and moderate sedation in pediatric patients: A systematic review.
Granier, LA; Guittet, C; Manso, MA; Vandenhende, F, 2019
)
1.18
" The decreased recovery of mainly sufentanil and propofol could lead to suboptimal dosing of patients during cardiac surgery with CPB."( In Vitro Recovery of Sufentanil, Midazolam, Propofol, and Methylprednisolone in Pediatric Cardiopulmonary Bypass Systems.
Bogers, AJJC; Kinzig, M; Koch, BCP; Sörgel, F; Stolker, RJ; Tibboel, D; van Hoeven, MPJ; van Rosmalen, J; van Saet, A; Wildschut, ED; Zeilmaker-Roest, GA, 2020
)
0.84
"To compare IN versus IV midazolam (MDZ) at the same dosage (0."( Comparison of intranasal versus intravenous midazolam for management of status epilepticus in dogs: A multi-center randomized parallel group clinical study.
Bhatti, SFM; Broeckx, BJG; Cappello, R; Charalambous, M; Coates, JR; Corlazzoli, D; Cozzi, F; De Risio, L; Erath, J; Gallucci, A; Gandini, G; Hasegawa, D; Huenerfauth, E; Musteata, M; Pancotto, T; Platt, S; Porcarelli, L; Rossmeisl, JH; Tipold, A; Tirrito, F; Van Ham, L; Vanhaesebrouck, A; Volk, HA, 2019
)
1.08
"While the developed preterm model for the prediction of PK behaviour in preterm patients is not intended to replace clinical studies, it can potentially help with deciding on first-time dosing in this population and study design in the absence of clinical data."( Preterm Physiologically Based Pharmacokinetic Model. Part II: Applications of the Model to Predict Drug Pharmacokinetics in the Preterm Population.
Abduljalil, K; Jamei, M; Johnson, TN; Pan, X; Pansari, A, 2020
)
0.56
" Results of simulations indicate the need for reduced dosing in certain groups of patients in order to maintain plasma concentrations of midazolam within recommended values."( Maturation of midazolam clearance in critically ill children with severe bronchiolitis: A population pharmacokinetic analysis.
Grabnar, I; Grosek, Š; Jovanović, M; Kos, MK; Miksić, M; Roškar, R, 2020
)
1.12
"The developed population pharmacokinetic model can contribute to the dosing optimisation of midazolam, especially in critically ill children as it includes the influence of size and maturation of clearance, which are important parameters for achieving the desired plasma concentrations of midazolam."( Maturation of midazolam clearance in critically ill children with severe bronchiolitis: A population pharmacokinetic analysis.
Grabnar, I; Grosek, Š; Jovanović, M; Kos, MK; Miksić, M; Roškar, R, 2020
)
1.14
"The average weight-based dosage of propofol was similar in both groups but was lower in the high-body mass index group for midazolam and fentanyl."( Perioperative Risks Are Similar for Normal versus Selected High-Body Mass Index Patients Undergoing Outpatient Hand and Elbow Surgery.
Banner, L; Beredjiklian, PK; Jones, C; Lutsky, K; Selverian, S; Warrender, W, 2019
)
0.72
" A prospective, double-blind, randomized, controlled study was performed to compare the efficacy of minimal dosage of midazolam versus dexmedetomidine to prevent ED in children undergoing tonsillectomy."( Comparison of single minimum dose administration of dexmedetomidine and midazolam for prevention of emergence delirium in children: a randomized controlled trial.
Ahn, JH; Cha, YB; Cho, EA; Lee, SH; Ryu, KH; Shim, JG, 2020
)
1
" In children and adolescents with obesity, midazolam pharmacokinetics may be altered, and the current dosing guidelines may therefore be insufficient."( Midazolam Pharmacokinetics in Obese and Non-obese Children and Adolescents.
Burhenne, J; Christensen, HR; Dalhoff, K; Gade, C; Holm, JC; Holst, H; Johansen, MØ; Lund, TM; Mikus, G; Sonne, J; Sverrisdóttir, E, 2020
)
2.26
" The current dosing guidelines for status epilepticus, where the midazolam dose is adjusted to total body weight or age, may lead to supra- and sub-therapeutic plasma concentrations, respectively, in adolescents with obesity."( Midazolam Pharmacokinetics in Obese and Non-obese Children and Adolescents.
Burhenne, J; Christensen, HR; Dalhoff, K; Gade, C; Holm, JC; Holst, H; Johansen, MØ; Lund, TM; Mikus, G; Sonne, J; Sverrisdóttir, E, 2020
)
2.24
" There was a wide variability with respect to dosing ranges for medications."( Variation in Prehospital Protocols for Pediatric Seizure Within the United States.
Martin-Gill, C; McCans, K; Owusu-Ansah, S; Ramgopal, S, 2021
)
0.62
" DS patients had a high probability of receiving a higher midazolam dosage and dexmedetomidine dosage over the study period (probability = 0."( Down Syndrome Reduces the Sedative Effect of Midazolam in Pediatric Cardiovascular Surgical Patients.
Enomoto, Y; Hiramatsu, Y; Hoshino, H; Inoue, Y; Mathis, BJ; Matsuishi, Y; Sakuramoto, H; Shimojo, N, 2020
)
1.06
" Utilization of this relatively simple methodology to evaluate DDIs for orally dosed drugs will have a significant impact on how DDIs are interpreted from a drug development and regulatory perspective."( A Simple Methodology to Differentiate Changes in Bioavailability From Changes in Clearance Following Oral Dosing of Metabolized Drugs.
Benet, LZ; Sodhi, JK, 2020
)
0.56
" The mean dosage of propofol in group A was significantly higher (62."( Pre-endoscopic tachycardia predicts increased sedation dose and lower adenoma detection rate in patients undergoing endoscopic procedures: a case control study.
Ahmad, HS; Baker, FA; Kadah, A; Khoury, T; Mahajnah, M; Mahamid, M; Mari, A; Pellicano, R; Sbeit, W, 2020
)
0.56
"Tachycardia prior to endoscopic procedures was associated with higher sedative dosage and lower adenoma detection rate, however no major complications were recorded."( Pre-endoscopic tachycardia predicts increased sedation dose and lower adenoma detection rate in patients undergoing endoscopic procedures: a case control study.
Ahmad, HS; Baker, FA; Kadah, A; Khoury, T; Mahajnah, M; Mahamid, M; Mari, A; Pellicano, R; Sbeit, W, 2020
)
0.56
"Drug dosing is challenging in patients with end-stage renal disease."( Chronic Inhibition of CYP3A is Temporarily Reduced by Each Hemodialysis Session in Patients With End-Stage Renal Disease.
Åsberg, A; Christensen, H; Egeland, EJ; Robertsen, I; Witczak, BJ; Zaré, HK, 2020
)
0.56
"The extent of a drug-drug interaction (DDI) mediated by cytochrome P450 (CYP) 3A inhibitors is highly variable during a dosing interval, as it depends on the temporal course of victim and perpetrator drug concentrations at intestinal and hepatic CYP3A expression sites."( A Novel Study Design Using Continuous Intravenous and Intraduodenal Infusions of Midazolam and Voriconazole for Mechanistic Quantitative Assessment of Hepatic and Intestinal CYP3A Inhibition.
Dahlinger, D; Frechen, S; Fuhr, U; Goeser, T; Jaehde, U; Junge, L; Kinzig, M; Li, X; Sörgel, F; Starke, C; Stelzer, C; Taubert, M; Töx, U; von Georg, A, 2020
)
0.78
"A prospective, randomized, crossover trial was conducted to compare the dosing accuracy and timeliness of the color-only syringe method versus the validation method."( Comparison Between a Color-only Method and a Food and Drug Administration-approved Validation Method for a Pediatric Color-coded Syringe Using Midazolam: A Randomized Crossover Trial.
Arana, AA; Howard, CM; Jeffers, KL; Montez, D; Rahm, SJ, 2022
)
0.92
"There was no significant difference in dosing errors between the FDA-approved validation method and the color-only method."( Comparison Between a Color-only Method and a Food and Drug Administration-approved Validation Method for a Pediatric Color-coded Syringe Using Midazolam: A Randomized Crossover Trial.
Arana, AA; Howard, CM; Jeffers, KL; Montez, D; Rahm, SJ, 2022
)
0.92
" Based on pharmacokinetics, safety, and efficacy data, and PBPK modeling, dosing modifications for ribociclib recommend avoiding concurrent use of strong CYP3A inhibitors/inducers, and caution regarding using CYP3A substrates with narrow therapeutic indices."( Ribociclib Drug-Drug Interactions: Clinical Evaluations and Physiologically-Based Pharmacokinetic Modeling to Guide Drug Labeling.
Chakraborty, A; Dhuria, SV; Elmeliegy, M; He, H; Heimbach, T; Huth, F; Ji, Y; Miller, M; Samant, TS; Schiller, H; Umehara, K, 2020
)
0.56
" When only inhibition or induction was incorporated into a model, the AUCR of midazolam changed depending on the dosing period and dose level of esaxerenone and the timing of midazolam administration."( Drug-Drug Interaction Risk Assessment of Esaxerenone as a Perpetrator by In Vitro Studies and Static and Physiologically Based Pharmacokinetic Models.
Fischer, T; Inoue, SI; Ishizuka, T; Rozehnal, V; Sugiyama, D; Yamada, M, 2020
)
0.79
" Upon treatment of CHIM with the estimated lumen concentration of the HS upon each oral administration (manufacturers' recommended dosage dissolved in 200 ml of culture medium), >80% CYP3A inhibition was observed for green tea extract, St."( Application of Cryopreserved Human Intestinal Mucosa and Cryopreserved Human Enterocytes in the Evaluation of Herb-Drug Interactions: Evaluation of CYP3A Inhibitory Potential of Grapefruit Juice and Commercial Formulations of Twenty-Nine Herbal Supplement
Alam, N; Ho, MD; Li, AP; Loretz, C; Mitchell, W, 2020
)
0.56
"Refractory status epilepticus (RSE) is often treated with midazolam boluses and continuous infusions, but there is considerable variability in dosing and efficacy."( Assessment of midazolam pharmacokinetics in the treatment of status epilepticus.
Abend, NS; Francoeur, C; Ichord, R; Topjian, AA; Welsh, SS; Zuppa, AF, 2020
)
1.16
" Once validated, this model may guide dosing and drive the development of more effective treatment pathways for continuous midazolam in RSE."( Assessment of midazolam pharmacokinetics in the treatment of status epilepticus.
Abend, NS; Francoeur, C; Ichord, R; Topjian, AA; Welsh, SS; Zuppa, AF, 2020
)
1.13
" This pharmacokinetic and pharmacodynamic analysis does not provide evidence for different dosing of midazolam in children with Down syndrome after cardiac surgery."( Sedation With Midazolam After Cardiac Surgery in Children With and Without Down Syndrome: A Pharmacokinetic-Pharmacodynamic Study.
Breatnach, CV; Goulooze, SC; Knibbe, CAJ; Mathôt, RAA; Peeters, MYM; Tibboel, D; Valkenburg, AJ; van Dijk, M, 2021
)
1.2
" The team created an automated monthly report to monitor prescribed seizure rescue medication dosing compliance."( Using quality improvement to implement the CNS/AAN quality measure on rescue medication for seizures.
Cohen, DM; Debs, A; Gibson, A; Herbst, J; Karn, M; Parker, W; Patel, AD; Terry, D; Yarosz, S, 2020
)
0.56
" Compliance with properly dosed diazepam orders continues to be the largest area of opportunity."( Using quality improvement to implement the CNS/AAN quality measure on rescue medication for seizures.
Cohen, DM; Debs, A; Gibson, A; Herbst, J; Karn, M; Parker, W; Patel, AD; Terry, D; Yarosz, S, 2020
)
0.56
" Although there are many studies regarding the route and dosage of administration, literature does not have any evidence on the outcome of medication acceptance based on the person administering the drug."( Comparison of medication acceptance of intranasal midazolam administered by parents versus doctors in children - A randomized trial.
Elakkumanan, LB; Kamaladevi, RK; Mohan, VK; Satya Prakash, MVS; Sivasankar, S,
)
0.38
" Dosing data were also stratified by age."( Lower-Dose Propofol Use for MRI: A Retrospective Review of a Pediatric Sedation Team's Experience.
Cochran, J; Johnson, KL; Webb, S, 2021
)
0.62
" Data extracted included information about study design, country of origin, number of participants and demographic details, type of surgery, type of anaesthesia, intervention and dosing regimens, preoperative anxiety outcome measures, and postoperative anxiety outcome measures."( Melatonin for preoperative and postoperative anxiety in adults.
Madsen, BK; Møller, AM; Rosenberg, J; Zetner, D, 2020
)
0.56
" Its use increases in the last days of hospice patients' lives while safe dosage can be challenging."( Midazolam and hydroxymidazolam plasma concentrations can be monitored with selected biochemical and physiological parameters of palliative care patients.
Gościniak, K; Grabowski, T; Sopata, M; Stachowiak-Szymczak, K; Teżyk, A; Zaporowska-Stachowiak, I, 2021
)
2.06
" We included any duration of drug treatment and any dosage given continuously or as bolus; we excluded studies that gave opioids to ventilated infants for procedures."( Opioids for newborn infants receiving mechanical ventilation.
Bellù, R; Bruschettini, M; de Waal, KA; Nava, C; Romantsik, O; Zanini, R, 2021
)
0.62
" Midazolam dosage was significantly lower in the DEX group than in the FEN group, and the duration of surgery was significantly longer in the DEX group."( Dexmedetomidine combined with midazolam infusion guided by bispectral index during bronchoscopy.
Dai, P; Dong, D; Guan, S; He, Q; Qiu, H; Wang, X; Xu, Q; Xu, X; Zhang, Q; Zhang, S; Zhou, J, 2021
)
1.82
" Pediatric subjects in convulsive SE received treatment with buccal MHOS with dosage based on their age."( A Phase 3 open-label study of the efficacy, safety and pharmacokinetics of buccally administered midazolam hydrochloride for the treatment of status epilepticus in pediatric Japanese subjects.
Benitez, A; Fournier, M; Kugler, AR; Takeda, S; Yoshinaga, H, 2021
)
0.84
"To assess sedation medication dosage differences between patients with and without opioid use disorder at the time of surgical abortion."( Pain medication requirements in patients with opioid use disorder at the time of surgical abortion: An exploratory study.
Ramanadhan, S; Srikanth, P; White, KO; Woodhams, E, 2021
)
0.62
" There are no studies to describe the use, effectiveness, and suitable dosing of OMM in adults with epilepsy in community settings."( Oro-mucosal midazolam maleate: Use and effectiveness in adults with epilepsy in the UK.
Boyle, A; Goodwin, M; Grant, A; Higgins, R; Hudson, S; Pearson, J; Reuber, M; Shankar, R; Storer, A; Toland, J, 2021
)
1
"To describe the use, effectiveness, and dosing of OMM in the emergency treatment of epileptic seizures in community settings."( Oro-mucosal midazolam maleate: Use and effectiveness in adults with epilepsy in the UK.
Boyle, A; Goodwin, M; Grant, A; Higgins, R; Hudson, S; Pearson, J; Reuber, M; Shankar, R; Storer, A; Toland, J, 2021
)
1
" Secondary endpoints included the total dosage of anesthetics and total times of target-controlled infusion pump adjustments."( Comparison of 2 effect-site concentrations of remifentanil with midazolam during percutaneous transluminal balloon angioplasty under monitored anesthesia care: A randomized controlled study.
Chan, SM; Huang, RC; Huang, YH; Lai, HC; Lin, BF; Tsai, YT; Wu, KL; Wu, ZF, 2021
)
0.86
" Patients were followed for 2 years, with four pharmacokinetic investigations using semisimultaneous oral and intravenous dosing to determine changes in midazolam absolute bioavailability and clearance, within and between groups."( Short- and long-term effects of body weight loss following calorie restriction and gastric bypass on CYP3A-activity - a non-randomized three-armed controlled trial.
Andersson, S; Andersson, TB; Angeles, PC; Artursson, P; Åsberg, A; Christensen, H; Hjelmesaeth, J; Hole, K; Jansson-Löfmark, R; Johnson, LK; Karlsson, C; Krogstad, V; Kvitne, KE; Robertsen, I; Sandbu, R; Skovlund, E; Wegler, C; Wollmann, BM, 2022
)
0.92
"25), if concomitantly administered drugs are dosed either 2 hours before or 8 hours after the 2-hour intravenous infusion of treosulfan."( Evaluation of the drug-drug interaction potential of treosulfan using a physiologically-based pharmacokinetic modelling approach.
Balazki, P; Baumgart, J; Beelen, DW; Böhm, S; Hemmelmann, C; Hilger, RA; Martins, FS; Ring, A; Schaller, S, 2022
)
0.72
" However, if the dosage of midazolam is improperly controlled, it may not produce forgetting effect, or bring obvious adverse side effects, such as respiratory depression, and delay of recovery."( ED50 for intravenous midazolam-induced amnesia and its duration in surgical patients.
Gao, C; Wang, Y; Wu, AS; Yan, J; Yue, Y, 2021
)
1.24
"A multidisciplinary committee created a sedation guideline that included standardized dexmedetomidine dosing escalation and weaning."( Reducing Benzodiazepine Exposure by Instituting a Guideline for Dexmedetomidine Usage in the NICU.
Hansen, A; Labrecque, M; Leeman, K; Moline, M; Morton, SU, 2021
)
0.62
" Survival analysis was used to analyze the association between alfaxalone dosage and premedication with time-related variables."( Induction of General Anesthesia With Alfaxalone in the Domestic Chicken.
de Gier, R; Doneley, R; Henning, J; Mastakov, A, 2021
)
0.62
" Sedative depth, a composite score comprised of five assessment criteria, was observed every 5-min from dosing until arousal."( Differential effects of four intramuscular sedatives on cardiorespiratory stability in juvenile guinea pigs (Cavia porcellus).
Berry, MJ; Dyson, RM; Gray, CL; Pacharinsak, C; Sixtus, RP, 2021
)
0.62
" Multiple dosing caused minor-to-moderate accumulation and a mean terminal half-life (15."( Pharmacokinetics, pharmacodynamics and safety of BAY 2433334, a novel activated factor XI inhibitor, in healthy volunteers: A randomized phase 1 multiple-dose study.
Distler, J; Heckmann, M; Kanefendt, F; Koechel, A; Kubitza, D; Schwers, S, 2022
)
0.72
"Multiple dosing of BAY 2433334 in healthy volunteers was well tolerated, with a predictable pharmacokinetic/pharmacodynamic profile and no clinically relevant CYP3A4 induction or inhibition."( Pharmacokinetics, pharmacodynamics and safety of BAY 2433334, a novel activated factor XI inhibitor, in healthy volunteers: A randomized phase 1 multiple-dose study.
Distler, J; Heckmann, M; Kanefendt, F; Koechel, A; Kubitza, D; Schwers, S, 2022
)
0.72
" Each dosing error was reviewed by two investigators."( Medication Errors in Pediatric Patients after Implementation of a Field Guide with Volume-Based Dosing.
Hulac, S; Markowitz, G; Rappaport, LD; Roosevelt, G, 2023
)
0.91
" A field guide with precalculated doses (in mL) may be an effective tool for reducing pediatric medication dosing errors by EMS providers."( Medication Errors in Pediatric Patients after Implementation of a Field Guide with Volume-Based Dosing.
Hulac, S; Markowitz, G; Rappaport, LD; Roosevelt, G, 2023
)
0.91
"For critically ill patients on ventilators, it is recommended to devise a means of assessing each patient daily as well as systematically reduce their dosage of midazolam or fentanyl."( Retrospective study on the factors influencing the severity of pressure injuries among intensive care unit patients.
Chang, WP; Weng, PW, 2023
)
1.11
" Variation in benzodiazepine dosage administration was 54."( Multicentre analysis of practice patterns regarding benzodiazepine use in cardiac surgery.
Belley-Côté, E; Dubovoy, T; Janda, AM; Kheterpal, S; Mathis, MR; Mentz, G; Spence, J, 2022
)
0.72
" Retrospective data extraction from patients' medical charts was done, registering demographics, dosage of anesthesia, surgical characteristics, complications, and reoperation rates."( Breast augmentation under local anesthesia with intercostal blocks and light sedation.
Ditlev, M; Hölmich, LR; Loentoft, E,
)
0.13
"This retrospective study compares the efficacy and safety of variable dosing of Midazolam (Mid) with and without Meperidine (Mep) combinations for managing varying levels of anxiety and uncooperative behavior of young pediatric dental patients over a thirty-five-year period."( Retrospective Comparisons of the Efficacy and Safety of Variable dosing of Midazolam with and without Meperidine for Management of Varying Levels of Anxiety of Pediatric Dental Patients: 35 years of Sedation Experience.
Nathan, JE, 2022
)
1.18
"Reviews of the sedation logs of 1,785 sedation visits are compared with emphasis on what dosing proves both safe and effective for differing levels of challenging pediatric behavior."( Retrospective Comparisons of the Efficacy and Safety of Variable dosing of Midazolam with and without Meperidine for Management of Varying Levels of Anxiety of Pediatric Dental Patients: 35 years of Sedation Experience.
Nathan, JE, 2022
)
0.95
" Serological profiling of patients was performed by dosing the serum concentration of nucleotide-binding domain (NOD) and leucine-rich repeat protein 3 (NLRP3) inflammasomes, interleukin (IL)-6, tumor necrosis factor-alpha (TNF-α), IL-10 before and two hours after the surgical procedure."( The perioperative effect of anesthetic drugs on the immune response in total intravenous anesthesia in patients undergoing minimally invasive gynecological surgery.
Boldeanu, L; Boldeanu, MV; Dijmărescu, AL; Manolea, MM; Mirea, CS; Neamţu, SD; Niculescu, M; Novac, MB; Radu, L; Rotaru, LT; Şerbănescu, MS; Vîlcea, AM,
)
0.13
" Five patients were sedated with initial lorazepam dose, but this side effect resolved on dosage reduction."( Enteral lorazepam is a promising weaning strategy for midazolam-responsive febrile infection-related epilepsy syndrome (FIRES): a case series
Chaitra, R; Jain, V; Konanki, R; Sharma, R; Srivastava, K, 2022
)
0.97
" The consistency of respiratory parameters during the entire exposure time is paramount to ensuring dosing accuracy."( Comparison of Alfaxalone-Midazolam, Tiletamine-Zolazepam, and KetamineAcepromazine Anesthesia during Plethysmography in Cynomolgus Macaques (
Astleford, SM; Bowling, PA; Casselman, AM; Dixon, BC; Ghering, JM; Marion, BM; White, CE, 2022
)
1.02
"The scoping review identified 57 studies with most data available on their tolerability (68% local, 54% systemic), clinical effects (82%), details on dosage (96%) and routes of application (100%)."( Subcutaneous Drugs and Off-label Use in Hospice and Palliative Care: A Scoping Review.
Dürr, F; Jean-Petit-Matile, S; Kobleder, A; Meyer-Massetti, C; Wernli, U, 2022
)
0.72
"Sedation and analgesia are recommended during targeted temperature management (TTM) after cardiac arrest, but there are few data to provide guidance on dosing to bedside clinicians."( Cardiac Arrest Treatment Center Differences in Sedation and Analgesia Dosing During Targeted Temperature Management.
Ceric, A; Cronberg, T; Dankiewicz, J; Friberg, H; Hassager, C; Haxhija, Z; Kjaergaard, J; Lybeck, A; May, TL; Nielsen, N; Riker, RR; Seder, DB, 2023
)
0.91
" We also compared dosing with time to awakening, incidence of clinical seizures, and survival."( Cardiac Arrest Treatment Center Differences in Sedation and Analgesia Dosing During Targeted Temperature Management.
Ceric, A; Cronberg, T; Dankiewicz, J; Friberg, H; Hassager, C; Haxhija, Z; Kjaergaard, J; Lybeck, A; May, TL; Nielsen, N; Riker, RR; Seder, DB, 2023
)
0.91
" There were associations between higher dosing at 48 h (p = 0."( Cardiac Arrest Treatment Center Differences in Sedation and Analgesia Dosing During Targeted Temperature Management.
Ceric, A; Cronberg, T; Dankiewicz, J; Friberg, H; Hassager, C; Haxhija, Z; Kjaergaard, J; Lybeck, A; May, TL; Nielsen, N; Riker, RR; Seder, DB, 2023
)
0.91
" Sedation and analgesia dosing and titration were associated with delayed awakening, incidence of clinical seizures, and survival, but the causal relation of these findings cannot be proven."( Cardiac Arrest Treatment Center Differences in Sedation and Analgesia Dosing During Targeted Temperature Management.
Ceric, A; Cronberg, T; Dankiewicz, J; Friberg, H; Hassager, C; Haxhija, Z; Kjaergaard, J; Lybeck, A; May, TL; Nielsen, N; Riker, RR; Seder, DB, 2023
)
0.91
" However, in real-world practice, it is frequently administered intranasally or intravenously and is dosed lower."( Real-World Midazolam Use and Outcomes With Out-of-Hospital Treatment of Status Epilepticus in the United States.
Betjemann, JP; Burke, JF; Crowe, RP; Guterman, EL; Josephson, SA; Lowenstein, DH; Newman, TB; Sporer, KA, 2022
)
1.11
" Understanding potential drug-drug interactions (DDIs) informs proper dosing when co-administering tucatinib with other therapies."( Evaluation of Safety and Clinically Relevant Drug-Drug Interactions with Tucatinib in Healthy Volunteers.
Abdulrasool, LI; Endres, CJ; Lee, A; Mayor, JG; Rustia, EL; Sun, H; Topletz-Erickson, A; Walker, L, 2022
)
0.72
" The extremely high concentrations of midazolam observed in some critically-ill children indicate that the current therapeutic dosing regimen for midazolam can lead to over-dosing."( Inflammation and cardiovascular status impact midazolam pharmacokinetics in critically ill children: An observational, prospective, controlled study.
Austin, R; Mulla, H; Neupane, B; Pandya, H; Pandya, T; Rudge, J; Spooner, N, 2022
)
1.25
" Capmatinib 400 mg bid was administered from day 4 on a continuous dosing schedule."( Effect of capmatinib on the pharmacokinetics of substrates of CYP3A (midazolam) and CYP1A2 (caffeine) in patients with MET-dysregulated solid tumours.
Chen, X; Cui, X; Giovannini, M; Isambert, N; Kapoor, S; López-López, R; Mau-Sorensen, M; Pognan, N; Quinlan, M; Rahmanzadeh, G; You, B, 2023
)
1.14
" Physiologically-based pharmacokinetic (PBPK) models are increasingly used to study PK and guide dosing decisions."( Feasibility of a Pragmatic PBPK Modeling Approach: Towards Model-Informed Dosing in Pediatric Clinical Care.
de Hoop-Sommen, MA; de Wildt, SN; Driessen, SHP; Freriksen, JJM; Greupink, R; Orlebeke, AEM; van Bussel, LPM; van der Heijden, JEM; Verscheijden, LFM, 2022
)
0.72
"Our in silico pharmacokinetic modeling of standard midazolam and pentobarbital dosing protocols for RSE suggests potential variables to optimize in future clinical studies."( Pharmacokinetic Modeling of Optimized Midazolam and Pentobarbital Dosing Used in Treatment Protocols of Refractory Status Epilepticus.
Akhondi-Asl, A; Au, CC; LaRovere, K; Luchette, M; Tasker, RC, 2023
)
1.43
" The potential difference in physiology can significantly affect the outcomes of treatment and may result in under dosing or over-dosage."( Pharmacokinetics of Midazolam in preterm neonates with an insight in brain Tissue: A PBPK approach.
Ahmed, M; Czejka, M; Hassan, A; Hassan, S; Mansoor, N; Sharib, S, 2022
)
1.04
" Questions were posed about the therapeutic and maximum dosing of INM and POM, consideration of Nothing-By-Mouth (NPO) status, use of cardiopulmonary monitors, as well as discharge criteria."( Physician Self-Reported Practice Patterns: Midazolam for Minor Procedures in Pediatric Patients.
Bhattarai, B; Mecham, C; Trotter, Z, 2023
)
1.17
"This study will determine the optimal dosage of remimazolam tosylate during upper gastrointestinal endoscopy and will describe its efficacy and safety."( Efficacy and safety of remimazolam tosylate for sedation during upper gastrointestinal endoscopy: study protocol for a multicenter randomized controlled trial.
Chen, C; Huai, X; Su, D; Su, Z; Zhang, X; Zhou, J; Zhu, H, 2022
)
0.72
"We demonstrate the accurate prediction of a three-drug response surface model for moderate sedation and simulation suggests a rational dosing strategy for moderate sedation with midazolam, alfentanil and propofol."( Pharmacodynamic modeling of moderate sedation and rationale for dosing using midazolam, propofol and alfentanil.
Chang, WK; Kuo, IT; Liou, JY; Ting, CK; Tsou, MY, 2023
)
1.33
"The theoretical basis for propofol dosing has recently been adapted."( A new view on old problems in paediatric anaesthesia: premedication, postoperative agitation and dosing.
Jöhr, M, 2023
)
0.91
" New data will allow more precise age-adapted dosing of propofol."( A new view on old problems in paediatric anaesthesia: premedication, postoperative agitation and dosing.
Jöhr, M, 2023
)
0.91
" Each dog received ALLO (1 mg/kg, IV), and after a washout period of 2 weeks, each dog was dosed with MDZ (0."( Tolerability and pharmacokinetics of intravenous allopregnanolone with and without midazolam pretreatment in two healthy dogs.
Aleman, M; Bruun, DA; Chen, YJ; Lein, PJ; Ma, B; Rogawski, MA; Smiley-Jewell, SM; Wu, CY; Zolkowska, D, 2023
)
1.14
" Employing our previously established rodent model system that mimics the exposure of MDZ in the NICU using an increasing dosage regimen, we isolated BDEVs from postnatal 21-days-old control and MDZ groups using a differential sucrose density gradient."( Identification of YWHAH as a Novel Brain-Derived Extracellular Vesicle Marker Post Long-Term Midazolam Exposure during Early Development.
Chand, S; Guda, C; Jagadesan, S; Meyer, D; Meyer, L; Miravite, M; Nguyen, NM; Pendyala, G; Yelamanchili, SV, 2023
)
1.13
" We conducted the Kruskal-Wallis H test to evaluate for medication dosing or maximum pain score differences among groups."( The association of patient age, race, and demographic features on reported pain and sedation dosing during procedural abortion: A retrospective cohort study.
Howard, M; Lee, J; Makar, E; Pace, L, 2023
)
0.91
" We found no difference in fentanyl or midazolam dosing by age."( The association of patient age, race, and demographic features on reported pain and sedation dosing during procedural abortion: A retrospective cohort study.
Howard, M; Lee, J; Makar, E; Pace, L, 2023
)
1.18
" Multiple demographic and psychosocial factors, as well as perhaps provider bias, play into both a patient's perception of pain and the dosage of fentanyl and midazolam they receive during abortion procedures."( The association of patient age, race, and demographic features on reported pain and sedation dosing during procedural abortion: A retrospective cohort study.
Howard, M; Lee, J; Makar, E; Pace, L, 2023
)
1.11
" Differential pulse voltammetric technique (DPV) was utilized for the selective assay of midazolam hydrochloride (MDZ) in the pure, parenteral dosage forms and plasma samples."( Eco-friendly electrochemical sensor for determination of conscious sedating drug "midazolam'' based on Au-NPs@Silica modified carbon paste electrode.
Elghobashy, MR; Mahmoud, AM; Sedik, GA; Soliman, SS; Zaazaa, HE, 2024
)
1.89
" The study also provided guidance on the appropriate dosage of remimazolam for achieving moderate sedation during dental procedures."( Efficacy and safety of remimazolam besilate for sedation in outpatients undergoing impacted third molar extraction: a prospective exploratory study.
Aikawa, T; Doi, M; Imado, E; Imamura, S; Kamio, H; Mukai, A; Oda, A; Ono, S; Oue, K; Sakuma, M; Sasaki, U; Shimizu, Y; Takahashi, T; Yoshida, M, 2023
)
0.91
" In addition, this article provides dosage guidelines based on the current scientific knowledge and recommendations for conversion equivalencies."( Surge of Midazolam Use in the Midst of Lorazepam Shortage.
Donlon, J; Frost, ED; Gandhi, RM; Koola, MM; Liu, TT; Mohammadi, T; Murray, BP; Shad, MU,
)
0.55
[information is derived through text-mining from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Roles (9)

RoleDescription
GABAA receptor agonistA GABA receptor agonist specific for GABAA receptors, ligand-gated ion channels (also known as ionotropic receptors).
anticonvulsantA drug used to prevent seizures or reduce their severity.
anxiolytic drugAnxiolytic drugs are agents that alleviate anxiety, tension, and anxiety disorders, promote sedation, and have a calming effect without affecting clarity of consciousness or neurologic conditions.
apoptosis inducerAny substance that induces the process of apoptosis (programmed cell death) in multi-celled organisms.
antineoplastic agentA substance that inhibits or prevents the proliferation of neoplasms.
muscle relaxantA drug used to produce muscle relaxation (excepting neuromuscular blocking agents). Its primary clinical and therapeutic use is the treatment of muscle spasm and immobility associated with strains, sprains, and injuries of the back and, to a lesser degree, injuries to the neck. Also used for the treatment of a variety of clinical conditions that have in common only the presence of skeletal muscle hyperactivity, for example, the muscle spasms that can occur in multiple sclerosis.
sedativeA central nervous system depressant used to induce drowsiness or sleep or to reduce psychological excitement or anxiety.
general anaestheticSubstance that produces loss of consciousness.
central nervous system depressantA loosely defined group of drugs that tend to reduce the activity of the central nervous system.
[role information is derived from Chemical Entities of Biological Interest (ChEBI), Hastings J, Owen G, Dekker A, Ennis M, Kale N, Muthukrishnan V, Turner S, Swainston N, Mendes P, Steinbeck C. (2016). ChEBI in 2016: Improved services and an expanding collection of metabolites. Nucleic Acids Res]

Drug Classes (3)

ClassDescription
organochlorine compoundAn organochlorine compound is a compound containing at least one carbon-chlorine bond.
imidazobenzodiazepineAny organic heterotricyclic compound that is any benzodiazepine which is ortho-fused with a imidazole.
monofluorobenzenesAny member of the class of fluorobenzenes containing a mono- or poly-substituted benzene ring carrying a single fluorine substitutent.
[compound class information is derived from Chemical Entities of Biological Interest (ChEBI), Hastings J, Owen G, Dekker A, Ennis M, Kale N, Muthukrishnan V, Turner S, Swainston N, Mendes P, Steinbeck C. (2016). ChEBI in 2016: Improved services and an expanding collection of metabolites. Nucleic Acids Res]

Protein Targets (31)

Potency Measurements

ProteinTaxonomyMeasurementAverage (µ)Min (ref.)Avg (ref.)Max (ref.)Bioassay(s)
euchromatic histone-lysine N-methyltransferase 2Homo sapiens (human)Potency1.99530.035520.977089.1251AID504332
gemininHomo sapiens (human)Potency18.83750.004611.374133.4983AID624296
peripheral myelin protein 22Rattus norvegicus (Norway rat)Potency10.18150.005612.367736.1254AID624032
[prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023]

Inhibition Measurements

ProteinTaxonomyMeasurementAverageMin (ref.)Avg (ref.)Max (ref.)Bioassay(s)
Gamma-aminobutyric acid receptor subunit piRattus norvegicus (Norway rat)Ki0.00200.00020.656110.0000AID41742
Solute carrier family 22 member 1 Homo sapiens (human)Ki3.70000.55004.26507.4600AID681146
Bile salt export pumpHomo sapiens (human)IC50 (µMol)41.71330.11007.190310.0000AID1443980; AID1443989; AID1473738
ATP-dependent translocase ABCB1Mus musculus (house mouse)IC50 (µMol)33.00000.06404.012610.0000AID150754; AID681128
ATP-dependent translocase ABCB1Homo sapiens (human)IC50 (µMol)50.00000.00022.318510.0000AID150752; AID150755; AID681122
Cytochrome P450 3A4Homo sapiens (human)IC50 (µMol)2.74270.00011.753610.0000AID1862578; AID1884506; AID54923
Gamma-aminobutyric acid receptor subunit beta-1Rattus norvegicus (Norway rat)Ki0.00200.00020.656110.0000AID41742
Translocator proteinRattus norvegicus (Norway rat)Ki0.00200.00010.65108.9300AID39933
UDP-glucuronosyltransferase 2B7Homo sapiens (human)IC50 (µMol)75.50000.10002.50004.9000AID1802994
Gamma-aminobutyric acid receptor subunit deltaRattus norvegicus (Norway rat)Ki0.00200.00020.656110.0000AID41742
Gamma-aminobutyric acid receptor subunit gamma-2Rattus norvegicus (Norway rat)Ki0.00200.00020.561410.0000AID41742
UDP-glucuronosyltransferase 1-6Homo sapiens (human)IC50 (µMol)75.50004.90004.90004.9000AID1802994
Gamma-aminobutyric acid receptor subunit alpha-5Rattus norvegicus (Norway rat)Ki0.00200.00020.635210.0000AID41742
Gamma-aminobutyric acid receptor subunit alpha-3Rattus norvegicus (Norway rat)Ki0.00200.00020.621710.0000AID41742
ATP-dependent translocase ABCB1Mus musculus (house mouse)IC50 (µMol)50.00000.20004.713010.0000AID150753; AID681119
UDP-glucuronosyltransferase 1A1 Homo sapiens (human)IC50 (µMol)75.50000.30003.25807.3000AID1802994
UDP-glucuronosyltransferase 1A4Homo sapiens (human)IC50 (µMol)75.50004.72004.81004.9000AID1802994
Gamma-aminobutyric acid receptor subunit gamma-1Rattus norvegicus (Norway rat)Ki0.00200.00020.675810.0000AID41742
Gamma-aminobutyric acid receptor subunit alpha-2Rattus norvegicus (Norway rat)Ki0.00200.00020.646910.0000AID41742
Gamma-aminobutyric acid receptor subunit alpha-4Rattus norvegicus (Norway rat)Ki0.00200.00020.656110.0000AID41742
Gamma-aminobutyric acid receptor subunit gamma-3Rattus norvegicus (Norway rat)Ki0.00200.00020.656110.0000AID41742
Gamma-aminobutyric acid receptor subunit alpha-6Rattus norvegicus (Norway rat)Ki0.00200.00020.671210.0000AID41742
UDP-glucuronosyltransferase 2B10 Homo sapiens (human)IC50 (µMol)75.50004.90004.90004.9000AID1802994
Gamma-aminobutyric acid receptor subunit alpha-1Rattus norvegicus (Norway rat)Ki0.00200.00020.557710.0000AID41742
Gamma-aminobutyric acid receptor subunit beta-3Rattus norvegicus (Norway rat)Ki0.00200.00020.640310.0000AID41742
Gamma-aminobutyric acid receptor subunit beta-2Rattus norvegicus (Norway rat)Ki0.00200.00020.570810.0000AID41742
GABA theta subunitRattus norvegicus (Norway rat)Ki0.00200.00020.656110.0000AID41742
Gamma-aminobutyric acid receptor subunit epsilonRattus norvegicus (Norway rat)Ki0.00200.00020.656110.0000AID41742
[prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023]

Biological Processes (99)

Processvia Protein(s)Taxonomy
xenobiotic metabolic processSolute carrier family 22 member 1 Homo sapiens (human)
neurotransmitter transportSolute carrier family 22 member 1 Homo sapiens (human)
serotonin transportSolute carrier family 22 member 1 Homo sapiens (human)
establishment or maintenance of transmembrane electrochemical gradientSolute carrier family 22 member 1 Homo sapiens (human)
organic cation transportSolute carrier family 22 member 1 Homo sapiens (human)
quaternary ammonium group transportSolute carrier family 22 member 1 Homo sapiens (human)
prostaglandin transportSolute carrier family 22 member 1 Homo sapiens (human)
monoamine transportSolute carrier family 22 member 1 Homo sapiens (human)
putrescine transportSolute carrier family 22 member 1 Homo sapiens (human)
spermidine transportSolute carrier family 22 member 1 Homo sapiens (human)
acetylcholine transportSolute carrier family 22 member 1 Homo sapiens (human)
dopamine transportSolute carrier family 22 member 1 Homo sapiens (human)
norepinephrine transportSolute carrier family 22 member 1 Homo sapiens (human)
thiamine transportSolute carrier family 22 member 1 Homo sapiens (human)
xenobiotic transportSolute carrier family 22 member 1 Homo sapiens (human)
epinephrine transportSolute carrier family 22 member 1 Homo sapiens (human)
serotonin uptakeSolute carrier family 22 member 1 Homo sapiens (human)
norepinephrine uptakeSolute carrier family 22 member 1 Homo sapiens (human)
thiamine transmembrane transportSolute carrier family 22 member 1 Homo sapiens (human)
metanephric proximal tubule developmentSolute carrier family 22 member 1 Homo sapiens (human)
purine-containing compound transmembrane transportSolute carrier family 22 member 1 Homo sapiens (human)
dopamine uptakeSolute carrier family 22 member 1 Homo sapiens (human)
monoatomic cation transmembrane transportSolute carrier family 22 member 1 Homo sapiens (human)
transport across blood-brain barrierSolute carrier family 22 member 1 Homo sapiens (human)
(R)-carnitine transmembrane transportSolute carrier family 22 member 1 Homo sapiens (human)
acyl carnitine transmembrane transportSolute carrier family 22 member 1 Homo sapiens (human)
spermidine transmembrane transportSolute carrier family 22 member 1 Homo sapiens (human)
cellular detoxificationSolute carrier family 22 member 1 Homo sapiens (human)
xenobiotic transport across blood-brain barrierSolute carrier family 22 member 1 Homo sapiens (human)
fatty acid metabolic processBile salt export pumpHomo sapiens (human)
bile acid biosynthetic processBile salt export pumpHomo sapiens (human)
xenobiotic metabolic processBile salt export pumpHomo sapiens (human)
xenobiotic transmembrane transportBile salt export pumpHomo sapiens (human)
response to oxidative stressBile salt export pumpHomo sapiens (human)
bile acid metabolic processBile salt export pumpHomo sapiens (human)
response to organic cyclic compoundBile salt export pumpHomo sapiens (human)
bile acid and bile salt transportBile salt export pumpHomo sapiens (human)
canalicular bile acid transportBile salt export pumpHomo sapiens (human)
protein ubiquitinationBile salt export pumpHomo sapiens (human)
regulation of fatty acid beta-oxidationBile salt export pumpHomo sapiens (human)
carbohydrate transmembrane transportBile salt export pumpHomo sapiens (human)
bile acid signaling pathwayBile salt export pumpHomo sapiens (human)
cholesterol homeostasisBile salt export pumpHomo sapiens (human)
response to estrogenBile salt export pumpHomo sapiens (human)
response to ethanolBile salt export pumpHomo sapiens (human)
xenobiotic export from cellBile salt export pumpHomo sapiens (human)
lipid homeostasisBile salt export pumpHomo sapiens (human)
phospholipid homeostasisBile salt export pumpHomo sapiens (human)
positive regulation of bile acid secretionBile salt export pumpHomo sapiens (human)
regulation of bile acid metabolic processBile salt export pumpHomo sapiens (human)
transmembrane transportBile salt export pumpHomo sapiens (human)
G2/M transition of mitotic cell cycleATP-dependent translocase ABCB1Homo sapiens (human)
xenobiotic metabolic processATP-dependent translocase ABCB1Homo sapiens (human)
response to xenobiotic stimulusATP-dependent translocase ABCB1Homo sapiens (human)
phospholipid translocationATP-dependent translocase ABCB1Homo sapiens (human)
terpenoid transportATP-dependent translocase ABCB1Homo sapiens (human)
regulation of response to osmotic stressATP-dependent translocase ABCB1Homo sapiens (human)
transmembrane transportATP-dependent translocase ABCB1Homo sapiens (human)
transepithelial transportATP-dependent translocase ABCB1Homo sapiens (human)
stem cell proliferationATP-dependent translocase ABCB1Homo sapiens (human)
ceramide translocationATP-dependent translocase ABCB1Homo sapiens (human)
export across plasma membraneATP-dependent translocase ABCB1Homo sapiens (human)
transport across blood-brain barrierATP-dependent translocase ABCB1Homo sapiens (human)
positive regulation of anion channel activityATP-dependent translocase ABCB1Homo sapiens (human)
carboxylic acid transmembrane transportATP-dependent translocase ABCB1Homo sapiens (human)
xenobiotic detoxification by transmembrane export across the plasma membraneATP-dependent translocase ABCB1Homo sapiens (human)
xenobiotic transport across blood-brain barrierATP-dependent translocase ABCB1Homo sapiens (human)
regulation of chloride transportATP-dependent translocase ABCB1Homo sapiens (human)
lipid hydroxylationCytochrome P450 3A4Homo sapiens (human)
lipid metabolic processCytochrome P450 3A4Homo sapiens (human)
steroid catabolic processCytochrome P450 3A4Homo sapiens (human)
xenobiotic metabolic processCytochrome P450 3A4Homo sapiens (human)
steroid metabolic processCytochrome P450 3A4Homo sapiens (human)
cholesterol metabolic processCytochrome P450 3A4Homo sapiens (human)
androgen metabolic processCytochrome P450 3A4Homo sapiens (human)
estrogen metabolic processCytochrome P450 3A4Homo sapiens (human)
alkaloid catabolic processCytochrome P450 3A4Homo sapiens (human)
monoterpenoid metabolic processCytochrome P450 3A4Homo sapiens (human)
calcitriol biosynthetic process from calciolCytochrome P450 3A4Homo sapiens (human)
xenobiotic catabolic processCytochrome P450 3A4Homo sapiens (human)
vitamin D metabolic processCytochrome P450 3A4Homo sapiens (human)
vitamin D catabolic processCytochrome P450 3A4Homo sapiens (human)
retinol metabolic processCytochrome P450 3A4Homo sapiens (human)
retinoic acid metabolic processCytochrome P450 3A4Homo sapiens (human)
long-chain fatty acid biosynthetic processCytochrome P450 3A4Homo sapiens (human)
aflatoxin metabolic processCytochrome P450 3A4Homo sapiens (human)
oxidative demethylationCytochrome P450 3A4Homo sapiens (human)
lipid metabolic processUDP-glucuronosyltransferase 2B7Homo sapiens (human)
xenobiotic metabolic processUDP-glucuronosyltransferase 2B7Homo sapiens (human)
androgen metabolic processUDP-glucuronosyltransferase 2B7Homo sapiens (human)
estrogen metabolic processUDP-glucuronosyltransferase 2B7Homo sapiens (human)
cellular glucuronidationUDP-glucuronosyltransferase 2B7Homo sapiens (human)
xenobiotic metabolic processUDP-glucuronosyltransferase 1-6Homo sapiens (human)
cellular glucuronidationUDP-glucuronosyltransferase 1-6Homo sapiens (human)
liver developmentUDP-glucuronosyltransferase 1A1 Homo sapiens (human)
bilirubin conjugationUDP-glucuronosyltransferase 1A1 Homo sapiens (human)
xenobiotic metabolic processUDP-glucuronosyltransferase 1A1 Homo sapiens (human)
acute-phase responseUDP-glucuronosyltransferase 1A1 Homo sapiens (human)
response to nutrientUDP-glucuronosyltransferase 1A1 Homo sapiens (human)
steroid metabolic processUDP-glucuronosyltransferase 1A1 Homo sapiens (human)
estrogen metabolic processUDP-glucuronosyltransferase 1A1 Homo sapiens (human)
animal organ regenerationUDP-glucuronosyltransferase 1A1 Homo sapiens (human)
response to lipopolysaccharideUDP-glucuronosyltransferase 1A1 Homo sapiens (human)
retinoic acid metabolic processUDP-glucuronosyltransferase 1A1 Homo sapiens (human)
response to starvationUDP-glucuronosyltransferase 1A1 Homo sapiens (human)
negative regulation of steroid metabolic processUDP-glucuronosyltransferase 1A1 Homo sapiens (human)
flavone metabolic processUDP-glucuronosyltransferase 1A1 Homo sapiens (human)
cellular glucuronidationUDP-glucuronosyltransferase 1A1 Homo sapiens (human)
flavonoid glucuronidationUDP-glucuronosyltransferase 1A1 Homo sapiens (human)
xenobiotic glucuronidationUDP-glucuronosyltransferase 1A1 Homo sapiens (human)
biphenyl catabolic processUDP-glucuronosyltransferase 1A1 Homo sapiens (human)
cellular response to ethanolUDP-glucuronosyltransferase 1A1 Homo sapiens (human)
cellular response to glucocorticoid stimulusUDP-glucuronosyltransferase 1A1 Homo sapiens (human)
cellular response to estradiol stimulusUDP-glucuronosyltransferase 1A1 Homo sapiens (human)
bilirubin conjugationUDP-glucuronosyltransferase 1A4Homo sapiens (human)
heme catabolic processUDP-glucuronosyltransferase 1A4Homo sapiens (human)
cellular glucuronidationUDP-glucuronosyltransferase 1A4Homo sapiens (human)
vitamin D3 metabolic processUDP-glucuronosyltransferase 1A4Homo sapiens (human)
lipid metabolic processUDP-glucuronosyltransferase 2B10 Homo sapiens (human)
cellular glucuronidationUDP-glucuronosyltransferase 2B10 Homo sapiens (human)
estrogen metabolic processUDP-glucuronosyltransferase 2B10 Homo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Molecular Functions (63)

Processvia Protein(s)Taxonomy
acetylcholine transmembrane transporter activitySolute carrier family 22 member 1 Homo sapiens (human)
neurotransmitter transmembrane transporter activitySolute carrier family 22 member 1 Homo sapiens (human)
dopamine:sodium symporter activitySolute carrier family 22 member 1 Homo sapiens (human)
norepinephrine:sodium symporter activitySolute carrier family 22 member 1 Homo sapiens (human)
protein bindingSolute carrier family 22 member 1 Homo sapiens (human)
monoamine transmembrane transporter activitySolute carrier family 22 member 1 Homo sapiens (human)
secondary active organic cation transmembrane transporter activitySolute carrier family 22 member 1 Homo sapiens (human)
organic anion transmembrane transporter activitySolute carrier family 22 member 1 Homo sapiens (human)
organic cation transmembrane transporter activitySolute carrier family 22 member 1 Homo sapiens (human)
prostaglandin transmembrane transporter activitySolute carrier family 22 member 1 Homo sapiens (human)
pyrimidine nucleoside transmembrane transporter activitySolute carrier family 22 member 1 Homo sapiens (human)
thiamine transmembrane transporter activitySolute carrier family 22 member 1 Homo sapiens (human)
putrescine transmembrane transporter activitySolute carrier family 22 member 1 Homo sapiens (human)
spermidine transmembrane transporter activitySolute carrier family 22 member 1 Homo sapiens (human)
quaternary ammonium group transmembrane transporter activitySolute carrier family 22 member 1 Homo sapiens (human)
toxin transmembrane transporter activitySolute carrier family 22 member 1 Homo sapiens (human)
identical protein bindingSolute carrier family 22 member 1 Homo sapiens (human)
xenobiotic transmembrane transporter activitySolute carrier family 22 member 1 Homo sapiens (human)
(R)-carnitine transmembrane transporter activitySolute carrier family 22 member 1 Homo sapiens (human)
protein bindingBile salt export pumpHomo sapiens (human)
ATP bindingBile salt export pumpHomo sapiens (human)
ABC-type xenobiotic transporter activityBile salt export pumpHomo sapiens (human)
bile acid transmembrane transporter activityBile salt export pumpHomo sapiens (human)
canalicular bile acid transmembrane transporter activityBile salt export pumpHomo sapiens (human)
carbohydrate transmembrane transporter activityBile salt export pumpHomo sapiens (human)
ABC-type bile acid transporter activityBile salt export pumpHomo sapiens (human)
ATP hydrolysis activityBile salt export pumpHomo sapiens (human)
protein bindingATP-dependent translocase ABCB1Homo sapiens (human)
ATP bindingATP-dependent translocase ABCB1Homo sapiens (human)
ABC-type xenobiotic transporter activityATP-dependent translocase ABCB1Homo sapiens (human)
efflux transmembrane transporter activityATP-dependent translocase ABCB1Homo sapiens (human)
ATP hydrolysis activityATP-dependent translocase ABCB1Homo sapiens (human)
transmembrane transporter activityATP-dependent translocase ABCB1Homo sapiens (human)
ubiquitin protein ligase bindingATP-dependent translocase ABCB1Homo sapiens (human)
ATPase-coupled transmembrane transporter activityATP-dependent translocase ABCB1Homo sapiens (human)
xenobiotic transmembrane transporter activityATP-dependent translocase ABCB1Homo sapiens (human)
carboxylic acid transmembrane transporter activityATP-dependent translocase ABCB1Homo sapiens (human)
phosphatidylcholine floppase activityATP-dependent translocase ABCB1Homo sapiens (human)
phosphatidylethanolamine flippase activityATP-dependent translocase ABCB1Homo sapiens (human)
ceramide floppase activityATP-dependent translocase ABCB1Homo sapiens (human)
floppase activityATP-dependent translocase ABCB1Homo sapiens (human)
monooxygenase activityCytochrome P450 3A4Homo sapiens (human)
steroid bindingCytochrome P450 3A4Homo sapiens (human)
iron ion bindingCytochrome P450 3A4Homo sapiens (human)
protein bindingCytochrome P450 3A4Homo sapiens (human)
steroid hydroxylase activityCytochrome P450 3A4Homo sapiens (human)
retinoic acid 4-hydroxylase activityCytochrome P450 3A4Homo sapiens (human)
oxidoreductase activityCytochrome P450 3A4Homo sapiens (human)
oxygen bindingCytochrome P450 3A4Homo sapiens (human)
enzyme bindingCytochrome P450 3A4Homo sapiens (human)
heme bindingCytochrome P450 3A4Homo sapiens (human)
vitamin D3 25-hydroxylase activityCytochrome P450 3A4Homo sapiens (human)
caffeine oxidase activityCytochrome P450 3A4Homo sapiens (human)
quinine 3-monooxygenase activityCytochrome P450 3A4Homo sapiens (human)
testosterone 6-beta-hydroxylase activityCytochrome P450 3A4Homo sapiens (human)
1-alpha,25-dihydroxyvitamin D3 23-hydroxylase activityCytochrome P450 3A4Homo sapiens (human)
anandamide 8,9 epoxidase activityCytochrome P450 3A4Homo sapiens (human)
anandamide 11,12 epoxidase activityCytochrome P450 3A4Homo sapiens (human)
anandamide 14,15 epoxidase activityCytochrome P450 3A4Homo sapiens (human)
aromatase activityCytochrome P450 3A4Homo sapiens (human)
vitamin D 24-hydroxylase activityCytochrome P450 3A4Homo sapiens (human)
estrogen 16-alpha-hydroxylase activityCytochrome P450 3A4Homo sapiens (human)
estrogen 2-hydroxylase activityCytochrome P450 3A4Homo sapiens (human)
1,8-cineole 2-exo-monooxygenase activityCytochrome P450 3A4Homo sapiens (human)
retinoic acid bindingUDP-glucuronosyltransferase 2B7Homo sapiens (human)
glucuronosyltransferase activityUDP-glucuronosyltransferase 2B7Homo sapiens (human)
retinoic acid bindingUDP-glucuronosyltransferase 1-6Homo sapiens (human)
glucuronosyltransferase activityUDP-glucuronosyltransferase 1-6Homo sapiens (human)
enzyme bindingUDP-glucuronosyltransferase 1-6Homo sapiens (human)
protein homodimerization activityUDP-glucuronosyltransferase 1-6Homo sapiens (human)
protein heterodimerization activityUDP-glucuronosyltransferase 1-6Homo sapiens (human)
ATPase-coupled transmembrane transporter activityATP-dependent translocase ABCB1Mus musculus (house mouse)
retinoic acid bindingUDP-glucuronosyltransferase 1A1 Homo sapiens (human)
enzyme inhibitor activityUDP-glucuronosyltransferase 1A1 Homo sapiens (human)
steroid bindingUDP-glucuronosyltransferase 1A1 Homo sapiens (human)
glucuronosyltransferase activityUDP-glucuronosyltransferase 1A1 Homo sapiens (human)
enzyme bindingUDP-glucuronosyltransferase 1A1 Homo sapiens (human)
protein homodimerization activityUDP-glucuronosyltransferase 1A1 Homo sapiens (human)
protein heterodimerization activityUDP-glucuronosyltransferase 1A1 Homo sapiens (human)
retinoic acid bindingUDP-glucuronosyltransferase 1A4Homo sapiens (human)
glucuronosyltransferase activityUDP-glucuronosyltransferase 1A4Homo sapiens (human)
enzyme bindingUDP-glucuronosyltransferase 1A4Homo sapiens (human)
protein homodimerization activityUDP-glucuronosyltransferase 1A4Homo sapiens (human)
protein heterodimerization activityUDP-glucuronosyltransferase 1A4Homo sapiens (human)
glucuronosyltransferase activityUDP-glucuronosyltransferase 2B10 Homo sapiens (human)
UDP-glycosyltransferase activityUDP-glucuronosyltransferase 2B10 Homo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Ceullar Components (23)

Processvia Protein(s)Taxonomy
plasma membraneSolute carrier family 22 member 1 Homo sapiens (human)
basal plasma membraneSolute carrier family 22 member 1 Homo sapiens (human)
membraneSolute carrier family 22 member 1 Homo sapiens (human)
basolateral plasma membraneSolute carrier family 22 member 1 Homo sapiens (human)
apical plasma membraneSolute carrier family 22 member 1 Homo sapiens (human)
lateral plasma membraneSolute carrier family 22 member 1 Homo sapiens (human)
presynapseSolute carrier family 22 member 1 Homo sapiens (human)
basolateral plasma membraneBile salt export pumpHomo sapiens (human)
Golgi membraneBile salt export pumpHomo sapiens (human)
endosomeBile salt export pumpHomo sapiens (human)
plasma membraneBile salt export pumpHomo sapiens (human)
cell surfaceBile salt export pumpHomo sapiens (human)
apical plasma membraneBile salt export pumpHomo sapiens (human)
intercellular canaliculusBile salt export pumpHomo sapiens (human)
intracellular canaliculusBile salt export pumpHomo sapiens (human)
recycling endosomeBile salt export pumpHomo sapiens (human)
recycling endosome membraneBile salt export pumpHomo sapiens (human)
extracellular exosomeBile salt export pumpHomo sapiens (human)
membraneBile salt export pumpHomo sapiens (human)
cytoplasmATP-dependent translocase ABCB1Homo sapiens (human)
plasma membraneATP-dependent translocase ABCB1Homo sapiens (human)
cell surfaceATP-dependent translocase ABCB1Homo sapiens (human)
membraneATP-dependent translocase ABCB1Homo sapiens (human)
apical plasma membraneATP-dependent translocase ABCB1Homo sapiens (human)
extracellular exosomeATP-dependent translocase ABCB1Homo sapiens (human)
external side of apical plasma membraneATP-dependent translocase ABCB1Homo sapiens (human)
plasma membraneATP-dependent translocase ABCB1Homo sapiens (human)
cytoplasmCytochrome P450 3A4Homo sapiens (human)
endoplasmic reticulum membraneCytochrome P450 3A4Homo sapiens (human)
intracellular membrane-bounded organelleCytochrome P450 3A4Homo sapiens (human)
endoplasmic reticulum membraneUDP-glucuronosyltransferase 2B7Homo sapiens (human)
membraneUDP-glucuronosyltransferase 2B7Homo sapiens (human)
plasma membraneGamma-aminobutyric acid receptor subunit gamma-2Rattus norvegicus (Norway rat)
endoplasmic reticulumUDP-glucuronosyltransferase 1-6Homo sapiens (human)
endoplasmic reticulum membraneUDP-glucuronosyltransferase 1-6Homo sapiens (human)
intracellular membrane-bounded organelleUDP-glucuronosyltransferase 1-6Homo sapiens (human)
endoplasmic reticulumUDP-glucuronosyltransferase 1-6Homo sapiens (human)
plasma membraneATP-dependent translocase ABCB1Mus musculus (house mouse)
endoplasmic reticulumUDP-glucuronosyltransferase 1A1 Homo sapiens (human)
endoplasmic reticulum membraneUDP-glucuronosyltransferase 1A1 Homo sapiens (human)
plasma membraneUDP-glucuronosyltransferase 1A1 Homo sapiens (human)
perinuclear region of cytoplasmUDP-glucuronosyltransferase 1A1 Homo sapiens (human)
endoplasmic reticulum chaperone complexUDP-glucuronosyltransferase 1A1 Homo sapiens (human)
cytochrome complexUDP-glucuronosyltransferase 1A1 Homo sapiens (human)
endoplasmic reticulumUDP-glucuronosyltransferase 1A1 Homo sapiens (human)
endoplasmic reticulumUDP-glucuronosyltransferase 1A4Homo sapiens (human)
endoplasmic reticulum membraneUDP-glucuronosyltransferase 1A4Homo sapiens (human)
endoplasmic reticulumUDP-glucuronosyltransferase 1A4Homo sapiens (human)
endoplasmic reticulum membraneUDP-glucuronosyltransferase 2B10 Homo sapiens (human)
plasma membraneGamma-aminobutyric acid receptor subunit alpha-1Rattus norvegicus (Norway rat)
plasma membraneGamma-aminobutyric acid receptor subunit beta-2Rattus norvegicus (Norway rat)
[Information is prepared from geneontology information from the June-17-2024 release]

Bioassays (342)

Assay IDTitleYearJournalArticle
AID504749qHTS profiling for inhibitors of Plasmodium falciparum proliferation2011Science (New York, N.Y.), Aug-05, Volume: 333, Issue:6043
Chemical genomic profiling for antimalarial therapies, response signatures, and molecular targets.
AID1346296Rat TRH1 receptor (Thyrotropin-releasing hormone receptors)1989Annals of the New York Academy of Sciences, , Volume: 553Use of receptor antagonist in elucidating the mechanism of action of TRH in GH3 cells.
AID1345993Rat alpha1B-adrenoceptor (Adrenoceptors)1999The Journal of pharmacology and experimental therapeutics, Dec, Volume: 291, Issue:3
Binding, partial agonism, and potentiation of alpha(1)-adrenergic receptor function by benzodiazepines: A potential site of allosteric modulation.
AID1159607Screen for inhibitors of RMI FANCM (MM2) intereaction2016Journal of biomolecular screening, Jul, Volume: 21, Issue:6
A High-Throughput Screening Strategy to Identify Protein-Protein Interaction Inhibitors That Block the Fanconi Anemia DNA Repair Pathway.
AID1472103Metabolic stability in BALB/c mouse liver microsomes assessed as parent compound remaining at 1 uM after 30 mins in presence of NADPH by LC-MS/MS analysis2017Journal of medicinal chemistry, 12-28, Volume: 60, Issue:24
4-Aminoquinoline Antimalarials Containing a Benzylmethylpyridylmethylamine Group Are Active against Drug Resistant Plasmodium falciparum and Exhibit Oral Activity in Mice.
AID1222400AUC (0 to last) in Por lox/lox wild type mouse at 2.5 mg/kg, po treated 10 days after 40 mg/kg, ip 3-methylcholanthrene administration by liquid chromatography-tandem mass spectrometry2013Drug metabolism and disposition: the biological fate of chemicals, Jan, Volume: 41, Issue:1
NADPH-cytochrome P450 oxidoreductase: roles in physiology, pharmacology, and toxicology.
AID681116TP_TRANSPORTER: transepithelial transport (basal to apical) in MDR1-expressing MDCKII cells2002The Journal of pharmacology and experimental therapeutics, Dec, Volume: 303, Issue:3
Passive permeability and P-glycoprotein-mediated efflux differentiate central nervous system (CNS) and non-CNS marketed drugs.
AID625289Drug Induced Liver Injury Prediction System (DILIps) training set; hepatic side effect (HepSE) score for liver disease2011PLoS computational biology, Dec, Volume: 7, Issue:12
Translating clinical findings into knowledge in drug safety evaluation--drug induced liver injury prediction system (DILIps).
AID1209258Drug metabolism in human liver microsomes assessed as maximum rate of reaction per mg protein by multiple depletion curves method2012Drug metabolism and disposition: the biological fate of chemicals, Dec, Volume: 40, Issue:12
Optimized experimental design for the estimation of enzyme kinetic parameters: an experimental evaluation.
AID26380Dissociation constant (pKa)2004Journal of medicinal chemistry, Feb-26, Volume: 47, Issue:5
Prediction of human volume of distribution values for neutral and basic drugs. 2. Extended data set and leave-class-out statistics.
AID715121Drug metabolism in rat liver microsomes at 3 uM after 1 hr2012Journal of medicinal chemistry, Oct-25, Volume: 55, Issue:20
Development of oseltamivir phosphonate congeners as anti-influenza agents.
AID1209247Drug metabolism in human liver microsomes assessed as intrinsic clearance per mg protein by multiple depletion curves method2012Drug metabolism and disposition: the biological fate of chemicals, Dec, Volume: 40, Issue:12
Optimized experimental design for the estimation of enzyme kinetic parameters: an experimental evaluation.
AID679595TP_TRANSPORTER: inhibition of Digoxin transepithelial transport (basal to apical)(Digoxin: 0.025 uM, Midazolam: 50 uM) in MDR1-expressing LLC-PK1 cells2001European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences, Feb, Volume: 12, Issue:4
Inhibitory effects of CYP3A4 substrates and their metabolites on P-glycoprotein-mediated transport.
AID715119Drug metabolism in human liver microsomes at 3 uM after 1 hr2012Journal of medicinal chemistry, Oct-25, Volume: 55, Issue:20
Development of oseltamivir phosphonate congeners as anti-influenza agents.
AID1473740Inhibition of human MRP3 overexpressed in Sf9 insect cell membrane vesicles assessed as uptake of [3H]-estradiol-17beta-D-glucuronide in presence of ATP and GSH measured after 10 mins by membrane vesicle transport assay2013Toxicological sciences : an official journal of the Society of Toxicology, Nov, Volume: 136, Issue:1
A multifactorial approach to hepatobiliary transporter assessment enables improved therapeutic compound development.
AID588217FDA HLAED, serum glutamic pyruvic transaminase (SGPT) increase2004Current drug discovery technologies, Dec, Volume: 1, Issue:4
Assessment of the health effects of chemicals in humans: II. Construction of an adverse effects database for QSAR modeling.
AID444052Hepatic clearance in human2010Journal of medicinal chemistry, Feb-11, Volume: 53, Issue:3
Physicochemical space for optimum oral bioavailability: contribution of human intestinal absorption and first-pass elimination.
AID1473738Inhibition of human BSEP overexpressed in Sf9 cell membrane vesicles assessed as uptake of [3H]-taurocholate in presence of ATP measured after 15 to 20 mins by membrane vesicle transport assay2013Toxicological sciences : an official journal of the Society of Toxicology, Nov, Volume: 136, Issue:1
A multifactorial approach to hepatobiliary transporter assessment enables improved therapeutic compound development.
AID1222402Cmax in Por lox/lox wild type mouse at 2.5 mg/kg, po treated 10 days after 40 mg/kg, ip 3-methylcholanthrene administration by liquid chromatography-tandem mass spectrometry2013Drug metabolism and disposition: the biological fate of chemicals, Jan, Volume: 41, Issue:1
NADPH-cytochrome P450 oxidoreductase: roles in physiology, pharmacology, and toxicology.
AID1222415Clearance in liver and gut Por deleted-reductase conditional null mouse at 2.5 mg/kg, po treated 10 days after 80 mg/kg, ip beta-naphthoflavone administration by liquid chromatography-tandem mass spectrometry2013Drug metabolism and disposition: the biological fate of chemicals, Jan, Volume: 41, Issue:1
NADPH-cytochrome P450 oxidoreductase: roles in physiology, pharmacology, and toxicology.
AID1222414Clearance in Por lox/lox wild type mouse at 2.5 mg/kg, po treated 10 days after 80 mg/kg, ip beta-naphthoflavone administration by liquid chromatography-tandem mass spectrometry2013Drug metabolism and disposition: the biological fate of chemicals, Jan, Volume: 41, Issue:1
NADPH-cytochrome P450 oxidoreductase: roles in physiology, pharmacology, and toxicology.
AID588214FDA HLAED, liver enzyme composite activity2004Current drug discovery technologies, Dec, Volume: 1, Issue:4
Assessment of the health effects of chemicals in humans: II. Construction of an adverse effects database for QSAR modeling.
AID7783Unbound fraction (plasma)2004Journal of medicinal chemistry, Feb-26, Volume: 47, Issue:5
Prediction of human volume of distribution values for neutral and basic drugs. 2. Extended data set and leave-class-out statistics.
AID1215127Ratio of fraction unbound in solid supported porcine brain membrane vesicles at 5 uM by TRANSIL assay to fraction unbound in Wistar rat brain homogenate at 5 uM after 5 hrs by equilibrium dialysis method2011Drug metabolism and disposition: the biological fate of chemicals, Feb, Volume: 39, Issue:2
Brain tissue binding of drugs: evaluation and validation of solid supported porcine brain membrane vesicles (TRANSIL) as a novel high-throughput method.
AID540230Dose normalised AUC in rat after po administration2005Xenobiotica; the fate of foreign compounds in biological systems, Feb, Volume: 35, Issue:2
Comparative evaluation of oral systemic exposure of 56 xenobiotics in rat, dog, monkey and human.
AID625279Drug Induced Liver Injury Prediction System (DILIps) training set; hepatic side effect (HepSE) score for bilirubinemia2011PLoS computational biology, Dec, Volume: 7, Issue:12
Translating clinical findings into knowledge in drug safety evaluation--drug induced liver injury prediction system (DILIps).
AID679619TP_TRANSPORTER: inhibition of Daunorubicin transepithelial transport (basal to apical)(Daunorubicin: 0.035 uM, Midazolam: 50 uM) in MDR1-expressing LLC-PK1 cells2001European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences, Feb, Volume: 12, Issue:4
Inhibitory effects of CYP3A4 substrates and their metabolites on P-glycoprotein-mediated transport.
AID1602381Half life in ICR mouse liver microsomes at 1 uM measured up to 45 mins in presence of NADPH by LC-MS/MS analysis2019Journal of medicinal chemistry, 03-14, Volume: 62, Issue:5
Discovery of Carboline Derivatives as Potent Antifungal Agents for the Treatment of Cryptococcal Meningitis.
AID373867Hepatic clearance in human hepatocytes in absence of fetal calf serum2009European journal of medicinal chemistry, Apr, Volume: 44, Issue:4
First-principle, structure-based prediction of hepatic metabolic clearance values in human.
AID1446389Apparent clearance in rat liver microsomes2017Journal of medicinal chemistry, 08-10, Volume: 60, Issue:15
Discovery and Optimization of Chromeno[2,3-c]pyrrol-9(2H)-ones as Novel Selective and Orally Bioavailable Phosphodiesterase 5 Inhibitors for the Treatment of Pulmonary Arterial Hypertension.
AID679459TP_TRANSPORTER: transepithelial transport (basal to apical) in Caco-2 cells1998European journal of pharmacology, Oct-09, Volume: 358, Issue:3
Interaction with P-glycoprotein and transport of erythromycin, midazolam and ketoconazole in Caco-2 cells.
AID1900025Hepatic clearance in rat liver microsomes at 1 uM incubated for 45 mins in presence of NADPH by LC-MS/MS analysis2022Journal of medicinal chemistry, 01-13, Volume: 65, Issue:1
Design, Synthesis, and Biological Evaluation of 1-(Indolizin-3-yl)ethan-1-ones as CBP Bromodomain Inhibitors for the Treatment of Prostate Cancer.
AID625281Drug Induced Liver Injury Prediction System (DILIps) training set; hepatic side effect (HepSE) score for cholelithiasis2011PLoS computational biology, Dec, Volume: 7, Issue:12
Translating clinical findings into knowledge in drug safety evaluation--drug induced liver injury prediction system (DILIps).
AID425652Total body clearance in human2009Journal of medicinal chemistry, Aug-13, Volume: 52, Issue:15
Physicochemical determinants of human renal clearance.
AID1219225Tmax in solid tumor patient at 2 mg, po administered as single dose followed by co-treatment with 27 mg/m2, iv carfilzomib over 2 to 10 mins on days 1, 2, 8, 9, 15 and 16 of single 28-day cycle measured on day 12013Drug metabolism and disposition: the biological fate of chemicals, Jan, Volume: 41, Issue:1
Clinical pharmacokinetics, metabolism, and drug-drug interaction of carfilzomib.
AID1602382Clearance in ICR mouse liver microsomes at 1 uM measured up to 45 mins in presence of NADPH by LC-MS/MS analysis2019Journal of medicinal chemistry, 03-14, Volume: 62, Issue:5
Discovery of Carboline Derivatives as Potent Antifungal Agents for the Treatment of Cryptococcal Meningitis.
AID1744238Metabolic stability in rat liver microsomes assessed as half-life at 10 uM incubated for 1 hr in presence of NADPH by LC-MS/MS analysis2021Journal of medicinal chemistry, 01-14, Volume: 64, Issue:1
Novel Sigma 1 Receptor Antagonists as Potential Therapeutics for Pain Management.
AID41742Binding affinity to rat benzodiazepine receptor2002Bioorganic & medicinal chemistry letters, Nov-04, Volume: 12, Issue:21
Identification and structure-activity studies of novel ultrashort-acting benzodiazepine receptor agonists.
AID1446420Drug metabolism in rat liver microsomes assessed as metabolic rate2017Journal of medicinal chemistry, 08-10, Volume: 60, Issue:15
Discovery and Optimization of Chromeno[2,3-c]pyrrol-9(2H)-ones as Novel Selective and Orally Bioavailable Phosphodiesterase 5 Inhibitors for the Treatment of Pulmonary Arterial Hypertension.
AID1190367Induction of anterograde amnesia in NMRI albino mouse assessed as reduction in latency to enter dark compartment at 1 mg/kg, ip by passive avoidance test2015Bioorganic & medicinal chemistry, Feb-01, Volume: 23, Issue:3
Novel agonists of benzodiazepine receptors: design, synthesis, binding assay and pharmacological evaluation of 1,2,4-triazolo[1,5-a]pyrimidinone and 3-amino-1,2,4-triazole derivatives.
AID540233Dose normalised AUC in human after po administration2005Xenobiotica; the fate of foreign compounds in biological systems, Feb, Volume: 35, Issue:2
Comparative evaluation of oral systemic exposure of 56 xenobiotics in rat, dog, monkey and human.
AID688286Allosteric modulation of gamma-aminobutyric acid receptor A alpha1beta2gamma2S expressed in Xenopus oocytes assessed as potentiation of GABA-mediated chloride current at 0.1 to 500 uM by voltage clamp analysis relative to control2011Journal of natural products, Aug-26, Volume: 74, Issue:8
Identification and characterization of GABA(A) receptor modulatory diterpenes from Biota orientalis that decrease locomotor activity in mice.
AID588219FDA HLAED, gamma-glutamyl transferase (GGT) increase2004Current drug discovery technologies, Dec, Volume: 1, Issue:4
Assessment of the health effects of chemicals in humans: II. Construction of an adverse effects database for QSAR modeling.
AID1443980Inhibition of human BSEP expressed in fall armyworm sf9 cell plasma membrane vesicles assessed as reduction in vesicle-associated [3H]-taurocholate transport preincubated for 10 mins prior to ATP addition measured after 15 mins in presence of [3H]-tauroch2010Toxicological sciences : an official journal of the Society of Toxicology, Dec, Volume: 118, Issue:2
Interference with bile salt export pump function is a susceptibility factor for human liver injury in drug development.
AID1443995Hepatotoxicity in human assessed as drug-induced liver injury2014Hepatology (Baltimore, Md.), Sep, Volume: 60, Issue:3
Human drug-induced liver injury severity is highly associated with dual inhibition of liver mitochondrial function and bile salt export pump.
AID1216349AUC (0 to infinity) in healthy human assessed as fold change in presence of casopitant 120 mg, po once daily administered for 3 days2011Drug metabolism and disposition: the biological fate of chemicals, Mar, Volume: 39, Issue:3
Casopitant: in vitro data and SimCyp simulation to predict in vivo metabolic interactions involving cytochrome P450 3A4.
AID1884506Inhibition of CYP3A4M in human liver microsomes incubated for 15 to 40 mins in presence of NADPH2022European journal of medicinal chemistry, Aug-05, Volume: 238Expansion of the S-CN-DABO scaffold to exploit the impact on inhibitory activities against the non-nucleoside HIV-1 reverse transcriptase.
AID1769114Intrinsic clearance in human liver microsomes preincubated for 10 mins followed by NADPH addition and further incubated upto 60 mins by LC-MS/MS analysis2021Journal of medicinal chemistry, 09-23, Volume: 64, Issue:18
Optimization of 4,6-Disubstituted Pyrido[3,2-
AID28681Partition coefficient (logD6.5)2000Journal of medicinal chemistry, Jun-29, Volume: 43, Issue:13
QSAR model for drug human oral bioavailability.
AID1702158Clearance in human liver pooled microsomes at pH 7.4 at 5 uM incubated upto 60 mins in presence of NADPH measured per mg of protein by LC-MS analysis2018Journal of medicinal chemistry, 02-22, Volume: 61, Issue:4
Design, Synthesis, and Preclinical Evaluation of Fused Pyrimidine-Based Hydroxamates for the Treatment of Hepatocellular Carcinoma.
AID624626Ratio of apparent permeability from basolateral to apical side over apical to basolateral side determined in MDR1-MDCKII cells2001The Journal of pharmacology and experimental therapeutics, Nov, Volume: 299, Issue:2
Rational use of in vitro P-glycoprotein assays in drug discovery.
AID539474Solubility of the compound at pH 7.952010Bioorganic & medicinal chemistry letters, Dec-15, Volume: 20, Issue:24
Experimental solubility profiling of marketed CNS drugs, exploring solubility limit of CNS discovery candidate.
AID1219224AUC(infinity) in solid tumor patient at 2 mg, po administered as single dose followed by co-treatment with 27 mg/m2, iv carfilzomib over 2 to 10 mins on days 1, 2, 8, 9, 15 and 16 of single 28-day cycle measured on day 12013Drug metabolism and disposition: the biological fate of chemicals, Jan, Volume: 41, Issue:1
Clinical pharmacokinetics, metabolism, and drug-drug interaction of carfilzomib.
AID1219220Half life in solid tumor patient at 2 mg, po administered as single dose measured on day 72013Drug metabolism and disposition: the biological fate of chemicals, Jan, Volume: 41, Issue:1
Clinical pharmacokinetics, metabolism, and drug-drug interaction of carfilzomib.
AID1446764Intrinsic clearance in human liver microsomes in presence of NADPH by LC-MS/MS method2017European journal of medicinal chemistry, Apr-21, Volume: 130Diphenylurea derivatives for combating methicillin- and vancomycin-resistant Staphylococcus aureus.
AID625283Drug Induced Liver Injury Prediction System (DILIps) training set; hepatic side effect (HepSE) score for elevated liver function tests2011PLoS computational biology, Dec, Volume: 7, Issue:12
Translating clinical findings into knowledge in drug safety evaluation--drug induced liver injury prediction system (DILIps).
AID150751Inhibition of P-glycoprotein using ATPase in MDR1 membranes2003Journal of medicinal chemistry, Apr-24, Volume: 46, Issue:9
Comparison of in vitro P-glycoprotein screening assays: recommendations for their use in drug discovery.
AID1472620Half life in human liver microsomes at 2 uM after 60 mins in presence of NADPH by LC-MS/MS method2018Journal of medicinal chemistry, 01-11, Volume: 61, Issue:1
Novel Terminal Bipheny-Based Diapophytoene Desaturases (CrtN) Inhibitors as Anti-MRSA/VISR/LRSA Agents with Reduced hERG Activity.
AID1756362Metabolic stability in rat hepatocytes assessed as half life measured upto 120 mins by LC-MS/MS analysis2021European journal of medicinal chemistry, Mar-05, Volume: 213Discovery and development of novel pyrimidine and pyrazolo/thieno-fused pyrimidine derivatives as potent and orally active inducible nitric oxide synthase dimerization inhibitor with efficacy for arthritis.
AID1422312Clearance in dog hepatocytes at 1 uM2018Bioorganic & medicinal chemistry letters, 11-15, Volume: 28, Issue:21
Design, synthesis and biological evaluation of (2S,3R,4R,5S,6R)-5-fluoro-6-(hydroxymethyl)-2-aryltetrahydro-2H-pyran-3,4-diols as potent and orally active SGLT dual inhibitors.
AID1744239Intrinsic clearance in rat liver microsomes at 10 uM incubated for 1 hr in presence of NADPH by LC-MS/MS analysis2021Journal of medicinal chemistry, 01-14, Volume: 64, Issue:1
Novel Sigma 1 Receptor Antagonists as Potential Therapeutics for Pain Management.
AID1534317Half life in rat liver microsomes at 1 uM after 5 to 60 mins in presence of NADPH by LC-MS/MS analysis2019European journal of medicinal chemistry, Feb-01, Volume: 163Discovery of a highly selective FLT3 inhibitor with specific proliferation inhibition against AML cells harboring FLT3-ITD mutation.
AID588218FDA HLAED, lactate dehydrogenase (LDH) increase2004Current drug discovery technologies, Dec, Volume: 1, Issue:4
Assessment of the health effects of chemicals in humans: II. Construction of an adverse effects database for QSAR modeling.
AID625284Drug Induced Liver Injury Prediction System (DILIps) training set; hepatic side effect (HepSE) score for hepatic failure2011PLoS computational biology, Dec, Volume: 7, Issue:12
Translating clinical findings into knowledge in drug safety evaluation--drug induced liver injury prediction system (DILIps).
AID1221739Drug uptake ratio assessed as enzyme-mediated uptake in HEK293 cells expressing human OATP1B3 at 10 uM at 37 degC for 3 mins cells pretreated with sodium butyrate by liquid scintillation spectroscopy relative to wild type2011Drug metabolism and disposition: the biological fate of chemicals, Jan, Volume: 39, Issue:1
Characterization of digoxin uptake in sandwich-cultured human hepatocytes.
AID1473801Ratio of drug concentration at steady state in human at 0.01 to 0.04 mg/kg, po after 24 hrs to IC50 for human BSEP overexpressed in Sf9 insect cells2013Toxicological sciences : an official journal of the Society of Toxicology, Nov, Volume: 136, Issue:1
A multifactorial approach to hepatobiliary transporter assessment enables improved therapeutic compound development.
AID1219218AUC(infinity) in solid tumor patient at 2 mg, po administered as single dose measured on day 72013Drug metabolism and disposition: the biological fate of chemicals, Jan, Volume: 41, Issue:1
Clinical pharmacokinetics, metabolism, and drug-drug interaction of carfilzomib.
AID600039Drug uptake by rat hepatic OATP1B2 transporters expressed in CHO cells at 1 uM relative to wild type CHO cells2011Bioorganic & medicinal chemistry letters, May-01, Volume: 21, Issue:9
Discovery of novel hepatoselective HMG-CoA reductase inhibitors for treating hypercholesterolemia: a bench-to-bedside case study on tissue selective drug distribution.
AID1446397Hepatic extraction ratio in rat liver microsomes2017Journal of medicinal chemistry, 08-10, Volume: 60, Issue:15
Discovery and Optimization of Chromeno[2,3-c]pyrrol-9(2H)-ones as Novel Selective and Orally Bioavailable Phosphodiesterase 5 Inhibitors for the Treatment of Pulmonary Arterial Hypertension.
AID1215122Percentage unbound in solid supported porcine brain membrane vesicles at 5 uM by TRANSIL assay2011Drug metabolism and disposition: the biological fate of chemicals, Feb, Volume: 39, Issue:2
Brain tissue binding of drugs: evaluation and validation of solid supported porcine brain membrane vesicles (TRANSIL) as a novel high-throughput method.
AID1222398AUC (0 to infinity) in Por lox/lox wild type mouse at 2.5 mg/kg, po treated 10 days after 40 mg/kg, ip 3-methylcholanthrene administration by liquid chromatography-tandem mass spectrometry2013Drug metabolism and disposition: the biological fate of chemicals, Jan, Volume: 41, Issue:1
NADPH-cytochrome P450 oxidoreductase: roles in physiology, pharmacology, and toxicology.
AID1219234Tmax in solid tumor patient at 2 mg, po administered as single dose followed by co-treatment with 27 mg/m2, iv carfilzomib over 2 to 10 mins on days 1, 2, 8, 9, 15 and 16 of single 28-day cycle measured on day 162013Drug metabolism and disposition: the biological fate of chemicals, Jan, Volume: 41, Issue:1
Clinical pharmacokinetics, metabolism, and drug-drug interaction of carfilzomib.
AID600335Drug uptake by human hepatic OATP1B3 transporter expressed in HEK293 cells at 10 uM relative to wild-type HEK293 cells2011Bioorganic & medicinal chemistry letters, May-01, Volume: 21, Issue:9
Discovery of novel hepatoselective HMG-CoA reductase inhibitors for treating hypercholesterolemia: a bench-to-bedside case study on tissue selective drug distribution.
AID298032Acid dissociation constant, pKa of the compound2007Journal of medicinal chemistry, Sep-20, Volume: 50, Issue:19
High-throughput screening of drug-brain tissue binding and in silico prediction for assessment of central nervous system drug delivery.
AID1446385Intrinsic clearance in rat liver microsomes2017Journal of medicinal chemistry, 08-10, Volume: 60, Issue:15
Discovery and Optimization of Chromeno[2,3-c]pyrrol-9(2H)-ones as Novel Selective and Orally Bioavailable Phosphodiesterase 5 Inhibitors for the Treatment of Pulmonary Arterial Hypertension.
AID1534318Intrinsic clearance in human liver microsomes assessed per mg protein at 1 uM after 5 to 60 mins in presence of NADPH by LC-MS/MS analysis2019European journal of medicinal chemistry, Feb-01, Volume: 163Discovery of a highly selective FLT3 inhibitor with specific proliferation inhibition against AML cells harboring FLT3-ITD mutation.
AID1216348AUC (0 to infinity) in healthy human assessed as fold change in presence of casopitant 30 mg, po once daily administered for 14 days2011Drug metabolism and disposition: the biological fate of chemicals, Mar, Volume: 39, Issue:3
Casopitant: in vitro data and SimCyp simulation to predict in vivo metabolic interactions involving cytochrome P450 3A4.
AID1209583Unbound drug partitioning coefficient, Kp of the compound assessed as ratio of unbound concentration in Sprague-Dawley rat brain to unbound concentration in plasma2011Drug metabolism and disposition: the biological fate of chemicals, Mar, Volume: 39, Issue:3
Measurement of unbound drug exposure in brain: modeling of pH partitioning explains diverging results between the brain slice and brain homogenate methods.
AID624628Drug-stimulated Pgp ATPase activity ratio determined in MDR1-Sf9 cell membranes with test compound at a concentration of 20uM2001The Journal of pharmacology and experimental therapeutics, Nov, Volume: 299, Issue:2
Rational use of in vitro P-glycoprotein assays in drug discovery.
AID540226Clearance in monkey after iv administration2006Drug metabolism and disposition: the biological fate of chemicals, Jul, Volume: 34, Issue:7
Extrapolation of preclinical pharmacokinetics and molecular feature analysis of "discovery-like" molecules to predict human pharmacokinetics.
AID1215672Drug metabolism in pooled human hepatocytes assessed as aldehyde oxidase-mediated drug metabolism at 10 uM up to 120 mins by HPLC analysis in presence of 50 uM of hydralazine2012Drug metabolism and disposition: the biological fate of chemicals, Jul, Volume: 40, Issue:7
Hydralazine as a selective probe inactivator of aldehyde oxidase in human hepatocytes: estimation of the contribution of aldehyde oxidase to metabolic clearance.
AID1652315Inhibition of human CYP3A4 at 10 uM2020Journal of medicinal chemistry, 07-09, Volume: 63, Issue:13
Novel Pyrrolopyridone Bromodomain and Extra-Terminal Motif (BET) Inhibitors Effective in Endocrine-Resistant ER+ Breast Cancer with Acquired Resistance to Fulvestrant and Palbociclib.
AID21859In vivo clearance in rat.1999Journal of medicinal chemistry, Dec-16, Volume: 42, Issue:25
Combining in vitro and in vivo pharmacokinetic data for prediction of hepatic drug clearance in humans by artificial neural networks and multivariate statistical techniques.
AID1473739Inhibition of human MRP2 overexpressed in Sf9 cell membrane vesicles assessed as uptake of [3H]-estradiol-17beta-D-glucuronide in presence of ATP and GSH measured after 20 mins by membrane vesicle transport assay2013Toxicological sciences : an official journal of the Society of Toxicology, Nov, Volume: 136, Issue:1
A multifactorial approach to hepatobiliary transporter assessment enables improved therapeutic compound development.
AID1219228AUC(last) in solid tumor patient at 2 mg, po administered as single dose followed by co-treatment with 27 mg/m2, iv carfilzomib over 2 to 10 mins on days 1, 2, 8, 9, 15 and 16 of single 28-day cycle measured on day 162013Drug metabolism and disposition: the biological fate of chemicals, Jan, Volume: 41, Issue:1
Clinical pharmacokinetics, metabolism, and drug-drug interaction of carfilzomib.
AID624622Apparent permeability (Papp) from apical to basolateral side determined in MDR1-MDCKII cells2001The Journal of pharmacology and experimental therapeutics, Nov, Volume: 299, Issue:2
Rational use of in vitro P-glycoprotein assays in drug discovery.
AID760238Half life in mouse liver microsomes at 10 uM2013ACS medicinal chemistry letters, Jul-11, Volume: 4, Issue:7
Discovery and characterization of carbamothioylacrylamides as EP
AID1862578Inhibition of CYP3A4M (unknown origin)
AID648845Binding affinity to BRD4-BD1 assessed as change in melting temperature at 10 uM by protein stability shift assay2012Bioorganic & medicinal chemistry, Mar-15, Volume: 20, Issue:6
Benzodiazepines and benzotriazepines as protein interaction inhibitors targeting bromodomains of the BET family.
AID1702159Clearance in mouse liver microsomes at pH 7.4 at 5 uM incubated upto 60 mins in presence of NADPH measured per mg of protein by LC-MS analysis2018Journal of medicinal chemistry, 02-22, Volume: 61, Issue:4
Design, Synthesis, and Preclinical Evaluation of Fused Pyrimidine-Based Hydroxamates for the Treatment of Hepatocellular Carcinoma.
AID625288Drug Induced Liver Injury Prediction System (DILIps) training set; hepatic side effect (HepSE) score for jaundice2011PLoS computational biology, Dec, Volume: 7, Issue:12
Translating clinical findings into knowledge in drug safety evaluation--drug induced liver injury prediction system (DILIps).
AID1744240Metabolic stability in human liver microsomes assessed as half-life at 10 uM incubated for 1 hr in presence of NADPH by LC-MS/MS analysis2021Journal of medicinal chemistry, 01-14, Volume: 64, Issue:1
Novel Sigma 1 Receptor Antagonists as Potential Therapeutics for Pain Management.
AID1472621In-vitro intrinsic clearance in human liver microsomes at 2 uM after 60 mins in presence of NADPH by LC-MS/MS method2018Journal of medicinal chemistry, 01-11, Volume: 61, Issue:1
Novel Terminal Bipheny-Based Diapophytoene Desaturases (CrtN) Inhibitors as Anti-MRSA/VISR/LRSA Agents with Reduced hERG Activity.
AID1739201Metabolic stability in human liver microsomes assessed as half life at 1 uM incubated up to 60 mins in presence of NADPH by LC-MS/MS analysis2020European journal of medicinal chemistry, Aug-15, Volume: 200Discovery of coumarin derivatives as potent and selective cyclin-dependent kinase 9 (CDK9) inhibitors with high antitumour activity.
AID1446766Intrinsic clearance in human liver microsomes in absence of NADPH by LC-MS/MS method2017European journal of medicinal chemistry, Apr-21, Volume: 130Diphenylurea derivatives for combating methicillin- and vancomycin-resistant Staphylococcus aureus.
AID187603Loss of righting reflex recovery time (initial) in rat was determined when treated with a dose of 30 mg/Kg2002Bioorganic & medicinal chemistry letters, Nov-04, Volume: 12, Issue:21
Identification and structure-activity studies of novel ultrashort-acting benzodiazepine receptor agonists.
AID1900026Hepatic extraction ratio in human liver microsomes at 1 uM incubated for 45 mins in presence of NADPH by LC-MS/MS analysis2022Journal of medicinal chemistry, 01-13, Volume: 65, Issue:1
Design, Synthesis, and Biological Evaluation of 1-(Indolizin-3-yl)ethan-1-ones as CBP Bromodomain Inhibitors for the Treatment of Prostate Cancer.
AID1189508Inhibition of human recombinant CYP3A4 in liver microsomes by mechanism based inhibition assay2015Journal of medicinal chemistry, Jan-08, Volume: 58, Issue:1
SAR156497, an exquisitely selective inhibitor of aurora kinases.
AID1222412Cmax in Por lox/lox wild type mouse at 2.5 mg/kg, po treated 10 days after 80 mg/kg, ip beta-naphthoflavone administration by liquid chromatography-tandem mass spectrometry2013Drug metabolism and disposition: the biological fate of chemicals, Jan, Volume: 41, Issue:1
NADPH-cytochrome P450 oxidoreductase: roles in physiology, pharmacology, and toxicology.
AID600044Drug uptake by human hepatic OATP1B1 transporter expressed in HEK293 cells at 1 uM relative to wild type HEK293 cells2011Bioorganic & medicinal chemistry letters, May-01, Volume: 21, Issue:9
Discovery of novel hepatoselective HMG-CoA reductase inhibitors for treating hypercholesterolemia: a bench-to-bedside case study on tissue selective drug distribution.
AID1221736Drug uptake ratio assessed as enzyme-mediated uptake in HEK293 cells expressing human OATP1B3 at 10 uM at 37 degC for 3 mins by liquid scintillation spectroscopy relative to wild type2011Drug metabolism and disposition: the biological fate of chemicals, Jan, Volume: 39, Issue:1
Characterization of digoxin uptake in sandwich-cultured human hepatocytes.
AID648851Binding affinity to PCAF assessed as change in melting temperature at 10 uM by protein stability shift assay2012Bioorganic & medicinal chemistry, Mar-15, Volume: 20, Issue:6
Benzodiazepines and benzotriazepines as protein interaction inhibitors targeting bromodomains of the BET family.
AID588215FDA HLAED, alkaline phosphatase increase2004Current drug discovery technologies, Dec, Volume: 1, Issue:4
Assessment of the health effects of chemicals in humans: II. Construction of an adverse effects database for QSAR modeling.
AID1219216AUC(last) in solid tumor patient at 2 mg, po administered as single dose measured on day 72013Drug metabolism and disposition: the biological fate of chemicals, Jan, Volume: 41, Issue:1
Clinical pharmacokinetics, metabolism, and drug-drug interaction of carfilzomib.
AID1446394Hepatic clearance in human microsomes2017Journal of medicinal chemistry, 08-10, Volume: 60, Issue:15
Discovery and Optimization of Chromeno[2,3-c]pyrrol-9(2H)-ones as Novel Selective and Orally Bioavailable Phosphodiesterase 5 Inhibitors for the Treatment of Pulmonary Arterial Hypertension.
AID1219227Cmax in solid tumor patient at 2 mg, po administered as single dose followed by co-treatment with 27 mg/m2, iv carfilzomib over 2 to 10 mins on days 1, 2, 8, 9, 15 and 16 of single 28-day cycle measured on day 162013Drug metabolism and disposition: the biological fate of chemicals, Jan, Volume: 41, Issue:1
Clinical pharmacokinetics, metabolism, and drug-drug interaction of carfilzomib.
AID1209244Drug metabolism in assessed as human CYP3A-mediated maximum rate of reaction per mg protein2012Drug metabolism and disposition: the biological fate of chemicals, Dec, Volume: 40, Issue:12
Optimized experimental design for the estimation of enzyme kinetic parameters: an experimental evaluation.
AID27167Delta logD (logD6.5 - logD7.4)2000Journal of medicinal chemistry, Jun-29, Volume: 43, Issue:13
QSAR model for drug human oral bioavailability.
AID1222401AUC (0 to last) in liver Por deleted-reductase conditional null mouse at 2.5 mg/kg, po treated 10 days after 40 mg/kg, ip 3-methylcholanthrene administration by liquid chromatography-tandem mass spectrometry2013Drug metabolism and disposition: the biological fate of chemicals, Jan, Volume: 41, Issue:1
NADPH-cytochrome P450 oxidoreductase: roles in physiology, pharmacology, and toxicology.
AID1443989Inhibition of recombinant human BSEP expressed in baculovirus infected sf9 cell plasma membrane vesicles assessed as reduction in ATP-dependent [3H]-taurocholate uptake in to vesicles preincubated for 10 mins followed by ATP addition measured after 10 to 2014Hepatology (Baltimore, Md.), Sep, Volume: 60, Issue:3
Human drug-induced liver injury severity is highly associated with dual inhibition of liver mitochondrial function and bile salt export pump.
AID1611244Intrinsic clearance in monkey liver microsomes incubated for 6 hrs by LC/MS analysis2019Bioorganic & medicinal chemistry letters, 12-15, Volume: 29, Issue:24
Design, synthesis and biological evaluation of novel desloratadine derivatives with anti-inflammatory and H
AID540210Clearance in human after iv administration2008Drug metabolism and disposition: the biological fate of chemicals, Jul, Volume: 36, Issue:7
Trend analysis of a database of intravenous pharmacokinetic parameters in humans for 670 drug compounds.
AID1446393Hepatic clearance in rat liver microsomes2017Journal of medicinal chemistry, 08-10, Volume: 60, Issue:15
Discovery and Optimization of Chromeno[2,3-c]pyrrol-9(2H)-ones as Novel Selective and Orally Bioavailable Phosphodiesterase 5 Inhibitors for the Treatment of Pulmonary Arterial Hypertension.
AID1209593Dissociation constant, pKa of the acidic compound by capillary electrophoresis-mass spectrometry analysis2011Drug metabolism and disposition: the biological fate of chemicals, Mar, Volume: 39, Issue:3
Measurement of unbound drug exposure in brain: modeling of pH partitioning explains diverging results between the brain slice and brain homogenate methods.
AID1222413Cmax in liver and gut Por deleted-reductase conditional null mouse at 2.5 mg/kg, po treated 10 days after 80 mg/kg, ip beta-naphthoflavone administration by liquid chromatography-tandem mass spectrometry2013Drug metabolism and disposition: the biological fate of chemicals, Jan, Volume: 41, Issue:1
NADPH-cytochrome P450 oxidoreductase: roles in physiology, pharmacology, and toxicology.
AID1899994Metabolic stability in rat liver microsomes assessed as parent compound remaining at 1 uM incubated for 45 mins in presence of NADPH by LC-MS/MS analysis2022Journal of medicinal chemistry, 01-13, Volume: 65, Issue:1
Design, Synthesis, and Biological Evaluation of 1-(Indolizin-3-yl)ethan-1-ones as CBP Bromodomain Inhibitors for the Treatment of Prostate Cancer.
AID444058Volume of distribution at steady state in human2010Journal of medicinal chemistry, Feb-11, Volume: 53, Issue:3
Physicochemical space for optimum oral bioavailability: contribution of human intestinal absorption and first-pass elimination.
AID611614Allosteric modulation of gamma-aminobutyric acid receptor A alpha1beta2gamma2S expressed in Xenopus oocytes assessed as potentiation of GABA-mediated chloride current at 1 uM by voltage clamp assay2011Journal of natural products, Jun-24, Volume: 74, Issue:6
Positive GABA(A) receptor modulators from Acorus calamus and structural analysis of (+)-dioxosarcoguaiacol by 1D and 2D NMR and molecular modeling.
AID648844Binding affinity to BRD3-BD1 assessed as change in melting temperature at 10 uM by protein stability shift assay2012Bioorganic & medicinal chemistry, Mar-15, Volume: 20, Issue:6
Benzodiazepines and benzotriazepines as protein interaction inhibitors targeting bromodomains of the BET family.
AID1473799AUC in human at 0.01 to 0.04 mg/kg, po after 24 hrs2013Toxicological sciences : an official journal of the Society of Toxicology, Nov, Volume: 136, Issue:1
A multifactorial approach to hepatobiliary transporter assessment enables improved therapeutic compound development.
AID760239Half life in human liver microsomes at 10 uM2013ACS medicinal chemistry letters, Jul-11, Volume: 4, Issue:7
Discovery and characterization of carbamothioylacrylamides as EP
AID1446421Drug metabolism in human liver microsomes assessed as metabolic rate2017Journal of medicinal chemistry, 08-10, Volume: 60, Issue:15
Discovery and Optimization of Chromeno[2,3-c]pyrrol-9(2H)-ones as Novel Selective and Orally Bioavailable Phosphodiesterase 5 Inhibitors for the Treatment of Pulmonary Arterial Hypertension.
AID1211295Unbound fraction in plasma (unknown origin) at pH 7.63 after 6 hrs by equilibrium dialysis method in presence of 5% CO22011Drug metabolism and disposition: the biological fate of chemicals, Mar, Volume: 39, Issue:3
Control and measurement of plasma pH in equilibrium dialysis: influence on drug plasma protein binding.
AID624629Inhibition of Pgp expressed in MDR1-MDCKII cells measured by calcein-AM assay2001The Journal of pharmacology and experimental therapeutics, Nov, Volume: 299, Issue:2
Rational use of in vitro P-glycoprotein assays in drug discovery.
AID540212Mean residence time in human after iv administration2008Drug metabolism and disposition: the biological fate of chemicals, Jul, Volume: 36, Issue:7
Trend analysis of a database of intravenous pharmacokinetic parameters in humans for 670 drug compounds.
AID699540Inhibition of human liver OATP1B3 expressed in HEK293 Flp-In cells assessed as reduction in [3H]E17-betaG uptake at 20 uM incubated for 5 mins by scintillation counting2012Journal of medicinal chemistry, May-24, Volume: 55, Issue:10
Classification of inhibitors of hepatic organic anion transporting polypeptides (OATPs): influence of protein expression on drug-drug interactions.
AID1219219Tmax in solid tumor patient at 2 mg, po administered as single dose measured on day 72013Drug metabolism and disposition: the biological fate of chemicals, Jan, Volume: 41, Issue:1
Clinical pharmacokinetics, metabolism, and drug-drug interaction of carfilzomib.
AID1702161Drug metabolism assessed as human recombinant CYP3A4-mediated clearance at pH 7.4 at 5 uM incubated upto 60 mins in presence of NADPH by LC-MS analysis2018Journal of medicinal chemistry, 02-22, Volume: 61, Issue:4
Design, Synthesis, and Preclinical Evaluation of Fused Pyrimidine-Based Hydroxamates for the Treatment of Hepatocellular Carcinoma.
AID1211296Unbound fraction in plasma (unknown origin) under normal atmospheric condition at pH 7.72 after 6 hrs by equilibrium dialysis method2011Drug metabolism and disposition: the biological fate of chemicals, Mar, Volume: 39, Issue:3
Control and measurement of plasma pH in equilibrium dialysis: influence on drug plasma protein binding.
AID1422308Half life in dog hepatocytes at 1 uM2018Bioorganic & medicinal chemistry letters, 11-15, Volume: 28, Issue:21
Design, synthesis and biological evaluation of (2S,3R,4R,5S,6R)-5-fluoro-6-(hydroxymethyl)-2-aryltetrahydro-2H-pyran-3,4-diols as potent and orally active SGLT dual inhibitors.
AID1222408AUC (0 to infinity) in Por lox/lox wild type mouse at 2.5 mg/kg, po treated 10 days after 80 mg/kg, ip beta-naphthoflavone administration by liquid chromatography-tandem mass spectrometry2013Drug metabolism and disposition: the biological fate of chemicals, Jan, Volume: 41, Issue:1
NADPH-cytochrome P450 oxidoreductase: roles in physiology, pharmacology, and toxicology.
AID21855In vivo clearance in dog; not available1999Journal of medicinal chemistry, Dec-16, Volume: 42, Issue:25
Combining in vitro and in vivo pharmacokinetic data for prediction of hepatic drug clearance in humans by artificial neural networks and multivariate statistical techniques.
AID1422311Clearance in Sprague-Dawley rat hepatocytes at 1 uM2018Bioorganic & medicinal chemistry letters, 11-15, Volume: 28, Issue:21
Design, synthesis and biological evaluation of (2S,3R,4R,5S,6R)-5-fluoro-6-(hydroxymethyl)-2-aryltetrahydro-2H-pyran-3,4-diols as potent and orally active SGLT dual inhibitors.
AID1739206Metabolic stability in dog liver microsomes assessed as intrinsic clearance at 1 uM incubated up to 60 mins in presence of NADPH by LC-MS/MS analysis2020European journal of medicinal chemistry, Aug-15, Volume: 200Discovery of coumarin derivatives as potent and selective cyclin-dependent kinase 9 (CDK9) inhibitors with high antitumour activity.
AID29359Ionization constant (pKa)2000Journal of medicinal chemistry, Jun-29, Volume: 43, Issue:13
QSAR model for drug human oral bioavailability.
AID540213Half life in human after iv administration2008Drug metabolism and disposition: the biological fate of chemicals, Jul, Volume: 36, Issue:7
Trend analysis of a database of intravenous pharmacokinetic parameters in humans for 670 drug compounds.
AID577298Metabolic stability in rat liver microsomes assessed as half life by LC-MS/MS analysis2011Journal of medicinal chemistry, Feb-24, Volume: 54, Issue:4
2-Aminothiazoles as therapeutic leads for prion diseases.
AID625285Drug Induced Liver Injury Prediction System (DILIps) training set; hepatic side effect (HepSE) score for hepatic necrosis2011PLoS computational biology, Dec, Volume: 7, Issue:12
Translating clinical findings into knowledge in drug safety evaluation--drug induced liver injury prediction system (DILIps).
AID1211293Unbound fraction in plasma (unknown origin) under normal atmospheric condition at pH 7.22 after 6 hrs by equilibrium dialysis method2011Drug metabolism and disposition: the biological fate of chemicals, Mar, Volume: 39, Issue:3
Control and measurement of plasma pH in equilibrium dialysis: influence on drug plasma protein binding.
AID1446765Half life in human liver microsomes in presence of NADPH by LC-MS/MS method2017European journal of medicinal chemistry, Apr-21, Volume: 130Diphenylurea derivatives for combating methicillin- and vancomycin-resistant Staphylococcus aureus.
AID648847Binding affinity to BAZ2B assessed as change in melting temperature at 10 uM by protein stability shift assay2012Bioorganic & medicinal chemistry, Mar-15, Volume: 20, Issue:6
Benzodiazepines and benzotriazepines as protein interaction inhibitors targeting bromodomains of the BET family.
AID540209Volume of distribution at steady state in human after iv administration2008Drug metabolism and disposition: the biological fate of chemicals, Jul, Volume: 36, Issue:7
Trend analysis of a database of intravenous pharmacokinetic parameters in humans for 670 drug compounds.
AID1222407Terminal half life in liver Por deleted-reductase conditional null mouse at 2.5 mg/kg, po treated 10 days after 40 mg/kg, ip 3-methylcholanthrene administration by liquid chromatography-tandem mass spectrometry2013Drug metabolism and disposition: the biological fate of chemicals, Jan, Volume: 41, Issue:1
NADPH-cytochrome P450 oxidoreductase: roles in physiology, pharmacology, and toxicology.
AID1474167Liver toxicity in human assessed as induction of drug-induced liver injury by measuring verified drug-induced liver injury concern status2016Drug discovery today, Apr, Volume: 21, Issue:4
DILIrank: the largest reference drug list ranked by the risk for developing drug-induced liver injury in humans.
AID21852In vitro clearance in rat in 1000000 cells1999Journal of medicinal chemistry, Dec-16, Volume: 42, Issue:25
Combining in vitro and in vivo pharmacokinetic data for prediction of hepatic drug clearance in humans by artificial neural networks and multivariate statistical techniques.
AID1222403Cmax in liver Por deleted-reductase conditional null mouse at 2.5 mg/kg, po treated 10 days after 40 mg/kg, ip 3-methylcholanthrene administration by liquid chromatography-tandem mass spectrometry2013Drug metabolism and disposition: the biological fate of chemicals, Jan, Volume: 41, Issue:1
NADPH-cytochrome P450 oxidoreductase: roles in physiology, pharmacology, and toxicology.
AID1457811Half life in mouse liver microsomes2017Journal of medicinal chemistry, 07-27, Volume: 60, Issue:14
Enantioselective Synthesis and in Vivo Evaluation of Regioisomeric Analogues of the Antimalarial Arterolane.
AID588216FDA HLAED, serum glutamic oxaloacetic transaminase (SGOT) increase2004Current drug discovery technologies, Dec, Volume: 1, Issue:4
Assessment of the health effects of chemicals in humans: II. Construction of an adverse effects database for QSAR modeling.
AID1429807Metabolic stability in Balb/c mouse liver microsomes assessed as compound remaining at 1 uM in presence of NADPH after 30 mins by LC-MS/MS analysis2017Journal of medicinal chemistry, 02-23, Volume: 60, Issue:4
Antimalarial Pyrido[1,2-a]benzimidazoles: Lead Optimization, Parasite Life Cycle Stage Profile, Mechanistic Evaluation, Killing Kinetics, and in Vivo Oral Efficacy in a Mouse Model.
AID1219215Cmax in solid tumor patient at 2 mg, po administered as single dose measured on day 72013Drug metabolism and disposition: the biological fate of chemicals, Jan, Volume: 41, Issue:1
Clinical pharmacokinetics, metabolism, and drug-drug interaction of carfilzomib.
AID540225Volume of distribution at steady state in dog after iv administration2006Drug metabolism and disposition: the biological fate of chemicals, Jul, Volume: 34, Issue:7
Extrapolation of preclinical pharmacokinetics and molecular feature analysis of "discovery-like" molecules to predict human pharmacokinetics.
AID1422313Clearance in monkey hepatocytes at 1 uM2018Bioorganic & medicinal chemistry letters, 11-15, Volume: 28, Issue:21
Design, synthesis and biological evaluation of (2S,3R,4R,5S,6R)-5-fluoro-6-(hydroxymethyl)-2-aryltetrahydro-2H-pyran-3,4-diols as potent and orally active SGLT dual inhibitors.
AID1209582Unbound volume of distribution in Sprague-Dawley rat brain slices at 100 nM after 5 hrs2011Drug metabolism and disposition: the biological fate of chemicals, Mar, Volume: 39, Issue:3
Measurement of unbound drug exposure in brain: modeling of pH partitioning explains diverging results between the brain slice and brain homogenate methods.
AID150752Inhibition of P-glycoprotein, human L-MDR1 expressed in LLC-PK1 epithelial cells using calcein-AM polarisation assay2003Journal of medicinal chemistry, Apr-24, Volume: 46, Issue:9
Comparison of in vitro P-glycoprotein screening assays: recommendations for their use in drug discovery.
AID1222417Terminal half life in liver and gut Por deleted-reductase conditional null mouse at 2.5 mg/kg, po treated 10 days after 80 mg/kg, ip beta-naphthoflavone administration by liquid chromatography-tandem mass spectrometry2013Drug metabolism and disposition: the biological fate of chemicals, Jan, Volume: 41, Issue:1
NADPH-cytochrome P450 oxidoreductase: roles in physiology, pharmacology, and toxicology.
AID1222399AUC (0 to infinity) in liver Por deleted-reductase conditional null mouse at 2.5 mg/kg, po treated 10 days after 40 mg/kg, ip 3-methylcholanthrene administration by liquid chromatography-tandem mass spectrometry2013Drug metabolism and disposition: the biological fate of chemicals, Jan, Volume: 41, Issue:1
NADPH-cytochrome P450 oxidoreductase: roles in physiology, pharmacology, and toxicology.
AID603954In-vivo blood/plasma to lung partition coefficients of the compound, logP(lung) in rat2008European journal of medicinal chemistry, Mar, Volume: 43, Issue:3
Air to lung partition coefficients for volatile organic compounds and blood to lung partition coefficients for volatile organic compounds and drugs.
AID1209581Fraction unbound in Sprague-Dawley rat brain homogenates at 5 uM by equilibrium dialysis analysis2011Drug metabolism and disposition: the biological fate of chemicals, Mar, Volume: 39, Issue:3
Measurement of unbound drug exposure in brain: modeling of pH partitioning explains diverging results between the brain slice and brain homogenate methods.
AID625290Drug Induced Liver Injury Prediction System (DILIps) training set; hepatic side effect (HepSE) score for liver fatty2011PLoS computational biology, Dec, Volume: 7, Issue:12
Translating clinical findings into knowledge in drug safety evaluation--drug induced liver injury prediction system (DILIps).
AID1209248Drug metabolism in human liver microsomes assessed as intrinsic clearance per mg protein by optimal design approach2012Drug metabolism and disposition: the biological fate of chemicals, Dec, Volume: 40, Issue:12
Optimized experimental design for the estimation of enzyme kinetic parameters: an experimental evaluation.
AID150755Inhibition of P-glycoprotein using calcein-AM assay transfected in porcine PBCEC2003Journal of medicinal chemistry, Apr-24, Volume: 46, Issue:9
Comparison of in vitro P-glycoprotein screening assays: recommendations for their use in drug discovery.
AID1443992Total Cmax in human administered as single dose2014Hepatology (Baltimore, Md.), Sep, Volume: 60, Issue:3
Human drug-induced liver injury severity is highly associated with dual inhibition of liver mitochondrial function and bile salt export pump.
AID625280Drug Induced Liver Injury Prediction System (DILIps) training set; hepatic side effect (HepSE) score for cholecystitis2011PLoS computational biology, Dec, Volume: 7, Issue:12
Translating clinical findings into knowledge in drug safety evaluation--drug induced liver injury prediction system (DILIps).
AID1900020Half life in rat liver microsomes at 1 uM incubated for 45 mins in presence of NADPH by LC-MS/MS analysis2022Journal of medicinal chemistry, 01-13, Volume: 65, Issue:1
Design, Synthesis, and Biological Evaluation of 1-(Indolizin-3-yl)ethan-1-ones as CBP Bromodomain Inhibitors for the Treatment of Prostate Cancer.
AID467613Volume of distribution at steady state in human2009European journal of medicinal chemistry, Nov, Volume: 44, Issue:11
Prediction of volume of distribution values in human using immobilized artificial membrane partitioning coefficients, the fraction of compound ionized and plasma protein binding data.
AID1211297Drug recovery in plasma (unknown origin)2011Drug metabolism and disposition: the biological fate of chemicals, Mar, Volume: 39, Issue:3
Control and measurement of plasma pH in equilibrium dialysis: influence on drug plasma protein binding.
AID600046Drug uptake by human hepatic OATP2B1 transporter expressed in HEK293 cells at 1 uM relative to wild-type HEK293 cells2011Bioorganic & medicinal chemistry letters, May-01, Volume: 21, Issue:9
Discovery of novel hepatoselective HMG-CoA reductase inhibitors for treating hypercholesterolemia: a bench-to-bedside case study on tissue selective drug distribution.
AID444051Total clearance in human2010Journal of medicinal chemistry, Feb-11, Volume: 53, Issue:3
Physicochemical space for optimum oral bioavailability: contribution of human intestinal absorption and first-pass elimination.
AID1216350AUC (0 to infinity) in healthy human assessed as fold change in presence of casopitant 120 mg, po once daily administered for 14 days2011Drug metabolism and disposition: the biological fate of chemicals, Mar, Volume: 39, Issue:3
Casopitant: in vitro data and SimCyp simulation to predict in vivo metabolic interactions involving cytochrome P450 3A4.
AID1219226Half life in solid tumor patient at 2 mg, po administered as single dose followed by co-treatment with 27 mg/m2, iv carfilzomib over 2 to 10 mins on days 1, 2, 8, 9, 15 and 16 of single 28-day cycle measured on day 12013Drug metabolism and disposition: the biological fate of chemicals, Jan, Volume: 41, Issue:1
Clinical pharmacokinetics, metabolism, and drug-drug interaction of carfilzomib.
AID1769106Metabolic stability in human liver microsomes assessed as half life preincubated for 10 mins followed by NADPH addition and further incubated upto 60 mins by LC-MS/MS analysis2021Journal of medicinal chemistry, 09-23, Volume: 64, Issue:18
Optimization of 4,6-Disubstituted Pyrido[3,2-
AID1472102Intrinsic clearance in BALB/c mouse liver microsomes at 1 uM in presence of NADPH by LC-MS/MS analysis2017Journal of medicinal chemistry, 12-28, Volume: 60, Issue:24
4-Aminoquinoline Antimalarials Containing a Benzylmethylpyridylmethylamine Group Are Active against Drug Resistant Plasmodium falciparum and Exhibit Oral Activity in Mice.
AID1215128Ratio, ratio of fraction unbound in solid supported porcine brain membrane vesicles at 5 uM dosed as discrete compounds after 5 hrs by TRANSIL assay to fraction unbound in solid supported porcine brain membrane vesicles at 5 uM using four compound cocktai2011Drug metabolism and disposition: the biological fate of chemicals, Feb, Volume: 39, Issue:2
Brain tissue binding of drugs: evaluation and validation of solid supported porcine brain membrane vesicles (TRANSIL) as a novel high-throughput method.
AID699541Inhibition of human liver OATP2B1 expressed in HEK293 Flp-In cells assessed as reduction in [3H]E3S uptake at 20 uM incubated for 5 mins by scintillation counting2012Journal of medicinal chemistry, May-24, Volume: 55, Issue:10
Classification of inhibitors of hepatic organic anion transporting polypeptides (OATPs): influence of protein expression on drug-drug interactions.
AID1443991Induction of mitochondrial dysfunction in Sprague-Dawley rat liver mitochondria assessed as inhibition of mitochondrial respiration per mg mitochondrial protein measured for 20 mins by A65N-1 oxygen probe based fluorescence assay2014Hepatology (Baltimore, Md.), Sep, Volume: 60, Issue:3
Human drug-induced liver injury severity is highly associated with dual inhibition of liver mitochondrial function and bile salt export pump.
AID1472622In-vivo intrinsic clearance in human liver microsomes at 2 uM after 60 mins in presence of NADPH by LC-MS/MS method2018Journal of medicinal chemistry, 01-11, Volume: 61, Issue:1
Novel Terminal Bipheny-Based Diapophytoene Desaturases (CrtN) Inhibitors as Anti-MRSA/VISR/LRSA Agents with Reduced hERG Activity.
AID540222Clearance in rat after iv administration2006Drug metabolism and disposition: the biological fate of chemicals, Jul, Volume: 34, Issue:7
Extrapolation of preclinical pharmacokinetics and molecular feature analysis of "discovery-like" molecules to predict human pharmacokinetics.
AID540228Clearance in human after iv administration2006Drug metabolism and disposition: the biological fate of chemicals, Jul, Volume: 34, Issue:7
Extrapolation of preclinical pharmacokinetics and molecular feature analysis of "discovery-like" molecules to predict human pharmacokinetics.
AID1222406Terminal half life in Por lox/lox wild type mouse at 2.5 mg/kg, po treated 10 days after 40 mg/kg, ip 3-methylcholanthrene administration by liquid chromatography-tandem mass spectrometry2013Drug metabolism and disposition: the biological fate of chemicals, Jan, Volume: 41, Issue:1
NADPH-cytochrome P450 oxidoreductase: roles in physiology, pharmacology, and toxicology.
AID187601Compound was tested for its total (rat) loss-of-righting reflex LORR recovery time at a dose of 30 mg/kg2002Bioorganic & medicinal chemistry letters, Nov-04, Volume: 12, Issue:21
Relating the structure, activity, and physical properties of ultrashort-acting benzodiazepine receptor agonists.
AID1611247Intrinsic clearance in mouse liver microsomes incubated for 6 hrs by LC/MS analysis2019Bioorganic & medicinal chemistry letters, 12-15, Volume: 29, Issue:24
Design, synthesis and biological evaluation of novel desloratadine derivatives with anti-inflammatory and H
AID600041Drug uptake by rat hepatic OATP1B2 transporters expressed in CHO cells at 10 uM relative to wild type CHO cells2011Bioorganic & medicinal chemistry letters, May-01, Volume: 21, Issue:9
Discovery of novel hepatoselective HMG-CoA reductase inhibitors for treating hypercholesterolemia: a bench-to-bedside case study on tissue selective drug distribution.
AID1473741Inhibition of human MRP4 overexpressed in Sf9 cell membrane vesicles assessed as uptake of [3H]-estradiol-17beta-D-glucuronide in presence of ATP and GSH measured after 20 mins by membrane vesicle transport assay2013Toxicological sciences : an official journal of the Society of Toxicology, Nov, Volume: 136, Issue:1
A multifactorial approach to hepatobiliary transporter assessment enables improved therapeutic compound development.
AID1457812Intrinsic clearance in mouse liver microsomes assessed per mg of protein2017Journal of medicinal chemistry, 07-27, Volume: 60, Issue:14
Enantioselective Synthesis and in Vivo Evaluation of Regioisomeric Analogues of the Antimalarial Arterolane.
AID21850In vitro clearance in dog in 1000000 cells; not available1999Journal of medicinal chemistry, Dec-16, Volume: 42, Issue:25
Combining in vitro and in vivo pharmacokinetic data for prediction of hepatic drug clearance in humans by artificial neural networks and multivariate statistical techniques.
AID1221732Drug uptake ratio assessed as enzyme-mediated uptake in HEK293 cells expressing human OATP1B1 at 1 uM at 37 degC for 3 mins by liquid scintillation spectroscopy relative to wild type2011Drug metabolism and disposition: the biological fate of chemicals, Jan, Volume: 39, Issue:1
Characterization of digoxin uptake in sandwich-cultured human hepatocytes.
AID1611240Half life in human liver microsomes incubated for 6 hrs by LC/MS analysis2019Bioorganic & medicinal chemistry letters, 12-15, Volume: 29, Issue:24
Design, synthesis and biological evaluation of novel desloratadine derivatives with anti-inflammatory and H
AID539464Solubility of the compound in 0.1 M phosphate buffer at 600 uM at pH 7.4 after 24 hrs by LC/MS/MS analysis2010Bioorganic & medicinal chemistry letters, Dec-15, Volume: 20, Issue:24
Experimental solubility profiling of marketed CNS drugs, exploring solubility limit of CNS discovery candidate.
AID600037Drug uptake by rat hepatic OATP1A1 transporters expressed in CHO cells at 1 uM relative to wild type CHO cells2011Bioorganic & medicinal chemistry letters, May-01, Volume: 21, Issue:9
Discovery of novel hepatoselective HMG-CoA reductase inhibitors for treating hypercholesterolemia: a bench-to-bedside case study on tissue selective drug distribution.
AID681146TP_TRANSPORTER: inhibition of TEA uptake in OCT1-expressing HeLa cells1998The Journal of pharmacology and experimental therapeutics, Jul, Volume: 286, Issue:1
Functional characterization of an organic cation transporter (hOCT1) in a transiently transfected human cell line (HeLa).
AID1446386Intrinsic clearance in human liver microsomes2017Journal of medicinal chemistry, 08-10, Volume: 60, Issue:15
Discovery and Optimization of Chromeno[2,3-c]pyrrol-9(2H)-ones as Novel Selective and Orally Bioavailable Phosphodiesterase 5 Inhibitors for the Treatment of Pulmonary Arterial Hypertension.
AID1209259Drug metabolism in human liver microsomes assessed as maximum rate of reaction per mg protein by optimal design approach2012Drug metabolism and disposition: the biological fate of chemicals, Dec, Volume: 40, Issue:12
Optimized experimental design for the estimation of enzyme kinetic parameters: an experimental evaluation.
AID1900019Metabolic stability in human liver microsomes assessed as parent compound remaining at 1 uM incubated for 45 mins in presence of NADPH by LC-MS/MS analysis2022Journal of medicinal chemistry, 01-13, Volume: 65, Issue:1
Design, Synthesis, and Biological Evaluation of 1-(Indolizin-3-yl)ethan-1-ones as CBP Bromodomain Inhibitors for the Treatment of Prostate Cancer.
AID1219221Cmax in solid tumor patient at 2 mg, po administered as single dose followed by co-treatment with 27 mg/m2, iv carfilzomib over 2 to 10 mins on days 1, 2, 8, 9, 15 and 16 of single 28-day cycle measured on day 12013Drug metabolism and disposition: the biological fate of chemicals, Jan, Volume: 41, Issue:1
Clinical pharmacokinetics, metabolism, and drug-drug interaction of carfilzomib.
AID1756363Metabolic stability in rat hepatocytes assessed as intrinsic clearance incubated up to 120 mins measured per million cells by LC-MS/MS analysis2021European journal of medicinal chemistry, Mar-05, Volume: 213Discovery and development of novel pyrimidine and pyrazolo/thieno-fused pyrimidine derivatives as potent and orally active inducible nitric oxide synthase dimerization inhibitor with efficacy for arthritis.
AID1611225Half life in dog liver microsomes incubated for 6 hrs by LC/MS analysis2019Bioorganic & medicinal chemistry letters, 12-15, Volume: 29, Issue:24
Design, synthesis and biological evaluation of novel desloratadine derivatives with anti-inflammatory and H
AID1219235Half life in solid tumor patient at 2 mg, po administered as single dose followed by co-treatment with 27 mg/m2, iv carfilzomib over 2 to 10 mins on days 1, 2, 8, 9, 15 and 16 of single 28-day cycle measured on day 162013Drug metabolism and disposition: the biological fate of chemicals, Jan, Volume: 41, Issue:1
Clinical pharmacokinetics, metabolism, and drug-drug interaction of carfilzomib.
AID54923Inhibition of human cytochrome P450 3A42003Journal of medicinal chemistry, Apr-24, Volume: 46, Issue:9
Comparison of in vitro P-glycoprotein screening assays: recommendations for their use in drug discovery.
AID455986Permeability across human Caco-2 cells2009Bioorganic & medicinal chemistry, Oct-01, Volume: 17, Issue:19
Computational modeling of novel inhibitors targeting the Akt pleckstrin homology domain.
AID1429808Metabolic stability in human liver microsomes assessed as compound remaining at 1 uM in presence of NADPH after 30 mins by LC-MS/MS analysis2017Journal of medicinal chemistry, 02-23, Volume: 60, Issue:4
Antimalarial Pyrido[1,2-a]benzimidazoles: Lead Optimization, Parasite Life Cycle Stage Profile, Mechanistic Evaluation, Killing Kinetics, and in Vivo Oral Efficacy in a Mouse Model.
AID1211294Unbound fraction in plasma (unknown origin) at pH 7.4 after 6 hrs by equilibrium dialysis method in presence of 5% CO22011Drug metabolism and disposition: the biological fate of chemicals, Mar, Volume: 39, Issue:3
Control and measurement of plasma pH in equilibrium dialysis: influence on drug plasma protein binding.
AID150756Inhibition of P-gp was determined using rhodamine-assay in human CaCo-2 cells2003Journal of medicinal chemistry, Apr-24, Volume: 46, Issue:9
Comparison of in vitro P-glycoprotein screening assays: recommendations for their use in drug discovery.
AID425653Renal clearance in human2009Journal of medicinal chemistry, Aug-13, Volume: 52, Issue:15
Physicochemical determinants of human renal clearance.
AID1702160Clearance in rat liver microsomes at pH 7.4 at 5 uM incubated upto 60 mins in presence of NADPH measured per mg of protein by LC-MS analysis2018Journal of medicinal chemistry, 02-22, Volume: 61, Issue:4
Design, Synthesis, and Preclinical Evaluation of Fused Pyrimidine-Based Hydroxamates for the Treatment of Hepatocellular Carcinoma.
AID1739203Metabolic stability in monkey liver microsomes assessed as half life at 1 uM incubated up to 60 mins in presence of NADPH by LC-MS/MS analysis2020European journal of medicinal chemistry, Aug-15, Volume: 200Discovery of coumarin derivatives as potent and selective cyclin-dependent kinase 9 (CDK9) inhibitors with high antitumour activity.
AID1473800Drug concentration at steady state in human at 0.01 to 0.04 mg/kg, po after 24 hrs2013Toxicological sciences : an official journal of the Society of Toxicology, Nov, Volume: 136, Issue:1
A multifactorial approach to hepatobiliary transporter assessment enables improved therapeutic compound development.
AID1900027Hepatic extraction ratio in rat liver microsomes at 1 uM incubated for 45 mins in presence of NADPH by LC-MS/MS analysis2022Journal of medicinal chemistry, 01-13, Volume: 65, Issue:1
Design, Synthesis, and Biological Evaluation of 1-(Indolizin-3-yl)ethan-1-ones as CBP Bromodomain Inhibitors for the Treatment of Prostate Cancer.
AID625291Drug Induced Liver Injury Prediction System (DILIps) training set; hepatic side effect (HepSE) score for liver function tests abnormal2011PLoS computational biology, Dec, Volume: 7, Issue:12
Translating clinical findings into knowledge in drug safety evaluation--drug induced liver injury prediction system (DILIps).
AID1222405Clearance in liver Por deleted-reductase conditional null mouse at 2.5 mg/kg, po treated 10 days after 40 mg/kg, ip 3-methylcholanthrene administration by liquid chromatography-tandem mass spectrometry2013Drug metabolism and disposition: the biological fate of chemicals, Jan, Volume: 41, Issue:1
NADPH-cytochrome P450 oxidoreductase: roles in physiology, pharmacology, and toxicology.
AID681122TP_TRANSPORTER: inhibition of Calcein-AM efflux in MDR1-expressing LLC-PK1 cells2003Journal of medicinal chemistry, Apr-24, Volume: 46, Issue:9
Comparison of in vitro P-glycoprotein screening assays: recommendations for their use in drug discovery.
AID1219222AUC(last) in solid tumor patient at 2 mg, po administered as single dose followed by co-treatment with 27 mg/m2, iv carfilzomib over 2 to 10 mins on days 1, 2, 8, 9, 15 and 16 of single 28-day cycle measured on day 12013Drug metabolism and disposition: the biological fate of chemicals, Jan, Volume: 41, Issue:1
Clinical pharmacokinetics, metabolism, and drug-drug interaction of carfilzomib.
AID187598Compound was tested for its initial (rat) loss-of-righting reflex LORR recovery time at a dose of 30 mg/kg2002Bioorganic & medicinal chemistry letters, Nov-04, Volume: 12, Issue:21
Relating the structure, activity, and physical properties of ultrashort-acting benzodiazepine receptor agonists.
AID681119TP_TRANSPORTER: inhibition of Calcein-AM efflux in Mdr1a-expressing LLC-PK1 cells2003Journal of medicinal chemistry, Apr-24, Volume: 46, Issue:9
Comparison of in vitro P-glycoprotein screening assays: recommendations for their use in drug discovery.
AID625287Drug Induced Liver Injury Prediction System (DILIps) training set; hepatic side effect (HepSE) score for hepatomegaly2011PLoS computational biology, Dec, Volume: 7, Issue:12
Translating clinical findings into knowledge in drug safety evaluation--drug induced liver injury prediction system (DILIps).
AID715120Drug metabolism in dog liver microsomes at 3 uM after 1 hr2012Journal of medicinal chemistry, Oct-25, Volume: 55, Issue:20
Development of oseltamivir phosphonate congeners as anti-influenza agents.
AID1611246Intrinsic clearance in Rat liver microsomes incubated for 6 hrs by LC/MS analysis2019Bioorganic & medicinal chemistry letters, 12-15, Volume: 29, Issue:24
Design, synthesis and biological evaluation of novel desloratadine derivatives with anti-inflammatory and H
AID540223Volume of distribution at steady state in rat after iv administration2006Drug metabolism and disposition: the biological fate of chemicals, Jul, Volume: 34, Issue:7
Extrapolation of preclinical pharmacokinetics and molecular feature analysis of "discovery-like" molecules to predict human pharmacokinetics.
AID395324Lipophilicity, log D at pH 7.4 by liquid chromatography2009Journal of medicinal chemistry, Mar-26, Volume: 52, Issue:6
Relationship between brain tissue partitioning and microemulsion retention factors of CNS drugs.
AID588211Literature-mined compound from Fourches et al multi-species drug-induced liver injury (DILI) dataset, effect in humans2010Chemical research in toxicology, Jan, Volume: 23, Issue:1
Cheminformatics analysis of assertions mined from literature that describe drug-induced liver injury in different species.
AID648843Binding affinity to BRD2-BD1 assessed as change in melting temperature at 10 uM by protein stability shift assay2012Bioorganic & medicinal chemistry, Mar-15, Volume: 20, Issue:6
Benzodiazepines and benzotriazepines as protein interaction inhibitors targeting bromodomains of the BET family.
AID1900024Hepatic clearance in human liver microsomes at 1 uM incubated for 45 mins in presence of NADPH by LC-MS/MS analysis2022Journal of medicinal chemistry, 01-13, Volume: 65, Issue:1
Design, Synthesis, and Biological Evaluation of 1-(Indolizin-3-yl)ethan-1-ones as CBP Bromodomain Inhibitors for the Treatment of Prostate Cancer.
AID625292Drug Induced Liver Injury Prediction System (DILIps) training set; hepatic side effect (HepSE) combined score2011PLoS computational biology, Dec, Volume: 7, Issue:12
Translating clinical findings into knowledge in drug safety evaluation--drug induced liver injury prediction system (DILIps).
AID1739202Metabolic stability in human liver microsomes assessed as intrinsic clearance at 1 uM incubated up to 60 mins in presence of NADPH by LC-MS/MS analysis2020European journal of medicinal chemistry, Aug-15, Volume: 200Discovery of coumarin derivatives as potent and selective cyclin-dependent kinase 9 (CDK9) inhibitors with high antitumour activity.
AID8002Observed volume of distribution2004Journal of medicinal chemistry, Feb-26, Volume: 47, Issue:5
Prediction of human volume of distribution values for neutral and basic drugs. 2. Extended data set and leave-class-out statistics.
AID1611226Half life in monkey liver microsomes incubated for 6 hrs by LC/MS analysis2019Bioorganic & medicinal chemistry letters, 12-15, Volume: 29, Issue:24
Design, synthesis and biological evaluation of novel desloratadine derivatives with anti-inflammatory and H
AID588220Literature-mined public compounds from Kruhlak et al phospholipidosis modelling dataset2008Toxicology mechanisms and methods, , Volume: 18, Issue:2-3
Development of a phospholipidosis database and predictive quantitative structure-activity relationship (QSAR) models.
AID1446767Half life in human liver microsomes in absence of NADPH by LC-MS/MS method2017European journal of medicinal chemistry, Apr-21, Volume: 130Diphenylurea derivatives for combating methicillin- and vancomycin-resistant Staphylococcus aureus.
AID1739207Metabolic stability in rat liver microsomes assessed as half life at 1 uM incubated up to 60 mins in presence of NADPH by LC-MS/MS analysis2020European journal of medicinal chemistry, Aug-15, Volume: 200Discovery of coumarin derivatives as potent and selective cyclin-dependent kinase 9 (CDK9) inhibitors with high antitumour activity.
AID1744241Intrinsic clearance in human liver microsomes at 10 uM incubated for 1 hr in presence of NADPH by LC-MS/MS analysis2021Journal of medicinal chemistry, 01-14, Volume: 64, Issue:1
Novel Sigma 1 Receptor Antagonists as Potential Therapeutics for Pain Management.
AID444057Fraction escaping hepatic elimination in human2010Journal of medicinal chemistry, Feb-11, Volume: 53, Issue:3
Physicochemical space for optimum oral bioavailability: contribution of human intestinal absorption and first-pass elimination.
AID681132TP_TRANSPORTER: ATP hydrolysis in MDR1-expressing Sf9 cells2001The Journal of pharmacology and experimental therapeutics, Nov, Volume: 299, Issue:2
Rational use of in vitro P-glycoprotein assays in drug discovery.
AID467612Fraction unbound in human plasma2009European journal of medicinal chemistry, Nov, Volume: 44, Issue:11
Prediction of volume of distribution values in human using immobilized artificial membrane partitioning coefficients, the fraction of compound ionized and plasma protein binding data.
AID298031Lipophilicity, log D at pH7.42007Journal of medicinal chemistry, Sep-20, Volume: 50, Issue:19
High-throughput screening of drug-brain tissue binding and in silico prediction for assessment of central nervous system drug delivery.
AID1216347AUC (0 to infinity) in healthy human assessed as fold change in presence of casopitant 30 mg, po once daily administered for 3 days2011Drug metabolism and disposition: the biological fate of chemicals, Mar, Volume: 39, Issue:3
Casopitant: in vitro data and SimCyp simulation to predict in vivo metabolic interactions involving cytochrome P450 3A4.
AID1221735Drug uptake ratio assessed as enzyme-mediated uptake in HEK293 cells expressing human OATP1B1 at 10 uM at 37 degC for 3 mins by liquid scintillation spectroscopy relative to wild type2011Drug metabolism and disposition: the biological fate of chemicals, Jan, Volume: 39, Issue:1
Characterization of digoxin uptake in sandwich-cultured human hepatocytes.
AID699539Inhibition of human liver OATP1B1 expressed in HEK293 Flp-In cells assessed as reduction in E17-betaG uptake at 20 uM by scintillation counting2012Journal of medicinal chemistry, May-24, Volume: 55, Issue:10
Classification of inhibitors of hepatic organic anion transporting polypeptides (OATPs): influence of protein expression on drug-drug interactions.
AID600045Drug uptake by human hepatic OATP1B3 transporter expressed in HEK293 cells at 1 uM relative to wild-type HEK293 cells2011Bioorganic & medicinal chemistry letters, May-01, Volume: 21, Issue:9
Discovery of novel hepatoselective HMG-CoA reductase inhibitors for treating hypercholesterolemia: a bench-to-bedside case study on tissue selective drug distribution.
AID1769115Intrinsic clearance in rat liver microsomes preincubated for 10 mins followed by NADPH addition and further incubated upto 60 mins by LC-MS/MS analysis2021Journal of medicinal chemistry, 09-23, Volume: 64, Issue:18
Optimization of 4,6-Disubstituted Pyrido[3,2-
AID1221733Drug uptake ratio assessed as enzyme-mediated uptake in HEK293 cells expressing human OATP1B3 at 1 uM at 37 degC for 3 mins by liquid scintillation spectroscopy relative to wild type2011Drug metabolism and disposition: the biological fate of chemicals, Jan, Volume: 39, Issue:1
Characterization of digoxin uptake in sandwich-cultured human hepatocytes.
AID1221738Drug uptake ratio assessed as enzyme-mediated uptake in HEK293 cells expressing human OATP1B3 at 1 uM at 37 degC for 3 mins cells pretreated with sodium butyrate by liquid scintillation spectroscopy relative to wild type2011Drug metabolism and disposition: the biological fate of chemicals, Jan, Volume: 39, Issue:1
Characterization of digoxin uptake in sandwich-cultured human hepatocytes.
AID1209249Drug metabolism in assessed as human CYP3A-mediated metabolism2012Drug metabolism and disposition: the biological fate of chemicals, Dec, Volume: 40, Issue:12
Optimized experimental design for the estimation of enzyme kinetic parameters: an experimental evaluation.
AID395327Dissociation constant, pKa by capillary electrophoresis2009Journal of medicinal chemistry, Mar-26, Volume: 52, Issue:6
Relationship between brain tissue partitioning and microemulsion retention factors of CNS drugs.
AID444053Renal clearance in human2010Journal of medicinal chemistry, Feb-11, Volume: 53, Issue:3
Physicochemical space for optimum oral bioavailability: contribution of human intestinal absorption and first-pass elimination.
AID1219232AUC(0 to 12 hrs) in solid tumor patient at 2 mg, po administered as single dose followed by co-treatment with 27 mg/m2, iv carfilzomib over 2 to 10 mins on days 1, 2, 8, 9, 15 and 16 of single 28-day cycle measured on day 162013Drug metabolism and disposition: the biological fate of chemicals, Jan, Volume: 41, Issue:1
Clinical pharmacokinetics, metabolism, and drug-drug interaction of carfilzomib.
AID688292Allosteric modulation of gamma-aminobutyric acid receptor A alpha1beta2gamma2S expressed in Xenopus oocytes assessed as potentiation of GABA-mediated chloride current by voltage clamp analysis2011Journal of natural products, Aug-26, Volume: 74, Issue:8
Identification and characterization of GABA(A) receptor modulatory diterpenes from Biota orientalis that decrease locomotor activity in mice.
AID39933Binding affinity against rat benzodiazepine (BZD) receptor2002Bioorganic & medicinal chemistry letters, Nov-04, Volume: 12, Issue:21
Relating the structure, activity, and physical properties of ultrashort-acting benzodiazepine receptor agonists.
AID444054Oral bioavailability in human2010Journal of medicinal chemistry, Feb-11, Volume: 53, Issue:3
Physicochemical space for optimum oral bioavailability: contribution of human intestinal absorption and first-pass elimination.
AID625286Drug Induced Liver Injury Prediction System (DILIps) training set; hepatic side effect (HepSE) score for hepatitis2011PLoS computational biology, Dec, Volume: 7, Issue:12
Translating clinical findings into knowledge in drug safety evaluation--drug induced liver injury prediction system (DILIps).
AID648850Binding affinity to PB1 assessed as change in melting temperature at 10 uM by protein stability shift assay2012Bioorganic & medicinal chemistry, Mar-15, Volume: 20, Issue:6
Benzodiazepines and benzotriazepines as protein interaction inhibitors targeting bromodomains of the BET family.
AID1219233AUC(infinity) in solid tumor patient at 2 mg, po administered as single dose followed by co-treatment with 27 mg/m2, iv carfilzomib over 2 to 10 mins on days 1, 2, 8, 9, 15 and 16 of single 28-day cycle measured on day 162013Drug metabolism and disposition: the biological fate of chemicals, Jan, Volume: 41, Issue:1
Clinical pharmacokinetics, metabolism, and drug-drug interaction of carfilzomib.
AID1222404Clearance in Por lox/lox wild type mouse at 2.5 mg/kg, po treated 10 days after 40 mg/kg, ip 3-methylcholanthrene administration by liquid chromatography-tandem mass spectrometry2013Drug metabolism and disposition: the biological fate of chemicals, Jan, Volume: 41, Issue:1
NADPH-cytochrome P450 oxidoreductase: roles in physiology, pharmacology, and toxicology.
AID600038Drug uptake by rat hepatic OATP1A4 transporters expressed in CHO cells at 1 uM relative to wild type CHO cells2011Bioorganic & medicinal chemistry letters, May-01, Volume: 21, Issue:9
Discovery of novel hepatoselective HMG-CoA reductase inhibitors for treating hypercholesterolemia: a bench-to-bedside case study on tissue selective drug distribution.
AID648858Binding affinity to BRD3-BD2 assessed as change in melting temperature at 10 uM by protein stability shift assay2012Bioorganic & medicinal chemistry, Mar-15, Volume: 20, Issue:6
Benzodiazepines and benzotriazepines as protein interaction inhibitors targeting bromodomains of the BET family.
AID1446381Half life in rat liver microsomes2017Journal of medicinal chemistry, 08-10, Volume: 60, Issue:15
Discovery and Optimization of Chromeno[2,3-c]pyrrol-9(2H)-ones as Novel Selective and Orally Bioavailable Phosphodiesterase 5 Inhibitors for the Treatment of Pulmonary Arterial Hypertension.
AID1474166Liver toxicity in human assessed as induction of drug-induced liver injury by measuring severity class index2016Drug discovery today, Apr, Volume: 21, Issue:4
DILIrank: the largest reference drug list ranked by the risk for developing drug-induced liver injury in humans.
AID1900023Intrinsic clearance in human liver microsomes at 1 uM incubated for 45 mins in presence of NADPH by LC-MS/MS analysis2022Journal of medicinal chemistry, 01-13, Volume: 65, Issue:1
Design, Synthesis, and Biological Evaluation of 1-(Indolizin-3-yl)ethan-1-ones as CBP Bromodomain Inhibitors for the Treatment of Prostate Cancer.
AID1215121Fraction unbound in Wistar rat brain homogenate at 5 uM after 5 hrs by equilibrium dialysis method2011Drug metabolism and disposition: the biological fate of chemicals, Feb, Volume: 39, Issue:2
Brain tissue binding of drugs: evaluation and validation of solid supported porcine brain membrane vesicles (TRANSIL) as a novel high-throughput method.
AID681128TP_TRANSPORTER: inhibition of Calcein-AM efflux in Mdr1b-expressing LLC-PK1 cells2003Journal of medicinal chemistry, Apr-24, Volume: 46, Issue:9
Comparison of in vitro P-glycoprotein screening assays: recommendations for their use in drug discovery.
AID1222411AUC (0 to last) in liver and gut Por deleted-reductase conditional null mouse at 2.5 mg/kg, po treated 10 days after 80 mg/kg, ip beta-naphthoflavone administration by liquid chromatography-tandem mass spectrometry2013Drug metabolism and disposition: the biological fate of chemicals, Jan, Volume: 41, Issue:1
NADPH-cytochrome P450 oxidoreductase: roles in physiology, pharmacology, and toxicology.
AID1422310Clearance in human hepatocytes at 1 uM2018Bioorganic & medicinal chemistry letters, 11-15, Volume: 28, Issue:21
Design, synthesis and biological evaluation of (2S,3R,4R,5S,6R)-5-fluoro-6-(hydroxymethyl)-2-aryltetrahydro-2H-pyran-3,4-diols as potent and orally active SGLT dual inhibitors.
AID150754Inhibition of P-glycoprotein, mouse L-mdr1b expressed in LLC-PK1 epithelial cells using calcein-AM polarisation assay2003Journal of medicinal chemistry, Apr-24, Volume: 46, Issue:9
Comparison of in vitro P-glycoprotein screening assays: recommendations for their use in drug discovery.
AID540231Dose normalised AUC in dog after po administration2005Xenobiotica; the fate of foreign compounds in biological systems, Feb, Volume: 35, Issue:2
Comparative evaluation of oral systemic exposure of 56 xenobiotics in rat, dog, monkey and human.
AID1222793Dissociation constant, pKa of the compound2013Drug metabolism and disposition: the biological fate of chemicals, May, Volume: 41, Issue:5
Which metabolites circulate?
AID648848Binding affinity to CREBBP assessed as change in melting temperature at 10 uM by protein stability shift assay2012Bioorganic & medicinal chemistry, Mar-15, Volume: 20, Issue:6
Benzodiazepines and benzotriazepines as protein interaction inhibitors targeting bromodomains of the BET family.
AID1222409AUC (0 to infinity) in liver and gut Por deleted-reductase conditional null mouse at 2.5 mg/kg, po treated 10 days after 80 mg/kg, ip beta-naphthoflavone administration by liquid chromatography-tandem mass spectrometry2013Drug metabolism and disposition: the biological fate of chemicals, Jan, Volume: 41, Issue:1
NADPH-cytochrome P450 oxidoreductase: roles in physiology, pharmacology, and toxicology.
AID444056Fraction escaping gut-wall elimination in human2010Journal of medicinal chemistry, Feb-11, Volume: 53, Issue:3
Physicochemical space for optimum oral bioavailability: contribution of human intestinal absorption and first-pass elimination.
AID681120TP_TRANSPORTER: inhibition of Rhodamine 123 efflux in Caco-2 cells2003Journal of medicinal chemistry, Apr-24, Volume: 46, Issue:9
Comparison of in vitro P-glycoprotein screening assays: recommendations for their use in drug discovery.
AID1739205Metabolic stability in dog liver microsomes assessed as half life at 1 uM incubated up to 60 mins in presence of NADPH by LC-MS/MS analysis2020European journal of medicinal chemistry, Aug-15, Volume: 200Discovery of coumarin derivatives as potent and selective cyclin-dependent kinase 9 (CDK9) inhibitors with high antitumour activity.
AID540232Dose normalised AUC in monkey after po administration2005Xenobiotica; the fate of foreign compounds in biological systems, Feb, Volume: 35, Issue:2
Comparative evaluation of oral systemic exposure of 56 xenobiotics in rat, dog, monkey and human.
AID1422309Half life in monkey hepatocytes at 1 uM2018Bioorganic & medicinal chemistry letters, 11-15, Volume: 28, Issue:21
Design, synthesis and biological evaluation of (2S,3R,4R,5S,6R)-5-fluoro-6-(hydroxymethyl)-2-aryltetrahydro-2H-pyran-3,4-diols as potent and orally active SGLT dual inhibitors.
AID540229Volume of distribution at steady state in human after iv administration2006Drug metabolism and disposition: the biological fate of chemicals, Jul, Volume: 34, Issue:7
Extrapolation of preclinical pharmacokinetics and molecular feature analysis of "discovery-like" molecules to predict human pharmacokinetics.
AID1409858Half life in human liver microsomes at 2 uM by LC-MS/MS analysis2018ACS medicinal chemistry letters, Mar-08, Volume: 9, Issue:3
Novel Staphyloxanthin Inhibitors with Improved Potency against Multidrug Resistant
AID1422306Half life in human hepatocytes at 1 uM2018Bioorganic & medicinal chemistry letters, 11-15, Volume: 28, Issue:21
Design, synthesis and biological evaluation of (2S,3R,4R,5S,6R)-5-fluoro-6-(hydroxymethyl)-2-aryltetrahydro-2H-pyran-3,4-diols as potent and orally active SGLT dual inhibitors.
AID1215671Drug metabolism in pooled human hepatocytes assessed as aldehyde oxidase-mediated drug metabolism at 10 uM up to 120 mins by HPLC analysis in presence of 25 uM of hydralazine2012Drug metabolism and disposition: the biological fate of chemicals, Jul, Volume: 40, Issue:7
Hydralazine as a selective probe inactivator of aldehyde oxidase in human hepatocytes: estimation of the contribution of aldehyde oxidase to metabolic clearance.
AID1534319Intrinsic clearance in rat liver microsomes assessed per mg protein at 1 uM after 5 to 60 mins in presence of NADPH by LC-MS/MS analysis2019European journal of medicinal chemistry, Feb-01, Volume: 163Discovery of a highly selective FLT3 inhibitor with specific proliferation inhibition against AML cells harboring FLT3-ITD mutation.
AID600043Drug uptake by rat hepatic OATP1A1 transporters expressed in CHO cells at 10 uM relative to wild type CHO cells2011Bioorganic & medicinal chemistry letters, May-01, Volume: 21, Issue:9
Discovery of novel hepatoselective HMG-CoA reductase inhibitors for treating hypercholesterolemia: a bench-to-bedside case study on tissue selective drug distribution.
AID1446398Hepatic extraction ratio in human microsomes2017Journal of medicinal chemistry, 08-10, Volume: 60, Issue:15
Discovery and Optimization of Chromeno[2,3-c]pyrrol-9(2H)-ones as Novel Selective and Orally Bioavailable Phosphodiesterase 5 Inhibitors for the Treatment of Pulmonary Arterial Hypertension.
AID1611242Half life in mouse liver microsomes incubated for 6 hrs by LC/MS analysis2019Bioorganic & medicinal chemistry letters, 12-15, Volume: 29, Issue:24
Design, synthesis and biological evaluation of novel desloratadine derivatives with anti-inflammatory and H
AID1756360Metabolic stability in human hepatocytes assessed as clearance incubated up to 120 mins measured per million cells by LC-MS/MS analysis2021European journal of medicinal chemistry, Mar-05, Volume: 213Discovery and development of novel pyrimidine and pyrazolo/thieno-fused pyrimidine derivatives as potent and orally active inducible nitric oxide synthase dimerization inhibitor with efficacy for arthritis.
AID1739208Metabolic stability in rat liver microsomes assessed as intrinsic clearance at 1 uM incubated up to 60 mins in presence of NADPH by LC-MS/MS analysis2020European journal of medicinal chemistry, Aug-15, Volume: 200Discovery of coumarin derivatives as potent and selective cyclin-dependent kinase 9 (CDK9) inhibitors with high antitumour activity.
AID1209245Drug metabolism in assessed as human CYP3A-mediated intrinsic clearance per mg protein2012Drug metabolism and disposition: the biological fate of chemicals, Dec, Volume: 40, Issue:12
Optimized experimental design for the estimation of enzyme kinetic parameters: an experimental evaluation.
AID540224Clearance in dog after iv administration2006Drug metabolism and disposition: the biological fate of chemicals, Jul, Volume: 34, Issue:7
Extrapolation of preclinical pharmacokinetics and molecular feature analysis of "discovery-like" molecules to predict human pharmacokinetics.
AID1769113Metabolic stability in rat liver microsomes assessed as half life preincubated for 10 mins followed by NADPH addition and further incubated upto 60 mins by LC-MS/MS analysis2021Journal of medicinal chemistry, 09-23, Volume: 64, Issue:18
Optimization of 4,6-Disubstituted Pyrido[3,2-
AID588213Literature-mined compound from Fourches et al multi-species drug-induced liver injury (DILI) dataset, effect in non-rodents2010Chemical research in toxicology, Jan, Volume: 23, Issue:1
Cheminformatics analysis of assertions mined from literature that describe drug-induced liver injury in different species.
AID600042Drug uptake by rat hepatic OATP1A4 transporters expressed in CHO cells at 10 uM relative to wild type CHO cells2011Bioorganic & medicinal chemistry letters, May-01, Volume: 21, Issue:9
Discovery of novel hepatoselective HMG-CoA reductase inhibitors for treating hypercholesterolemia: a bench-to-bedside case study on tissue selective drug distribution.
AID648859Binding affinity to BRD4-BD2 assessed as change in melting temperature at 10 uM by protein stability shift assay2012Bioorganic & medicinal chemistry, Mar-15, Volume: 20, Issue:6
Benzodiazepines and benzotriazepines as protein interaction inhibitors targeting bromodomains of the BET family.
AID1756359Metabolic stability in human hepatocytes assessed as half life measured upto 120 mins by LC-MS/MS analysis2021European journal of medicinal chemistry, Mar-05, Volume: 213Discovery and development of novel pyrimidine and pyrazolo/thieno-fused pyrimidine derivatives as potent and orally active inducible nitric oxide synthase dimerization inhibitor with efficacy for arthritis.
AID1219217AUC(0 to 12 hrs) in solid tumor patient at 2 mg, po administered as single dose measured on day 72013Drug metabolism and disposition: the biological fate of chemicals, Jan, Volume: 41, Issue:1
Clinical pharmacokinetics, metabolism, and drug-drug interaction of carfilzomib.
AID588212Literature-mined compound from Fourches et al multi-species drug-induced liver injury (DILI) dataset, effect in rodents2010Chemical research in toxicology, Jan, Volume: 23, Issue:1
Cheminformatics analysis of assertions mined from literature that describe drug-induced liver injury in different species.
AID1900022Intrinsic clearance in rat liver microsomes at 1 uM incubated for 45 mins in presence of NADPH by LC-MS/MS analysis2022Journal of medicinal chemistry, 01-13, Volume: 65, Issue:1
Design, Synthesis, and Biological Evaluation of 1-(Indolizin-3-yl)ethan-1-ones as CBP Bromodomain Inhibitors for the Treatment of Prostate Cancer.
AID1446382Half life in human microsomes2017Journal of medicinal chemistry, 08-10, Volume: 60, Issue:15
Discovery and Optimization of Chromeno[2,3-c]pyrrol-9(2H)-ones as Novel Selective and Orally Bioavailable Phosphodiesterase 5 Inhibitors for the Treatment of Pulmonary Arterial Hypertension.
AID681166TP_TRANSPORTER: Western blot, LS180 cell1996Molecular pharmacology, Feb, Volume: 49, Issue:2
Modulators and substrates of P-glycoprotein and cytochrome P4503A coordinately up-regulate these proteins in human colon carcinoma cells.
AID600336Drug uptake by human hepatic OATP2B1 transporter expressed in HEK293 cells at 10 uM relative to wild-type HEK293 cells2011Bioorganic & medicinal chemistry letters, May-01, Volume: 21, Issue:9
Discovery of novel hepatoselective HMG-CoA reductase inhibitors for treating hypercholesterolemia: a bench-to-bedside case study on tissue selective drug distribution.
AID1209250Drug metabolism in human liver microsomes by multiple depletion curves method2012Drug metabolism and disposition: the biological fate of chemicals, Dec, Volume: 40, Issue:12
Optimized experimental design for the estimation of enzyme kinetic parameters: an experimental evaluation.
AID29812Oral bioavailability in human2000Journal of medicinal chemistry, Jun-29, Volume: 43, Issue:13
QSAR model for drug human oral bioavailability.
AID21857In vivo clearance in human.1999Journal of medicinal chemistry, Dec-16, Volume: 42, Issue:25
Combining in vitro and in vivo pharmacokinetic data for prediction of hepatic drug clearance in humans by artificial neural networks and multivariate statistical techniques.
AID1772562n-Octanol/PBS buffer distribution coefficient, logD of the compound at pH 7.42021European journal of medicinal chemistry, Nov-05, Volume: 223Non-carboxylic acid inhibitors of aldose reductase based on N-substituted thiazolidinedione derivatives.
AID1529095Binding affinity to His-tagged CYP3A5 (unknown origin) expressed in Escherichia coli DH5alpha assessed as five-coordinate HS ferric heme iron state formation with displacement of distal water ligand by EPR spectroscopy2020Journal of medicinal chemistry, 02-13, Volume: 63, Issue:3
Clobetasol Propionate Is a Heme-Mediated Selective Inhibitor of Human Cytochrome P450 3A5.
AID1446390Apparent clearance in human microsomes2017Journal of medicinal chemistry, 08-10, Volume: 60, Issue:15
Discovery and Optimization of Chromeno[2,3-c]pyrrol-9(2H)-ones as Novel Selective and Orally Bioavailable Phosphodiesterase 5 Inhibitors for the Treatment of Pulmonary Arterial Hypertension.
AID1222410AUC (0 to last) in Por lox/lox wild type mouse at 2.5 mg/kg, po treated 10 days after 80 mg/kg, ip beta-naphthoflavone administration by liquid chromatography-tandem mass spectrometry2013Drug metabolism and disposition: the biological fate of chemicals, Jan, Volume: 41, Issue:1
NADPH-cytochrome P450 oxidoreductase: roles in physiology, pharmacology, and toxicology.
AID1129361Unbound fraction in HEK293 cell homogenate at 0.1 uM by equilibrium dialysis based UPLC-MS/MS analysis2014Journal of medicinal chemistry, Apr-10, Volume: 57, Issue:7
A high-throughput cell-based method to predict the unbound drug fraction in the brain.
AID540211Fraction unbound in human after iv administration2008Drug metabolism and disposition: the biological fate of chemicals, Jul, Volume: 36, Issue:7
Trend analysis of a database of intravenous pharmacokinetic parameters in humans for 670 drug compounds.
AID625282Drug Induced Liver Injury Prediction System (DILIps) training set; hepatic side effect (HepSE) score for cirrhosis2011PLoS computational biology, Dec, Volume: 7, Issue:12
Translating clinical findings into knowledge in drug safety evaluation--drug induced liver injury prediction system (DILIps).
AID520313Inhibition of CYP3A activity in orally dosed human2008Antimicrobial agents and chemotherapy, May, Volume: 52, Issue:5
Rapid clinical induction of hepatic cytochrome P4502B6 activity by ritonavir.
AID1529088Binding affinity to heme in His-tagged CYP3A5 (unknown origin) expressed in Escherichia coli DH5alpha assessed as formation of five-coordinate ferric heme iron by measuring type 1 Soret shift from 417 nm (low spin) to 395 nm (high spin) by UV-vis spectrop2020Journal of medicinal chemistry, 02-13, Volume: 63, Issue:3
Clobetasol Propionate Is a Heme-Mediated Selective Inhibitor of Human Cytochrome P450 3A5.
AID1220241Intrinsic clearance in human intestinal microsomes assessed CYP450-mediated glucuronidation clearance2012Drug metabolism and disposition: the biological fate of chemicals, Sep, Volume: 40, Issue:9
Quantitative prediction of human intestinal glucuronidation effects on intestinal availability of UDP-glucuronosyltransferase substrates using in vitro data.
AID395325Lipophilicity, log P by microemulsion electrokinetic chromatography2009Journal of medicinal chemistry, Mar-26, Volume: 52, Issue:6
Relationship between brain tissue partitioning and microemulsion retention factors of CNS drugs.
AID1611241Half life in rat liver microsomes incubated for 6 hrs by LC/MS analysis2019Bioorganic & medicinal chemistry letters, 12-15, Volume: 29, Issue:24
Design, synthesis and biological evaluation of novel desloratadine derivatives with anti-inflammatory and H
AID540227Volume of distribution at steady state in monkey after iv administration2006Drug metabolism and disposition: the biological fate of chemicals, Jul, Volume: 34, Issue:7
Extrapolation of preclinical pharmacokinetics and molecular feature analysis of "discovery-like" molecules to predict human pharmacokinetics.
AID1611245Intrinsic clearance in dog liver microsomes incubated for 6 hrs by LC/MS analysis2019Bioorganic & medicinal chemistry letters, 12-15, Volume: 29, Issue:24
Design, synthesis and biological evaluation of novel desloratadine derivatives with anti-inflammatory and H
AID1211298Dissociation constant, pKa of the compound2011Drug metabolism and disposition: the biological fate of chemicals, Mar, Volume: 39, Issue:3
Control and measurement of plasma pH in equilibrium dialysis: influence on drug plasma protein binding.
AID732420Efflux ratio of permeability from basolateral to apical side over apical to basolateral in pig LLC-PK1 cells overexpressing human MDR1 relative to efflux ratio in parental cell line2013ACS medicinal chemistry letters, Jan-10, Volume: 4, Issue:1
De novo prediction of p-glycoprotein-mediated efflux liability for druglike compounds.
AID444055Fraction absorbed in human2010Journal of medicinal chemistry, Feb-11, Volume: 53, Issue:3
Physicochemical space for optimum oral bioavailability: contribution of human intestinal absorption and first-pass elimination.
AID577579Inhibition of CYP3A4 in human liver microsome2011Bioorganic & medicinal chemistry letters, Feb-15, Volume: 21, Issue:4
Conformationally constrained farnesoid X receptor (FXR) agonists: heteroaryl replacements of the naphthalene.
AID1611243Intrinsic clearance in human liver microsomes incubated for 6 hrs by LC/MS analysis2019Bioorganic & medicinal chemistry letters, 12-15, Volume: 29, Issue:24
Design, synthesis and biological evaluation of novel desloratadine derivatives with anti-inflammatory and H
AID1900021Half life in human liver microsomes at 1 uM incubated for 45 mins in presence of NADPH by LC-MS/MS analysis2022Journal of medicinal chemistry, 01-13, Volume: 65, Issue:1
Design, Synthesis, and Biological Evaluation of 1-(Indolizin-3-yl)ethan-1-ones as CBP Bromodomain Inhibitors for the Treatment of Prostate Cancer.
AID1739204Metabolic stability in monkey liver microsomes assessed as intrinsic clearance at 1 uM incubated up to 60 mins in presence of NADPH by LC-MS/MS analysis2020European journal of medicinal chemistry, Aug-15, Volume: 200Discovery of coumarin derivatives as potent and selective cyclin-dependent kinase 9 (CDK9) inhibitors with high antitumour activity.
AID1219223AUC(0 to 12 hrs) in solid tumor patient at 2 mg, po administered as single dose followed by co-treatment with 27 mg/m2, iv carfilzomib over 2 to 10 mins on days 1, 2, 8, 9, 15 and 16 of single 28-day cycle measured on day 12013Drug metabolism and disposition: the biological fate of chemicals, Jan, Volume: 41, Issue:1
Clinical pharmacokinetics, metabolism, and drug-drug interaction of carfilzomib.
AID678835TP_TRANSPORTER: transepithelial transport (basal to apical) in MDR1-expressing LLC-PK1 cells1999Pharmaceutical research, Mar, Volume: 16, Issue:3
Interrelationship between substrates and inhibitors of human CYP3A and P-glycoprotein.
AID648857Binding affinity to BRD2-BD2 assessed as change in melting temperature at 10 uM by protein stability shift assay2012Bioorganic & medicinal chemistry, Mar-15, Volume: 20, Issue:6
Benzodiazepines and benzotriazepines as protein interaction inhibitors targeting bromodomains of the BET family.
AID1209251Drug metabolism in human liver microsomes by optimal design approach2012Drug metabolism and disposition: the biological fate of chemicals, Dec, Volume: 40, Issue:12
Optimized experimental design for the estimation of enzyme kinetic parameters: an experimental evaluation.
AID444050Fraction unbound in human plasma2010Journal of medicinal chemistry, Feb-11, Volume: 53, Issue:3
Physicochemical space for optimum oral bioavailability: contribution of human intestinal absorption and first-pass elimination.
AID648846Binding affinity to BRDT-BD1 assessed as change in melting temperature at 10 uM by protein stability shift assay2012Bioorganic & medicinal chemistry, Mar-15, Volume: 20, Issue:6
Benzodiazepines and benzotriazepines as protein interaction inhibitors targeting bromodomains of the BET family.
AID187604Loss of righting reflex recovery time (total) in rat was determined when treated with a dose of 30 mg/Kg2002Bioorganic & medicinal chemistry letters, Nov-04, Volume: 12, Issue:21
Identification and structure-activity studies of novel ultrashort-acting benzodiazepine receptor agonists.
AID21851In vitro clearance in human in 1000000 cells1999Journal of medicinal chemistry, Dec-16, Volume: 42, Issue:25
Combining in vitro and in vivo pharmacokinetic data for prediction of hepatic drug clearance in humans by artificial neural networks and multivariate statistical techniques.
AID1215125Percentage unbound in solid supported porcine brain membrane vesicles at 5 uM using four compound cocktail after 5 hrs by TRANSIL assay2011Drug metabolism and disposition: the biological fate of chemicals, Feb, Volume: 39, Issue:2
Brain tissue binding of drugs: evaluation and validation of solid supported porcine brain membrane vesicles (TRANSIL) as a novel high-throughput method.
AID679925TP_TRANSPORTER: inhibition of Rhodamine 123 transepithelial transport (basal to apical)(R123: 5 uM, Midazolam: 100 uM) in Caco-2 cells1998European journal of pharmacology, Oct-09, Volume: 358, Issue:3
Interaction with P-glycoprotein and transport of erythromycin, midazolam and ketoconazole in Caco-2 cells.
AID411793Metabolic stability in human liver microsomes assessed as intrinsic clearance per mg of protein2009Journal of medicinal chemistry, Jan-22, Volume: 52, Issue:2
Metabolic soft spot identification and compound optimization in early discovery phases using MetaSite and LC-MS/MS validation.
AID1422307Half life in Sprague-Dawley rat hepatocytes at 1 uM2018Bioorganic & medicinal chemistry letters, 11-15, Volume: 28, Issue:21
Design, synthesis and biological evaluation of (2S,3R,4R,5S,6R)-5-fluoro-6-(hydroxymethyl)-2-aryltetrahydro-2H-pyran-3,4-diols as potent and orally active SGLT dual inhibitors.
AID624623Apparent permeability (Papp) from basolateral to apical side determined in MDR1-MDCKII cells2001The Journal of pharmacology and experimental therapeutics, Nov, Volume: 299, Issue:2
Rational use of in vitro P-glycoprotein assays in drug discovery.
AID1529097Binding affinity to His-tagged CYP3A4 (unknown origin) expressed in Escherichia coli DH5alpha assessed as induction of HS formation by EPR spectroscopy2020Journal of medicinal chemistry, 02-13, Volume: 63, Issue:3
Clobetasol Propionate Is a Heme-Mediated Selective Inhibitor of Human Cytochrome P450 3A5.
AID648849Binding affinity to LOC93349 assessed as change in melting temperature at 10 uM by protein stability shift assay2012Bioorganic & medicinal chemistry, Mar-15, Volume: 20, Issue:6
Benzodiazepines and benzotriazepines as protein interaction inhibitors targeting bromodomains of the BET family.
AID600334Drug uptake by human hepatic OATP1B1 transporter expressed in HEK293 cells at 10 uM relative to wild type HEK293 cells2011Bioorganic & medicinal chemistry letters, May-01, Volume: 21, Issue:9
Discovery of novel hepatoselective HMG-CoA reductase inhibitors for treating hypercholesterolemia: a bench-to-bedside case study on tissue selective drug distribution.
AID19468Partition coefficient (logP)2003Journal of medicinal chemistry, Apr-24, Volume: 46, Issue:9
Comparison of in vitro P-glycoprotein screening assays: recommendations for their use in drug discovery.
AID150753Inhibition of P-glycoprotein, mouse L-mdr1a expressed in LLC-PK1 epithelial cells using calcein-AM polarisation assay2003Journal of medicinal chemistry, Apr-24, Volume: 46, Issue:9
Comparison of in vitro P-glycoprotein screening assays: recommendations for their use in drug discovery.
AID1534316Half life in human liver microsomes at 1 uM after 5 to 60 mins in presence of NADPH by LC-MS/MS analysis2019European journal of medicinal chemistry, Feb-01, Volume: 163Discovery of a highly selective FLT3 inhibitor with specific proliferation inhibition against AML cells harboring FLT3-ITD mutation.
AID680525TP_TRANSPORTER: inhibition of Digoxin transepithelial transport (basal to apical)(Digoxin: 5 uM, Midazolam: 100 uM) in Caco-2 cells1999Pharmaceutical research, Mar, Volume: 16, Issue:3
Interrelationship between substrates and inhibitors of human CYP3A and P-glycoprotein.
AID311524Oral bioavailability in human2007Bioorganic & medicinal chemistry, Dec-15, Volume: 15, Issue:24
Hologram QSAR model for the prediction of human oral bioavailability.
AID1472101Half life in BALB/c mouse liver microsomes at 1 uM in presence of NADPH by LC-MS/MS analysis2017Journal of medicinal chemistry, 12-28, Volume: 60, Issue:24
4-Aminoquinoline Antimalarials Containing a Benzylmethylpyridylmethylamine Group Are Active against Drug Resistant Plasmodium falciparum and Exhibit Oral Activity in Mice.
AID1222416Terminal half life in Por lox/lox wild type mouse at 2.5 mg/kg, po treated 10 days after 80 mg/kg, ip beta-naphthoflavone administration by liquid chromatography-tandem mass spectrometry2013Drug metabolism and disposition: the biological fate of chemicals, Jan, Volume: 41, Issue:1
NADPH-cytochrome P450 oxidoreductase: roles in physiology, pharmacology, and toxicology.
AID20881Aqueous solubility at pH 3 was determined2002Bioorganic & medicinal chemistry letters, Nov-04, Volume: 12, Issue:21
Relating the structure, activity, and physical properties of ultrashort-acting benzodiazepine receptor agonists.
AID1802994UDP-glucuronosyltransferase Activity Assay from Article 10.3109/14756366.2010.518965: \\The inhibition study of human UDP-glucuronosyltransferases with cytochrome P450 selective substrates and inhibitors.\\2011Journal of enzyme inhibition and medicinal chemistry, Jun, Volume: 26, Issue:3
The inhibition study of human UDP-glucuronosyltransferases with cytochrome P450 selective substrates and inhibitors.
[information is prepared from bioassay data collected from National Library of Medicine (NLM), extracted Dec-2023]

Research

Studies (9,189)

TimeframeStudies, This Drug (%)All Drugs %
pre-1990938 (10.21)18.7374
1990's2216 (24.12)18.2507
2000's2476 (26.95)29.6817
2010's2635 (28.68)24.3611
2020's924 (10.06)2.80
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Market Indicators

Research Demand Index: 117.22

According to the monthly volume, diversity, and competition of internet searches for this compound, as well the volume and growth of publications, there is estimated to be very strong demand-to-supply ratio for research on this compound.

MetricThis Compound (vs All)
Research Demand Index117.22 (24.57)
Research Supply Index9.47 (2.92)
Research Growth Index4.83 (4.65)
Search Engine Demand Index222.83 (26.88)
Search Engine Supply Index2.00 (0.95)

This Compound (117.22)

All Compounds (24.57)

Study Types

Publication TypeThis drug (%)All Drugs (%)
Trials3,191 (32.45%)5.53%
Reviews480 (4.88%)6.00%
Case Studies758 (7.71%)4.05%
Observational119 (1.21%)0.25%
Other5,286 (53.75%)84.16%
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Clinical Trials (989)

Trial Overview

TrialPhaseEnrollmentStudy TypeStart DateStatus
Changes of Skin Resistance After Midazolam and After the End of Anaesthesia [NCT03791424]Phase 428 participants (Actual)Interventional2014-10-01Completed
MIDAZOLAM EFFECTIVENESS TO THE SEDATION IN FLEXIBLE BRONCHOSCOPY. A RANDOMIZED STUDY [NCT01038882]238 participants (Actual)Interventional2008-10-31Completed
Interventional, Open-label, Multiple-dose Study to Investigate the Effects of Multiple Doses of Lu AF35700 on the Pharmacokinetics of Cytochrome P450 (CYP450) Substrates Dextromethorphan (CYP2D6), Caffeine (CYP1A2), Omeprazole (CYP2C19), and Midazolam (CY [NCT03195946]Phase 124 participants (Actual)Interventional2017-06-16Completed
[NCT02391688]Phase 130 participants (Actual)Interventional2014-11-30Completed
Sedation Effect on the Global Quality Colonoscopy [NCT02220530]7,000 participants (Anticipated)Observational [Patient Registry]2014-10-31Enrolling by invitation
Decreasing the Incidence of Delirium After Cardiac Surgery [NCT02119806]Phase 40 participants (Actual)Interventional2017-08-31Withdrawn(stopped due to Study was never initiated.)
Open-label, Single Center, Non-randomized, Fixed Sequence Phase 1 Drug-drug Interaction Study With LEO 32731 and Midazolam [NCT03126578]Phase 132 participants (Actual)Interventional2017-05-31Completed
Shaping Anesthetic Techniques to Reduce Post-Operative Delirium [NCT03133845]218 participants (Anticipated)Interventional2015-10-31Completed
Effect of Single Dose Dexmedetomidine Versus Midazolam on Emergence Agitation and Recovery Profile When Added to Ketamine for Procedural Sedation and Analgesia in Pediatric Patients Undergoing Bone Marrow Aspiration and Biopsy [NCT03647579]100 participants (Actual)Interventional2018-08-30Completed
A Prospective, Multi-center, Randomized Controlled Study of Neuromuscular Blocking Effect and Safety of Mivacurium Chloride in Pediatric Patients [NCT02117401]Phase 41,152 participants (Actual)Interventional2012-01-31Completed
Efficacy, Safety and Cost-effectiveness of Intranasal Sedation With Ketamine and Midazolam in Pediatric Dentistry: a Randomized Clinical Trial [NCT02447289]Phase 484 participants (Actual)Interventional2015-05-21Completed
Effective Dose of Dexmedetomidine or Midazolam in Monitored Anesthesia Care for Patients Undergoing Ophthalmologic Surgery With Retrobulbar Nerve Block [NCT04018703]150 participants (Anticipated)Interventional2019-11-01Recruiting
A Phase 1, Open Label, Multiple Dose Study Of The Effect Of PF-04171327 On Midazolam Pharmacokinetics In Healthy Volunteers [NCT00987038]Phase 112 participants (Actual)Interventional2009-09-30Completed
[NCT01051271]225 participants (Actual)Interventional2009-07-31Completed
Randomized Drug Interaction Study of RO4929097 for Advanced Solid Tumors [NCT01218620]Phase 117 participants (Actual)Interventional2010-09-30Completed
A Single- and Multiple-Ascending Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of LY3502970 in Healthy Subjects [NCT03929744]Phase 1133 participants (Actual)Interventional2019-06-12Completed
A PHASE 1, RANDOMIZED, OPEN LABEL, 2-WAY CROSSOVER STUDY TO EVALUATE THE EFFECT OF REPEATED DOSING OF PF-06835919 ON THE PHARMACOKINETICS OF A SINGLE ORAL DOSE OF MIDAZOLAM IN HEALTHY PARTICIPANTS [NCT03916406]Phase 110 participants (Actual)Interventional2019-04-18Completed
A Single-center, Randomized, Double-blind, Double-dummy, Parallel-group Study Comparing Oral Sedation to Intravenous Sedation for Ocular Procedures. [NCT03246724]Phase 4327 participants (Actual)Interventional2017-10-16Completed
The Influence of HRV-changing Premedication on Hemodynamic Parameters After Spinal Anesthesia [NCT01066247]60 participants (Anticipated)Interventional2009-09-30Completed
Nebulized Midazolam, Dexmedetomidine, and Their Combination in Sedation of Preschoolers Undergoing Dental Treatment: A Randomized Clinical Trial [NCT03827408]Phase 272 participants (Actual)Interventional2017-11-27Completed
Intranasal Midazolam for Pediatric Pre-procedural Sedation and Pre-procedural Anti-anxiety Using sipNose Device - a Randomized Controlled Study [NCT03635398]300 participants (Anticipated)Interventional2018-08-31Not yet recruiting
Assessing Goldenseal-drug Interactions Using a Probe Drug Cocktail Approach [NCT03772262]Early Phase 116 participants (Actual)Interventional2018-04-05Completed
A Open-Label, Two-sequence Phase I Drug-drug Interaction Clinical Study to Investigate the Pharmacokinetics of Leritrelvir With Midazolam, Omeprazole, Rosuvastatin, Verapamil, and Rifampin in Healthy Participants [NCT06031454]Phase 156 participants (Anticipated)Interventional2023-09-01Recruiting
Comparison of Remimazolam vs. Midazolam for Sedation During Cataract Surgery [NCT05980117]Phase 4120 participants (Anticipated)Interventional2024-01-31Not yet recruiting
The Effect of Remifentanil on Established Sunburn-induced Hyperalgesia in Human Volunteers [NCT00811837]Phase 424 participants (Anticipated)Interventional2009-01-31Recruiting
Pediatric Dose Optimization for Seizures in EMS (PediDOSE) [NCT05121324]Phase 36,000 participants (Anticipated)Interventional2022-08-08Recruiting
A TWO-PART, PHASE 1A/B, OPEN-LABEL, MULTICENTER TRIAL EVALUATING PHARMACOKINETICS, SAFETY AND EFFICACY OF PF-07284890 (ARRY 461) IN PARTICIPANTS WITH BRAF V600 MUTANT SOLID TUMORS WITH AND WITHOUT BRAIN INVOLVEMENT [NCT04543188]Phase 157 participants (Actual)Interventional2021-01-08Active, not recruiting
The Effects of Anesthetic Method on Cerebral Oxygen Saturation in Geriatric Patients Undergoing Transurethral Surgery [NCT01147146]64 participants (Actual)Interventional2010-06-30Completed
Comparison of Sufentanil, Fentanyl and Remifentanil in Combination With Midazolam During Bronchoscopy Under Conscious Sedation: A Randomized Double-blind Prospective Study [NCT03901716]Phase 460 participants (Actual)Interventional2019-01-15Completed
Propofol and Fentanyl Versus Midazolam and Fentanyl for Sedation During Diagnostic or Therapeutic Gastrointestinal Endoscopy in Cirrhotic Patients [NCT00906139]Phase 4210 participants (Actual)Interventional2008-03-31Active, not recruiting
"Single-center, Randomized, Five-way Crossover Study to Investigate Low-dose Combinations of Caffeine, Efavirenz, Losartan, Omeprazole, Metoprolol, Chlorzoxazone and Midazolam (Basel Cocktail) for Simultaneous Phenotyping of CYP1A2, CYP2B6, CYP2C9, CYP2C1 [NCT01187862]Phase 116 participants (Actual)Interventional2010-07-31Completed
Comparison of Postoperative Delirium in Elders Anaesthetised With Midazolam and Without Midazolam During Non-cardiac Surgery [NCT05456230]11,927 participants (Actual)Observational2020-04-01Completed
Study of Potential for Drug Interactions Mediated by CYP3A4 Inhibition With Aramchol in Healthy Volunteers [NCT03760848]Phase 115 participants (Actual)Interventional2018-11-12Completed
Oral Sedation With/Without Nitrous Oxide in Pediatric Dental Patients [NCT03728894]Phase 330 participants (Actual)Interventional2018-11-17Completed
A Phase 1, Open-label, 2-cohort, Fixed-sequence, Drug-drug Interaction Study to Investigate the Potential Interaction Between ATI-2173 When Coadministered With Midazolam or Clarithromycin in Healthy Subjects [NCT05137600]Phase 136 participants (Actual)Interventional2021-10-28Completed
Pharmacokinetic Evaluation of MDZ028 After Single Administration of a New Oral Form, at the Time of Anesthetic Premedication in Children. [NCT03639428]37 participants (Actual)Observational2011-06-23Completed
Effects of Sedation on Clinical, Gasometric and Respiratory Muscle Parameters in Critically Ill COPD Patients [NCT03678532]97 participants (Actual)Interventional2016-07-01Completed
An Open-label, Two-treatment Crossover Pharmacokinetic Interaction Study of Repeated Doses of SAR302503 on Pharmacokinetics of a Single Dose Cocktail of Omeprazole, Metoprolol, and Midazolam Used as Probe Substrates for CYP2C19, CYP2D6 and CYP3A4 Activiti [NCT01585623]Phase 116 participants (Actual)Interventional2012-06-30Completed
Lidocaine as an Adjuvant for Ketamine in Induction of Anesthesia in Septic Shock Patients: a Randomized Controlled Trial [NCT03640468]Phase 336 participants (Anticipated)Interventional2018-12-20Not yet recruiting
A Phase 1 Study of an ERK1/2 Inhibitor (LY3214996) Administered Alone or in Combination With Other Agents in Advanced Cancer [NCT02857270]Phase 1210 participants (Actual)Interventional2016-09-29Completed
Propofol and Remifentanyl Versus Midazolam and Fentanyl for Diagnostic Colonoscopy in Patients With Compensated Cirrhosis Child A-B [NCT01148277]90 participants (Anticipated)Interventional2011-08-31Not yet recruiting
Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Multiple Rising Oral Doses of BI 705564 (Double-blind, Randomised, Placebo-controlled, Parallel-group Design) and Evaluation of Midazolam Interaction (Nested, Open, Fixed-sequence, Intra-indiv [NCT03325712]Phase 160 participants (Actual)Interventional2017-11-17Completed
An Open-Label, Phase I/II, Dose-Escalation Study Evaluating the Safety and Tolerability of GDC-0032 in Patients With Locally Advanced or Metastatic Solid Tumors or Non-Hodgkin's Lymphoma and in Combination With Endocrine Therapy in Patients With Locally A [NCT01296555]Phase 1686 participants (Actual)Interventional2011-03-16Completed
A Double-Blind, Parallel, Randomized, Placebo-Controlled, Repeat Dose Escalation Study to Investigate the Safety, Tolerability and Pharmacokinetics of GSK1322322 in Healthy Subjects [NCT00896558]Phase 152 participants (Actual)Interventional2009-05-11Completed
A Phase 1, Open-Label, Drug Interaction Study to Investigate the Effect of Multiple Doses of Cyclosporine on the Pharmacokinetics of LY3502970 in Healthy Participants [NCT05573230]Phase 132 participants (Actual)Interventional2022-10-17Completed
A Randomized, Controlled Trial on Dexmedetomidine for Providing Adequate Sedation and Preserved Neurologic Examination for Endovascular Treatment of Acute Ischemic Stroke or Cerebral Vasospasm. [NCT01845441]Phase 27 participants (Actual)Interventional2012-04-30Terminated(stopped due to The principal investigator left employment at the sponsoring Institution)
A Three-Part Phase 1 Study to Determine the Potential Drug Interaction Between ACH-0144471 and Midazolam, Fexofenadine and Mycophenolate Mofetil in Healthy Subjects [NCT03108274]Phase 135 participants (Actual)Interventional2017-04-18Completed
A Phase 1, Open-label, Non-Randomized Study to Assess the Effect of DZD9008 on the Pharmacokinetics of the Cocktail Probes Representative for CYP3A4, P-gp, BCRP and OATP1B1 in Patients With EGFR or HER2 Mutant Advanced Non-small Cell Lung Cancer [NCT05926180]Phase 131 participants (Anticipated)Interventional2023-07-31Recruiting
Clinical Study on Sedative Effect and Safety of Remimazolam Besylate in ARDS Patients With Mechanical Ventilation [NCT05758597]Phase 4100 participants (Anticipated)Interventional2023-12-20Not yet recruiting
Does Single Dose Dexmedetomidine for Procedural Sedation Reduce Post-operative Pain in Total Knee Arthroplasty? A Randomized Control Study [NCT02466022]Phase 354 participants (Actual)Interventional2015-06-30Completed
Ketamine-based Versus Opioid-based for Rapid-sequence Induction of Anesthesia in Patients With Septic Shock [NCT03251170]Phase 442 participants (Actual)Interventional2018-01-25Completed
Combining Neurobiology and New Learning: Ketamine and Prolonged Exposure: A Potential Rapid Treatment for Post Traumatic Stress Disorder (PTSD) [NCT02727998]Phase 228 participants (Actual)Interventional2015-12-31Terminated(stopped due to Study ran out of funding)
Improving Patient Outcomes With Inguinal Hernioplasty - a Randomized Controlled Trial of Local Anaesthesia Versus Local Anaesthesia and Conscious Sedation [NCT02444260]Phase 3180 participants (Anticipated)Interventional2013-12-31Recruiting
A Phase 1, Randomized, Double-Blind, Single-Ascending-Dose, and Food Effect Study to Assess the Safety, Tolerability, Ventricular Repolarization, and Pharmacokinetics of S-648414 in Healthy Adult Study Participants (Part 1); A Phase 1, Randomized, Double- [NCT04147715]Phase 198 participants (Actual)Interventional2019-10-09Completed
Evaluation of the Effect of LY3871801 on the Pharmacokinetics of CYP450 Substrates and an OAT1/3 Substrate in Healthy Participants [NCT05602675]Phase 139 participants (Actual)Interventional2022-11-02Completed
A Phase I, 2-Part, Open-Label Study to Investigate the Safety, Tolerability, and Pharmacokinetics of Multiple Doses of Risdiplam and the Effect of Risdiplam on the Pharmacokinetics of Midazolam Following Oral Administration in Healthy Participants [NCT03988907]Phase 135 participants (Actual)Interventional2019-06-18Completed
A Single-center, Open-label, Two-period, Fixed-sequence Study to Investigate the Effect of a Single Oral Dose of ACT-1014-6470 on the Pharmacokinetics of Omeprazole, Midazolam, and Their Metabolites in Healthy Male Subjects [NCT05123820]Phase 120 participants (Actual)Interventional2021-11-13Completed
A Phase 1 Combined Single and Multiple Ascending Oral Dose Study to Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of ASP6282 in Healthy Nonelderly and Elderly Male and Female Subjects, Including a Food Effect Cohort and Drug-drug [NCT02420782]Phase 1116 participants (Actual)Interventional2015-05-31Completed
Buccal Midazolam Versus Nasal or Oral Midazolam Sedation for Minor Invasive Procedures in Children: A Prospective Randomized Control Study [NCT02408302]Phase 490 participants (Anticipated)Interventional2015-04-30Not yet recruiting
Narcotrend Versus Bispectral Index Monitoring During Sufentanil-Midazolam Anesthesia for Bronchoscopy Under Conscious Sedation [NCT03738137]80 participants (Actual)Interventional2018-08-01Completed
A Phase 1, Open-label, Drug Interaction Study to Evaluate the Effect of Guselkumab (CNTO 1959) on Cytochrome P450 Enzyme Activities Following a Single Subcutaneous Administration in Subjects With Moderate to Severe Plaque-type Psoriasis [NCT02397382]Phase 116 participants (Actual)Interventional2015-06-18Completed
Effects of Multiple Doses of Abemaciclib on the Pharmacokinetics of Cytochrome P450 (CYP) 1A2, CYP2C9, CYP2D6, and CYP3A Substrates (Caffeine, Warfarin, Dextromethorphan, and Midazolam) in Cancer Patients [NCT02688088]Phase 148 participants (Actual)Interventional2016-03-08Completed
A Phase 1, Open-label, 1-sequence Crossover, Drug-drug Interaction Study to Assess the Effect of Repeated Doses of Cefiderocol on the Pharmacokinetics of Midazolam in Healthy Adult Participants [NCT05395104]Phase 114 participants (Actual)Interventional2022-05-24Completed
Safety and Pharmacokinetics of ODM-208 in Patients With Metastatic Castration-resistant Prostate Cancer [NCT03436485]Phase 1/Phase 2204 participants (Anticipated)Interventional2018-03-19Recruiting
A Phase 1, Open-Label, Fixed-sequence, 5-part, Drug-drug Interaction Study of Tucatinib to Evaluate the Effects of CYP3A4 and CYP2C8 Inhibition and Induction on the Pharmacokinetics of Tucatinib and to Evaluate the Effects of Tucatinib on the Pharmacokine [NCT03723395]Phase 1116 participants (Actual)Interventional2018-09-17Completed
Childhood Convulsive Status Epilepticus - In Search Of Optimal Drug Management In A Resource Limited Setting [NCT03650270]Phase 3198 participants (Actual)Interventional2015-03-01Completed
Multimodal Intrathecal Analgesia for Cesarean Section [NCT05186454]Phase 260 participants (Anticipated)Interventional2021-05-23Recruiting
Interactive Tablet Compared to Oral Midazolam as Premedication in Preoperative Anxiety in Children [NCT04049201]112 participants (Actual)Interventional2018-05-04Completed
A Phase 1, Multi-center, Open-label, 3-arm, Fixed Sequence Study to Assess the Effect of Co-administration of AZD9833 on the Pharmacokinetics of Midazolam (CYP3A4/5 Substrate), of Omeprazole (CYP2C19 Substrate), of Celecoxib (CYP2C9 Substrate) and of Dabi [NCT05438303]Phase 159 participants (Actual)Interventional2022-06-13Completed
A Double-blind, Randomized-controlled Trial Using a Low Dose of Ketamine vs. Active Placebo in Treating Severe Depression and Suicide [NCT03666390]48 participants (Anticipated)Interventional2018-09-10Recruiting
The Effects of Remimazolam Tosilate Sedation Compared With Midazolam Sedation in Dental Patients: A Double Blind, Prospective , Randomized Controlled Trial [NCT04602845]Phase 481 participants (Actual)Interventional2021-04-01Completed
A Phase 1, Drug-Drug Interaction Study to Evaluate the Effect of PBI-4050 on the Pharmacokinetics of Midazolam, a Sensitive Cytochrome P450 3A Substrate, in Healthy Adult Subjects [NCT03637049]Phase 122 participants (Actual)Interventional2018-07-17Completed
A PHASE 1, RANDOMIZED, 2-WAY CROSSOVER, MULTIPLE DOSE, OPEN LABEL STUDY OF THE EFFECT OF PF-04965842 ON MIDAZOLAM PHARMACOKINETICS IN HEALTHY VOLUNTEERS [NCT03647670]Phase 125 participants (Actual)Interventional2018-07-03Completed
Comparison of Post Anesthetic Recovery Time in Sedated Patients for Colonoscopy: Midazolam and Propofol or Fentanyl and Propofol. [NCT03813303]Phase 450 participants (Actual)Interventional2018-03-20Completed
Comparison Between Dexmedetomidine and Propofol for Sedation When Combined With Midazolam and Remifentanil During Awake Endotracheal Intubation: A Randomized Double-blind Controlled Study [NCT04753515]Phase 4100 participants (Actual)Interventional2021-03-05Completed
Comparing the Pharmacodynamics of Nasal and Buccal Midazolam Using EEG [NCT01316445]Phase 19 participants (Actual)Interventional2011-07-31Terminated(stopped due to Funding agency no longer provide support.)
A Pharmacokinetic, Multi-cohort Study in Healthy Adult Subjects to Assess Gepotidacin as Victim and as Perpetrator of Drug-Drug Interactions Via CYP450, Renal and Intestinal Transporters, and to Assess Gepotidacin Pharmacokinetics in Japanese Healthy Adul [NCT04493931]Phase 164 participants (Actual)Interventional2020-08-14Completed
Safety, Tolerability, and Pharmacokinetics of Multiple Rising Oral Doses of BI 1358894 (Double-blind, Randomised, Placebo-controlled, Parallel-group Design) and Evaluation of Midazolam Interaction (Nested, Open, Fixed-sequence, Intra-individual Comparison [NCT03754959]Phase 150 participants (Actual)Interventional2018-12-18Completed
A Comparison of Dexmedetomidine Versus Propofol for Use in Intravenous Sedation [NCT03255824]Phase 4144 participants (Actual)Interventional2018-03-20Completed
A Single Center, Prospective, Randomized, Double Blind, Placebo-controlled, Three-way Cross-over Study of the Analgesic Effects of Midazolam Versus Placebo With Fentanyl as an Active Control in Human Volunteers [NCT02629146]Phase 424 participants (Actual)Interventional2015-12-31Completed
An Open-Label Drug Interaction Study in Healthy Subjects to Evaluate the Effects of Multiple Doses of JNJ55308942 on the Cytochrome P450 CYP3A4, CYP2D6 and CYP2C19 Activity and on the Pharmacokinetics of Levonorgestrel/Ethinyl Estradiol [NCT03547024]Phase 114 participants (Actual)Interventional2018-06-08Completed
The Effect and Safety of Different Sedation Strategies for Diagnostic Bronchoscopy [NCT03983889]200 participants (Anticipated)Interventional2019-06-17Not yet recruiting
Randomized Controlled Trial Comparing Effects of Sedation for Upper Gastrointestinal Endoscopy With Propofol Versus Midazolam on Psychometric Tests and Critical Flicker Frequency in Cirrhotics [NCT01356121]Phase 4120 participants (Anticipated)Interventional2010-11-30Recruiting
Optimization of Procedural Sedation Protocol Used for Dental Care Delivery in People With Mental Disability [NCT02078336]Phase 440 participants (Anticipated)Interventional2013-12-31Recruiting
An Open-label, Multi Centre Drug-drug Interaction Trial to Investigate the Effects of Tralokinumab on the Pharmacokinetics of Selected Cytochrome P450 Substrates in Adult Subjects With Moderate-to-severe Atopic Dermatitis [NCT03556592]Phase 140 participants (Actual)Interventional2018-08-13Completed
Nasal Versus Oral Midazolam Sedation in Routine Pediatric Dental Care [NCT02679781]70 participants (Actual)Interventional2017-03-28Completed
Impact of Various Sedation Regimens on the Incidence of Post-sedation Delirium in Patients Receiving Mechanical Ventilation [NCT02117726]Phase 4320 participants (Anticipated)Interventional2014-05-31Not yet recruiting
A Randomized, Double-Blind, Multiple-Ascending Dose, Placebo-Controlled Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of LY3549492 in Patients With Type 2 Diabetes Mellitus [NCT05327595]Phase 196 participants (Anticipated)Interventional2022-05-09Recruiting
UNderstanding CONSciousness Connectedness and Intraoperative Unresponsiveness Study [NCT03284307]Phase 435 participants (Actual)Interventional2017-08-10Completed
A Phase 1, Single-center, Fixed-sequence, Open Label Study to Evaluate the Effect of Oral Repeated Doses of AZD1722 on the Pharmacokinetics of Oral Midazolam in Healthy Volunteers [NCT02140268]Phase 165 participants (Actual)Interventional2014-05-31Completed
The Effect of Multiple Doses of BI 187004 on the Single Dose Pharmacokinetics of Cytochrome P450 Substrates (Caffeine, Warfarin, Omeprazole, Metoprolol and Midazolam) and a P-glycoprotein Substrate (Digoxin) Administered Orally in an Open-label, One-seque [NCT02254148]Phase 124 participants (Actual)Interventional2014-10-31Completed
Induction Agent and Incidence of Hypotension in Heart Failure Patients Undergoing LVAD-Implantation [NCT04934410]50 participants (Anticipated)Observational2021-11-01Not yet recruiting
A Phase 1, Open-Label, Multicenter, Drug-Drug Interaction Study of TAK-788 and Midazolam, a Sensitive CYP3A Substrate, in Patients With Advanced Non-Small Cell Lung Cancer [NCT04051827]Phase 126 participants (Actual)Interventional2019-12-23Completed
Efficacy of Median Nerve Hydrodissection by Hyalase Versus Midazolam in the Treatment of Carpal Tunnel Syndrome: A Randomized, Clinical Trial. [NCT05344495]Early Phase 1100 participants (Anticipated)Interventional2022-01-10Recruiting
Dexmedetomidine Versus Morphine and Midazolam in Prevention and Treatment of Delirium After Adult Cardiac Surgery; a Randomized, Double-blind Clinical Trial [NCT03078946]Phase 460 participants (Actual)Interventional2013-03-31Completed
A Comparison of Dexmedetomidine Versus Midazolam for Conscious Sedation During Endobronchial Ultrasound Guided Transbronchial Needle Aspiration (EBUS-TBNA) [NCT02157818]110 participants (Actual)Interventional2014-06-30Completed
Safety and Efficacy of Fentanyl Citrate in Combination With Midazolam in Critically Ill Children With Mechanical Ventilation [NCT02172014]Phase 244 participants (Actual)Interventional2013-06-30Completed
[NCT02174588]22 participants (Actual)Interventional2013-01-07Completed
A Phase I, Open-Label, Multiple-Dose, Dose-Escalation Study to Investigate the Safety, Pharmacokinetics, and Pharmacodynamics of the BRAF Inhibitor GSK2118436 in Subjects With Solid Tumors [NCT00880321]Phase 1170 participants (Actual)Interventional2009-06-04Completed
Sedation of Mechanically Ventilated Critically Ill Patients: Midazolam Versus Dexmedetomidine [NCT01256866]Phase 4146 participants (Anticipated)Interventional2010-11-30Recruiting
Prospective Observational Investigation of Olanzapine Versus Midazolam for the Treatment of Acute Undifferentiated Agitation in the Emergency Department [NCT03899506]206 participants (Actual)Observational2018-06-18Terminated(stopped due to Investigator Voluntary Pause)
Resveratrol and Midazolam Metabolism [NCT01173640]6 participants (Actual)Interventional2010-07-31Completed
A Phase I, Non-randomized Open-label Study to Evaluate the Effect of BAY73-4506 (Regorafenib) on Probe Substrates of CYP 2C9 (Warfarin), 2C19 (Omeprazole) and 3A4 (Midazolam) in a Cocktail Approach (Group A) and on a Probe Substrate of CYP 2C8 (Rosiglitaz [NCT01287598]Phase 141 participants (Actual)Interventional2011-08-02Completed
Lidocaine-Ketamine Versus Ketamine for Induction of Anesthesia in Septic Shock Patients: a Randomized Controlled Trial [NCT03844984]Phase 343 participants (Actual)Interventional2019-02-20Completed
A Phase 1, Open-label, Study in Subjects With Rheumatoid Arthritis to Evaluate the Effect of a Single Dose of Olokizumab on the Pharmacokinetics of Substrates for CYP1A2, CYP2C9, CYP2C19, and CYP3A4 [NCT04246762]Phase 116 participants (Actual)Interventional2021-04-06Completed
An Adaptive, Part Open-label, Part Randomised Phase 1 Clinical Trial in Healthy Volunteers to Study Drug Interactions With RV521 Including Those Mediated by CYP3A4 and P-glycoprotein [NCT03782662]Phase 182 participants (Actual)Interventional2018-11-06Completed
A PHASE 1, RANDOMIZED, OPEN LABEL, 2-WAY CROSSOVER STUDY TO ESTIMATE THE EFFECT OF MULTIPLE DOSE PF-06651600 ON THE PHARMACOKINETICS OF SINGLE DOSE MIDAZOLAM AND EFAVIRENZ IN HEALTHY PARTICIPANTS [NCT03762928]Phase 112 participants (Actual)Interventional2018-12-07Completed
Phenotyping Study of CYP3A4 Activity in Patients With Prostate Cancer Versus Male Patients With Other Types of Solid Tumours With Midazolam [NCT05518799]18 participants (Actual)Interventional2021-04-22Completed
An Open-Label, One-Sequence, Two-Part Drug-Drug Interaction Study in Healthy Volunteers to Assess the CYP1A2 and CYP3A4 Perpetrator Interaction Potential and CYP1A2 Victim Potential of TEV-56286 (anle138b) [NCT05532358]Phase 154 participants (Actual)Interventional2022-09-12Completed
A Phase 1 Open-label Study to Assess the Effect of BMS-986419 on the Single Dose Pharmacokinetics of Probe Substrates (Caffeine, Bupropion, Flurbiprofen, Omeprazole, Midazolam, and Fexofenadine) in Healthy Participants [NCT05932277]Phase 122 participants (Actual)Interventional2023-06-29Completed
A Randomized, Double-Blind (Sponsor Unblinded), Placebo-Controlled Study to Evaluate the Safety, Tolerability and Pharmacokinetics of Orally Administered VH4011499 in Healthy Participants [NCT05393271]Phase 173 participants (Actual)Interventional2022-05-27Completed
Effect of Acute Ethanol Consumption on The Activity of Major Cytochrome P450 Enzymes, NAT2 and P-glycoprotein [NCT02515526]16 participants (Actual)Interventional2015-06-30Completed
The Efficacy and Optimal Dose of Sufentanil in Patient Controlled Analgesia After Moderate Surgery [NCT02503826]Phase 460 participants (Anticipated)Interventional2015-01-31Enrolling by invitation
A Phase I Open-label Study to Evaluate the Effect of Multiple Doses of AZD1775 on the Pharmacokinetics of Substrates for CYP3A, CYP2C19, CYP1A2 and to Provide Data on the Effect of AZD1775 on QT Interval in Patients With Advanced Solid Tumours [NCT03333824]Phase 133 participants (Actual)Interventional2017-12-01Completed
An Open-label, Fixed Sequence Phase I Study in Healthy Male Volunteers to Assess Sequentially the Effects of Multiple Doses of BI 207127 NA, BI 201335 NA Followed by the Combination of BI 207127 NA and BI 201335 NA, on the Single Dose Pharmacokinetics of [NCT02182401]Phase 137 participants (Actual)Interventional2009-07-31Terminated
Comparative Study of Hemodynamic Changes Caused by Diazepam and Midazolam During Third Molar Surgery. A Prospective Randomized Study [NCT02177955]Phase 4120 participants (Actual)Interventional2011-01-31Completed
A Study to Evaluate the Effect of Multiple Doses of 500 mg of BIRT 2584 XX Tablets on the Pharmacokinetic Parameters of Warfarin, Omeprazole, Caffeine, and Dextromethorphan Dosed Orally and Midazolam Dosed IV, in Healthy Male Volunteers [NCT02256813]Phase 120 participants (Actual)Interventional2005-09-30Completed
A Randomized Comparison of Midazolam With Meperidine and Dexmedetomidine Versus Midazolam With Meperidine and Propofol for Sedation During ERCP [NCT02475824]Phase 4258 participants (Actual)Interventional2015-05-31Completed
Efficacy of Combined Ketamine and Midazolam for Treatment of Generalized Convulsive Status Epilepticus in Children . [NCT05779657]Phase 2/Phase 3144 participants (Anticipated)Interventional2023-03-21Recruiting
Comparison of Perioperative Conscious Sedation During Endovascular Thrombectomy in Acute Ischemic Stroke (PEACE) A Randomised Multicentre Trial [NCT06139692]Phase 4810 participants (Anticipated)Interventional2023-11-21Recruiting
Feasibility Study Comparing a Ketamine and Midazolam Infusion to a Midazolam-Only Infusion for Complex Regional Pain Syndrome [NCT05945147]Phase 24 participants (Anticipated)Interventional2024-01-01Not yet recruiting
Randomized Controlled Trial of IN Midazolam vs IN Dexmedetomidine vs IN Ketamine Evaluating Length of Stay After Medication Administration and Anxiolysis During Minimal Procedures in Pediatric Population in Pediatric Emergency Department [NCT05934669]Phase 490 participants (Anticipated)Interventional2024-01-31Not yet recruiting
" Effect of Sedative and Anxiolytic Premedication on Children Experience After General Anesthesia The pediaPREM Study." [NCT05681572]Phase 31,000 participants (Anticipated)Interventional2023-04-18Recruiting
Effects of Different Doses of Dexmedetomidine on Postoperative Cognitive Dysfunction in Elderly Hypertensive Patients-A Single Center,Randomized, Double-blinded,Controlled Study [NCT02224443]Phase 490 participants (Anticipated)Interventional2014-09-30Not yet recruiting
Comparing Efficacy of Oral Midazolam and Sublingual Alprazolam in Reducing Anxiety and Pain/Discomfort Related to Diagnostic Upper Gastrointestinal Endoscopy in Adults [NCT03130842]Phase 2/Phase 3136 participants (Actual)Interventional2016-09-17Completed
Ketamine Interleaved With Electroconvulsive Therapy for Depression, A Pragmatic Randomised Controlled Pilot Trial [NCT04082858]Phase 13 participants (Actual)Interventional2020-01-06Terminated(stopped due to Inadequate recruitment due to COVID-19)
A Phase I, Non-randomized, Open-label, Fixed-sequence Study to Investigate the Effect of Darolutamide (ODM-201) on the Pharmacokinetics of a Probe Substrate of CYP3A4 and P-gp in Healthy Male Volunteers [NCT03237416]Phase 115 participants (Actual)Interventional2017-08-02Completed
Physiological Study of the Human CYP3A Activity (PiSA) [NCT03204578]Phase 412 participants (Actual)Interventional2017-08-18Completed
An Investigator-and-subject Blind, Phase 1 Study To Characterize The Safety, Tolerability, Pharmacokinetics, And Pharmacodynamics Of Repeat Doses Of Pf-06648671 In Healthy Adult Subjects And Healthy Elderly Subjects [NCT02440100]Phase 192 participants (Anticipated)Interventional2015-05-31Completed
A Non-Randomized, Multiple-Dose, Open-Label, Single Sequence Study to Evaluate the Effect of Concomitant Administration of EDP-305 on the Pharmacokinetics and Safety of Midazolam, Caffeine, and Rosuvastatin in Healthy Human Volunteers [NCT03187496]Phase 124 participants (Actual)Interventional2017-05-11Completed
Cocktail Phenotypic Approach to Explore Antidepressant Pharmacokinetic Variability: a Pilot Study [NCT02438072]100 participants (Anticipated)Interventional2014-12-31Recruiting
Effects of Midazolam or Tramadol Premedication on Early Cognitive Function in ERCP: a Randomized Controlled Double-Blind Study [NCT02436980]Phase 440 participants (Actual)Interventional2009-01-31Completed
The Use of Propofol/Ketamine Anesthesia With Bispectral Monitoring (PKA-BIS) Versus Inhalational Anesthetics in Rhytidoplasty - A Prospective, Double-blinded, Randomized Comparison Study [NCT02410460]30 participants (Actual)Interventional2013-09-30Completed
Premedication With Intranasal Dexmedetomidine or Midazolam for Prevention of Emergence Agitation in Children: Superiority Randomized Clinical Trial [NCT03171740]Phase 322 participants (Actual)Interventional2017-06-01Completed
A Double-Blind, Randomized, Placebo-Controlled, Single- And-Multiple-Dose Study to Evaluate the Safety, PK, and PD of CRN00808 in Healthy Volunteers and to Determine the Effect of CRN00808 on Midazolam PK [NCT03276858]Phase 199 participants (Actual)Interventional2017-09-22Completed
Randomized Controlled Trial of Repeated Dose Ketamine in Post Traumatic Stress Disorder (PTSD) [NCT02398136]Phase 2/Phase 30 participants (Actual)Interventional2014-12-31Withdrawn(stopped due to FDA and IRB recommended different mode of medication administration)
Effect of Ketamine on Fatigue Following Cancer Therapy [NCT02317341]Early Phase 12 participants (Actual)Interventional2014-12-13Terminated
A Randomized, Double-blind, Placebo-controlled Study to Assess Safety, Tolerability, Pharmacokinetics and Exploratory Pharmacodynamics of Multiple Oral Doses of BAY1834845 in Healthy Male Subjects and in Female and Male Patients With Psoriasis Over an Ext [NCT03493269]Phase 172 participants (Actual)Interventional2018-04-16Completed
Effects of Concomitant Administration of BMS-986195 on the Single-dose Pharmacokinetics of Methotrexate and Probe Substrates for Cytochrome P450 1A2, 2C8, 2C9, 2C19, 3A4, Organic Anion Transporter Polypeptide 1B1 and P-glycoprotein in Healthy Participants [NCT03131973]Phase 126 participants (Actual)Interventional2017-05-13Completed
Comparative Evaluation of Three Anxiety Control Protocols in Third Molar Extraction With Midazolam, Diazepam and Nitrous Oxide - Randomized Clinical Trial. [NCT03165500]Early Phase 13 participants (Actual)Interventional2015-12-23Completed
The Effect of Midazolam Premedication on Copeptine Concentration in Blood [NCT03474939]Phase 440 participants (Actual)Interventional2017-04-03Completed
"Effectiveness Study HospiAvontuur: Validation of a Serious Game for the Preparation of Children (4 - 6 Year Old) for a Hospital Admission for an Elective Surgical Procedure (ORL Surgery)." [NCT03671057]164 participants (Anticipated)Interventional2017-10-01Recruiting
Intramuscular Olanzapine Versus Haloperidol or Midazolam for the Management of Acute Agitation in the Emergency Department - a Multicentre Randomised Clinical Trial [NCT02380118]Phase 4167 participants (Actual)Interventional2014-12-31Terminated(stopped due to Primary endpoint reached based on data projection from interim analysis.)
Intranasal Midazolam in Children as a Pre-Operative Sedative - Part 2 [NCT02356705]Phase 442 participants (Actual)Interventional2015-01-31Completed
Evaluation of the Effect of Ixekizumab on the Pharmacokinetics of Cytochrome P450 Substrates in Patients With Moderate-to-Severe Plaque Psoriasis [NCT02993471]Phase 128 participants (Actual)Interventional2016-12-22Completed
An Open Labe Study to Evaluate the Drug-Drug Interaction of Itraconazole, Rifampicin and Midazolam With SIM0417/Ritonavir in Healthy Adult Chinese Participants [NCT05665647]Phase 136 participants (Actual)Interventional2022-12-29Completed
Population Pharmacokinetics and Pharmacodynamics of Sorafenib in HCC Patients With Child-Pugh B Liver Cirrhosis (SORBE-trial) [NCT04051853]Phase 25 participants (Actual)Interventional2014-05-31Terminated(stopped due to Slow accrual.)
Phase 1, Open-Label, Comparison Study to Evaluate the Safety and Pharmacokinetics of a Single Intramuscular Administration of 10 mg Midazolam Using an Auto-Injector vs Marketed Midazolam Vials in Healthy Adults. [NCT04679623]Phase 140 participants (Actual)Interventional2021-06-09Completed
Psilocybin Versus Ketamine - Fast Acting Antidepressant Strategies in Treatment-resistant Depression [NCT05383313]Phase 260 participants (Anticipated)Interventional2021-05-01Recruiting
Comparison of the Effectiveness of the Use of Ropivacaine and Midazolam by Intraarticular vs Epidural Administration on Post-operative Analgesia After Isolated Arthroscopic ACL Reconstruction With Hamstring Autograft. [NCT05078372]Phase 2108 participants (Actual)Interventional2019-01-31Completed
Single Centre Open-label, Non-randomised, 3-treatment, 2-period, Pharmacokinetic Drug Interaction Study of Single Oral Dose of Acoziborole With Sequential Co-administration of Midazolam and Dextromethorphan in Healthy Male Participants [NCT05947604]Phase 120 participants (Actual)Interventional2023-02-09Completed
The Effect of Multiple Doses of BI 730357 on the Single Dose Pharmacokinetics of Caffeine, Warfarin, Omeprazole and Midazolam Administered Orally as a Cocktail in Healthy Subjects (an Open-label, Two-period Fixed Sequence Design Trial) [NCT04679948]Phase 116 participants (Actual)Interventional2020-12-21Completed
Effects of Dexmedetomidine Sedation on Delirium and Haemodynamic in Mechanical Ventilated Elderly Patients -a Single Center,Randomized and Controlled Trial [NCT02225210]Phase 480 participants (Anticipated)Interventional2014-09-30Not yet recruiting
INFLAMMATION AND DRUG METABOLISM - Does the Effect of Drugs Decrease When Patients With Type 2 Diabetes Initiate Antidiabetic Treatment? [NCT04504045]Phase 110 participants (Actual)Interventional2020-09-01Terminated(stopped due to Slow recruitment due to COVID-19, the study was stopped when recruited numbers fulfilled the pre-defined lower sample size.)
A Phase 1, Open-Label, Two-Period, Fixed-Sequence, Drug-Drug Interaction Study to Evaluate the Pharmacokinetics and Safety of CTX 4430 and Midazolam in Healthy Adult Subjects [NCT02233244]Phase 120 participants (Actual)Interventional2014-09-30Completed
Pharmacokinetics of 7.5 mg Midazolam, Given Orally With and Without Concomitant Administration of 175 mg Crobenetine, Given as a 6 Hrs i.v. Infusion (One Hour Loading Dose Directly Followed by a Five Hours Maintenance Dose). A Randomised, Single Blind, Tw [NCT02269202]Phase 120 participants (Actual)Interventional2002-02-28Completed
Ketamine for Combined Depression and Alcohol Use Disorder: A Blinded Randomized Active Placebo-controlled Trial (the KeDA Trial) [NCT06090422]Phase 1/Phase 234 participants (Anticipated)Interventional2024-01-01Not yet recruiting
Opioid vs. Benzodiazepine-based Sedation for Mechanically Ventilated Patients in the Internal Medicine Ward [NCT04983615]50 participants (Anticipated)Interventional2021-08-01Recruiting
Multiple Dose Escalation Study in a Randomized, Double-blind, Placebo-controlled Design to Investigate Safety, Tolerability, Pharmacokinetics, Drug-drug Interaction and Exploratory Pharmacodynamics of Multiple Oral Doses of BAY1830839 in Healthy Male Part [NCT03965728]Phase 167 participants (Actual)Interventional2019-06-05Completed
The Effect of Multiple Oral Doses of BI 425809 on Metabolism of Midazolam Administered Orally in Healthy Male Subjects (Open-label, Two-period, One-sequence Trial) [NCT05258110]Phase 115 participants (Actual)Interventional2022-03-18Completed
A Phase I, Open Label Study to Assess the Effects of TA-8995 on the Pharmacokinetics of Midazolam and Digoxin in Healthy Male Subjects [NCT02124954]Phase 118 participants (Actual)Interventional2014-05-31Completed
The Safety and Effectiveness of Remimazolam Tosilate Versus Midazolam in Elderly Patients Undergoing Gastrointestinal Endoscopy: A Multicenter ,Prospective, Double-Blinded, Randomized Controlled Study [NCT04656964]353 participants (Actual)Interventional2021-04-01Completed
Effects of Type 2 Diabetes on CYP450s Activities; Intersubject Variability in Drug Metabolism. [NCT02291666]Phase 473 participants (Actual)Interventional2015-04-30Completed
A Single-centre, Open-label, Fixed-sequence Trial to Evaluate the Impact of C21 on the Exposure of CYP1A2, CYP2C9, CYP3A4 and P-gp Substrates in Healthy Volunteers [NCT05830799]Phase 118 participants (Actual)Interventional2023-03-29Completed
The Effect of Remimazolam on Postoperative New-onset Atrial Fibrillation in Patients Undergoing Coronary Artery Bypass Grafting [NCT05891145]50 participants (Anticipated)Interventional2023-02-01Recruiting
A Phase II, Open-Label, Multicenter, Escalating Dose, Study to Determine Pharmacokinetic and Pharmacodynamic Profile of Dexmedetomidine in Pediatric Subjects Ages ≥ 2 Through < 17 Years Old [NCT00652028]Phase 269 participants (Actual)Interventional2008-11-30Completed
A Single-Center, Randomized, Double-Blind, Single and Multiple Ascending Dose, Placebo-Controlled Study to Investigate the Safety, Tolerability and Pharmacokinetics of RO6889678 and the Combination of RO6889678 With Ritonavir Following Oral Administration [NCT02321384]Phase 1100 participants (Actual)Interventional2014-12-15Terminated
Does Preoperative Midazolam Dose Affect Postoperative Pain? - a Multicentric Observational Study in Open Inguinal Hernia Repair [NCT03499730]300 participants (Actual)Observational2018-09-12Completed
A Phase 1, Open-Label, Single-Center, 2-Period, Single-Sequence Drug-Drug Interaction Study to Evaluate the Effects of Multiple-Dose Telotristat Etiprate on the Pharmacokinetics of Single-Dose Midazolam, a Sensitive P450-3A4 Substrate, in Healthy Male and [NCT02147808]Phase 124 participants (Actual)Interventional2014-05-31Completed
Effects of Different Premedication on Preoperative Sedation and Postoperative Agitation in Children Undergoing Ophthalmic and Otorhinolaryngologic Operations [NCT04266340]320 participants (Actual)Interventional2020-12-13Completed
A Two Cohort, Open-Label, Fixed Sequence Study to Investigate the Effect of CYP3A4 Inhibition on the Single Dose Pharmacokinetics of ASTX660 and the Effect of a Single Dose of ASTX660 on the Pharmacokinetics of the CYP3A4 Substrate Midazolam [NCT04411030]Phase 136 participants (Actual)Interventional2020-05-20Completed
A Phase I, Open Label Study to Assess the Effects of PQ912 on the Pharmacokinetics of Midazolam and Omeprazole in Healthy Male Subjects [NCT02190708]Phase 118 participants (Actual)Interventional2014-06-30Completed
Randomized, Double-Blind, Placebo-Controlled Multiple Ascending Dose Study to Evaluate the Safety, Tolerability and Pharmacokinetics of Multiple Oral Doses of BMS-986120 in Healthy Subjects and the Effect of BMS-986120 on the Pharmacokinetics of Midazolam [NCT02208882]Phase 124 participants (Actual)Interventional2014-08-31Completed
Comparison of Granisetron Versus Midazolam and Thier Combination for Prophylaxis of Postoperative Nausea and Vomiting in Laparoscopic Surgery in Children [NCT03483350]Phase 390 participants (Anticipated)Interventional2018-03-31Not yet recruiting
A Fixed Sequence, Open-label Study to Assess the Effect of Multiple Doses of AZD4831 on the Pharmacokinetics of Oral Midazolam (a CYP450 3A Probe) in Healthy Subjects [NCT05052710]Phase 114 participants (Actual)Interventional2021-10-05Completed
Reducing Adolescent Suicide Risk: Safety, Efficacy, and Connectome Phenotypes of Intravenous Ketamine [NCT04613453]Phase 266 participants (Anticipated)Interventional2022-01-21Recruiting
Impact of Preoperative Midazolam on Outcome of Elderly Patients: a Multicentre Randomised Controlled Trial [NCT03052660]Phase 4782 participants (Actual)Interventional2017-10-12Completed
[NCT02050893]Phase 1/Phase 240 participants (Actual)Interventional2012-05-31Completed
Clinical Trials on Evaluate the Red Ginseng and Fermented-Red Ginseng Affect to Drug Metabolizing Enzyme and Transporter in Healthy Volunteers; Open-label, Parallel Group [NCT02056743]Phase 130 participants (Actual)Interventional2013-09-30Completed
A Randomized, Double-blind, Controlled Trial of Cycling Continuous Sedative Infusions in Critically Ill Pediatric Patients Requiring Mechanical Ventilation [NCT01333059]25 participants (Actual)Interventional2010-09-30Terminated(stopped due to Unable to adequately enroll over a reasonable enrollment period.)
US Guided Interscalene Block Compared With Sedation for Shoulder Dislocation Reduction in the ER [NCT03041506]90 participants (Anticipated)Interventional2017-02-15Not yet recruiting
An Open Label Benzodiazepine Study for the Treatment of Seizure Clusters in a Third Level Mexican Neurological Center [NCT06056349]150 participants (Anticipated)Interventional2023-05-01Recruiting
Anxiolysis for Laceration Repair in Children: A Multicenter Adaptive Randomized Trial [NCT05383495]Phase 3300 participants (Anticipated)Interventional2023-11-20Recruiting
Sedation Versus Protective Stabilization for Dental Treatment of Children With Caries and Negative Behavior at the Dentist: a Non-randomized Clinical Trial [NCT04119180]Phase 4152 participants (Anticipated)Interventional2020-01-30Recruiting
Assessment of the Effects of Melatonin on Preoperative Anxiety and Postoperative Analgesia in Children Undergoing Surgery: a Prospective, Randomized Clinical Trial [NCT02265822]Phase 492 participants (Actual)Interventional2012-09-30Completed
Low-dose Ketamine Infusion Among Adolescents With Treatment-resistant Depression: a Randomized, Double-blind Placebo-control Study [NCT05045378]Phase 454 participants (Anticipated)Interventional2022-03-15Recruiting
Three-level Injection Paravertebral Block Using Paravertebral Catheter Compared to General Anesthesia in Mastectomy Surgery [NCT02065947]Phase 1/Phase 260 participants (Actual)Interventional2013-10-31Completed
[NCT02071407]Phase 460 participants (Anticipated)Interventional2013-10-31Recruiting
The Effect of Three Different Interventions on Preoperative Anxiety in Children [NCT03530670]Phase 4138 participants (Actual)Interventional2018-08-06Completed
The Effect of Three Different Interventions on the Recovery Agitation and Delirium in the Pacu Pediatric Patients [NCT03426020]Phase 490 participants (Anticipated)Interventional2018-02-20Not yet recruiting
A Multiple-Dose Drug-Drug Interaction Study to Determine the Effect of LY3437943 on Drug Metabolizing Enzymes [NCT05445232]Phase 132 participants (Actual)Interventional2022-07-08Completed
A Phase I, Multicenter, Open-label, Single-sequence Drug-drug Interaction Study to Assess the Effect of INC280 on the Pharmacokinetics of Midazolam and Caffeine in Patients With cMET-dysregulated Advanced Solid Tumors [NCT02520752]Phase 137 participants (Actual)Interventional2015-12-10Completed
Comparison of Intranasal Midazolam or Dexmedetomidine on Epileptiform EEG During Sevoflurane Mask Induction in Children [NCT03394430]Phase 445 participants (Anticipated)Interventional2018-10-01Not yet recruiting
The Psychological Effects of Different Sedation Protocol on Mechanically Ventilated Critically Ill adults-a Prospective, Randomized and Controlled Trial [NCT02123589]Phase 4150 participants (Anticipated)Interventional2014-04-30Not yet recruiting
The Efficacy OF Oral DexmedetomidineVersus Oral Midazolam/Ketamine ON Parental Separation AND Face Mask Acceptance IN Pediatrics Undergoing Adenotonsillectomy [NCT03551067]Phase 474 participants (Actual)Interventional2016-08-01Completed
Quadratus Lumborum Block Versus Local Anesthetic Infiltration Combined With Monitored Anesthesia Care for Percutaneous Nephrostomy [NCT02121951]Phase 40 participants (Actual)Interventional2014-05-31Withdrawn
Effect of Midazolam on Inflammatory Response and Organ Function in Mechanically Ventilated Sepsis Patients With Different Immune Status. [NCT02135055]Phase 480 participants (Anticipated)Interventional2014-05-31Not yet recruiting
Adjunctive Sedation With Dexmedetomidine for the Prevention of Severe Inflammation and Septic Encephalopathy: a Pilot Randomized Controlled Study. [NCT04076826]70 participants (Actual)Interventional2019-09-01Completed
Ketamine Therapy in Obsessive-compulsive Disorder and Its Effects on Neuropsychological Function Under Stress in a Cross-over Trial [NCT05577585]30 participants (Anticipated)Interventional2022-08-01Recruiting
Effects of Dexmedetomidine at Different Doses on Hemodynamics and Recovery Quality in Elderly Patients Undergoing Hip Replacement Surgery Under General Anesthesia [NCT05567523]Phase 4200 participants (Actual)Interventional2019-06-01Completed
Ketamine's Efficiency in the Treatment of Chronic Pain With an Added Inflammatory Component Exploring the Kynurenin Pathway. A Randomized, Double Blind, Placebo-controlled Trial [NCT03513822]Phase 348 participants (Anticipated)Interventional2018-02-16Recruiting
Identification and Evaluation of Endogenous Markers for the Assessment of CYP3A Activity Using Metabolomics [NCT01215214]Phase 124 participants (Anticipated)Interventional2010-10-31Completed
A Single-center, Open-label Study to Investigate the Effect of Single- and Multiple-dose Daridorexant on the Pharmacokinetics of Midazolam and Its Metabolite 1-hydroxymidazolam, and the Effect of Single-dose Daridorexant on the Pharmacokinetics and Pharma [NCT05480488]Phase 118 participants (Actual)Interventional2022-08-23Completed
Propofol Versus Midazolam for Upper Endoscopy in Cirrhotic Patients [NCT01141036]60 participants (Anticipated)Interventional2008-07-31Completed
A Randomized Controlled Trial: Role of EFTs (Emotional Freedom Techniques) in Reducing Postoperative Nausea and Vomiting After Laparoscopic Cholecystectomy. [NCT02169856]50 participants (Actual)Interventional2013-07-31Completed
Evaluation of the Effects of Single Oral Dose and Multiple Oral Doses of BI 201335 NA on Cytochrome P450 and P-glycoprotein Activity Using a Probe Drug Cocktail. An Open-label, Single-arm Phase I Study in Healthy Human Volunteers [NCT02182336]Phase 123 participants (Actual)Interventional2008-06-30Completed
A Study to Evaluate the Effect of Multiple Doses of 500 mg of BIRT 2584 XX Tablets on the Pharmacokinetic Parameters of Midazolam in Healthy Male Volunteers [NCT02256748]Phase 120 participants (Actual)Interventional2005-06-30Completed
Two-part, Double-blind, Placebo-controlled, Randomized, Parallel-group Study: (Part 1) in Healthy Male Subjects to Assess Safety and Tolerability of Ascending Repeated Oral Doses of BAY1902607 Including Its Effect on the Pharmacokinetics of a Sub-therapeu [NCT03535168]Phase 1/Phase 259 participants (Actual)Interventional2018-05-29Completed
Reduction of Preoperative Anxiety in Children: Electronic Tab vs Midazolam [NCT02192710]Phase 3118 participants (Actual)Interventional2013-05-31Completed
The Effect of Intravenous Ketamine on Non-suicidal Self-injuries in Women Suffering From Complex Post Traumatic Stress Disorder (cPTSD) [NCT04242914]Phase 1/Phase 230 participants (Anticipated)Interventional2019-02-25Recruiting
Effects of Premedication by Midazolam on Preoperative Anxiety for Emergency Surgery [NCT02213302]Phase 459 participants (Actual)Interventional2014-07-31Completed
[NCT02226328]Phase 4128 participants (Anticipated)Interventional2014-11-30Recruiting
A Drug-Drug Interaction Study To Investigate The Ginkgolides Meglumine Injection To Alter The Pharmacokinetics Of Midazolam. [NCT02233972]Phase 415 participants (Actual)Interventional2014-08-31Completed
Use of Sevoflurane, Midazolam and Ketamine in Children for Dental Sedation Treatment: Occurrence of Adverse Events [NCT02284204]Phase 227 participants (Actual)Interventional2012-01-31Completed
A Comparison of the Sedative Effect of Ketamine and Midazolam During Spinal Anaesthesia for Elective Unilateral Inguinal Hernia Repair: A Randomized Comparative Trial [NCT03133780]Phase 280 participants (Actual)Interventional2018-07-14Completed
Observational Study to Understand Acceptability of Various Available Midazolam Formulations (Syrup, Rectal Suppository, Oro-dispersible Tablet) in Clinical Practice [NCT05894057]100 participants (Anticipated)Observational2023-06-06Recruiting
Sodium Oxybate Versus Midazolam for Comfort Sedation [NCT05085873]Phase 422 participants (Actual)Interventional2021-10-14Completed
Effect of Gender-Affirming Testosterone Therapy on Drug Metabolism, Transport, and Gut Microbiota [NCT05116293]12 participants (Anticipated)Observational2021-05-01Active, not recruiting
Comparison of Oral 30 % Dextrose and iv Midazolam Sedation During MRI in Neonates [NCT02645279]Phase 4112 participants (Actual)Interventional2015-01-31Active, not recruiting
The Impact of Anesthesia on the Absorption of Glycine in Operative Hysteroscopy: a Randomized Controlled Trial [NCT01124383]95 participants (Actual)Interventional2008-08-31Completed
Interventional Bronchoscopy Under Noninvasive Ventilation for Central Airway Stenosis [NCT02289586]40 participants (Anticipated)Interventional2014-07-31Recruiting
Intranasal Versus Nebulized Midazolam in Behaviuor Modification of Preschool Children Undergoing Dental Treatment: A Randomized Clinical Trial [NCT05883150]Phase 2/Phase 368 participants (Actual)Interventional2022-11-10Completed
A Single Center, Open-label, 3-period Fixed-sequence, Phase I Clinical Study to Evaluate the Effect of BV100 on the Pharmacokinetics of Midazolam and Its Metabolite 1-hydroxymidazolam in Healthy Volunteers [NCT05537090]Phase 116 participants (Actual)Interventional2022-09-01Completed
A Randomized Controlled Trial of the Effect of Dexmedetomidine Compared With Midazolam on Airway Reflex and Recovery Quality During Emergence From General Anesthesia After Partial and Total Laryngectomy [NCT03918889]120 participants (Anticipated)Interventional2019-05-01Enrolling by invitation
Nalbuphine Versus Midazolam as an Adjuvant to Intrathecal Bupivacaine for Postoperative Analgesia in Patients Undergoing Cesarean Section [NCT03918187]Phase 190 participants (Actual)Interventional2019-04-10Completed
A Phase I Open-Labeled, Fixed Sequence Study to Determine the Effect of Multiple Doses of AZD7325 on the Pharmacokinetics of Midazolam (CYP3A4) and Caffeine (CYP1A2) [NCT00790114]Phase 124 participants (Actual)Interventional2008-07-31Completed
Nasogastric Tube Insertion Using Midazolam in the Emergency Department [NCT01375634]Phase 449 participants (Actual)Interventional2011-05-31Completed
A Phase 1, Open-label, Fixed-Sequence, Drug-Drug Interaction Study Between Multiple Oral Doses of Inarigivir Soproxil and a Single Oral Dose of Midazolam in Healthy Subjects [NCT03493698]Phase 117 participants (Actual)Interventional2018-05-07Completed
A Study in Healthy Female Participants to Investigate the Effect of JNJ-64530440 on the Single-dose of Ethinylestradiol and Drospirenone (Oral Contraceptive), and Midazolam, and the Effect of a High-fat Meal on the Single-dose of JNJ-64530440 [NCT03890341]Phase 10 participants (Actual)Interventional2021-06-01Withdrawn(stopped due to Stopped due to a strategic decision.)
Could Music be an Alternative to Sedation in Patients Treated Total Knee Arthroplasty With Regional Anesthesia?: A Randomized Clinical Trial [NCT03882541]85 participants (Actual)Interventional2017-01-08Completed
Therapeutic Drug Monitoring of Anxiolytics in Children [NCT03960671]Phase 4500 participants (Anticipated)Interventional2018-08-01Recruiting
A Fixed-Sequence Trial to Examine the Effect of Multiple-Dose CT1812 Administration on Standard Probes of CYP2C19 (Omeprazole), CYP2C9 (Tolbutamide), CYP2D6 (Dextromethorphan), and CYP3A4/5 (Midazolam) Activity in Healthy Adult Volunteers [NCT03716427]Phase 116 participants (Actual)Interventional2016-11-10Completed
Effect of an Adjunctive Sedative for the Patients With Histories of Paradoxical Reaction to Midazolam During Sedative Endoscopy [NCT03940391]220 participants (Anticipated)Interventional2019-05-01Enrolling by invitation
Variation of the Neutrophil To Lymphocyte Ratio During Opioid-Free General Anesthesia Associated With Thoracic Wall Blocks Vs General Anesthesia, in Breast Cancer Quadrantectomy: a Randomized Controlled Trial [NCT04172220]68 participants (Actual)Interventional2019-10-31Completed
Impact of Adding Midzolam to Bupavicaine 0.5% in Regional Spinal Anaesthesia on Maternal Middle Cerebral Artery Velocimetry in Parturients With Severer Preeclampsia [NCT04283110]100 participants (Anticipated)Interventional2019-01-12Recruiting
Comparison of Palonosetron With Combined Palonosetron and Midazolam for Preventing Postoperative Nausea and Vomiting After Laparoscopic Cholecystectomy [NCT03933605]88 participants (Actual)Interventional2017-07-10Completed
Determination Of The 90% Effective Sedation Dose Of Midazolam In Patients Undergoing Diagnostic Upper Gastric-Endoscopy [NCT03813043]40 participants (Anticipated)Interventional2019-02-15Not yet recruiting
Midazolam Effect on Agitation Postnasal Surgery: A Double Blinded Randomized Controlled Trial [NCT05165914]100 participants (Actual)Interventional2021-05-27Completed
The Effect of Bispectral Index Controlled Sedation on QT Distance and P Dispersion in ECG in Patients Having Bronchoscopy in the Intensive Care Unit [NCT05434624]40 participants (Anticipated)Interventional2022-06-25Enrolling by invitation
Midazolam Used Alone or Sequential Use of Midazolam and Propofol/Dexmedetomidine for Long-Term Sedation in Critically Ill, Mechanically Ventilated Patients: a Prospective, Randomized Study [NCT02528513]Phase 4240 participants (Anticipated)Interventional2015-12-31Enrolling by invitation
Phase II Study of Comparison of Two Sedation Regimen for Transesophageal Echocardiography in Point of View of Blood Pressure Response, Safety and Patient Comfort [NCT01567657]Phase 2200 participants (Actual)Interventional2012-01-31Completed
A Study to Assess the Pharmacokinetics of Midazolam, Dabigatran, Pitavastatin, Atorvastatin, and Rosuvastatin Administered as Microdoses in Subjects With Varying Degrees of Renal Insufficiency in the Presence and Absence of Rifampin [NCT03311841]Phase 132 participants (Actual)Interventional2018-03-01Completed
PECS Block vs. Multimodal Analgesia for Prevention of Persistent Postoperative Pain in Breast Surgery [NCT03084536]Phase 2134 participants (Actual)Interventional2017-06-07Completed
An Open-label, Single Sequence, Crossover Drug-drug Interaction Study Assessing the Effect of Pexidartinib on the Pharmacokinetics of CYP3A4 and CYP2C9 Substrates in Patients [NCT03291288]Phase 132 participants (Actual)Interventional2018-02-26Completed
The Effects of Esketamine Sedation Compared With Fentanyl Sedation in Pediatric Dental Patients: A Double Blind, Randomized Controlled Trial [NCT04597320]Phase 448 participants (Actual)Interventional2022-01-01Completed
Lecturer of Anesthesia ,Intensive Care and Pain Management in Faculty of Medicine Ain Shams University [NCT03860831]Phase 140 participants (Anticipated)Interventional2019-03-06Recruiting
Propofol Versus Midazolam Plus Alfentanil for Sedation During Flexible Bronchoscopy: Respiratory Depression Comparison Inspected by Cutaneous Carbon Dioxide Tension Level [NCT01289327]115 participants (Actual)Interventional2010-04-30Completed
Oral Dexmedetomidine vs Midazoam For Premedication And Emergence Delirium in Children Undergoing Dental Treatment [NCT03357718]Phase 452 participants (Actual)Interventional2016-11-01Completed
An Open-label Study to Evaluate the Pharmacokinetics, Safety and Tolerability of BAY 1817080 in Participants With Impaired Hepatic Function (Classified as Child-Pugh A, B or C) in Comparison to Matched Controls With Normal Hepatic Function [NCT04454424]Phase 137 participants (Actual)Interventional2020-07-23Completed
Safety, Tolerability and Pharmacokinetics of Multiple Rising Oral Doses of BI 1595043 (Double-blind, Randomised, Placebocontrolled, Parallel Group Design) in Healthy Male Subjects [NCT04789304]Phase 130 participants (Actual)Interventional2021-04-01Completed
Intranasal vs Buccal vs Intramuscular Midazolam for the Home and Emergency Treatment of Acute Seizures in Pediatric Egyptian Patients [NCT05670509]Phase 4305 participants (Actual)Interventional2019-01-19Completed
A Phase I, Randomized, Placebo-controlled, Multiple Ascending Dose Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of AMG 581 in Healthy Subjects or Subjects With Schizophrenia or Schizoaffective Disorder on Antipsychotic Medication [NCT02504476]Phase 152 participants (Actual)Interventional2015-08-31Completed
[NCT02504164]72 participants (Actual)Interventional2014-09-30Completed
The Effectiveness of Topical Lidocaine in Relieving Pain Related To Intranasal Midazolam Sedation: A Randomized, Placebo-Controlled Clinical Trial [NCT03725995]Phase 2/Phase 363 participants (Actual)Interventional2017-06-01Completed
The Effect of Mild Sedation and Analgesia on Radial Artery Cannulation in Novice Operators [NCT05863455]100 participants (Anticipated)Interventional2023-05-17Recruiting
Comparison of Dexmedetomidine and Midazolam for Prevention of Emergence Delirium in Children [NCT03337672]70 participants (Actual)Interventional2017-12-05Completed
A Phase I/II Multi-center Study of HDM201 Added to Chemotherapy in Adult Subjects With Relapsed/Refractory (R/R) or Newly Diagnosed Acute Myeloid Leukemia (AML) [NCT03760445]Phase 1/Phase 20 participants (Actual)Interventional2019-11-15Withdrawn(stopped due to It was determined that the study design may not be optimal given the changing AML treatment landscape.)
Standardised Drug Provocation Testing in Perioperative Hypersensitivity [NCT06065137]Phase 450 participants (Anticipated)Interventional2023-10-31Not yet recruiting
Effects on Recovery of Children Undergoing Elective Surgery: Comparison of Intravenous Formulation of Fentanyl Citrate and Midazolam Administered Orally for Premedication [NCT05500599]60 participants (Anticipated)Interventional2022-03-01Active, not recruiting
Ketamine for Treatment Resistant Late-Life Depression [NCT02556606]Phase 333 participants (Actual)Interventional2015-10-01Completed
Clowns as Treatment for Preoperative Anxietyin Children- a Randomized Controlled Trial [NCT00609960]65 participants (Actual)Interventional2006-01-31Completed
A Phase 1, Open-label, Drug-Drug Interaction Study to Investigate the Effect of Rocatinlimab (AMG 451) on the Pharmacokinetics of Multiple CYP450 Substrates in Patients With Moderate to Severe Atopic Dermatitis [NCT05891119]Early Phase 120 participants (Anticipated)Interventional2023-06-03Recruiting
A Phase 1, Randomized, Double-blind, Placebo-controlled, Single- and Multiple-dose Escalation Study Evaluating the Safety, Pharmacokinetics, and Pharmacodynamics of VX-973 in Healthy Adults [NCT05866055]Phase 180 participants (Anticipated)Interventional2023-05-10Recruiting
A Phase 1, Single-center, Open-label, Sequential Study to Evaluate the Drug-drug Interaction Potential of BMS-986196 in Healthy Participants [NCT05852769]Phase 118 participants (Actual)Interventional2023-05-31Completed
A Single-center, Single-arm, Open-label, Fixed-sequence, Self-controlled Study of the Effects of HRS5091 on the Pharmacokinetics of Midazolam, S-warfarin, Omeprazole, Digoxin and Rosuvastatin in Healthy Volunteers [NCT05273775]Phase 122 participants (Actual)Interventional2022-04-29Completed
To Compare Pharmacological and Non-Pharmacological Interventions (Use of Technology) For Alleviating Preoperative Anxiety In Children Undergoing General Anesthesia In A Tertiary Care Hospital Of Pakistan: A Randomized Controlled Trial. [NCT05469412]84 participants (Anticipated)Interventional2023-03-20Recruiting
Late Onset Postoperative Nausea and Vomiting Following Strabismus Surgery in Pediatric.What Combination is Better [NCT00918190]75 participants (Anticipated)Interventional2009-06-30Completed
A Phase 1, Open-label Study in Healthy Adult Subjects to Evaluate Effects of Cytochrome P450 Inhibition and Induction on the Pharmacokinetics of CC-99677 and the Effects of CC-99677 on the Pharmacokinetics of Digoxin, Metformin, Methotrexate, Midazolam, R [NCT04268394]Phase 148 participants (Actual)Interventional2020-03-13Completed
The Effect of Repeat Dosing of Imlunestrant on CYP3A Activity in Healthy Women of Non-childbearing Potential [NCT05509816]Phase 120 participants (Actual)Interventional2022-09-12Completed
Nitrous Oxide for Posttraumatic Stress Disorder (PTSD): A Phase IIa Trial [NCT04378426]Phase 21 participants (Actual)Interventional2021-10-07Terminated(stopped due to Use of VA hospital research space is indefinitely delayed due to prioritization of clinical cases delayed by COVID)
Hemodynamic Change Between Loading of Dexmedetomidine or Midazolam as a Sedative Agents During Knee Arthroscopy [NCT02634021]Phase 40 participants (Actual)Interventional2015-07-31Withdrawn(stopped due to The investigator had no more scientific interest about this issue.)
Intervention Study to Relieve Pain and Anxiety in Acute Myocardial Disease Focusing on Treatment With Benzodiazepines(Midazolam)and the Importance of a Caring Relation. [NCT00792181]Phase 12,800 participants (Anticipated)Interventional2008-06-30Completed
A Randomized, 5-Part, Intravenous Study of the Safety, Tolerability, Bioequivalence, and Drug Interaction Potential of Final Market Image Formulation of MK0517 in Young Healthy Subjects [NCT00990821]Phase 1188 participants (Actual)Interventional2005-01-31Completed
A NON-RANDOMIZED, MULTIPLE-DOSE, OPEN-LABEL, SINGLE SEQUENCE STUDY TO EVALUATE THE EFFECT OF CONCOMITANT ADMINISTRATION OF EDP-235 ON THE PHARMACOKINETICS AND SAFETY OF MIDAZOLAM, CAFFEINE, AND ROSUVASTATIN IN HEALTHY PARTICIPANTS [NCT05594615]Phase 124 participants (Actual)Interventional2022-10-06Completed
Prospective, Randomized, Open Label Controlled Trial To Evaluate The Safety And Efficacy Of Dexmedetomidine Use Beyond 24 Hours Compared With Midazolam In Children Admitted To Pediatric Intensive Care Unit (PICU) at KASCH-MNGHA. [NCT05485519]Phase 3430 participants (Anticipated)Interventional2022-04-21Recruiting
An Open-label, Single-sequence Study to Assess the Effect of Multiple Doses of Tradipitant on Cytochrome P450 3A4 Using Midazolam as a Substrate in Healthy Subjects. [NCT02621385]Phase 124 participants (Actual)Interventional2015-11-30Completed
Randomized Trial Comparing Intermittent Sedation and Daily Interruption of Sedation in Mechanically Ventilated Patients [NCT00824239]Phase 360 participants (Actual)Interventional2008-09-30Completed
Prevention of Emergence Delirium in Pediatric Ambulatory Surgery: Single Blinded Randomized Control Study Comparing Intra-nasal Dexmedetomidine With Oral Midazolam. [NCT04669457]Phase 460 participants (Anticipated)Interventional2021-04-27Recruiting
Bronchoscopy Under Titrated Sedation With Propofol or Midazolam: a Randomized Trial. [NCT00839371]Phase 484 participants (Actual)Interventional2005-01-31Completed
Dose-Finding Study of Intranasal Midazolam for Procedural Sedation in Children [NCT04586504]Phase 1/Phase 2150 participants (Anticipated)Interventional2021-09-08Recruiting
The Effect of Multiple Oral Doses of BI 1015550 on Metabolism of Midazolam Administered Orally in Healthy Male Subjects (Open-label, Two-period Fixed Sequence Design Trial) [NCT05550636]Phase 115 participants (Actual)Interventional2022-10-11Completed
Randomized Clinical Trial Comparing Propofol and Midazolam in Mechanically Ventilated Critically Ill Patients With Alcohol Use Disorders: An Open Label Pilot Study [NCT00871039]Phase 40 participants (Actual)Interventional2009-03-31Withdrawn(stopped due to Due to logistical purposes)
To Serenade or To Sedate? That is Still The Question - A Followup Trial On Anxiolytic Options Before Peripheral Nerve Blocks [NCT05610969]Phase 1/Phase 2160 participants (Anticipated)Interventional2021-09-01Recruiting
Effect of Midazolam Premedication on Opioid-induced Mask Ventilation Difficulty During General Anesthesia Induction: A Randomized Clinical Trial [NCT05369819]Phase 4120 participants (Anticipated)Interventional2022-05-24Recruiting
A Study to Investigate the Effects of Multiple Doses of BI 425809 on the Single Dose Pharmacokinetics of Cytochrome P450 Substrates (Midazolam, Warfarin and Omeprazole) and a P Glycoprotein Substrate (Digoxin) Administered Orally in an Open-label, One-seq [NCT02783040]Phase 113 participants (Actual)Interventional2015-09-30Completed
An Open-label Study to Assess the Potential for Pre-systemic Inhibition of Cytochrome P450 3A4 (CYP3A) by Idebenone in Healthy Male Subjects Using Midazolam as a Substrate [NCT02887443]Phase 132 participants (Actual)Interventional2016-09-30Completed
Influence of Sepsis, Age and SLCO1A2 Genetic Polymorphisms on Rocuronium Pharmacokinetics-pharmacodynamics in ASA I-III Surgical Patients [NCT02399397]Phase 436 participants (Actual)Interventional2014-02-28Completed
Measurement of Psychomotor Function Recovery in Patients After General Anesthesia Using 4-Choice Reaction Time Test [NCT02232139]Phase 2124 participants (Actual)Interventional2016-03-31Completed
An Open-label, Single-center, Three-part Study in Healthy Subjects to Investigate the Effect of Givinostat on the Pharmacokinetics of Midazolam and Dabigatran, the Effect of Clarithromycin on the Pharmacokinetics of Givinostat and the Pharmacokinetics of [NCT05492318]Phase 154 participants (Actual)Interventional2022-03-21Completed
An Open-Label, Fixed-Sequence Study to Evaluate the Effect of Multiple Doses of LOXO-292 on the Single Dose Pharmacokinetics of Midazolam in Healthy Adult Subjects [NCT05338476]Phase 116 participants (Actual)Interventional2018-07-12Completed
Can we Avoid Intravenous Sedation in Patients Undergoing Knee Surgery Under Spinal Anesthesia? A Prospective Randomized Controlled Study Comparing Virtual Reality Hypnosis to Standard of Care [NCT05707234]Phase 460 participants (Anticipated)Interventional2023-02-15Recruiting
Fentanyl Versus Midazolam as an Adjunct to Intrathecal Bupivacaine for Postoperative Analgesia in Children Undergoing Infraumbilical Surgery [NCT03592537]Phase 2/Phase 390 participants (Actual)Interventional2018-08-15Completed
RANDOMİZED,DOUBLE-BLİND TRİAL OF EFFECT OF DEXMEDETOMİDİNE AND MİDAZOLAM SEDATİON ON HEART RATE VARİABİLİTY AFTER CORONARY ARTERY BYPASS GRAFT SURGERY [NCT03601091]80 participants (Actual)Interventional2018-03-22Active, not recruiting
A Comparison of Midazolam Versus Dexamethasone-ondansetron in Preventing Postoperative Nausea-vomiting in High Risk Patients Undergoing Laparoscopic Surgeries [NCT03603119]120 participants (Actual)Interventional2018-05-01Completed
Oral Anxiolysis for the Older Pediatric Patient-Which Medication is Preferred? [NCT03360123]4 participants (Actual)Interventional2018-01-26Completed
3-part Study to Assess Safety, Tolerability, PK and PD of Single and Multiple Ascending Doses of EXS21546, and to Evaluate the Relative Bioavailability of 2 Formulations, in Healthy Male Subjects [NCT04727138]Phase 164 participants (Actual)Interventional2020-12-08Completed
Remifentanil Pharmacodynamics During Conscious Sedation From the Algometry Perspective. An Essential Standpoint to be Considered in Opioids Time-course Modelling Validation [NCT05115578]100 participants (Actual)Observational2017-03-01Completed
Randomized Controlled Trial Assessing the Effectiveness of Midazolam Premedication as an Anxiolytic, Analgesic, Sedative, and Hemodynamic Stabilizer [NCT03325335]128 participants (Actual)Interventional2016-07-19Completed
Impact of Roux-en-Y Gastric Bypass (RYGB) Bariatric Surgery on System Pharmacology: Single-dose Cross-over Pharmacokinetic Study of Simvastatin and Carvedilol. [NCT04049786]Phase 4120 participants (Anticipated)Interventional2019-06-01Enrolling by invitation
Synaptic Imaging and Brain Network Activity Following Ketamine in Treatment Resistant Depression [NCT05870501]50 participants (Anticipated)Interventional2021-10-20Recruiting
Effect of Dexmedetomidine Versus Midazolam Versus a Combination of the Two as a Premedication for Children Undergoing Bilateral Myringotomy Tube Insertion: A Randomized, Blinded Study [NCT02134327]0 participants (Actual)Interventional2014-04-30Withdrawn(stopped due to Decided not to proceed)
Randomized Trial to Compare Propofol to Fentanyl and Midazolam for Colonoscopy. [NCT01488045]289 participants (Actual)Interventional2011-06-30Completed
Ketamine for Depression Relapse Prevention Following ECT: a Randomised Pilot Trial With Blood Biomarker Evaluation [NCT02414932]Early Phase 16 participants (Actual)Interventional2015-04-30Completed
Persistent Inflammation, Immunosuppression and Catabolism Syndrome (PICS): A New Horizon for Surgical Critical Care: Project 4B: Lower Extremity Strength Training in ICU Patients [NCT02467023]5 participants (Actual)Interventional2015-09-30Completed
Comparative Study of the Effectiveness of Three Anxiolytic Drugs Used in Third Molar Surgery [NCT02065843]Phase 2/Phase 330 participants (Actual)Interventional2014-03-31Completed
Organ Protective Effect of Histamine H1 Receptor Antagonist In Patients With Severe Burns: A Clinical Study [NCT06126991]Phase 1/Phase 232 participants (Anticipated)Interventional2023-11-01Recruiting
The Application of Balanced Propofol Sedation in Fiberoptic Bronchoscopy [NCT06116955]500 participants (Anticipated)Observational2023-12-01Not yet recruiting
SUPER-refractory Status Epilepticus After Cardiac Arrest: a Multicenter, Retrospective, Cohort Study of Dual Anti-glutamate Therapy With Ketamine and Perampanel [NCT05756621]80 participants (Anticipated)Observational2022-01-15Recruiting
NMDAR Modulation As a Therapeutic Target and Probe of Neural Dysfunction in OCD [NCT02624596]Phase 2120 participants (Anticipated)Interventional2016-06-30Active, not recruiting
[NCT02085967]Phase 1106 participants (Actual)Interventional2014-02-28Completed
An Open-label, Phase 1 Dose Escalation Study of Oral ASP8273 in Subjects With Non-Small-Cell Lung Cancer (NSCLC) Who Have Epidermal Growth Factor Receptor (EGFR) Mutations [NCT02113813]Phase 1133 participants (Actual)Interventional2014-04-09Completed
Effects of Dexmedetomidine on Postoperative Cognitive Dysfunction During One-lung Ventilation in Elder Patients -a Single-center, Randomized ,Double-blinded and Controlled Trial [NCT02134093]Phase 4120 participants (Anticipated)Interventional2014-07-31Not yet recruiting
Effectiveness of Combined Levetiracetam and Midazolam in Treatment of Generalized Convulsive Status Epilepticus in Children [NCT04926844]Phase 2144 participants (Actual)Interventional2021-06-20Completed
Effect of Paravertebral Muscle Fat Infiltration on Rocuronium Use in Lumbar Surgery [NCT05619848]Early Phase 187 participants (Actual)Interventional2022-10-25Completed
Randomised Controlled Study Comparing Use of Popofol Plus Fentanyl Versus Midazolam Plus Fentanyl as Sedation in Diagnostic Endoscopy in Patients With Advanced Liver Disease. [NCT03063866]Phase 4100 participants (Anticipated)Interventional2017-02-21Recruiting
Does the Use of Dexmedetomidine for Premedication Provide Hemodynamic Stability in Hypertensive Patients? [NCT02058485]Phase 3162 participants (Actual)Interventional2012-01-31Completed
Safety and Efficacy of Combined Sedation With Midazolam and Dexmedetomidine in ICU Patients [NCT02080169]Phase 4600 participants (Anticipated)Interventional2014-02-28Recruiting
Effect of Pretreatment of Lignocaine Versus Midazolam in the Prevention of Etomidate Induced Myoclonus [NCT04921046]Phase 4224 participants (Actual)Interventional2015-01-01Completed
The Effect of Multiple Doses of Cenobamate (YKP3089) on the Single Dose Pharmacokinetics of Cytochrome P450 Substrates (Midazolam, Warfarin, Omeprazole and Bupropion) Administered Orally in an Open-label, One-sequence Study in Healthy Subjects [NCT03234699]Phase 124 participants (Actual)Interventional2017-02-22Completed
[NCT02254759]Phase 112 participants (Actual)Interventional2014-10-31Completed
Effect of Pre-injection of Lidocaine on Myoclonus Induced by Induction With Etomidate in Elderly Patients During General Anesthesia [NCT02141737]Phase 4272 participants (Anticipated)Interventional2014-05-31Recruiting
Comparison of the Postoperative Sleep Quality of Patients Sedation With i.v. Dexmedetomidine or Midazolam Undergoing Transurethral Prostatic Resection(TURP) [NCT02142595]Phase 4111 participants (Actual)Interventional2014-05-31Completed
Open-label, Fixed Sequence Crossover Study to Investigate the Effects of Carbamazepine on the Pharmacokinetics of Elinzanetant (BAY 3427080) in Healthy Participants. [NCT05028608]Phase 116 participants (Actual)Interventional2021-09-06Completed
IV Sedation Plus TAP Block for Placement of Percutaneous Endoscopic Gastrostomy Tube [NCT04878926]60 participants (Actual)Interventional2017-08-01Completed
An Open-label Phase 1 Study to Evaluate the Effects of Dabrafenib (GSK2118436) on the Single Dose Pharmacokinetics of an OATP1B1/1B3 Substrate and of a CYP3A4 Substrate in Subjects With BRAF V600 Mutation Positive Tumors [NCT02082665]Phase 16 participants (Actual)Interventional2015-02-19Completed
The Effect of Dexmedetomidine on the Microcirculation in Patients With Severe Sepsis and Septic Shock [NCT02109965]Phase 412 participants (Actual)Interventional2014-07-31Terminated
Ketamine Versus Midazolam for Prehospital Agitation [NCT03554915]314 participants (Actual)Observational2017-08-01Completed
A Phase 1/2, Open-label Study Evaluating the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Efficacy of Sotorasib (AMG 510) Monotherapy in Subjects With Advanced Solid Tumors With KRAS p.G12C Mutation and Sotorasib (AMG 510) Combination The [NCT03600883]Phase 1/Phase 2713 participants (Actual)Interventional2018-08-27Active, not recruiting
A Prospective Randomized Comparative Study to Evaluate the Use of Remifentanil as a Sole Agent or in Combination With Midazolam Versus Fentanyl/Midazolam During Sedation for Colonoscopy [NCT03037892]75 participants (Actual)Interventional2015-06-01Completed
Anesthetist Controlled Versus Patient-controlled Sedation: Risks and Benefits, a Randomized Controlled Trial [NCT04823390]Phase 130 participants (Actual)Interventional2019-09-14Completed
A Phase 1, Open Label, Crossover, Drug Interaction Study of the Pharmacokinetics of ASP015K and Midazolam After Separate and Concomitant Administration to Healthy Adult Subjects [NCT01182077]Phase 130 participants (Actual)Interventional2010-06-30Completed
Sequential Use of Propofol/Midazolam and Dexmedetomidine for Sedation in Mechenical Ventialtion Patients in ICU, A Randomized Controlled Study. [NCT02122055]Phase 4100 participants (Anticipated)Interventional2014-06-30Not yet recruiting
Study of Comparison of the Effectiveness of Three Diagrams for Sedation in Spinal Anesthesia [NCT02136641]Phase 475 participants (Actual)Interventional2011-06-30Completed
Effect of Early 48-hour Sevoflurane Inhalation on Gas Exchange and Inflammation in Patients Presenting With Acute Respiratory Distress Syndrome (ARDS) : a Monocentric, Prospective, Randomized Study. [NCT02166853]Phase 450 participants (Actual)Interventional2014-04-30Completed
Safety and Efficacy of Dexmedetomidine vs Ketamine vs Midazolam Combined With Propofol in Gastrointestinal Procedures for Cancer Patients [NCT04597268]75 participants (Actual)Interventional2020-11-01Completed
Does the Preoperative Midazolam Dose Affect Postoperative Pain? - a Multicentric Randomized Controlled Trial in Ambulatory Surgery [NCT03534895]Phase 4168 participants (Anticipated)Interventional2019-05-31Not yet recruiting
The Effects of Sedatives on Tobacco Use Disorder Version 2 [NCT05505630]Early Phase 152 participants (Anticipated)Interventional2023-01-31Recruiting
The Effect of Virtual Reality Glasses on Anxiety During Surgery Under Spinal Anesthesia: A Randomize Controlled Study [NCT03475810]100 participants (Actual)Interventional2017-11-07Completed
Psychological Influences on Postoperative Recovery [NCT00581139]Phase 2241 participants (Actual)Interventional2003-04-30Completed
A Randomised, Open-label, Crossover, Phase I Study to Assess the Effect of Multiple Oral Doses of ZD4054 (Zibotentan) on the Pharmacokinetics of a CYP450 3A Probe (Midazolam) in Healthy Male Subjects [NCT00709553]Phase 112 participants (Anticipated)Interventional2008-07-31Completed
An Open-label, Single-sequence Study to Evaluate the Effect of Coadministration of Danicamtiv on the Pharmacokinetics of Midazolam in Patients With Stable Heart Failure With Reduced Ejection Fraction [NCT05952089]Phase 116 participants (Anticipated)Interventional2023-08-17Recruiting
Midazolam as an Adjuvant to Bupivacaine in Quadratus Lumborum Block After Caesarean Section; Does it Offer Better Pain Control? a Randomized Double Blind Clinical Trial [NCT05261672]60 participants (Anticipated)Interventional2022-03-15Recruiting
A Multi-Center, Phase II, Randomized, Double-Blind, Prospective, Active Placebo- Controlled Trial of Sub-Anesthetic Intravenous Infusion of Ketamine to Treat Levodopa- Induced Dyskinesia in Subjects With Parkinson's Disease [NCT04912115]Phase 230 participants (Actual)Interventional2021-10-05Suspended(stopped due to Seeking Pivotal study initiation)
A PHASE 1, MULTI-PART RANDOMIZED, DOUBLE-BLIND, SPONSOR-OPEN, PLACEBO CONTROLLED STUDY TO EVALUATE THE SAFETY, TOLERABILITY, AND PHARMACOKINETICS OF MULTIPLE ASCENDING ORAL DOSES OF PF-07293893 IN HEALTHY ADULT PARTICIPANTS [NCT06177457]Phase 1108 participants (Anticipated)Interventional2023-12-12Not yet recruiting
The Effect of Etomidate on Outcomes of Trauma Patients [NCT00938990]0 participants (Actual)InterventionalWithdrawn
An Open-label Study to Evaluate the Safety, Tolerability and Pharmacokinetics of Cytochrome P450 Probe Drugs in Healthy Adult Subjects [NCT00964106]Phase 187 participants (Actual)Interventional2009-08-26Completed
Propofol Versus Midazolam and Fentanyl for Diagnostic and Screening Colonoscopy in Patients With Advanced Liver Disease [NCT00978978]60 participants (Anticipated)Interventional2009-10-31Not yet recruiting
PERIOPERATIVE EFFECTS OF ORAL DEXMEDETOMIDINE, KETAMINE, OR MIDAZOLAM PREMEDICATION IN CHILDREN UNDERGOING ADENOTONSILLECTOMY [NCT05874245]Phase 4222 participants (Anticipated)Interventional2023-03-01Recruiting
A Randomized Active Placebo Controlled Trial of Ketamine in Borderline Personality Disorder [NCT03395314]Phase 222 participants (Actual)Interventional2018-02-15Terminated(stopped due to assessment of project in wake of covid-19 related interruptions)
[NCT00783731]0 participants Interventional2008-10-31Completed
A Phase 1b Study of Aurora A Kinase Inhibitor LY3295668 Erbumine in Monotherapy and Combination Therapy in Patients With Metastatic Breast Cancer Post CDK4/6 Inhibitor and Endocrine Therapy [NCT03955939]Phase 15 participants (Actual)Interventional2019-08-02Completed
A Single-center, Open-label, Four-period, Fixed-sequence Study to Investigate the Effect of Single and Repeated Oral Doses of ACT-539313 on the Pharmacokinetics of Flurbiprofen, Omeprazole, Midazolam, and Their Respective Metabolites in Healthy Subjects [NCT05254548]Phase 122 participants (Actual)Interventional2022-02-18Completed
Comparison of Polysomnographic Findings in Mechanically Ventilated Patients Sedated With α2 Agonists Versus GABA Agonists [NCT00826553]Phase 16 participants (Actual)Interventional2009-01-31Terminated(stopped due to poor recruitment)
Profiling Study for the Hepatic Cytochrome P450 (CYP) Isozymes CYP1A2, CYP2C9, CYP2C19, CYP2D6 and CYP3A in Healthy Subjects and in Patients With Stage 4 (F4) Liver Fibrosis / Cirrhosis by the Combined Administration of the Probe Substrates (the Cocktail) [NCT05741385]30 participants (Anticipated)Interventional2023-04-25Recruiting
A Phase 1, Randomized, Double-blind, Placebo-controlled, Multiple-dose Escalation Study Evaluating the Safety, Pharmacokinetics, and Pharmacodynamics of VX-708 in Healthy Subjects [NCT05518734]Phase 164 participants (Actual)Interventional2022-09-17Completed
A Phase 1, Randomized, Open-Label Study to Evaluate the Effect of Vapendavir (BTA798) on the Pharmacokinetics of Orally Administered Midazolam, a CYP3A4 Substrate, in Healthy Male and Female Volunteers [NCT02204501]Phase 124 participants (Actual)Interventional2014-05-31Completed
Phase 1 Study of Circadian Rhythm of Salivary Cortisol in Health Children ;Phase 2 Study of Circadian Rhythm of Salivary Cortisol of Children Undergoing Surgery Using Etomidate or Not Using Etomidate. [NCT02013986]Phase 430 participants (Anticipated)Interventional2013-09-30Recruiting
Randomized Controlled Trial of Oral Sedatives for Moderate Sedation in Young Children [NCT00902395]Phase 441 participants (Actual)Interventional2008-06-30Completed
Platform Adaptive Embedded Trial for Acute Respiratory Distress Syndrome [NCT05658692]Phase 41,000 participants (Anticipated)Interventional2022-10-01Recruiting
Ketamine vs Propofol for Sedation During Pediatric Bronchoscopy [NCT02743104]150 participants (Anticipated)Interventional2016-05-31Suspended(stopped due to Protocol being reconsidered)
Effect of Ketamine on Laboratory-induced Stress in Healthy Subjects: A Proof-of-Concept Translational Study [NCT04173962]Phase 224 participants (Actual)Interventional2019-08-08Completed
A Phase 1, First-in-human Study of Safety, Tolerability, and Pharmacokinetics of VX-828 [NCT06154447]Phase 1157 participants (Anticipated)Interventional2023-12-12Recruiting
A Single-center, Open-label Study to Investigate the Effect of a Single Oral Dose of HEC74647 and HEC110114 on the Pharmacokinetics of Midazolam, and Their Metabolites in Healthy Subjects [NCT05504876]Phase 114 participants (Actual)Interventional2022-11-07Completed
An Open-Label, Phase 1 Study in Healthy Volunteers to Evaluate the Drug-Drug Interaction Potential of CCX168 With Concomitant Medications [NCT06004947]Phase 132 participants (Actual)Interventional2016-01-14Completed
A PHASE 1, RANDOMIZED, DOUBLE-BLIND, SPONSOR-OPEN, PLACEBO-CONTROLLED STUDY TO INVESTIGATE THE SAFETY, TOLERABILITY, PHARMACOKINETICS, AND PHARMACOKINETIC INTERACTION WITH MIDAZOLAM OF MULTIPLE ASCENDING ORAL DOSES OF PF-07258669 IN HEALTHY NON-JAPANESE A [NCT05113940]Phase 140 participants (Actual)Interventional2021-11-08Completed
Midazolam's Anterograde Amnesia Efficacy in Noisy Orthopedic Surgery: Does Midazolam Cause Effective Anterograde Amnesia in Noisy Orthopedic Surgeries? [NCT04232150]116 participants (Actual)Interventional2019-06-01Completed
A Phase 2, Factorial-Designed, Randomized, Double-Blind, Placebo-Controlled, Parallel- Cohort Study to Evaluate Efficacy and Safety of MELT-300 and the Contribution of Midazolam and Ketamine Components to Sedation and Intraoperative Ocular Analgesia in Su [NCT05133518]Phase 2338 participants (Actual)Interventional2021-07-20Completed
Clinical Trial of Oral Midazolam in Pediatric Endoscopy [NCT00636428]Phase 450 participants (Actual)Interventional2007-03-31Completed
A Comparison of the Sedation With Intermittent Bolus Midazolam-Ketamine Versus Intermittent Bolus Propofol-Fentanyl During Endoscopy in Children: Randomized Trial [NCT02732132]Phase 4238 participants (Actual)Interventional2015-01-31Completed
A Single Center, Single Sequence, Open-Label, Repeat-Dose Study to Investigate the Effect of GSK376501 on Hepatic Cytochrome P450 Activity in Healthy Adult Subjects [NCT00615212]Phase 123 participants (Actual)Interventional2008-01-02Completed
A Comparative Study Between Dexmedetomidine and Midazolam as Adjuvant to Bupivacaine During Epidural Anesthesia For Elective Gynecological Operations [NCT04174872]Phase 4150 participants (Actual)Interventional2019-12-01Completed
Safety, Tolerability, and Pharmacokinetics of Multiple Rising Oral Doses of BI 1584862 in Healthy Subjects (Single-blind, Randomised, Placebo-controlled, Parallel Group Design) [NCT06006598]Phase 150 participants (Anticipated)Interventional2023-08-28Recruiting
A Two-cohort, Two-part, Phase 1, Multicenter, Open-label, Fixed-sequence, Drug-Drug Interaction and QTc Assessments of Sitravatinib Followed by Combination Treatment With Nivolumab in Patients With Advanced Solid Malignancies [NCT04887194]Phase 140 participants (Actual)Interventional2021-03-26Completed
A Phase 1, Open-Label, 4-Part, Drug-Drug Interaction Study With Omaveloxolone in Healthy Subjects [NCT04008186]Phase 161 participants (Actual)Interventional2019-06-14Completed
An Open-Label, Drug-Drug Interaction Study to Examine the Effects of Dupilumab on the Pharmacokinetics of Selected Cytochrome P450 Substrates in Adult Patients With Moderate to Severe Atopic Dermatitis [NCT02647086]Phase 114 participants (Actual)Interventional2015-12-31Completed
An Open Label, 2 Period, Fixed-sequence Study to Assess the Effect of Savolitinib on the Pharmacokinetics of Oral Midazolam (a CYP450 3A Probe) in Healthy Subjects [NCT04187456]Phase 114 participants (Actual)Interventional2019-12-27Completed
An Open Label Study in Healthy Volunteers to Evaluate the Potential for Cytochrome P450 3A4 Inhibition by F901318 Using Oral Midazolam as a Probe [NCT02680808]Phase 120 participants (Actual)Interventional2016-01-31Completed
Impact of Analgesia on Success of External Version: Comparison of Spinal Anesthesia Versus Sedation; Prospective, Controlled, Randomized Study [NCT02801201]Phase 3200 participants (Anticipated)Interventional2016-05-31Recruiting
Sedation of Ventilated Traumatic Brain Injury Patients With Midazolam Alone Versus Combination With Dexmedetomidine or Magnesium Sulfate; Monitored by Ultrasonograghic Optic Nerve Sheath Diameter [NCT05340803]Phase 3108 participants (Anticipated)Interventional2022-11-01Not yet recruiting
Comparison of Nebulized Fentanyl, Midazolam and Dexmedetomidine as a Sedative Premedication in Outpatient Pediatric Dental Surgeries : A Randomized Double Blind Study. [NCT04226885]39 participants (Actual)Interventional2019-03-01Completed
Maximizing Efficacy of Goal-Directed Sedation to Reduce Neurological Dysfunction in Mechanically Ventilated Infants and Children Study [NCT04801589]Phase 3372 participants (Anticipated)Interventional2021-05-10Recruiting
Evaluation and Validation of Endogenous Markers for the Assessment of CYP3A Activity in Korean Healthy Subjects Using Metabolomics [NCT02579434]Phase 1102 participants (Actual)Interventional2014-12-31Completed
A Phase I, Double-Blind, Randomized, Placebo-Controlled, Multicenter, Single- and Multiple-Ascending-Dose Study to Determine Initial Safety, Tolerability, and Pharmacokinetics of GDC-0134 in Patients With Amyotrophic Lateral Sclerosis [NCT02655614]Phase 154 participants (Actual)Interventional2016-05-31Completed
Effects of Concomitant Administration of BMS-986142 on the Single-dose Pharmacokinetics of Probe Substrates for CYP2C8, CYP2C9, CYP2C19, CYP3A4, and P-gp in Healthy Subjects [NCT02762123]Phase 128 participants (Actual)Interventional2016-05-31Completed
A 3-Part, Phase 1 Study to Assess the Drug Interactions of BBT-877 and Midazolam, Itraconazole, and Esomeprazole in Healthy Adult Subjects [NCT04138836]Phase 148 participants (Actual)Interventional2019-09-17Completed
A Phase I Open-labeled, Fixed Sequence Study to Determine the Effect of Multiple Doses of AZD6280 on the Pharmacokinetics of Midazolam (CYP3A4) and Caffeine (CYP1A2) [NCT00824057]Phase 124 participants (Actual)Interventional2009-01-31Completed
[NCT00848861]92 participants (Actual)Interventional2006-02-28Completed
Comparative Study on the Effects of Capacities of Midazolam on Delirium After Sevoflurane Anesthesia in Pediatric Strabismus Surgery : a Randomized Double- Blinded Trial [NCT01680471]90 participants (Actual)Interventional2012-07-31Completed
A Phase 1, Open-label Study to Evaluate Pharmacokinetic Drug-drug Interactions Between VX-548 and Midazolam and Digoxin in Healthy Subjects [NCT05541471]Phase 137 participants (Actual)Interventional2022-09-22Completed
Posttraumatic Stress Disorder (PTSD) Treatment: Using Ketamine to Enhance Memory Reconsolidation and Extinction of Overgeneralized Fear in Individuals Diagnosed With PTSD [NCT05737693]Phase 2162 participants (Anticipated)Interventional2023-08-21Recruiting
COVID-19: A MULTIPART, PHASE 1 STUDY WITH RANDOMIZED, DOUBLE-BLIND, SPONSOR-OPEN, PLACEBO-CONTROLLED, SINGLE- AND MULTIPLE-DOSE ESCALATION TO EVALUATE THE SAFETY, TOLERABILITY AND PHARMACOKINETICS OF PF-07817883 AND OPTIONAL OPEN-LABEL, RANDOMIZED STUDY T [NCT05580003]Phase 194 participants (Actual)Interventional2022-10-17Completed
The Effect of High-dose Remifentanil on Established Sunburn-induced Hyperalgesia in Human Volunteers (HighDose RemiSun) [NCT01015482]Phase 424 participants (Anticipated)Interventional2009-11-30Recruiting
Midazolam Sedation for Neonatal Lumbar Puncture in the Emergency Department: A Randomized Controlled Trial [NCT00942539]Phase 212 participants (Actual)Interventional2009-07-31Terminated
A Randomized Trial of Etomidate Versus Midazolam for Intubation of Patients With Sepsis. [NCT00441792]122 participants (Actual)Interventional2007-10-31Completed
A Phase I Open-label, Fixed Sequence Study to Determine the Effect of Multiple Intravenous Doses of AZD6765 on the Pharmacokinetics of Oral Midazolam (CYP3A4 Substrate) in Healthy Subjects [NCT01069822]Phase 146 participants (Actual)Interventional2010-02-28Completed
A Study to Evaluate the Effect of Multiple Doses of Ridaforolimus (AP23573; MK-8669) on the Single Dose Pharmacokinetics of Midazolam. [NCT01071304]Phase 116 participants (Actual)Interventional2010-03-31Completed
Sleep Intervention During Acute Lung Injury [NCT01050699]Phase 490 participants (Anticipated)Interventional2009-08-31Completed
A Prospective Randomized Study to Assess the Efficacy and Safety of Bolus-dose Lusedra (Fospropofol Disodium) 6.5 mg/kg or 10 mg/kg Versus a Placebo (With Midazolam Rescue) for Minimal-to-moderate Sedation in Patients Undergoing Procedural Sedation for Re [NCT01195103]Phase 413 participants (Actual)Interventional2011-02-28Terminated(stopped due to Funding terminated by funding source.)
Does Sugared or Sugar Free Chewing Gum Reduces Postoperative Ileus After Laparoscopic Cholecystectomy [NCT02162134]90 participants (Actual)Interventional2013-01-31Completed
Comparing Pediatric Oral Sedation Outcomes Using Midazolam and Hydroxyzine With and Without Meperidine [NCT04068948]Phase 437 participants (Actual)Interventional2019-06-25Completed
A Phase I, Double Blind, Randomized, Two-Way Cross Over, Single- Centre Study in Healthy CYP2D6 Extensive Metabolizers and Poor Metabolizers to Investigate the Potential of AZD3480 to Inhibit Cytochrome P450 1A2, 2C19, 3A4, 2C8, 2B6 and UGT1A1 Activity [NCT00692510]Phase 118 participants (Anticipated)Interventional2007-11-30Completed
A Phase I, Multi-Centre, Randomised, Double-blind, Placebo-controlled Study to Investigate the Safety, Tolerability and Pharmacokinetics of AZD1940, Including an Interaction Study, After Administration of Oral Multiple Ascending Doses in Adult Subjects Wi [NCT00689780]Phase 160 participants (Anticipated)Interventional2008-03-31Completed
Efficacy of Combined US-Guided Supraclavicular Block and Interscalene Analgesia Versus an Intercostobrachial Nerve Block Versus PCA With Fentanyl on Preventing Tourniquet Pain in Forearm Surgery: A Randomized Clinical Trial [NCT05602636]Phase 460 participants (Anticipated)Interventional2022-12-10Recruiting
Effects of Clonidine and Midazolam Premedication on Bispectral Index and Recovery After Elective Surgery [NCT00638729]60 participants (Actual)Interventional2005-08-31Completed
Repeated Ketamine Treatment to Accelerate Efficacy of Prolonged Exposure in PTSD [NCT04560660]Phase 2100 participants (Anticipated)Interventional2021-03-09Recruiting
A Phase I, Single-Sequence, Open-Label, Single- and Multiple-Dose Study of the Effect of Evobrutinib on Midazolam Pharmacokinetics in Healthy Participants [NCT04697511]Phase 116 participants (Actual)Interventional2021-01-11Completed
A Phase 1, Open-label, Drug Interaction Study to Evaluate the Effect of Ustekinumab on Cytochrome P450 Enzyme Activities Following Induction and Maintenance Dosing in Participants With Active Crohn's Disease or Ulcerative Colitis. [NCT03358706]Phase 157 participants (Anticipated)Interventional2018-02-02Suspended(stopped due to unavailability of probe substrates)
Short Term Application of Sevoflurane in Patients With Subarachnoid Haemorrhage: a Feasibility and Safety Study [NCT02946437]Phase 20 participants (Actual)Interventional2015-11-01Withdrawn(stopped due to Patients failed to be enrolled because of tight exclusion criteria.)
A Pharmacokinetic Interaction Study Evaluating the Effect of Qualaquin (Quinine Sulfate) Capsules on Midazolam [NCT00785486]Phase 124 participants (Actual)Interventional2007-03-31Completed
Procedural Sedation for Painful Orthopedic Manipulations With Propofol vs. Midazolam/Ketamine in the Adult Emergency Department [NCT00784498]Phase 460 participants (Anticipated)Interventional2008-11-30Completed
A Double-Blind (3rd Party Open), Placebo-Controlled, Crossover, Dose Escalating Study To Evaluate The Safety, Tolerability And Pharmacokinetics Of Single Oral Doses Of PF-03716539, To Assess The Potential Of PF-03716539 To Inhibit CYP3A4 (In Vivo) And To [NCT00783484]Phase 137 participants (Actual)Interventional2008-10-31Completed
Effectiveness of Nitrous Oxide Administration Prior to Intranasal Midazolam for Moderate Sedation in Pediatric Dental Patients [NCT04083105]Phase 4150 participants (Anticipated)Interventional2019-07-12Recruiting
Effects of 100 mg and 500 mg BI 44370 TA Orally Applied as 50 mg Tablets on the Pharmacokinetics of 2 mg Orally Administered Midazolam Solution. An Open-label, Randomised, Parallel Group, Fixed-sequence Study With Intraindividual Comparison of Midazolam P [NCT02217514]Phase 148 participants (Actual)Interventional2008-02-29Completed
An Open-label, Single Sequence Crossover, Study Investigating the Influence of Secukinumab Treatment on the Pharmacokinetics of Midazolam as a CYP3A4 Substrate in Patients With Moderate to Severe Plaque Psoriasis [NCT02607774]Phase 125 participants (Actual)Interventional2015-12-17Completed
An Open-label, Fixed-sequence Study to Assess the Effect of Repeated Doses of Capivasertib on the Pharmacokinetics of Oral Midazolam (a CYP450 3A Probe) in Patients With Advanced Solid Tumours [NCT04958226]Phase 121 participants (Actual)Interventional2021-10-15Completed
An Open-Label Clinical Pharmacology Study of Brentuximab Vedotin (SGN-35) in Patients With CD30-Positive Hematologic Malignancies: CYP3A4 Drug-Drug Interactions, Excretion, and Special Populations [NCT01026415]Phase 173 participants (Actual)Interventional2009-12-31Completed
Onset Time of Brachial Plexus Anesthesia With the Axillary or Infraclavicular Approach Under Real-Time Ultrasound Guidance: a Randomized Controlled Trial [NCT00724035]Phase 452 participants (Anticipated)Interventional2008-05-31Completed
A Phase I Study to Evaluate the Effect of Darunavir/Ritonavir and Lopinavir/Ritonavir on GSK2248761 Pharmacokinetics and to Assess the Effect of GSK2248761 on CYP450 Probe Drugs in Healthy Adult Subjects [NCT00920088]Phase 124 participants (Actual)Interventional2009-06-30Completed
Efficacy and Safety of Intramuscular Midazolam Compared to Buccal Midazolam in Pediatric Seizures: A Randomized Controlled Trial [NCT02897856]Phase 4150 participants (Actual)Interventional2016-09-30Completed
A Phase 1 Dose-Escalation Study of the Safety and Pharmacokinetics of GDC-0973/XL518 Administered Orally Daily to Subjects With Solid Tumors [NCT00467779]Phase 1119 participants (Actual)Interventional2007-05-31Completed
Comparison of Efficacy of Premedication Between Dexmedetomidine and Midazolam Intranasal for the Prevention of Emergence Delirium in Children Undergoing Ophthalmic Surgery [NCT04263844]Phase 466 participants (Actual)Interventional2019-01-10Completed
Propofol vs. Midazolam With Propofol for Sedative Endoscopy in Patients With Previous Paradoxical Reaction to Midazolam [NCT04072328]Phase 230 participants (Actual)Interventional2018-10-19Completed
Effect of Epidural Morphine and Midazolam on Postoperative Painin Patients Undergoing Major Abdominal Cancer Surgery [NCT04033471]Phase 1/Phase 220 participants (Anticipated)Interventional2019-07-01Recruiting
Effect of Concomitant Administration of BMS-708163 on the Pharmacokinetics of Midazolam, Warfarin, Caffeine, Omeprazole and Dextromethorphan in Healthy Male Subjects by Administration of a Modified Cooperstown Cocktail [NCT00726726]Phase 122 participants (Actual)Interventional2008-08-31Completed
A Phase Ia/Ib, Open-label, Multicentre Dose-escalation and Expansion Study to Investigate the Safety, Pharmacokinetics and Preliminary Efficacy of BI 1823911 as a Monotherapy and in Combination With Other Anti-cancer Therapies in Patients With Advanced or [NCT04973163]Phase 130 participants (Actual)Interventional2021-08-03Active, not recruiting
A Partially Double-Blinded, Randomized, Controlled, Placebo-Controlled Study, a Phase III Trial of Safety and Efficacy of Premedication With Dexmedetomidine and Midazolam in Pediatric Patients [NCT04356638]Phase 380 participants (Anticipated)Interventional2021-10-17Recruiting
A Randomized, Investigator- /Subject-blind, Single- and Multiple-ascending Dose, Placebo-controlled Study to Investigate Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Food Effect of RO6953958 (Including RO6953958 Effect on Midazolam) Follow [NCT04475848]Phase 188 participants (Actual)Interventional2020-07-15Completed
Pain Management Following Myringotomy and Tube Placement: Intranasal Dexmedetomidine Versus Fentanyl [NCT01188551]Phase 2/Phase 3100 participants (Actual)Interventional2011-01-31Completed
LEO 32731 - A Phase I Drug-Drug Interaction Study With LEO 32731 and Midazolam in Healthy Male Subjects [NCT02753218]Phase 112 participants (Actual)Interventional2016-04-30Terminated(stopped due to Due to tolerability issues related to the dose titration, unexpected withdrawals were observed and it was unlikely for the trial to meet its objectives)
Clinical Study to Investigate the Effect of the Combination of Psychotropic Drugs and an Opioid on Ventilation [NCT04310579]Phase 155 participants (Actual)Interventional2020-06-15Completed
Effectiveness of Ketamine Treatment in Difficult-to-treat Depression Comparing With Midazolam: a Double-blind Randomized Controlled Trial and Its Cost Effectiveness Analysis [NCT05026203]Phase 424 participants (Anticipated)Interventional2021-09-01Recruiting
Intranasal Dexmedetomidine and Fentanyl Versus Intravenous Midazolam and Ketamine in Sedation for Painful Outpatient Procedures [NCT04621110]Phase 360 participants (Anticipated)Interventional2021-06-01Not yet recruiting
Comparing the Effect of Dexmedetomidine With Midazolam on Sedation, Oxidative Stress, and Microcirculation in Intensive Care Unit [NCT00886275]Phase 433 participants (Actual)Interventional2010-07-31Completed
An Open-Label, Single-Sequence Study to Assess the Effect of Multiple Doses of Tasimelteon on the Cytochrome P450 3A4 and 2C8 Enzymes Using Midazolam and Rosiglitazone as Substrates in Healthy Subjects [NCT01402076]Phase 124 participants (Actual)Interventional2011-08-31Completed
Evaluation of Pediatric Procedural Sedation With Rectal Chloral Hydrate or Intranasal Midazolam - a Randomized Controlled Trial [NCT01402596]Phase 20 participants (Actual)Interventional2011-08-31Withdrawn(stopped due to Institution decided on starting a new protocol of sedation, with another methods and that´s why this study has not started.)
Pharmacokinetics of Sedatives and Analgesics During Extracorporeal Membrane Oxygenation (ECMO) Support [NCT03593408]20 participants (Anticipated)Observational2019-02-08Recruiting
A Phase 1, Open-Label, Drug Interaction Study of the Pharmacokinetics of Isavuconazole and Midazolam After Separate and Concomitant Administration to Healthy Adult Subjects [NCT01406171]Phase 124 participants (Actual)Interventional2011-05-31Completed
Study to Evaluate the Effect of BMS-791325 on the Pharmacokinetics of the CYP3A4 Probe Midazolam Administered Orally in Healthy Subjects [NCT00996879]Phase 148 participants (Actual)Interventional2013-05-31Completed
Cerebral Protection of Dexmedetomidine Against Paroxysmal Sympathetic Overexcited in Patients With Traumatic Brain Injury [NCT04006054]Phase 482 participants (Anticipated)Interventional2019-06-06Recruiting
The Effect of High-dose Remifentanil on Established Capsaicin-induced Hyperalgesia in Human Volunteers [NCT00886106]Phase 424 participants (Anticipated)Interventional2009-06-30Recruiting
[NCT01053871]104 participants (Anticipated)Interventional2010-01-31Completed
Effect of Regional Anesthesia and Sedation With Ketamine Versus Regional Anesthesia and Sedation With Midazolam in Cognitive Function in Patients Over 60 Years of Age in Elective Surgery at 3 Months of Postoperative Follow-up [NCT04134052]Phase 368 participants (Anticipated)Interventional2021-01-24Recruiting
A Phase IIa, Randomized, Controlled, Double-Blind, Dose-Finding Study Evaluating the Safety and Pharmacodynamics of CNS 7056 in Patients Undergoing Diagnostic Upper GI Endoscopy [NCT00869440]Phase 2100 participants (Actual)Interventional2009-03-31Completed
An Open-Label Drug Interaction Study to Assess the Effect of Multiple-Dose Administration of JNJ-42847922 on the Single-Dose Pharmacokinetics of Midazolam and the Single Dose Pharmacokinetics and Pharmacodynamics of Warfarin in Healthy Subjects [NCT02617810]Phase 118 participants (Actual)Interventional2015-11-30Completed
A Double-blind, Randomized Crossover Study to Assess the Subjective Abuse Potential of Intravenous Remimazolam Compared to Midazolam and Placebo in Recreational CNS Depressant Users [NCT04110535]Phase 183 participants (Actual)Interventional2015-06-23Completed
Is Preoperative Distraction With a Hand Held Video Game Boy as Effective as Midazolam in Reducing Preoperative Anxiety Levels in Children as Weel as Emergence Agitation? [NCT00932685]119 participants (Actual)Interventional2005-12-31Completed
Comparison of Lormetazepam and Midazolam Used as Sedatives for Patients That Require Intensive Care [NCT02022592]Phase 484 participants (Actual)Interventional2014-07-17Completed
Non-anesthesiologist-administered Propofol is Not Related to a Higher Increase in Transcutaneous CO2 Pressure During the Flexible Bronchoscopy Compared to Guideline-based Sedation: A Randomized Controlled Trial [NCT02820051]91 participants (Actual)Interventional2014-02-28Completed
A Phase I, Open Interaction Study Between Oral Doses of GLPG1837 and Single Doses of Midazolam in Healthy Male Subjects [NCT02562950]Phase 124 participants (Actual)Interventional2015-09-30Completed
A Single-center, Open-label, Randomized, Two-treatment Crossover Study to Investigate the Effect of Selexipag on the Pharmacokinetics of Midazolam and Its Metabolite 1-hydroxymidazolam in Healthy Male Subjects [NCT02791815]Phase 120 participants (Actual)Interventional2016-07-31Completed
An Open-Label, 2-Part, Multicenter, Post-marketing Study to Evaluate the Effect of Moderately or Severely Active Ulcerative Colitis or Crohn's Disease on Cytochrome P-450 Enzyme Substrates Compared to Healthy Subjects and the Effect of Vedolizumab Treatme [NCT02760615]Phase 40 participants (Actual)Interventional2016-11-01Withdrawn(stopped due to No enrollment)
Comparison Between Dexmedetomidine and Midazolam Nebulization as Procedural Sedation During Cesarean Delivery Under Spinal Anesthesia in Pre-eclamptic Parturients [NCT04873596]Phase 294 participants (Anticipated)Interventional2021-05-15Recruiting
A Phase I, Open Label, Fixed-sequence Drug Interaction Study to Investigate the Effect of Multiple Oral Doses of LOXO-305 on the Pharmacokinetics of a Single Dose of Intravenous and Oral Midazolam (CYP3A4 Substrate) in Healthy Subjects [NCT06180967]Phase 115 participants (Actual)Interventional2020-09-03Completed
Sustained Mood Improvement With Laughing Gas Exposure: A Randomized Controlled Pilot Trial - Sub-Study Protocol to Include Neuroimaging [NCT05528718]20 participants (Anticipated)Observational2023-03-07Recruiting
Comparison Between Continuous Infusion and Intermittent Bolus Injection of Propofol for Deep Sedation During Endoscopic Retrograde Cholangiopancreatography: a Prospective Randomized Controlled Study [NCT01900938]210 participants (Anticipated)Interventional2013-09-30Not yet recruiting
Nurse Administered Propofol Sedation vs. Standard Therapy for Colonoscopy in Patients With IBD. A Randomised Controlled Study on Satisfaction and Adherence to Treatment Program. [NCT01934088]Phase 4130 participants (Actual)Interventional2014-01-31Completed
A Phase 3, Multicenter, Open-label Study to Determine the Efficacy, Safety, and Pharmacokinetics of Buccally Administered MHOS/SHP615 in Pediatric Patients With Status Epilepticus (Convulsive) in the Hospital or Emergency Room [NCT03336645]Phase 325 participants (Actual)Interventional2017-10-23Completed
Substudy of the NONSEDA-trial (NCT01967680): Non-sedation Versus Sedation With a Daily Wake-up Trial in Critically Ill Patients Receiving Me-chanical Ventilation - Effects on Posttraumatic Stress Disorder [NCT02040649]205 participants (Actual)Interventional2014-01-31Completed
An Open-label, Single-Dose, 4-Period, Sequential Study to Determine the Effect of Moxidectin on CYP3A4 Activity in Healthy Subjects Using Midazolam as a Probe Substrate [NCT00856362]Phase 138 participants (Anticipated)Interventional2009-04-30Completed
A Phase 1 Randomized, Double-blind, Single and Multiple-dose Study to Assess the Safety, Tolerability, Pharmacokinetics, Food Effect, and Drug-Drug Interactions of S-309309 in Healthy and Obese Adult Study Participants [NCT05247970]Phase 174 participants (Actual)Interventional2022-01-04Completed
The Effect of Remifentanil on Established Capsaicin-Induced Hyperalgesia in Human Volunteers [NCT00789386]Phase 424 participants (Anticipated)Interventional2008-11-30Recruiting
A Double-blind Pilot Trial of the Effect of Ketamine vs. Active Placebo on Suicidal Ideation in Depressed Inpatients With Major Depressive Disorder or Bipolar Depression. [NCT02593643]Early Phase 19 participants (Actual)Interventional2016-01-31Completed
A Phase 1, Open-Label, Single-Sequence Crossover Study in Healthy Subjects to Determine the Effect of Relacorilant on Exposure to Probe Substrates for Cytochrome P450s 3A4, 2C8, 2C9, 2C19, and 2D6 [NCT03457597]Phase 127 participants (Actual)Interventional2018-03-06Completed
[NCT00886314]80 participants (Anticipated)Interventional2009-06-30Not yet recruiting
Pharmacokinetic Study of CPT-11, Raltegravir and Midazolam With Characterisation of UGT1A1 Genotype [NCT00808184]Phase 425 participants (Actual)Interventional2010-04-30Completed
A Phase III Randomized, Double-blind, Dose-Controlled, Multicenter Study Evaluating the Safety and Efficacy of Dexmedetomidine in Intubated and Mechanically Ventilated Pediatric Intensive Care Unit Subjects [NCT00875550]Phase 3175 participants (Actual)Interventional2010-01-31Completed
Propofol Patient-controlled Sedation Versus Target-controlled Infusion in Outpatient Colonoscopy [NCT04686058]Phase 3105 participants (Actual)Interventional2014-03-31Completed
A Centre-Randomized, Open-Label, Cross-Over Study to Compare the Pharmaco-Economic Consequences of an Ultiva (Remifentanil Hydrochloride) Based Regimen With Conventional Sedative Based Regimens in ICU Subjects Requiring Short-Term Mechanical Ventilation W [NCT00158873]Phase 4224 participants Interventional2004-09-30Completed
A Phase I, Open Label, Multi Centre Study in Healthy Volunteers to Estimate the Effect of Multiple Doses of AZD2066 on the Activity of CYP1A2, CYP2B6, CYP2C9, CYP2C19, CYP2D6 and CYP3A4 by Administering a Cocktail of Caffeine, Bupropion, Tolbutamide, Omep [NCT00930306]Phase 115 participants (Actual)Interventional2009-06-30Completed
Mechanisms Underlying Drug-Diet Interactions [NCT01034124]19 participants (Actual)Interventional2007-01-31Completed
A Drug Interaction Study of KW-6356 With Midazolam, Caffeine, or Rosuvastatin [NCT03970798]Phase 150 participants (Actual)Interventional2019-05-22Completed
A Fixed Sequence, Open-label Study to Assess the Effect of Multiple Doses of AZD5462 on the Pharmacokinetics of Oral Midazolam (CYP3A4 Probe), Rosuvastatin (OATP1B1/3, BCRP Probe), and Digoxin (P-gp Probe) in Healthy Participants [NCT05395117]Phase 132 participants (Actual)Interventional2022-06-30Completed
The Effect of Preoperative Anxiolysis With Intravenous Midazolam on Intraoperative Sevoflurane Gas Consumption: A Prospective Randomized Controlled Study [NCT05371600]Phase 480 participants (Anticipated)Interventional2022-12-02Recruiting
A Randomized, Double-blind, Placebo-controlled Study of the Safety and Efficacy of Intranasal Midazolam (USL261) in the Outpatient Treatment of Subjects With Seizure Clusters. ARTEMIS-1: Acute Rescue Therapy in Epilepsy With Midazolam Intranasal Spray-1 [NCT01390220]Phase 3292 participants (Actual)Interventional2011-06-30Terminated
Intranasal Midazolam Versus Rectal Diazepam for the Home Treatment of Seizure Activity in Pediatric Patients With Epilepsy [NCT00326612]Phase 2358 participants (Actual)Interventional2006-06-30Completed
A Prospective, Double-blind Study of Dexmedetomidine Versus Midazolam for Intensive Care Sedation of Children [NCT01091818]Phase 340 participants (Anticipated)Interventional2010-03-31Recruiting
[NCT02202239]Phase 460 participants (Anticipated)Interventional2014-09-30Not yet recruiting
An Open-label, Single-sequence Study to Evaluate the Potential CYP 3A4 Pharmacokinetic Interaction of Darapladib (SB-480848) in Healthy Subjects [NCT01873339]Phase 126 participants (Actual)Interventional2013-06-19Completed
Conscious Sedation With Midazolam in Dentally Anxious Patients: Effect of the Administration Route (Oral Versus Intravenous Administration) [NCT01874717]Phase 3131 participants (Actual)Interventional2005-06-30Completed
Preoperatively Administered Single Dose Diclofenac Reduces the Intensity of Acute Postcraniotomy Headache and Decreases Postoperative Analgesic Requirements- a Randomized, Controlled Trial [NCT01907984]Phase 4200 participants (Actual)Interventional2012-12-31Completed
A Phase I Open-label Study to Evaluate the Effect of Multiple Doses of MDV3100 (ASP9785) on the Pharmacokinetics of Substrates for CYP2C8, CYP2C9, CYP2C19, and CYP3A4 in Patients With Castration-resistant Prostate Cancer [NCT01911728]Phase 114 participants (Actual)Interventional2011-07-25Completed
Evaluation Of The Effect Of PF-05089771 On The Metabolism Of Multiple Cytochrome P450 And OATP1B1 Transporter Substrates [NCT01934569]Phase 117 participants (Actual)Interventional2013-09-30Completed
Effect of Gender-Affirming Estrogen Therapy on Drug Metabolism, Transport, and Gut Microbiota [NCT05469204]13 participants (Anticipated)Observational2022-11-01Recruiting
Comparison of Dexmedetomidine and Midazolam as Intramuscular Premedication for Suspension Laryngoscopy [NCT01937611]Phase 440 participants (Anticipated)Interventional2013-03-31Recruiting
Phase IV Study of Propofol TCI (Target Controlled Infusion)Administered by Gastroenterologists During Endoscopy in Moderate Sedation: a Randomized Double Blind Controlled Study [NCT01941888]Phase 4140 participants (Actual)Interventional2012-05-31Completed
Phase 1b Study of Pharmacokinetic Interaction, Evaluating the Effect of a Single IV Infusion of GGF2 or Placebo on Midazolam Pharmacokinetics in Patients With Heart Failure [NCT01944683]Phase 122 participants (Actual)Interventional2013-09-30Completed
Phase 2 Optimization of the Antidepressant Action of Ketamine in Treatment-Resistant Depression and Investigations on Its Mechanism of Action [NCT01945047]Phase 2/Phase 346 participants (Actual)Interventional2013-05-31Completed
[NCT01945476]82 participants (Actual)Interventional2013-09-30Completed
"Study Design and Rationale of A Multicenter, Open-Labeled, Randomized Controlled Trial Comparing MIdazolam Versus MOrphine in Acute Pulmonary Edema: MIMO Trial" [NCT02856698]Phase 4111 participants (Actual)Interventional2017-04-08Terminated(stopped due to The study was stopped because of the adverse events)
A Placebo- and Midazolam-Controlled, Phase Ia, Single Ascending-Dose Study Evaluating the Safety, Pharmacokinetics, and Pharmacodynamics of Remimazolam Tosylate [NCT01970072]Phase 179 participants (Actual)Interventional2013-10-14Completed
Assessing the Pharmacokinetics and Drug Interaction Liability of Kratom, an Opioid-like Natural Product [NCT04392011]Early Phase 115 participants (Actual)Interventional2019-10-09Completed
Ontogeny of Voriconazole Pharmacokinetics and Metabolism in Children and Adolescents [NCT01976078]45 participants (Actual)Observational2012-09-30Completed
[NCT01979653]0 participants (Actual)Interventional2013-11-30Withdrawn
Use of Volatile Anesthetics for Long-Term Sedation In Critically Ill Patients [NCT01983800]60 participants (Actual)Interventional2013-07-31Completed
Can we Gain an Advantage by Combining Distal Median, Radial and Ulnar Nerve Blocks With Supraclavicular Block? A Randomized Controlled Study [NCT01989312]Phase 475 participants (Actual)Interventional2012-02-29Completed
Effectiveness of Oral Midazolam for Sedation in Patients Undergoing Upper Gastrointestinal Endoscopy [NCT01990937]Phase 4260 participants (Anticipated)Interventional2013-10-31Recruiting
A Randomized Controlled Trial on the Effects of Midazolam on the Quality of Postoperative Recovery in Patients [NCT01993459]Phase 4192 participants (Actual)Interventional2014-02-28Completed
Prothrombotic Factors , Angiogenic Growth Factor and Different Anaesthetic Techniques in Cancer Patients Undergoing Prostatectomy [NCT01998685]200 participants (Actual)Interventional2013-06-30Completed
Comparison of Remimazolam and Midazolam for Preventing Intraoperative Nausea and Vomiting During Cesarean Section Under Spinal Anesthesia [NCT05736341]80 participants (Anticipated)Interventional2023-05-18Recruiting
Ketamine vs. Midazolam in Bipolar Depression [NCT01944293]Phase 1/Phase 216 participants (Actual)Interventional2013-09-30Completed
Can Nasal Fentanyl and Buccal Midazolam Give Better Symptom Control for Dying Patients When Compared With Standard Subcutaneous Medication? Pilot Randomised Controlled Trial and Qualitative Interview Study. [NCT02009306]Phase 420 participants (Actual)Interventional2017-01-23Completed
A Phase I, Single-center, Open-label, 3-group, Fixed-sequence Study to Assess the Effect of Itraconazole, a Potent CYP3A4 Inhibitor, or Diltiazem, a Moderate CYP3A4 Inhibitor, on the Pharmacokinetics of AZD3293 and the Effects of AZD3293 on the Pharmacoki [NCT02010970]Phase 156 participants (Actual)Interventional2013-12-31Completed
Hydroxyzine Dihydrochloride Premedication is a Necessity for Pediatric Patients Undergoing Strabismus Surgery; An Observational Clinical Trial Controlled With Midazolam [NCT03806270]45 participants (Actual)Observational [Patient Registry]2018-10-01Completed
A Phase 1/2 Open-Label, Dose Escalation Study Investigating the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of ASP2215 in Patients With Relapsed or Refractory Acute Myeloid Leukemia [NCT02014558]Phase 1/Phase 2265 participants (Actual)Interventional2013-10-09Completed
[NCT02016976]40 participants (Anticipated)Interventional2014-01-31Not yet recruiting
A SINGLE CENTER, OPEN LABEL, FIXED SEQUENCE STUDY TO INVESTIGATE THE EFFECT OF MULTIPLE DOSE BITOPERTIN ON SINGLE DOSE PHARMACOKINETICS OF MIDAZOLAM IN HEALTHY VOLUNTEERS [NCT02019290]Phase 10 participants (Actual)Interventional2014-02-10Withdrawn
Prevention of Emergence Agitation in Children After Sevoflurane Anesthesia With Ketamine-midazolam Combination: A Prospective Randomized Clinical Trial [NCT02022488]Phase 478 participants (Actual)Interventional2012-02-29Completed
Dexmedetomidine-ketamine Combination Versus Fentanyl-midazolam for Patient Sedation During Flexible Bronchoscopy: a Prospective, Single-blind, Randomized Controlled Trial [NCT06185127]Phase 350 participants (Actual)Interventional2019-09-01Completed
A PHASE 1/2A STUDY EVALUATING THE SAFETY, TOLERABILITY, PHARMACOKINETICS, PHARMACODYNAMICS, AND ANTI-TUMOR ACTIVITY OF PF-07220060 AS A SINGLE AGENT AND AS PART OF COMBINATION THERAPY IN PARTICIPANTS WITH ADVANCED SOLID TUMORS [NCT04557449]Phase 1/Phase 2337 participants (Anticipated)Interventional2020-09-23Recruiting
Remifentanil and Propofol Versus Fentanyl and Midazolam for Sedation During Therapeutic Hypothermia. A Randomised, Controlled Trial [NCT00667043]Phase 460 participants (Actual)Interventional2008-04-30Completed
Phase I Dose Escalation Study of the Pharmacokinetics, Safety and Tolerability of Rifapentine and the Effects of Increasing Doses of Rifapentine on Induction of Metabolizing Enzymes in Healthy Volunteers [NCT01162486]Phase 137 participants (Actual)Interventional2010-04-30Completed
"Randomized Trial of Diphenhydramine Versus Continued Midazolam in Difficult-to-sedate Patients Undergoing Colonoscopy" [NCT01769586]200 participants (Actual)Interventional2013-02-28Completed
Premedication With Oral Midazolam in Patients Undergoing Rigid Cystoscopy: A Randomized, Double-blind, Placebo-controlled Trial [NCT00563069]120 participants (Anticipated)Interventional2005-09-30Recruiting
Efficacy of Buccal Versus Intranasal Route of Administration of Midazolam Spray in Behavior Management of Pre-School Dental Patients [NCT04608734]Phase 236 participants (Actual)Interventional2015-06-10Completed
A Safety, Tolerability, Pharmacokinetic, and Pharmacodynamic Study of Single- and Multiple-Ascending Doses of LY3522348 in Healthy Participants [NCT04559568]Phase 165 participants (Actual)Interventional2020-10-15Completed
Effect of Midazolam and Dexmedetomidine on Heart Function - A Randomized MRI-based Study. [NCT04529187]Phase 430 participants (Actual)Interventional2018-01-01Completed
A Phase 1, Open-Label Study to Evaluate CYP3A4 Drug-Drug Interactions of Edasalonexent in Healthy Adult Subjects [NCT04543370]Phase 126 participants (Actual)Interventional2020-08-08Completed
A First-in-human, Participant and Investigator-blinded, Randomized, Placebo-controlled, Single-and Multiple-Ascending Dose Study With Drug-Drug Interaction, to Investigate the Safety, Tolerability, and Pharmacokinetic Profile of AB521, in Healthy Voluntee [NCT05117554]Phase 168 participants (Actual)Interventional2021-11-09Completed
Dex vs Dazzle: Dexmedetomidine vs Midazolam for Intraoperative Sedation [NCT02878837]Phase 4120 participants (Actual)Interventional2016-01-31Completed
Sedation and Analgesia for Transjugular Liver Biopsy: A Randomized Double Blind Placebo Controlled Trial [NCT00596414]Phase 4180 participants (Actual)Interventional2003-05-31Completed
Sedation for Flexible Bronchoscopy and Real Time Endobronchial Ultrasound -A Comparison Between Bispectral Index-guided Sedation and Conventional Sedation [NCT00789815]Phase 4500 participants (Actual)Interventional2008-04-30Completed
A Randomised Active-controlled Study to Compare Efficacy & Safety of Inhaled Isoflurane Delivered by the AnaConDa-S (Anaesthetic Conserving Device) vs IV Midazolam for Sedation in Mechanically Ventilated Paediatric Patients 3-17 Years Old [NCT04684238]Phase 397 participants (Actual)Interventional2021-01-14Completed
Low Dose Fentanyl/Midazolam Improves Sevoflurane Induction in Adults [NCT00723164]80 participants (Actual)Interventional2005-10-31Completed
An Open-Label Study to Evaluate the Pharmacokinetics of Intranasal Esketamine and Its Effects on the Pharmacokinetics of Orally-Administered Midazolam and Bupropion in Healthy Subjects [NCT02568176]Phase 171 participants (Actual)Interventional2015-10-31Completed
An Open-Label, Fixed Sequence, Clinical Drug Interaction Study to Evaluate the Time-Dependent Inhibition Potential of Vonoprazan on a Sensitive CYP3A4 Substrate, Midazolam, in Healthy Volunteers [NCT04545944]Phase 120 participants (Actual)Interventional2020-09-15Completed
A Phase 1, Randomized, 2-Way Crossover, Multiple Dose, Open Label Study Of The Effect Of CP-690,550 On Midazolam Pharmacokinetics In Healthy Volunteers [NCT00902460]Phase 125 participants (Actual)Interventional2009-06-30Completed
Intranasal Dexmedetomidine or Oral Midazolam Alone Versus Combination With Intranasal Dexmedetomidine and Oral Midazolam for Premedication in Pediatric Patients Undergoing Minor Surgery [NCT04135014]Phase 4138 participants (Anticipated)Interventional2019-10-25Recruiting
Effects of Dexmedetomidine vs Propofol on Inflammatory Response and Intra-abdominal Pressure in Patients With Intra-abdominal Sepsis; a Randomized Clinical Trial [NCT04718714]Phase 460 participants (Actual)Interventional2021-01-23Completed
the Research of Analgesia and Sedation Effect of Remifentanil on ICU Short Operation [NCT02635802]Phase 41,500 participants (Anticipated)Interventional2015-12-31Not yet recruiting
Effect of Sedation on Cognitive Performance in the Elderly (Pilot Study) [NCT03089866]20 participants (Actual)Observational2015-03-31Active, not recruiting
A Phase III Randomised, Triple-blind Controlled Superiority Trial of Remimazolam (CNS 7056), Compared to Midazolam, in Adults Having Lower Third Molar Wisdom Tooth Extraction Under Intravenous Conscious Sedation to Assess Cognitive and Motor Recovery at N [NCT05220462]Phase 3128 participants (Anticipated)Interventional2022-03-09Recruiting
Low-Dose Ketamine Infusion for the Treatment of Multiple Sclerosis Fatigue (INKLING-MS) [NCT05378100]Phase 2110 participants (Anticipated)Interventional2023-01-01Recruiting
Sedating Effects of Dexmedetomidine Versus Midazolam in Agitated Patients Undergoing Weaning in ICU [NCT05264077]Early Phase 166 participants (Anticipated)Interventional2022-06-01Not yet recruiting
Conventional Sedation Compaired With THRIVE Under General Anesthesia in Endotracheal Intubation by Fiberbronchoscope in Patients With Difficult Airways,A Randomized Controlled Study [NCT04924621]42 participants (Anticipated)Interventional2021-06-10Recruiting
A Single-center, Open-label, Single-arm, Fixed-sequence Study to Evaluate the Pharmacokinetic Effects of SHR0302 Tablets on Substrates of CYP3A4, CYP2C8, CYP2C9, CYP2C19 in Healthy Volunteers [NCT05392127]Phase 124 participants (Actual)Interventional2022-07-15Completed
Effects of Addition of Systemic Tramadol or Adjunct Tramadol to Lidocaine Used for Intravenous Regional Anesthesia in Patients Undergoing Hand Surgery [NCT02658721]Phase 360 participants (Actual)Interventional2013-01-31Completed
Impact of Premedication With Midazolam in Aspiration Procedures On Stress Levels During IVF Procedures [NCT04160611]Phase 340 participants (Anticipated)Interventional2019-09-01Recruiting
Safety, Tolerability, and Pharmacokinetics of Multiple Rising Oral Doses of BI 706321 in Healthy Male and Female Subjects (Doubleblind, Randomised, Placebo-controlled, Parallel Group Design) [NCT04241458]Phase 139 participants (Actual)Interventional2020-01-30Completed
A Phase 1, Randomized, Participant-and Investigator-Blind, Placebo-Controlled, Single-and Multiple-Ascending Dose, Drug-Drug Interaction and Food Effect Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of LY3509754 in Healthy Non-Japanese [NCT04586920]Phase 1104 participants (Actual)Interventional2020-10-20Terminated(stopped due to Terminated due to safety findings)
Comparison of the Effectiveness of Sedation With i.v. Dexmedetomidine in Combination With Midazolam Alone or Midazolam and Low Dose Ketamine for Extraction of Third Molars. [NCT01017237]Phase 418 participants (Actual)Interventional2009-07-31Terminated(stopped due to Protocol proved to be ineffective for adequate sedation for third molar surgery.)
The Effect of Remifentanil and Midazolam on Propofol for Loss of Consciousness During Induction of Anesthesia [NCT02536690]120 participants (Actual)Interventional2015-08-31Completed
Intranasal Ketamine Versus Intranasal Midazolam Plus Fentanyl in Treating Pain Associated With Incision and Drainage of Abscesses in the Pediatric Emergency Department: A Randomized Controlled Trial [NCT02635282]Phase 419 participants (Actual)Interventional2016-08-31Completed
A Phase-1, Open-label, Four Group, Fixed-Sequence Study to Evaluate the Effect of AL-794 on the Pharmacokinetics of Oseltamivir, JNJ-63623872, and Probes for P-glycoprotein, CYP3A and OATP1B1 in Healthy Volunteers [NCT02888327]Phase 168 participants (Actual)Interventional2016-07-31Completed
A Phase IIb Study Evaluating the Safety and Efficacy of Multiple Doses of CNS 7056 Compared to Midazolam in Patients Undergoing Colonoscopy [NCT01145222]Phase 2162 participants (Actual)Interventional2010-05-31Completed
Treatment of Supraventricular Tachycardia in Patients With Non-cardiac Surgery by Dexmedetomidine During the Perioperative Period [NCT04284150]60 participants (Anticipated)Interventional2020-02-26Not yet recruiting
The Use of ADV6209 for Premedication in Pediatric Anesthesia: a Controlled, Randomized, Double Blinded Study [NCT03931057]Phase 480 participants (Actual)Interventional2020-11-16Completed
To Compare Dexmedetomidine and Midazolam for Intra-op Sedation in TIVA in Children Undergoing Inguinal Hernia Repair [NCT05337085]Phase 1185 participants (Anticipated)Interventional2022-06-30Not yet recruiting
The Effect of Remifentanil and Midazolam on Propofol for Loss of Consciousness During Induction of Anesthesia in Elderly Patients [NCT02818387]120 participants (Anticipated)Interventional2015-10-31Recruiting
Triple Drug Response Surface Modeling for Patients Receiving Airway Managements [NCT03813875]100 participants (Actual)Observational2019-06-12Completed
Comparative Study of Dexmedetomidine-midazolam Combination and Propofol-midazolam Combination for MRI Brain in Paediatric Patient [NCT02776189]Phase 470 participants (Actual)Interventional2012-10-31Completed
The Use of Midazolam and Remifentanil During Arteriovenous Fistula Placement Procedure and Monitored Anesthesia Care [NCT04226443]99 participants (Actual)Interventional2012-08-28Completed
The Effect of Multiple Subcutaneous Doses of Risankizumab on the Single Dose Pharmacokinetics of Cytochrome P450 Substrates (Caffeine, Warfarin, Omeprazole, Metoprolol and Midazolam) Administered Orally in an Open-label, One-sequence Trial in Patients Wit [NCT02772601]Phase 121 participants (Actual)Interventional2016-09-15Completed
A Prospective Study Investigating the Effect of Midazolam Sedation on Diagnostic Lumbar Medial Branch Blocks [NCT04453449]95 participants (Actual)Observational2020-06-25Completed
Cytochrom p450 3A4 and 1A2 Phenotyping for the Individualization of Treatment With Sunitinib or Erlotinib in Cancer Patients [NCT01402089]Phase 454 participants (Actual)Interventional2012-01-31Completed
[NCT01404442]Phase 1/Phase 290 participants (Actual)Interventional2011-05-31Completed
An Open-label, Single Centre, Randomised, Cross-over Study to Examine the Effect of Ulimorelin on the Pharmacokinetics of Midazolam After Repeat Dose Administration of Ulimorelin in Healthy Volunteers [NCT01405612]Phase 114 participants (Actual)Interventional2011-06-30Completed
Restorative Sleep: Effect of Dexmedetomidine [NCT00333632]Phase 40 participants (Actual)Interventional2006-06-30Withdrawn
[NCT01806753]157 participants (Actual)Interventional2013-03-31Completed
Phase Ib Evaluation of the Safety and Tolerability and Effect on Midazolam Metabolism of the Administration of Multiple Rising Doses of BI 730357 to Healthy Volunteers [NCT03279978]Phase 183 participants (Actual)Interventional2018-01-09Completed
Effects of GSK3640254 on the Single-Dose Pharmacokinetics of Probe Substrates (Caffeine, Metoprolol, Montelukast, Flurbiprofen, Omeprazole, Midazolam, Digoxin, and Pravastatin) in Healthy Subjects [NCT04425902]Phase 120 participants (Actual)Interventional2020-12-16Completed
A Phase 1, Open-Label, Single-Sequence Crossover Study Assessing the Effect of Tivantinib (ARQ 197) on the Pharmacokinetics of Omeprazole/S-Warfarin/Caffeine/Midazolam and Digoxin in Cancer Subjects [NCT01517399]Phase 128 participants (Actual)Interventional2011-12-31Completed
Comparing Low Dose IV Ketamine-midazolam Versus IV Morphine Regarding ED Pain Control in Patients Sustaining Closed Limb Fracture(s) [NCT01807429]Phase 2/Phase 3236 participants (Actual)Interventional2012-12-31Completed
Is Preoperative Distraction With a Hand Held Game Boy as Effective as Midazolam in Reducing Preoperative Anxiety Levels in Children? [NCT00176670]Phase 2158 participants Interventional2004-01-31Completed
Safety and Efficacy of Remimazolam Compared With Midazolam During Bronchoscopy: A Single Center, Randomized Controlled Study [NCT05994547]Phase 4100 participants (Actual)Interventional2022-04-14Completed
A Phase I, Open-label, Single-center Study to Assess the Pharmacokinetics of Midazolam, a CYP3A4 Substrate, in Healthy Subjects When Administered Alone and in Combination With a Single Dose of 800-mg Vandetanib (CAPRELSA) [NCT01544140]Phase 116 participants (Actual)Interventional2012-04-30Completed
A Phase I, Open, Randomised, Non-Comparative, Parallel Group Study of a Potential Cytochrome P450 3A Induction After Repeat Twice Daily Oral Dosing With 100 and 500 mg AZD1981 Tablets for 14 Days to Healthy Male Volunteers With Single Oral Doses of Midazo [NCT00859352]Phase 128 participants (Anticipated)Interventional2009-03-31Completed
Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Multiple Rising Oral Doses of BI 1323495 Versus Placebo in Healthy Subjects, Including an Investigation of Drug-drug Interaction With Microdose Midazolam (Double-blind, Randomised, Placebo-co [NCT04107805]Phase 187 participants (Actual)Interventional2019-11-04Completed
A Randomized Controlled Clinical Trial of Remimazolam Benzenesulfonate Usage in the Extraction of Impacted Wisdom Teeth [NCT05350085]150 participants (Anticipated)Interventional2022-04-18Recruiting
BUCCOLAM OROMUCOSAL SOLUTION - Special Drug Use Surveillance [NCT05313308]50 participants (Anticipated)Observational2021-06-01Recruiting
Ketamine as a Rapid Treatment for Post-traumatic Stress Disorder [NCT00749203]Phase 241 participants (Actual)Interventional2009-01-31Completed
Efficacy and Safety of Dexmedetomidine vs. Midazolam Sedation in Patients Undergoing Convex-probe Endobronchial Ultrasound: a Randomized Double Blind Trial [NCT02713191]Phase 2/Phase 3197 participants (Actual)Interventional2016-03-31Completed
Optimization of Intravenous Ketamine for Treatment-Resistant Depression: A Randomized, Placebo-Controlled, Triple-masked, Clinical Trial [NCT00768430]Phase 273 participants (Actual)Interventional2008-11-30Completed
A Phase I Study to Assess Safety, Tolerability, Pharmacokinetics and Effect of Food on Multiple Rising Oral Doses of BI 1839100 (Single-blind, Randomised, Placebo-controlled, Parallel Group Design) and the Effect of Multiple Doses of BI 1839100 on the Sin [NCT05738291]Phase 158 participants (Anticipated)Interventional2023-04-26Recruiting
A Double-Blind, Randomized, Single- and Multiple-Dose Study to Investigate the Safety, Tolerability, and Pharmacokinetics of JNJ-38518168 in Japanese and Caucasian Healthy Adult Male Subjects and an Open-Label Drug-Drug Interaction Study to Evaluate the E [NCT01442532]Phase 194 participants (Actual)Interventional2011-09-30Completed
A Randomized Clinical Trial Comparing Oral Conscious Sedation With Intravenous Conscious Sedation for First Trimester Surgical Abortion [NCT00337792]132 participants (Actual)Interventional2006-06-30Terminated(stopped due to DSMB review at 50% recruitment, further recruitment unlikely to change result)
Comparative Randomized Controlled Trial Study of General Balanced Anesthesia Based on Opioid and Opioid Sparing Balanced Anesthesia for Cholecystectomy Surgery Via Laparoscopy: Intraoperative and Postoperative Outcomes [NCT02953210]Phase 440 participants (Anticipated)Interventional2016-11-30Enrolling by invitation
A Parallel Group, Single-Blind, Randomised, Placebo Controlled Study to Evaluate the Safety, Tolerability and Pharmacokinetics of GW823296 and Its Effect on the Pharmacokinetics of Midazolam After Once-Daily Repeated Oral Doses in Healthy Subjects [NCT00511654]Phase 136 participants (Actual)Interventional2007-06-12Completed
A Phase 1, Open-Label, Two-Part, Fixed-Sequence, Drug-Drug Interaction Study to Evaluate the Effect of Voxelotor on the Pharmacokinetics of Selected CYP and Transporter Probe Substrates in Healthy Participants [NCT05981365]Phase 118 participants (Actual)Interventional2023-04-17Completed
Inducibility and Stability of Ventricular Tachycardia in Patients With Structural Heart Disease Undergoing VT Ablation Under General Anesthesia (Pilot Study) [NCT02419547]11 participants (Actual)Interventional2014-07-31Completed
Feasibility Study of Biomarker Development for Response Prediction by Large Scale DNA Mutational Analysis of Metastatic Lesions [NCT01855061]79 participants (Actual)Observational2011-05-31Terminated
Trial on The Efficacy of Sedation in Mechanically Ventilated Critically Ill Patients [NCT00221520]Phase 3126 participants Interventional2003-02-28Active, not recruiting
A Study of Methods to Reduce Anxiety in Preoperative Elective Surgical Patients [NCT01866605]Phase 4120 participants (Actual)Interventional2008-07-31Completed
Premedication With Different Nebulized Ketamine,Dexmedetomidine Versus Midazolam in Oncologic Preschool Children [NCT02935959]Phase 1/Phase 290 participants (Actual)Interventional2016-10-31Completed
Ketamine Versus Etomidate for Procedural Sedation for Pediatric Orthopedic Reductions [NCT00596050]Phase 450 participants (Actual)Interventional2006-08-31Completed
Analgesic Efficacy of Ropivacaine Alone or in Combination With Adjuvants on Post-operative Analgesia Following Video-Assisted Thoracoscopic Surgery (VATS) - A Randomized Controlled Trial. [NCT03809442]Phase 4120 participants (Anticipated)Interventional2019-06-25Recruiting
Intrathecal Midazolam is a Comparable Alternative to Fentanyl and Nalbuphine as Adjuvant to Bupivacaine in Spinal Anesthesia for Elective Cesarean Section; a Randomized Controlled Double-blind Trial [NCT04932083]100 participants (Actual)Interventional2021-06-20Completed
A Single and Multiple Ascending Dose Study to Evaluate the Safety, Tolerability and Pharmacokinetics of PBI-0451 in Healthy Subjects. [NCT05011812]Phase 1130 participants (Actual)Interventional2021-08-14Completed
A Randomized, Double-Blind, Placebo-Controlled Study Examining the Efficacy of Oral Midazolam in Reducing Anxiety in Children Undergoing Voiding Cystourethrogram [NCT00894465]44 participants (Actual)Interventional2006-08-31Terminated(stopped due to Most pts requested to be treated with versed. It was difficult to randomize pts.)
A Phase 3, Multicenter, Open-label Extension Study of Buccally Administered MHOS/SHP615 in Pediatric Patients With Status Epilepticus (Convulsive) in Community Settings [NCT03336450]Phase 33 participants (Actual)Interventional2018-04-23Completed
Safety and Efficacy of Four Intramuscular Interventions for the Management of Acute Psychomotor Agitation [NCT01485692]120 participants (Actual)Interventional2009-02-28Completed
A Single Centre, Single Sequence, Open-Label, Repeat-Dose Study to Investigate the Effect of GSK1605786 on Hepatic Cytochrome P450, and BCRP and OATP1B1 Transport in Healthy Adult Subjects [NCT01489943]Phase 124 participants (Actual)Interventional2011-09-19Completed
[NCT01491009]40 participants (Actual)Interventional2006-05-31Completed
Department of Anesthesiology, Cancer Hospital of the University of Chinese Academy of Sciences(Zhejiang Cancer Hospital), Research Center for Neuro-Oncology Interaction , Institute of Basic Medicine and Cancer, Chinese Academy of Sciences. [NCT05466279]130 participants (Anticipated)Interventional2021-01-07Recruiting
[NCT00440960]Phase 40 participants InterventionalCompleted
Post Operative Cognitive Recovery and Neuropsychological Complications After General Anesthesia. A Comparison Between Different Techniques of Anesthesia: A Multi-Center Observational Study [NCT00507195]1,200 participants (Anticipated)Observational2007-05-31Recruiting
[NCT02929095]70 participants (Actual)Interventional2016-10-01Completed
A Proof-of-Concept Trial on the Effect of Ketamine on Fatigue [NCT04141696]Phase 1/Phase 259 participants (Anticipated)Interventional2021-07-26Recruiting
An Open-Label, Single-Sequence Study to Evaluate the Potential CYP 3A4 Pharmacokinetic Interaction of GW876008 in Healthy Subjects [NCT00423761]Phase 125 participants (Actual)Interventional2006-12-31Completed
Comparison of the Analgesic Efficacy of Two Adjuvants to Hyperbaric Bupivacaine During Spinal Anaesthesia for Caesarean Section. [NCT03458078]Phase 2/Phase 3150 participants (Actual)Interventional2017-02-01Completed
Comparison of Intraoperative Complications in Patients With or Without High Risk for Obstructive Sleep Apnea During Sedation With Midazolam or Dexmedetomidine Within Transurethral Resections of Bladder and Prostate [NCT04817033]Phase 4115 participants (Actual)Interventional2021-04-01Completed
A Randomized, Placebo-controlled, Concealed Allocation Comparison of Respiratory Depression and Coughing During Bronchoscopy With Dexmedetomidine-ketamine as an Adjunct to Fentanyl-midazolam Sedation [NCT01158820]Phase 450 participants (Actual)Interventional2010-06-30Completed
A Phase 1, Open-Label, Fixed-Sequence, Drug-Drug Interaction Study To Evaluate The Effect Of Multiple Doses of CTP-543 On The Pharmacokinetics Of Single Doses of Midazolam In Healthy Subjects [NCT05467709]Phase 120 participants (Actual)Interventional2022-06-21Completed
Phase I, Open-Label, Single-Center Study to Evaluate the Safety and Dose Linearity of Intramuscular Administration of Midazolam Using [NCT00534378]Phase 139 participants (Actual)Interventional2006-07-31Completed
Impact of Virtual Reality Hypno-sedation on Functional Recovery and Anxiety in Foot Surgery With Regional Anesthesia: a Randomized Clinical Trial. [NCT05558449]Phase 457 participants (Anticipated)Interventional2022-12-14Recruiting
Sedation Efficacy of Dexmedetomidine Versus Midazolam in Critically Ill Ventilated Children [NCT04082767]Phase 3120 participants (Anticipated)Interventional2021-06-08Recruiting
A PHASE 1, OPEN-LABEL, TWO-PART STUDY TO EVALUATE THE EFFECT OF TWO STEADY-STATE DOSE LEVELS OF PF-06882961 ON THE PHARMACOKINETICS OF SINGLE ORAL DOSES OF ATORVASTATIN AND MIDAZOLAM IN HEALTHY ADULTS AND AN ORAL CONTRACEPTIVE IN HEALTHY POST-MENOPAUSAL F [NCT05093205]Phase 135 participants (Actual)Interventional2021-10-25Completed
The Effect of Tasisulam on CYP3A-mediated Metabolism of Midazolam: A Pharmacokinetic Interaction Study in Cancer Patients With Advanced and/or Metastatic Tumors or Lymphoma [NCT01209832]Phase 111 participants (Actual)Interventional2010-09-30Terminated(stopped due to Terminated based on safety results from another trial)
Double-Blind Randomized Controlled Trial of Acute-Course of Ketamine Versus Midazolam for Recurrence of Suicidality in Adolescents [NCT04592809]Phase 3264 participants (Anticipated)Interventional2022-10-03Recruiting
Open Randomized Clinical Trial to Examine Individual Pain Tolerance in the Use of Two Anesthetic Techniques to Perform Saturation Prostate Biopsy [NCT02909049]Phase 4100 participants (Actual)Interventional2016-04-30Completed
Effect of Affective Content on Drug Induced Amnesia of Episodic Memory [NCT00142493]Phase 179 participants (Actual)Interventional2004-09-30Completed
Cognitive Impairment Following Sedation for Colonoscopy With Propofol, Midazolam and Fentanyl Combinations [NCT00446420]Phase 4200 participants (Actual)Interventional2007-02-28Completed
The Effects of Denosumab on the Pharmacokinetics (PK) of Midazolam, a Cytochrome P450 3A4/P-gp (CYP3A4) Substrate, in Postmenopausal Osteoporotic Women [NCT01221727]Phase 130 participants (Actual)Interventional2010-11-30Completed
Effect of Midazolam Premedication on Mask Ventilation Difficulty During General Anesthesia Induction in Children: A Randomized Clinical Study [NCT05368441]Phase 4120 participants (Actual)Interventional2022-05-24Completed
A Comparison of Midazolam or Haloperidol Premedication Versus Placebo for Reducing Ketamine Induced Agitation After Adult Procedural Sedation in the Emergency Department [NCT02909465]Phase 4185 participants (Actual)Interventional2016-07-31Completed
A Phase 1 First-in-Human Dose Study of LY3023414 in Patients With Advanced Cancer [NCT01655225]Phase 1156 participants (Actual)Interventional2012-07-31Completed
A Pivotal Phase 1, Randomized, Single-Dose, 4-Period, Crossover Relative Bioavailability Study of MELT-100, IV Midazolam, and IV Ketamine Under Fasted Conditions in Healthy Volunteers [NCT04767035]Phase 125 participants (Actual)Interventional2020-12-01Completed
Cardioprotective Effect of Ketamine-dexmeditomidine Versus Fentanyl-midazolam in Open-heart Surgery in Pediatrics: A Randomized Controlled Double-blinded Study [NCT05314569]Phase 181 participants (Anticipated)Interventional2022-04-15Recruiting
A PHASE 1, OPEN -LABEL, FIXED SEQUENCE STUDY TO EVALUATE THE EFFECT OF TWO STEADY STATE DOSE LEVELS OF PF-06882961 ON THE PHARMACOKINETICS OF SINGLE ORAL DOSES OF ROSUVASTATIN AND MIDAZOLAM IN OTHERWISE HEALTHY ADULT PARTICIPANTS WITH OBESITY [NCT04621227]Phase 116 participants (Actual)Interventional2020-12-15Completed
The Effect and Safety of Different Sedation Strategies for Diagnostic Bronchoscopy [NCT03406533]28 participants (Actual)Interventional2018-02-01Terminated(stopped due to The sample size should be re-calculated based on the first 28 cases.)
Evaluating the Effects of Tipranavir (With Ritonavir) Capsule and Liquid Formulation on Cytochrome P450 and P-glycoprotein Activity Using a Biomarker Cocktail in Healthy Human Volunteers [NCT02243553]Phase 134 participants (Actual)Interventional2006-01-31Completed
Efficacy of the Intravenous Formulation of Fentanyl Citrate Administered Orally as Premedication in Paediatric Patients Undergoing Open Cardiac Surgery [NCT04991298]60 participants (Anticipated)Interventional2021-06-01Recruiting
A Double-blinded Randomized Controlled Trial of Dexmedetomidine Versus Propofol for Sedation in Mechanically Ventilated Medical Intensive Care Unit Patients. [NCT01059929]Phase 441 participants (Actual)Interventional2009-09-30Terminated(stopped due to drug and placebo unavailable)
Hypnosis for Sedation in Transesophageal Echocardiography: Comparison With Midazolam [NCT01749475]98 participants (Actual)Observational2010-06-30Completed
The Safety of Driving in Patients After Minor Surgery With Monitored Anesthesia Care [NCT00577200]Phase 4625 participants (Anticipated)Interventional2008-01-31Active, not recruiting
A Phase 1, Open-Label Study to Evaluate the Potential Effects of PPI-668 on the Pharmacokinetics of Midazolam and Omeprazole, and Potentially Telaprevir, in Healthy Adult Subjects [NCT01786382]Phase 124 participants (Actual)Interventional2013-02-28Completed
The Assessment of Postoperative Cognitive Dysfunction After Transurethral Resection of Bladder Tumor Under Spinal Anesthesia [NCT03029676]Phase 4200 participants (Anticipated)Interventional2017-01-01Recruiting
Intravenous Ketamine in the Treatment of Obsessive-Compulsive Disorder [NCT01371110]Phase 1/Phase 23 participants (Actual)Interventional2012-06-30Terminated(stopped due to no funding)
An Open-label, Non-randomized Study to Investigate the Effects of Twice-Daily Milvexian Administration on the Pharmacokinetics of Single Doses of Midazolam, Ethinylestradiol and Drospirenone in Healthy Adult Females [NCT05706753]Phase 120 participants (Actual)Interventional2023-01-25Completed
An Open-Label, Two-Period, Sequential Drug Interaction Study to Evaluate the Effect of Multiple Doses of Desvenlafaxine Succinate Sustained Release (DVS SR) on the Pharmacokinetics of Midazolam When Coadministered in Healthy Subjects [NCT00952653]Phase 428 participants (Actual)Interventional2010-06-30Completed
A Randomized, Double-Blind, Dose-Response Study to Assess the Efficacy and Safety of AQUAVAN® Injection for Procedural Sedation in Patients Undergoing Colonoscopy [NCT00125424]Phase 2/Phase 3125 participants Interventional2005-07-31Completed
Comparative Evaluation of Intranasal Midazolam, Dexmedetomidine, Ketamine for Their Sedative Effect and the Ability to Facilitate Venous Cannulation in Pediatric Patients: a Prospective Randomized Study. [NCT04704622]Phase 2/Phase 3150 participants (Actual)Interventional2021-01-01Completed
A Randomized, Blinded, Placebo-controlled Study to Investigate the Safety, and Pharmacokinetics of Single and Repeat Dose Escalation of the Oral YAK3/DYRK3 Inhibitor GSK626616AC in Healthy Subjects [NCT00443170]Phase 190 participants (Actual)Interventional2006-11-30Completed
Effects of Midazolam on the Occurrence of Intraoperative Movement in Patients Undergoing Unruptured Intracranial Aneurysm Clipping Surgery: a Prospective Randomized Controlled Trial [NCT05553678]Phase 464 participants (Anticipated)Interventional2022-09-29Recruiting
Comparison of Propofol-fentanyl and Midazolam-fentanyl for Conscious Sedation in Painful Procedures [NCT01749579]Phase 460 participants (Anticipated)Interventional2012-05-31Recruiting
A Prospective, Multi-centre, Randomised, Double-blind Comparison of Intravenous Dexmedetomidine With Midazolam for Continuous Sedation of Ventilated Patients in Intensive Care Unit [NCT00481312]Phase 3501 participants (Actual)Interventional2007-06-30Completed
Comparison of Extubation Delay After Prolonged Sedation With Inhaled Isoflurane Using the MIRUS® Device or Continuous Intravenous Midazolam in Patients With Septic Shock in Intensive Care [NCT04710914]Phase 459 participants (Anticipated)Interventional2020-12-15Recruiting
A Randomized, Double-Masked, Controlled, Single Site Investigator Initiated, Exploratory Study of the Midazolam/Ketamine Melt vs Ketamine Melt Alone vs Midazolam Melt Alone in Subjects Undergoing Intraocular Surgery. [NCT04725747]Phase 450 participants (Anticipated)Interventional2021-01-25Not yet recruiting
A Phase 1 Randomized, Open-Label, 2-Sequence, 2-Period Crossover Study Of The Effect Of Multiple Doses Of PD-0332991 On Midazolam Pharmacokinetics In Healthy Women of Non-Childbearing Potential [NCT01756781]Phase 126 participants (Actual)Interventional2013-05-31Completed
Intranasal Dexmedetomidine Versus Intranasal Midazolam as a Premedication in Pediatrics Undergoing Upper GI Endoscopy [NCT06181682]Phase 470 participants (Anticipated)Interventional2024-01-31Not yet recruiting
The Use of Ketamine for Conscious Sedation in Flexible Bronchoscopy [NCT06181188]Phase 466 participants (Actual)Interventional2019-07-15Completed
[NCT00376831]Phase 491 participants (Actual)Interventional2007-01-31Completed
A Drug-drug Interaction Study to Investigate the Effect of Avapritinib on the Pharmacokinetics of Midazolam in Patients With Unresectable or Metastatic Gastrointestinal Stromal Tumors (GIST) and Other Advanced Solid Tumors [NCT04908176]Phase 120 participants (Anticipated)Interventional2022-08-24Recruiting
Clinical Evaluation of the Pharmacokinetic Goldenseal-Metformin Interaction in Diabetic Patients [NCT05081583]Early Phase 122 participants (Actual)Interventional2021-09-16Active, not recruiting
Randomized Controlled and Prospective Studies of Safety and Efficacy of Oral Midazolam for Perioperative Anxiolysis of Patients Undergoing Mohs Micrographic Surgery. [NCT00578214]75 participants (Actual)Interventional2007-03-31Completed
An Open-Label, Multiple-Dose, Non-Randomized Study to Assess the Drug-Drug Interactions of Proellex® (CDB-4124) With Cytochrome P450 Isoenzymes CYP1A2, 2C9, 2C19, 2D6, and 3A4 in Healthy Female Subjects [NCT00741468]Phase 118 participants (Actual)Interventional2008-07-31Completed
Intranasal Dexmedetomidine Versus Intranasal Midazolam as Sole Sedative Agents for MRI In Pediatrics: A Randomized Double-Blind Trial [NCT04652661]Phase 460 participants (Actual)Interventional2020-12-10Completed
Incidence of Sedation Related Complications With Propofol Alone Versus Propofol With Benzodiazepines and Opiates in a High Risk Group Undergoing Advanced Endoscopic Procedures: A Randomized Controlled Trial [NCT01315158]36 participants (Actual)Interventional2011-01-31Terminated(stopped due to - The research team is not able to obtain the necessary support to continue the study.)
Study of the Safety of Administration of Sevoflurane for Long-term Critically Ill Patients Sedation Undergoing Mechanical Ventilation. Prospective, Controlled, Randomized, Multicenter, Clinical Trial. [NCT01802255]Phase 30 participants (Actual)Interventional2013-03-31Withdrawn(stopped due to Lack of recruitment in the Centres)
A Two-cohort, Open-label, Fixed-sequence, Two-period, Two-treatment Pharmacokinetic Interaction Study of Repeated Oral Doses of Sotagliflozin on a Single Dose Cocktail of Metoprolol and Midazolam Used as Probe Substrates for CYP2D6 and CYP3A Activities, R [NCT02940379]Phase 124 participants (Actual)Interventional2016-10-31Completed
A Single Center, Single Dose, Open Label, Randomized, Four-period Crossover Study in Healthy Subjects to Describe and Compare the Plasma Pharmacokinetics of Midazolam After Intramuscular Injection as a Solution by a Conventional Syringe or by the Needle-f [NCT05026567]Phase 140 participants (Actual)Interventional2022-05-09Completed
Based on the Real-time Monitoring of Nociceptive Index, Dexmedetomidine as a Neuraxial Adjuvant Facilitate Analgesia [NCT04675372]Phase 4181 participants (Actual)Interventional2021-01-19Completed
A First-in-Human Multi-Part Phase 1 Study in Healthy Volunteers to Evaluate the Safety, Tolerability, Pharmacokinetics, and Drug-Drug Interaction Potential of Single and Multiple Doses of ALG-097558 [NCT05840952]Phase 1144 participants (Anticipated)Interventional2023-07-04Recruiting
RemImazolam Besylate for ICU-sedation in Patients With Mechanical Ventilation After Oral and Maxillofacial Surgery: a Single-center, Randomized, Non-inferiority Clinical Study [NCT05606315]Phase 4285 participants (Anticipated)Interventional2022-03-16Recruiting
A Phase 1, Open-Label Study in Healthy Participants Aged 18 to 65 Years to Investigate the CYP3A4 Induction Potential of GSK3882347 [NCT05760261]Phase 130 participants (Anticipated)Interventional2023-03-06Suspended(stopped due to To allow analysis of data from supplementary non-clinical study.)
Induction in the Dark: a Prospective Randomized Control Trial for Perioperative Pediatric Anxiety [NCT06144177]Phase 4240 participants (Anticipated)Interventional2023-12-15Not yet recruiting
Role of CYP2B6, CYP3A4, and MDR1 in the Metabolic Clearance of Methadone in Human Subjects [NCT00504413]Phase 120 participants (Anticipated)Interventional2007-07-31Recruiting
A Phase IIB, Open-Label, Randomized Controlled Dose Ranging Multi-Center Trial to Evaluate the Safety, Tolerability, Pharmacokinetics and Exposure-Response Relationship of Different Doses of Sutezolid in Combination With Bedaquiline, Delamanid and Moxiflo [NCT03959566]Phase 275 participants (Actual)Interventional2021-05-06Completed
Fentanyl Use for Sedation in Esophagogastroduodenoscopy (FUSE): a Phase 4, Randomized, Double-blind, Placebo-controlled Trial of Fentanyl Added to Midazolam Compared to Midazolam Alone for Sedation in Routine Upper Endoscopy [NCT01514695]Phase 4139 participants (Actual)Interventional2012-02-29Completed
A Comparison of Patient Satisfaction Between Sedation Using Medication and Sedation Using Virtual Reality During Surgery Under Spinal Anesthesia: A Randomized Controlled Trial [NCT03055663]37 participants (Actual)Interventional2017-02-20Completed
Intranasal Midazolam Versus Intranasal Ketamine to Sedate Newborns for Intubation in Delivery Room. [NCT01517828]Phase 362 participants (Actual)Interventional2012-01-31Active, not recruiting
CYP3A4 Metabolism Before and After Surgery Induced Weight Loss in Morbidly Obese Patients Using Midazolam as a Model Drug [NCT01519726]Phase 420 participants (Anticipated)Interventional2011-12-31Completed
The Efficacy of Oral Melatonin in Preventing Postoperative Delirium for Patients Undergoing Orthopedic Surgery Under General Anesthesia [NCT05236907]36 participants (Actual)Interventional2020-07-01Completed
An Evaluation of Oral Midazolam for Anxiety and Pain in First-trimester Surgical Abortion: a Randomized Controlled Trial [NCT01830881]Phase 4124 participants (Actual)Interventional2013-04-30Completed
TRK-700 Drug-Drug Interaction Study With Digoxin and Midazolam in Healthy Adults [NCT03043248]Phase 148 participants (Actual)Interventional2017-02-06Completed
Sedation of Surgical Patients in the Intensive Care Unit: A Randomized Comparison Between Propofol-Remifentanil and Midazolam-Remifentanil Sedation [NCT01527903]Phase 477 participants (Actual)Interventional2009-09-30Completed
The Effect of Low Dose of Midazolam on Blood Pressure and Anxiety Scale in White-coat Hypertensive Dental Patients [NCT01528371]40 participants (Anticipated)Interventional2010-10-31Completed
Interventional, Open-label, One-sequence Study to Investigate the Effects of Lu AG06466 on the Pharmacokinetics of the Cytochrome P450 Substrates Midazolam (CYP3A4), Bupropion (CYP2B6), and Metoprolol (CYP2D6) in Healthy Young Men and Women [NCT04713254]Phase 115 participants (Actual)Interventional2020-12-08Completed
Efficacy of Topical Lidocaine to Decrease Discomfort With Intranasal Midazolam Administration: A Double-blind, Randomized, Placebo-controlled Trial [NCT02396537]77 participants (Actual)Interventional2014-01-31Completed
Dexmedetomidine Improves the Surgical Field and Postoperative Recovery of Nasal Endoscopic Surgery [NCT04276545]Phase 3118 participants (Actual)Interventional2018-01-01Completed
[NCT01548859]Phase 450 participants (Anticipated)Interventional2011-07-31Active, not recruiting
Pilot Study of Spinal Manipulation for Chronic Neck Pain [NCT00030004]Phase 130 participants Interventional2000-05-31Terminated
A Phase 1, Open-label, Study in Healthy Participants to Evaluate the Effect of Steady State Concentrations of Lazertinib (JNJ-73841937) on the Single-dose Pharmacokinetics of Probe Substrates (Midazolam, Rosuvastatin, and Metformin) [NCT05076877]Phase 120 participants (Actual)Interventional2021-09-17Completed
Comparison Between Infraclavicular Brachial Plexus Block Versus Local Infiltration for Postoperative Analgesia After Wrist Arthroscopy, a Prospective Randomized Open Label Study [NCT02970097]0 participants (Actual)Interventional2016-09-30Withdrawn(stopped due to lack of resources)
Effect of Medazolam or Dexmedetomidine on Regional Cerebral Oxygen Saturation During Spinal Anesthesia in the Elderly Patients [NCT02966743]0 participants (Actual)Interventional2016-11-30Withdrawn
A Phase 1 Placebo-Controlled Study To Assess Safety, Tolerability, Pharmacokinetics And Effect On Midazolam Pharmacokinetics Of Multiple Oral Doses Of PF-05175157 Administered In A Tablet Formulation In Otherwise Healthy Overweight And Obese Subjects [NCT01807377]Phase 115 participants (Actual)Interventional2013-04-30Completed
Ketamine for Severe Adolescent Depression: Intermediate-term Safety and Efficacy [NCT03889756]Phase 2/Phase 33 participants (Actual)Interventional2019-07-17Terminated(stopped due to No more funding available to continue since we could not recruit throughout the pandemic.)
Comparison of Sedative Effect of Dexmedetomidine and Midazolam for TIVA in Pediatric Population Undergoing Inguinal Hernia Repair, Randomized Controlled Trial [NCT05574179]Early Phase 160 participants (Anticipated)Interventional2023-01-01Not yet recruiting
Preoxygenation With Optiflow™, a High Flow Nasal Cannula (HFNC), is Superior to Preoxygenation With Facemask in Morbidly Obese Patients Undergoing General Anesthesia [NCT03009877]0 participants (Actual)Interventional2018-07-31Withdrawn(stopped due to withdrawn prior to IRB approval)
A Phase 4, Randomized, Double-Blind, Multi-Center, Comparator Study Evaluating the Safety and Efficacy of Dexmedetomidine Compared to IV Midazolam in ICU Subjects Requiring Greater Than Twenty-Four Hours of Continuous Sedation [NCT00216190]Phase 4420 participants (Actual)Interventional2005-03-31Completed
The PedINDex Study: Comparing Intranasal Dexmedetomidine With Oral or Rectal Midazolam for Procedural Sedation in the Pediatric Emergency Department. [NCT03399838]Phase 40 participants (Actual)Interventional2023-08-31Withdrawn(stopped due to Sponsor left the hospital)
The Effectiveness of Sedation and Analgesia in Colonoscopy Treatment of Colorectal Polyps: a Single-center, Prospective, Randomized Controlled Study [NCT04906317]340 participants (Anticipated)Interventional2020-12-01Recruiting
Influence of MDR1 Genotype on Indinavir and Saquinavir Pharmacokinetics in Healthy Volunteers [NCT00050180]Phase 481 participants (Actual)Interventional2002-11-22Completed
Assessment of Change in CYP3A Activity by Route of Administration Using Metabolic Markers in Healthy Male Volunteers [NCT03366974]Phase 116 participants (Actual)Interventional2017-12-28Completed
Comparison of Three Different Pain and Anxiety Reducing Methods in Adult Patients Undergoing Bone Marrow Puncture [NCT00188227]Phase 4748 participants Interventional2001-09-30Completed
An Open Label, Single-Dose Midazolam, Multiple-Dose HCV-796, Sequential 3-Period Study to Determine the Pharmacokinetics of the Potential Drug Interaction Between HCV-796 and Midazolam [NCT00410254]Phase 138 participants (Anticipated)Interventional2007-06-30Completed
the Effect of Single Dose of Etomidate Used During Emergency Intubation on Hemodynamics and Adrenal Cortex: a Randomized Clinical Trial [NCT01792037]Phase 490 participants (Actual)Interventional2012-12-31Completed
A Phase 1 Double-Blind (Sponsor-unblinded), Placebo-Controlled Randomized, Single and Multiple Ascending Dose First-Time-in-Human Study to Investigate the Safety, Tolerability, and Pharmacokinetics of VH4524184 and the Potential for Changes in Cytochrome [NCT05631704]Phase 1105 participants (Anticipated)Interventional2022-12-02Recruiting
Quelling of Excitotoxicity in Acute Stroke With Ketamine [NCT03223220]Phase 2/Phase 3120 participants (Anticipated)Interventional2024-07-01Not yet recruiting
Prospective, Randomized Comparative Study of Intravenous Dexmedetomidine for Sedation in Orthopedic Surgery Under Regional Anesthesia [NCT04149626]Phase 260 participants (Anticipated)Interventional2020-01-29Recruiting
A Phase 1, Open-Label, Fixed-Sequence Study to Evaluate CYP3A4-Mediated, Oral Contraceptive, and pH Modifier Drug Interactions for ABI-H2158 in Healthy Adult Subjects [NCT04142762]Phase 180 participants (Actual)Interventional2019-10-18Completed
A Pilot Study to Evaluate the Efficacy of Virtual Reality on Pre-Operative Anxiety and Induction of Anesthesia in a Children's Hospital [NCT03239743]80 participants (Anticipated)Interventional2017-07-20Recruiting
The Effects of Dexmedetomidine/Remifentanil and Midazolam/Remifentanil on Auditory-evoked Potentials and Electroencephalogram at Light-to-moderate Sedation Levels in Healthy Subjects [NCT00641563]10 participants (Actual)Interventional2004-03-31Completed
An Open-label, Single-sequence, Drug-drug Interaction Study in Healthy Participants to Assess the Effect of Phenytoin on the Pharmacokinetics of a Single Oral Dose of Afimetoran (BMS-986256) (Part 1) and the Effect of Steady-state Afimetoran on the Pharma [NCT05901714]Phase 150 participants (Anticipated)Interventional2023-06-19Recruiting
A Phase I, Open Interaction Study Between Oral Doses of GLPG0634 (200 mg QD) and Single Oral Doses of Midazolam (2 mg) in Healthy Subjects [NCT01798979]Phase 120 participants (Actual)Interventional2013-02-28Completed
The Analgesic Effect of Combined Treatment With Intranasal S-Ketamine and Intranasal Midazolam Compared With Morphine Patient Controlled Analgesia in Spinal Surgery Patients [NCT01275547]Phase 2/Phase 322 participants (Actual)Interventional2011-01-31Completed
Patient Satisfaction and Safety With Propofol Based Sedation With or Without Fentanyl for Gastrointestinal Endoscopy :a Prospective ,Randomized ,and Cohort Study [NCT03803449]Phase 4500 participants (Anticipated)Interventional2019-01-01Not yet recruiting
A Phase 1, Open-label, 1-sequence Crossover Drug-drug-interaction Study to Assess the Effect of Single and Multiple Doses of CKD-506 on the Single-Dose Pharmacokinetics of Midazolam, A CYP3A4 Substrate, in Healthy Male Subjects [NCT05238948]Phase 117 participants (Actual)Interventional2022-02-28Completed
Sedation and Pain (The Effect of IV Sedation on Pain Perception) [NCT00853333]86 participants (Actual)Interventional2008-11-30Completed
Prospective Observational Investigation of Olanzapine Versus Haloperidol Versus Ziprasidone Versus Midazolam for the Treatment of Acute Undifferentiated Agitation in the Emergency Department [NCT03211897]737 participants (Actual)Observational2017-06-15Completed
A Prospective, Non-inferiority Randomized Double-blinded Trial Comparing Fentanyl and Midazolam vs Diazepam and Pethidine for Pain Relief During Oocyte Retrieval [NCT02494180]Phase 4170 participants (Actual)Interventional2016-03-31Completed
Ultrasound Guided Distal Sciatic Nerve Block - a Randomised Comparison With Nerve Stimulator Technique [NCT01643616]250 participants (Actual)Interventional2010-11-30Completed
Effect of Repeated Dosing of Clarithromycin on PK of Linaprazan Glurate/Linaprazan, Effect of Single Dose of Linaprazan Glurate on PK of Clarithromycin, Single/Repeated Dosing of Linaprazan Glurate on PK of Midazolam to Healthy Subjects [NCT05633147]Phase 135 participants (Actual)Interventional2022-11-27Completed
Assessment of Multiple-Dose Pharmacokinetics and Safety of the Co-administration of Galicaftor, Navocaftor and ABBV-576 and Potential of ABBV-576 for CYP3A Induction in Healthy Volunteers [NCT05530278]Phase 124 participants (Actual)Interventional2022-09-20Completed
Randomized Controlled Trial of Intranasal Ketamine vs. Intranasal Midazolam in Individuals With Obsessive Compulsive Disorder (OCD) [NCT02206776]Phase 22 participants (Actual)Interventional2014-09-30Terminated(stopped due to poor tolerability and low enrollment rate)
A Randomized Study of Midazolam and Fentanyl Versus Midazolam Alone for Sedation in Gastrointestinal Endoscopy [NCT04807101]Early Phase 1772 participants (Anticipated)Interventional2021-04-05Recruiting
Intranasal Dexmedetomidine Versus Midazolam for Premedication in Deep-sedated Pediatric Dental Patients: a Double-blinded, Prospective, Randomized Controlled Trial [NCT04509414]Phase 4100 participants (Actual)Interventional2020-04-10Completed
The Effect of Different Sedation Regimes Administered by Anesthesiologists or Endoscopists on Cognitive Functions in Lower Gastrointestinal System Endoscopy [NCT02486328]Phase 4103 participants (Actual)Interventional2015-05-31Completed
Modulation of Long-term Memory by the Experience of Pain During Sedation With Anesthetics [NCT02515890]Phase 132 participants (Actual)Interventional2015-11-19Completed
TELSTAR: Treatment of ELectroencephalographic STatus Epilepticus After Cardiopulmonary Resuscitation [NCT02056236]172 participants (Actual)Interventional2014-04-30Completed
Atomized Intranasal Midazolam for Anxiolysis and Facilitation of Laceration Repair in the Pediatric Emergency Department: A Randomized Controlled Trial [NCT02618772]Phase 479 participants (Actual)Interventional2010-01-31Completed
A Safety, Tolerability, Pharmacokinetics and Efficacy Study of ro7049389 in: (1) Single- (With or Without Food) and Multiple- (With Midazolam) Ascending Doses in Healthy Volunteers; (2) Patients Chronically Infected With Hepatitis b Virus (3) Patients Wit [NCT02952924]Phase 1192 participants (Actual)Interventional2016-12-14Completed
Intrathecal Dexmedetomidine Versus Midazolam as Adjuvants With Intrathecal Bupivacaine for Postoperative Analgesia in High Tibial Osteotomy. A Randomized, Prospective, Double- Blinded, Comparative Study. [NCT06082232]Phase 490 participants (Anticipated)Interventional2023-11-01Not yet recruiting
"An Open-Label, Fixed-Sequence Study in Healthy Male Subjects to Assess the Drug Interaction Potential of Multiple-Doses of JNJ-54861911 With a Drug Cocktail Representative for CYP3A4, CYP2B6, CYP2C9, and CYP1A2 Substrates" [NCT02211079]Phase 116 participants (Actual)Interventional2014-09-30Completed
Study of the ADVANCE Behavioral Preparation Program for Children and Their Parents [NCT00261261]400 participants Interventional2001-01-31Completed
An Open Label, Fixed-sequence Study to Evaluate the Potential CYP3A4 Induction Effect of INDV-2000 Using Oral Midazolam as a Probe in Healthy Adults Participants [NCT05694533]Phase 120 participants (Actual)Interventional2023-03-15Completed
A Phase 1, Open-label, Multiple-probe Drug-drug Interaction Study to Determine the Effect of Rucaparib on Pharmacokinetics of Caffeine, S-Warfarin, Omeprazole, Midazolam, and Digoxin in Patients With Advanced Solid Tumors [NCT02740712]Phase 117 participants (Actual)Interventional2016-04-30Completed
Comparing Strategies of Pairing Sedation and Weaning Protocols on Outcomes of Mechanical Ventilation: A Pilot Study [NCT02219659]90 participants (Actual)Interventional2014-04-30Completed
Etomidate Versus Midazolam for Pre-Hospital Intubation: A Prospective, Randomized Trial [NCT00248729]Phase 20 participants Interventional2002-10-31Completed
Comparison Between Midazolam and Loxapine in the Treatment of Agitated Patients in the Emergency Department [NCT00290082]Phase 3120 participants (Anticipated)Interventional2005-12-31Terminated(stopped due to 2 complications with midazolam)
Sedation and Analgesia in Intensive Care: Comparison of Morphine and Fentanyl/Midazolam [NCT01602640]90 participants (Actual)Interventional2009-01-31Completed
A Four-Way Cross-Over Study to Examine the Effects of Lapatinib on the Pharmacokinetics of Orally and Intravenously Administered Midazolam in Cancer Patients [NCT00258050]Phase 124 participants (Actual)Interventional2005-11-21Completed
A Two-Part Phase 1 Study to Evaluate the Potential Drug Interaction Between ACH-0145228 and Midazolam, Digoxin, and Itraconazole in Healthy Adult Subjects [NCT04709081]Phase 138 participants (Actual)Interventional2019-12-22Completed
A Phase 3, Randomized, Double-Blind, Dose-Controlled Study to Assess the Efficacy and Safety of AQUAVAN® (Fospropofol Disodium) Injection for Minimal to Moderate Sedation in Patients Undergoing Colonoscopy [NCT00261599]Phase 3300 participants Interventional2006-03-31Completed
Clinical Randomized Study of Sublingual Midazolam in Association With Morphine by Oral Route in Arm Fracture in Children at the Emergency Children Care [NCT00416039]Phase 360 participants (Actual)Interventional2007-01-31Completed
Evaluation of the Intraoperative and PO Analgesic Outcome of Using Midazolam as Adjuvant to Bupivacaine Intrathecal Anesthesia for Children Undergoing Lower Abdominal Surgeries. [NCT04718259]Early Phase 1120 participants (Actual)Interventional2020-01-18Completed
Anaesthesia With Propofol Versus Midazolam : Effect on Oxidative Stress in the Brain of Head Trauma Patients [NCT00336882]Phase 330 participants (Actual)Interventional2006-06-30Terminated
Re-hospital Agitation and Sedation Trial: A Randomized Controlled Trial of Haloperidol Versus Midazolam for the Sedation of the Agitated Patient [NCT01501123]10 participants (Actual)Interventional2011-11-30Completed
Periprocedural Sedation for the Prevention of Post Dural Puncture Headache [NCT01503788]Phase 2100 participants (Anticipated)Interventional2012-02-29Not yet recruiting
Effects of Sedatives on Sublingual Microcirculation of Patients With Septic Shock [NCT01618396]16 participants (Actual)Interventional2011-03-31Completed
A Study to Investigate the Effects of BI 1181181 on the Pharmacokinetics of Midazolam, Warfarin, Omeprazole and Digoxin in Healthy Male Subjects [NCT02345304]Phase 10 participants (Actual)Interventional2015-03-31Withdrawn
A Phase I, Open-label, Drug Interaction Study to Evaluate the Effect of a Single-dose of CNTO 136 (Sirukumab) on CYP450 Enzyme Activities After Subcutaneous Administration in Subjects With Rheumatoid Arthritis [NCT01636557]Phase 112 participants (Actual)Interventional2012-10-11Completed
[NCT01652586]90 participants (Actual)Interventional2011-04-30Completed
A Phase 1 Drug-Drug Interaction Study Between Brigatinib and the CYP3A Substrate Midazolam in Patients With ALK-Positive or ROS1-Positive Solid Tumors [NCT03420742]Phase 124 participants (Actual)Interventional2019-06-26Completed
A Phase I, Open-label, Fixed-sequence, Two-period, Crossover, Drug-drug Interaction Study to Evaluate the Effect of Multiple Doses of Ganaplacide and Lumefantrine Combination on the Pharmacokinetics of Midazolam, Repaglinide, Dextromethorphan, Metformin, [NCT05236530]Phase 148 participants (Actual)Interventional2022-03-09Completed
A Randomized, Single-Blind, Investigator Initiative Trial Study of Remimazolam Versus Midazolam for Sedation in Diagnostic Upper Gastrointestinal Endoscopy [NCT05836545]Phase 3132 participants (Anticipated)Interventional2023-05-01Not yet recruiting
Virtual Parental Presence on Induction of Anesthesia Versus Premedication With Midazolam: A Non-Inferiority Study [NCT05834049]322 participants (Anticipated)Interventional2023-07-01Not yet recruiting
Dexmedetomidine Compared to Midazolam for Symptom Control in Advanced Cancer Patients: A Pilot Randomized Controlled Trial (RCT) [NCT01687751]Phase 20 participants (Actual)Interventional2012-11-30Withdrawn(stopped due to Study design determined to be not likely feasible)
A Phase II/III, Open-Label, Multicenter, Safety, and Efficacy Study of Dexmedetomidine in Preterm Subjects Ages ≥28 Weeks to <36 Weeks Gestational Age [NCT01508455]Phase 2/Phase 36 participants (Actual)Interventional2012-03-31Completed
Propofol or Midazolam for Sedation and Early Extubation Following Coronary Artery Bypass Graft Surgery [NCT05290324]60 participants (Actual)Interventional2019-02-01Completed
Prospective, Randomized, Double-blind, Double-dummy, Active-controlled, Phase 3 Clinical Trial Comparing the Safety and Efficacy of Intranasal Dexmedetomidine to Oral Midazolam as Premedication for Propofol Sedation in Pediatric Patients Undergoing Magnet [NCT05192629]Phase 3250 participants (Anticipated)Interventional2022-03-09Recruiting
SEDATION OF ADULT PATIENTS UNDERGOING GASTROINTESTINAL ENDOSCOPY: A NETWORK META-ANALYSIS [NCT03632330]6,963 participants (Actual)Observational2018-02-05Completed
Nitrous Oxide as a Putative Novel Dual-Mechanism Treatment for Bipolar Disorder [NCT02351869]Phase 225 participants (Actual)Interventional2015-08-31Terminated(stopped due to This study was terminated due to COVID-19 pandemic-related halting of recruitment in the context of an upcoming replacement of the study MRI scanner.)
A Phase 1, Randomized, Placebo-Controlled, Multiple Dose Study To Evaluate The Safety, Pharmacokinetics And Pharmacodynamics Of PF-06282999 In Healthy Overweight Subjects And A Fixed-Sequence Study To Assess The Effect Of PF-06282999 On The Pharmacokineti [NCT01707082]Phase 169 participants (Actual)Interventional2012-10-31Completed
Propofol Versus Midazolam for Sedation in Mechanically Ventilated Critically Ill Patients Who Presented With Traumatic Brain Injury: Cytokine Response and Neuropsychological Assessment (IRRC#1201M) [NCT01712477]Phase 41 participants (Actual)Interventional2011-11-30Terminated(stopped due to Difficulty in recruiting)
[NCT01731067]Phase 110 participants (Anticipated)Interventional2012-11-30Completed
Randomized Double-blind Placebo-controlled Trial: Administration of Morphine-Placebo vs. Morphine-Midazolam in Pre-hospital Traumatic Patients With Severe Acute Pain. [NCT01731184]Phase 3100 participants (Actual)Interventional2006-11-30Completed
Comparison of Two Techniques of Ultrasound-guided Sciatic Nerve Block Using Levobupivacaine 0.5% in Orthopedic Surgery at the Hospital Pablo Tobon Uribe - Clínica CES, 2013, Randomized Clinical Trial [NCT01734954]66 participants (Anticipated)Interventional2013-04-30Not yet recruiting
The Influence of Genotype/Phenotype, Grapefruit Juice and Orange Juice on the Pharmacokinetics of Sunitinib (Sutent, SU011248) in Patient With Imatinib Resistant Gastrointestinal Stromal Cell Tumor (GIST) or Metastatic Renal Cell Carcinoma [NCT01743300]Phase 115 participants (Actual)Interventional2007-07-31Completed
A Single-centre, Randomised Controlled Study of Entonox Versus Midazolam Sedation in Gastroscopy. [NCT01744184]Phase 4200 participants (Anticipated)Interventional2013-05-31Recruiting
Baskent University Institutional Review Board [NCT02325583]Phase 319 participants (Actual)Interventional2014-01-31Completed
Pain, Fentanyl Consumption, and Delirium in Children After Scoliosis Surgery: Dexmedetomidine Versus Midazolam [NCT01748630]Phase 442 participants (Actual)Interventional2012-02-29Completed
A Single-Center Randomized, Open-Label, Study to Assess the Relative Bioavailability of New Formulations of GSK1265744 LAP in Healthy Adult Subjects. [NCT01754116]Phase 143 participants (Actual)Interventional2013-01-31Completed
A Phase 1 Placebo-Controlled Study To Assess The Safety, Tolerability, Pharmacokinetics And Effect On Midazolam Pharmacokinetics Of Multiple Oral Doses Of PF-05175157 In Otherwise Healthy Overweight And Obese Subjects [NCT01757756]Phase 112 participants (Actual)Interventional2012-10-31Completed
Identification and Evaluation of Endogenous Markers for the Assessment of CYP3A Activity in Female Subjects Using Metabolomics [NCT01760642]Phase 116 participants (Actual)Interventional2012-12-31Completed
A Phase 1, Open-label, Multi-Dose Study to Assess Pharmacokinetic Interaction Between PA-824 and Midazolam [NCT01768273]Phase 114 participants (Actual)Interventional2009-12-31Completed
Comparison of in Intubation With Nerve Block and Intubation With Sedation in Awake Patients in Terms of Efficacy, Complications and Physician's Satisfaction [NCT01768377]Phase 370 participants (Anticipated)Interventional2012-11-30Recruiting
Open Label Study for the Functional Characterization of Drug Metabolism and Transport [NCT01788254]Phase 1144 participants (Actual)Interventional2012-01-31Completed
Clinical Predictors and Epigenetic Markers for Liver Fibrosis in Alpha-1 Antitrypsin Deficiency [NCT01810458]109 participants (Actual)Observational2013-10-31Completed
A Phase I, Multiple-Dose, Open-Label, Crossover Study in Healthy Subjects to Assess the Effect of Dolutegravir (DTG) on the Pharmacokinetics (PK) of Cenicriviroc (CVC) and the Effect of CVC on the PK of DTG and on a Single Dose of Midazolam [NCT01827540]Phase 120 participants (Actual)Interventional2013-03-31Completed
The Effect of Dexmedetomine Premedication on the Bispectral Index Values Using Sedation With Propofol During Spinal Anesthesia on Geriatric Chronic Renal Failure Patients Undergoing Hip Fracture Surgery The Effect of Dexmedetomine Premedication on the Bis [NCT01837290]Phase 360 participants (Actual)Interventional2012-12-31Completed
Open Label Repeated Dose Study for the Evaluation of Heritability of and Genetic Influences on Drug Pharmacokinetics (TWINS II) [NCT01845194]Phase 1117 participants (Actual)Interventional2009-12-31Completed
A Phase II/III, Open-Label, Multicenter, Safety, Efficacy and Pharmacokinetic Study of Dexmedetomidine in Neonates Ages ≥28 Weeks to ≤44 Weeks Gestational Age [NCT01159262]Phase 2/Phase 336 participants (Actual)Interventional2010-07-31Completed
A Phase 1 Study of Oprozomib to Assess Food Effect, Drug-Drug Interaction With Midazolam, and Safety and Tolerability in Patients With Advanced Malignancies [NCT02244112]Phase 143 participants (Actual)Interventional2014-08-31Terminated(stopped due to "Why study stopped revised to A program evaluation identified that the safety profile and pharmacokinetic (PK) characteristics of the formulation used in all oprozomib studies required further optimization and thus enrollment in OPZ009 was halted")
The Platelet Aggregation After tiCagrelor Inhibition and FentanYl Trial [NCT02683707]Phase 4212 participants (Actual)Interventional2016-03-31Completed
Effects of BMS-986142 on the Single-dose Pharmacokinetics of Methotrexate and Probe Substrates Montelukast (CYP2C8), Flurbiprofen (CYP2C9), Midazolam (CYP3A4), Digoxin (P-gp), and Pravastatin (OATP1B1) in Healthy Subjects [NCT02456844]Phase 124 participants (Actual)Interventional2015-05-31Completed
Analgesic Effect of Single Dose Intravenous Acetaminophen in Pediatric Patients Undergoing Tonsillectomy [NCT01691690]Phase 2250 participants (Actual)Interventional2012-10-31Completed
Ketamine for Treatment of Multiple Sclerosis-related Fatigue [NCT03500289]Phase 1/Phase 218 participants (Actual)Interventional2018-08-10Completed
Patient-controlled Sedation With Propofol Versus Combined Sedation During Bronchoscopy - a Randomized Controlled Trial [NCT03357393]150 participants (Actual)Interventional2016-04-04Completed
A Clinical Study to Evaluate the Pharmacokinetics of Microdose Midazolam, Dabigatran, Pitavastatin, Atorvastatin and Rosuvastatin in Healthy Volunteers and Renal Impairment Patients [NCT05747768]Phase 460 participants (Anticipated)Interventional2022-07-15Recruiting
Comparing Intranasal Dexmedetomidine With Oral Midazolam as Premedication for Older Children Undergoing General Anesthesia for Dental Rehabilitation [NCT02250703]Phase 375 participants (Actual)Interventional2014-09-30Completed
Ketamine Infusion for Rapid Reduction of Suicidality in Pediatrics: a Pilot Randomized Controlled Trial [NCT04955470]Phase 1/Phase 296 participants (Anticipated)Interventional2022-06-01Recruiting
A Study of Ketamine as an Antidepressant [NCT01441505]Phase 242 participants (Anticipated)Interventional2011-09-30Recruiting
The Effect of Sedation During Transesophageal Echocardiography on Heart Rate Variability:A Comparison of Hypnotic Sedation With Medical Sedation [NCT01444976]76 participants (Actual)Interventional2010-12-31Completed
Ketamine/Midazolam Premedication Versus Pre-extubation Ketofol. Effect on Emergence Agitation and Recovery Profile After Pediatric Adenotonsillectomy: A Randomized Comparative Study. [NCT06010927]Phase 4140 participants (Anticipated)Interventional2023-08-25Recruiting
Safety, Tolerability, Pharmacokinetic and Pharmacodynamic Effects of Single and Multiple Escalating Doses of ODM-108: A Single Centre Study in Healthy Male Volunteers [NCT02432664]Phase 185 participants (Actual)Interventional2015-04-14Terminated(stopped due to The study was terminated after the second cohort had completed Part II due complex PK results. There were no safety concerns.)
Remifentanil Plus Ketamine Versus Midazolam Plus Fentanyl for Dynamic Flexible Bronchoscopy: Randomized Double-blind Clinical Trial [NCT03613792]Phase 40 participants (Actual)Interventional2023-09-30Withdrawn(stopped due to Change in procedure means limited value for study question)
Comparison of Two Methods Using Intranasal Lidocaine to Alleviate Discomfort Associated With Administration of Intranasal Midazolam in Children. [NCT03054844]Phase 255 participants (Actual)Interventional2017-04-03Completed
Ketamine as an Adjunctive Therapy for Major Depression - a Randomised Controlled Pilot Trial: The KARMA-Dep Trial [NCT03256162]Phase 125 participants (Actual)Interventional2017-09-07Completed
The Effect of Dexmedetomidine vs Midazolam on Resting Energy Expenditure in Critically Ill Patients: Randomized Controlled Study [NCT03030911]Phase 430 participants (Actual)Interventional2017-01-01Completed
Efficacy of Virtual Reality Distraction Technique for Anxiety and Pain Control in Orthopedic Forearm Surgeries Performed Under Supraclavicular Brachial Plexus Block [NCT05512728]30 participants (Anticipated)Interventional2020-12-20Active, not recruiting
A Single-center, Open-label Study to Investigate the Food Effect on the Pharmacokinetics of ACT-541468 and the Effect of Single- and Multiple-dose ACT-541468 on the Pharmacokinetics of Midazolam and Its Metabolite 1-Hydroxymidazolam in Healthy Male Subjec [NCT03017495]Phase 120 participants (Actual)Interventional2017-01-01Completed
The Comparison of Different Administration Routes of Pediatric Premedication-Single Center,Randomized,Controlled Trial [NCT02313337]Phase 480 participants (Anticipated)Interventional2014-12-31Not yet recruiting
Association Between Variations in CYP Pheno- and Genotypes and Plasma Concentration of Chlordiazepoxide in the Treatment of Alcohol Withdrawal Symptoms [NCT05563350]26 participants (Anticipated)Observational [Patient Registry]2022-01-29Recruiting
Pericapsular Nerve Group Block for Positional Pain and Postoperative Analgesia [NCT05079087]100 participants (Anticipated)Interventional2021-04-01Recruiting
The Effect of Premedication Methods to be Applied to Prevent Preoperative Anxiety in Patients Who Will be Operated for Breast Cancer, on Postoperative Anxiety and Pain [NCT05647642]80 participants (Anticipated)Observational2022-10-16Recruiting
Prospective Randomized Clinical Trial to Evaluate the Use of Paravertebral Blocks in Reconstructive Breast Surgery [NCT00542542]Phase 389 participants (Actual)Interventional2007-09-30Completed
A Prospective, Randomized, Single-Blind Study to Evaluate the Efficacy of Transversus Abdominis Plane Versus Paravertebral Regional Blockade in Patients Undergoing Laparoscopic Colectomy [NCT02164929]17 participants (Actual)Interventional2013-12-31Terminated(stopped due to Poor recruitment)
A Randomized Controlled Trial Comparing Lorazepam With Midazolam for Sedation of Mechanically Ventilated Pediatric Patients [NCT00109395]Phase 2/Phase 3179 participants (Actual)Interventional2004-09-30Completed
Clinical Effects of Esketamine Induction Intubation Versus Conventional Induction Intubation in ICU Patients: a Single-center Randomized Clinical Trial [NCT05464979]Phase 4100 participants (Anticipated)Interventional2022-08-01Recruiting
Phase 1, Open-label, Single Sequence, Two-Period Crossover Trial to Evaluate the Effect of Tepotinib on CYP3A by Investigating the PK of the CYP3A Substrate Midazolam in Healthy Subjects [NCT03628339]Phase 112 participants (Actual)Interventional2018-08-20Completed
Physiologic Determinants of PPI Disposition in Children [NCT04248335]Phase 4150 participants (Anticipated)Interventional2018-07-03Recruiting
Does Camel Milk Consumption Decrease The Efficacy Of Midazolam For Sedation: A Pilot Study [NCT04397393]26 participants (Actual)Observational2020-07-01Terminated(stopped due to insufficient data)
Interventional, Open-label, One-sequence Study to Investigate the Effects of Multiple Doses of Foliglurax on the Pharmacokinetics of Cytochrome P450 (CYP450) Substrates Caffeine (CYP1A2), Montelukast (CYP2C8), and Midazolam (CYP3A4) in Healthy Subjects [NCT04275115]Phase 120 participants (Actual)Interventional2020-02-10Completed
A Phase 1, Open-Label, Single-Sequence, 2-Period Study to Evaluate the Effect of IPI-145 on Single-Dose Pharmacokinetics of Midazolam (a CYP3A Substrate) in Healthy Subjects [NCT01925911]Phase 114 participants (Actual)Interventional2013-08-31Completed
Effect of Remimazolam With Protocolized Sedation on Critical Ill, Mechanical Ventilated Patients Compared With Midazolam - A Parallel, Multicenter, Single-blind Randomized Controlled Trial [NCT05160987]440 participants (Anticipated)Interventional2022-03-29Recruiting
The Effects of Multiple Dose Fluoxetine and Metabolites on CYP1A2, CYP2C19, CYP2D6 and CYP3A4 Activity [NCT01361217]10 participants (Actual)Interventional2011-09-30Completed
Effects of Cannabis Use on Sedation Requirements for Oral Surgery Procedures [NCT05873465]Phase 460 participants (Anticipated)Interventional2023-05-22Not yet recruiting
Comparative Study Between Nebulised Dexmedetomidine and Nebulised Midazolam in Reducing Preoperative Anxiety and Emergence Delirium in Children Undergoing Lower Abdominal Surgeries [NCT05872087]Phase 160 participants (Anticipated)Interventional2022-11-01Recruiting
Elucidating the Neurocircuitry of Irritability With High-Field Neuroimaging to Identify Novel [NCT05046184]Phase 2180 participants (Anticipated)Interventional2022-05-05Recruiting
A Phase 1, Randomized, Open Label, Crossover Study to Evaluate the Pharmacokinetic Interaction Between SSP-004184 (SPD602) and Midazolam in Healthy Adult Subjects [NCT01989169]Phase 130 participants (Actual)Interventional2013-11-26Completed
Combination Use of Intravenous Ketamine-midazolam as a Sedative Agent in Endoscopic Retrograde Cholangiopancreatography ; A Randomized Control Trial [NCT06111872]Phase 290 participants (Anticipated)Interventional2023-07-18Recruiting
Evaluation of Renal Protection Of Dexmedetomidine Versus Midazolam As a Sedative For Septic Patients In Intensive Care Unit [NCT05903963]Phase 140 participants (Anticipated)Interventional2023-05-22Recruiting
Comparison Between Music Therapy and Intravenous Midazolam 0,02 mg/kgBW in Reducing Preoperative Anxiety: Study on Patient Undergoing Brachytherapy With Spinal Anesthesia [NCT03269929]60 participants (Actual)Interventional2017-01-01Completed
Dexmedetomidine Versus Midazolam Premedication on Emergence Agitation After Strabismus Surgery in Children [NCT01895023]Phase 4156 participants (Actual)Interventional2013-09-30Completed
[NCT01535937]Phase 1/Phase 255 participants (Actual)Interventional2012-02-29Terminated(stopped due to An analysis demonstrated that running the final participants was unnecessary.)
An Open-Label Study Evaluating the Effect of Food on the Pharmacokinetics of Palovarotene and the Effect of Palovarotene on the Pharmacokinetics of the CYP3A4 Substrate Midazolam in Two Cohorts of Healthy Adult Subjects [NCT04829773]Phase 148 participants (Actual)Interventional2019-01-03Completed
Non-randomized, Non-blinded, Non-placebo-controlled Study to Investigate the Influence of Repeated Daily Administration of 600 mg Rifampicin Given Once Daily Over 11 Days on the Pharmacokinetics, Safety, and Tolerability of a Single Oral Dose of 4 mg Vila [NCT02975440]Phase 112 participants (Actual)Interventional2016-11-10Completed
Efficacy of Rapid-Acting NMDA Antagonist for Treatment of Adolescent Depression and Anxiety Disorders [NCT02579928]Phase 417 participants (Actual)Interventional2015-10-31Completed
The Effect of Intraoperative Administration of Dexmedetomidine, Propofol and Midazolam on Postoperative Levels of Inflammatory Markers and Development of Postoperative Cognitive Dysfunction After Pertrochanteric Fracture Surgery. [NCT05398757]80 participants (Anticipated)Interventional2022-07-01Recruiting
A Phase 1, Drug-Drug Interaction Study to Evaluate the Safety, Tolerability, and the Induction Potential of TBAJ-876 on CYP3A4 and P-glycoprotein and the Inhibition Potential of TBAJ-876 on P-glycoprotein in Healthy Adult Subjects [NCT05526911]Phase 128 participants (Actual)Interventional2022-07-20Completed
Role of Bilateral Ultrasound Guided Superficial Cervical Plexus Block as a Part of Enhanced Recovery After Thyroid Surgery [NCT05476003]45 participants (Anticipated)Interventional2022-08-15Not yet recruiting
A Study to Characterize LY3314814 Pharmacokinetics as a Function of Dosing Duration and to Determine the Effect of LY3314814 on the Pharmacokinetics of CYP3A Substrates in Healthy Subjects [NCT02406261]Phase 182 participants (Actual)Interventional2015-04-30Completed
Personalizing Preprocedural Sedation for Regional Anesthesia: A Randomized Trial and Qualitative Assessment of Patient-Centered Outcomes and Experience [NCT05579509]Early Phase 1150 participants (Anticipated)Interventional2022-10-01Recruiting
Recall of Experience and Conscious Awareness in Psilocybin Treatment of Depression (The RECAP Study): Pilot Phase in Healthy Adult Volunteers [NCT04842045]Phase 18 participants (Actual)Interventional2021-05-21Completed
A Phase 1, Drug-Drug Interaction Study to Evaluate the Effect of Itraconazole on the Pharmacokinetics of TAK-272 and the Effect of TAK-272 on the Pharmacokinetics of Digoxin or Midazolam In the Healthy Adult Participants [NCT02370615]Phase 134 participants (Actual)Interventional2015-02-28Completed
Comparison of Outcomes During MRI Sedation With Midazolam-dexmedetomidine Versus Ketamine-dexmedetomidine [NCT02129426]21 participants (Actual)Interventional2014-08-31Terminated(stopped due to Unable to recruit the adequate number of subjects)
Long Term Evaluation and Management of Atrial Fibrillation in Pacemaker Patients (AF-pacemaker Tx Study) [NCT03401593]135 participants (Anticipated)Interventional2019-10-31Not yet recruiting
The Effect of Different Sedation Protocols on Skeletal Muscle Metabolism in Mechanical Ventilated Patients [NCT03402113]360 participants (Anticipated)Interventional2017-12-20Recruiting
The Effect of Sedation on Eye Movements [NCT00646646]65 participants (Actual)Interventional2007-04-30Completed
A Double-blind, Randomized, Psychoactive Placebo-controlled, Study to Evaluate the Efficacy and Safety of 3 Fixed Doses (28 mg, 56 mg and 84 mg) of Intranasal Esketamine in Addition to Comprehensive Standard of Care for the Rapid Reduction of the Symptoms [NCT03185819]Phase 2147 participants (Actual)Interventional2017-10-05Completed
Intravenous Sub-anesthetic Ketamine Treatment in Treatment-Resistant Depression [NCT02360280]Phase 262 participants (Actual)Interventional2015-04-01Completed
The Effects of Sedatives on Tobacco Use Disorder [NCT03813121]Phase 1/Phase 210 participants (Actual)Interventional2019-06-01Completed
Development of High-throughput Minidose Inje Cocktail Method for Simultaneous Evaluating Five Cytochrome P450 Isoforms in Human [NCT01570569]Phase 126 participants (Actual)Interventional2011-01-31Completed
A Phase I, Multi-center, Open-label, Drug-drug Interaction Study to Assess the Effect of TKI258 on the Pharmacokinetics of Caffeine, Diclofenac, Omeprazole and Midazolam Administered as a Four-drug Cocktail in Patients With Advanced Solid Tumors, Excludin [NCT01596647]Phase 139 participants (Actual)Interventional2012-05-31Completed
A Randomized, Clinical Trial of Oral Midazolam Versus Oral Ketamine for Sedation During Laceration Repair. [NCT01925898]Phase 460 participants (Anticipated)Interventional2013-08-31Recruiting
Randomized, Double-blind, Placebo-controlled Study to Evaluate the Efficacy of Propofol or Midazolam Versus Placebo for Preoperative Medication in Patients Undergoing Elective Orthopedic Surgery [NCT01976845]Phase 4139 participants (Actual)Interventional2013-11-30Completed
The Effects of Mild Sedation on Compensatory Upper Limb Motor Function Networks Based on Multimodal Magnetic Resonance Imaging in With Gliomas in Brain Eloquent Areas [NCT03984240]100 participants (Anticipated)Interventional2020-09-01Recruiting
Ketamine as a Sedation Adjunct for Endoscopic Procedures [NCT03461718]Phase 266 participants (Actual)Interventional2018-03-05Completed
A Comparison of Intranasal Midazolam and Nitrous Oxide (N2O) Minimal Sedation for Minor Procedures in a Pediatric Emergency Department [NCT03085563]Phase 463 participants (Actual)Interventional2017-05-24Completed
An Open-Label Phase 1 Study to Determine the Effect of Lenvatinib (E7080) on the Pharmacokinetics of Midazolam, a CYP3A4 Substrate, in Subjects With Advanced Solid Tumors [NCT02686164]Phase 151 participants (Actual)Interventional2016-04-18Completed
Safe and Effective Sedation in Chronic Alcoholic Patients Underwent Diagnostic Endoscopic Procedures: a Prospective, Randomized Study Comparing Midazolam and Propofol With Midazolam [NCT01617707]11 participants (Actual)Interventional2012-05-09Terminated(stopped due to because of difficulties for participants enrollment)
Administration of Subanesthetic Dose of Ketamine and Electroconvulsive Treatment on Alternate Week Days in Patients With Treatment Resistant Depression: A Double Blind Placebo Controlled Trial [NCT02522377]15 participants (Actual)Interventional2015-08-31Completed
Impact of Timing of Midazolam Administration on Incidence of Postoperative Nausea and Vomiting in Patients Undergoing Laparoscopic Gynecological Surgery; a Randomized Double-blinded Controlled Study [NCT05057767]120 participants (Actual)Interventional2021-09-10Completed
Intravenous Ketamine in Treatment-Resistant Bipolar Depression [NCT00947791]Phase 41 participants (Actual)Interventional2009-07-31Terminated(stopped due to Change in available resources for study procedures)
A Phase 1 Randomized, Double-Blind, Placebo-Controlled, Single-and Multiple-Dose Study Evaluating Safety, Tolerability, and Pharmacokinetics, With an Open-Label Initial Food Effect and CYP3A Drug-Drug Interaction Study, of FTX-6058 in Healthy Adult Subjec [NCT04586985]Phase 1109 participants (Actual)Interventional2020-10-26Completed
[NCT00004424]120 participants Interventional1996-07-31Completed
An Open-Label Safety Study of USL261 in the Outpatient Treatment of Adolescent and Adult Subjects With Seizure Clusters [NCT02161185]Phase 37 participants (Actual)Interventional2014-05-31Terminated(stopped due to Study terminated due to slow enrollment. There were no safety concerns.)
A Study on the Relationship Between Biodiversity of Intestinal Microbiota in Patients and Different Sedative-hypnotics Undergoing Mechanical Ventilation [NCT03401736]0 participants (Actual)Interventional2018-03-01Withdrawn(stopped due to Can't get enough participant)
A Single-centre, Open-label Study in Healthy Men to Investigate the Effect of Repeated Oral Doses of ASP2151 on the Pharmacokinetics of Midazolam in Healthy Men [NCT02403635]Phase 127 participants (Actual)Interventional2015-04-30Completed
"An Open-label, Single-sequence Study of the Effect of Belatacept on the Pharmacokinetics of Caffeine, Losartan, Omeprazole, Dextromethorphan, and Midazolam Administered as Inje Cocktail in Healthy Subjects" [NCT01766050]Phase 445 participants (Actual)Interventional2013-01-31Completed
Nebulized Lidocaine and Intranasal Midazolam for Reducing Pain/Anxiety of Nasogastric Tube Insertion in Children: A Randomized Clinical Trial [NCT04571879]Phase 348 participants (Anticipated)Interventional2021-08-25Recruiting
The Effect of Audiovisual Aids on Perioperative Stress Response, Pain and Overall Experience - a Randomized Controlled Pilot Study [NCT02506673]26 participants (Actual)Interventional2016-01-14Completed
A Single-center, Open-label Study to Investigate the Effect of a Single Oral Dose and Repeated Oral Doses of ID-082 on the Pharmacokinetics of Midazolam and Its Metabolite 1-hydroxymidazolam in Healthy Male Subjects. [NCT03363984]Phase 120 participants (Actual)Interventional2017-11-27Completed
Propofol Administered by Gastroenterologists by Target Controlled Infusion Pump During Endoscopy: a Randomized Double Blind Controlled Study [NCT02062177]Phase 4140 participants (Actual)Interventional2014-02-28Completed
Spinal Versus General Anesthesia With Popliteal and Adductor Canal Blocks for Ambulatory Foot and Ankle Surgery: A Double-Blinded Randomized Controlled Trial. [NCT02996591]Phase 436 participants (Actual)Interventional2017-01-31Completed
Music vs Midazolam During Preoperative Nerve Block Placement: A Prospective, Randomized Controlled Study [NCT03069677]Phase 3160 participants (Actual)Interventional2017-04-12Completed
An Open-label, Fixed-sequence, Drug-drug Interaction Study in Healthy Subjects to Evaluate the Effect of GLPG3667 on the Pharmacokinetics of Midazolam, a Sensitive Index Substrate of CYP3A4 [NCT04736927]Phase 114 participants (Actual)Interventional2021-01-15Completed
AGItated Patients Management: intraNASAL Midazolam vs Intramuscular Loxapine, a Randomized Non Inferiority Trial [NCT05324852]Phase 3830 participants (Anticipated)Interventional2023-04-14Recruiting
ICU Delirium: Can Dexmedetomidine Reduce Its Incidence? [NCT00417664]90 participants (Actual)Observational2002-04-30Completed
The Effect of Handheld-multimedia Versus Oral Midazolam Preanesthetic on the Level of Perioperative Anxiety in Pediatric Day-care Surgery: A Randomized Controlled Trial [NCT04273035]Phase 4150 participants (Anticipated)Interventional2020-02-01Recruiting
Clinical Study of Oral Midazolam Combined With Esketamine Administered Intranasally for Pediatric Preoperative Sedation [NCT05925283]Phase 4126 participants (Anticipated)Interventional2023-06-30Recruiting
Possible Immuno-Modulatory Effect of Tocilizumab in Patients With Refractory Status Epilepticus. [NCT05346666]Phase 350 participants (Anticipated)Interventional2022-06-25Recruiting
Sustained Mood Improvement With Laughing Gas Exposure: A Randomized Controlled Pilot Trial [NCT04957368]Phase 440 participants (Anticipated)Interventional2021-11-03Recruiting
A Single-center, Open-label, Fixed-sequence Phase I Drug-drug Interaction Clinical Study to Investigate the Pharmacokinetics of SHR3680 With Midazolam (CYP3A4 Substrates), S-Warfarin (CYP2C9 Substrates) and Omeprazole (CYP2C19 Substrates) in Prostate Canc [NCT04676035]Phase 118 participants (Actual)Interventional2020-06-15Completed
Cohort Study of Sedatives' Effects on Neurological Function in Patients With Eloquent Area Glioma: Comparison With a Control Group Without Intracranial Pathology [NCT02439164]36 participants (Actual)Interventional2015-05-26Completed
A Comparative Study Between Intrathecal Magnesium Sulphate Versus Midazolam Along With Epidural 0.75% Ropivacaine in Combined Spinal Epidural Technique for Preeclampsia Parturients Undergiong Elective Caesarean Section [NCT02619799]Phase 2/Phase 350 participants (Actual)Interventional2015-01-31Completed
A Double-blinded, Randomized Trial Comparing the Safety & Efficacy of Intranasal Dexmedetomidine, Intranasal Fentanyl & Intranasal Midazolam in the Pediatric Emergency Room [NCT05057689]Phase 2180 participants (Anticipated)Interventional2022-10-31Not yet recruiting
Pain, Agitation and Delirium Protocol in Ventilated Patients in the Duke CICU [NCT02903407]Phase 47 participants (Actual)Interventional2017-09-01Terminated(stopped due to All enrolled participants completed the study protocol but the study was terminated prior to the goal number of participants due to low recruitment)
Patient Satisfaction With Propofol for Out Patient Colonoscopy: A Prospective, Randomized, Double-Blind Study [NCT02937506]Phase 4600 participants (Actual)Interventional2013-11-30Completed
Anxiolysis for Emergency Department Procedures in Pediatric Patients Using Intranasal Ketamine Compared With Intranasal Midazolam: A Randomized Controlled Trial [NCT03043430]Phase 410 participants (Actual)Interventional2016-05-31Terminated(stopped due to Research manpower shortage)
A Comparison of Midazolam vs. Midazolam/Ketamine for Conscious Sedation in Patients Undergoing Phacoemulsification Under Topical Anesthesia [NCT03054103]Phase 4105 participants (Actual)Interventional2016-05-03Completed
Comparison of Sedation, Pain, and Care Provider Satisfaction Between the Use of Intranasal Ketamine Versus Intranasal Midazolam and Fentanyl During Laceration Repair [NCT03528512]Phase 45 participants (Actual)Interventional2018-09-04Terminated(stopped due to Staffing for study was eliminated)
Study: Persistent Inflammation, Immunosuppression and Catabolism Syndrome (PICS): A New Horizon for Surgical Critical Care: Project 4A: Inspiratory Muscle Training and Diaphragm Strength [NCT02367170]Phase 1/Phase 21 participants (Actual)Interventional2015-03-31Terminated(stopped due to Unable to recruit sufficient number of patients)
A Comparative Study Between Inhalational Sevoflurane Sedation With Intravenous Midazolam Sedation for Upper Endoscopy Procedure. [NCT04410211]30 participants (Actual)Interventional2018-06-01Completed
A Randomized Controlled Trial Comparing the Efficacy of Intranasal Midazolam and Conventional Treatment With Intravenous Diazepam for Control of Seizures in Children [NCT04885075]Phase 460 participants (Anticipated)Interventional2021-05-30Not yet recruiting
Safety and Efficacy of Intranasal Dexmedetomidine as a Sedative in Pediatric Dentistry: a Randomized, Double-blind Clinical Study [NCT02985697]Phase 4100 participants (Anticipated)Interventional2017-01-31Not yet recruiting
Clinical Predictors of Intravenous Ketamine Response in Treatment-Resistant Depression: A Randomized, Double-Blind, Midazolam-Controlled Pilot Study [NCT05625555]Phase 340 participants (Anticipated)Interventional2023-12-31Not yet recruiting
Dexmedetomidine Versus Ketorolac/ Midazolam on Perioperative Outcome During Retinal Surgery. [NCT03143244]Phase 460 participants (Actual)Interventional2016-01-01Completed
Ultrasound-guided Block of the Brachial Plexus Using Prilocaine: Effects of Local-anesthetic Dose Reduction on Parameters of Block Quality and Adverse Effects in Outpatients [NCT01309360]Phase 4120 participants (Actual)Interventional2009-09-30Completed
A Fixed Sequence, Open-Label Study to Assess the Effect of Multiple Doses of AZD5718 on the Pharmacokinetics of Oral Midazolam (a CYP450 3A Probe) in Healthy Subjects [NCT04492709]Phase 114 participants (Actual)Interventional2020-07-30Completed
Comparison of Maximum Blood Concentrations of Colchicine Between Responders and Non-responders to Colchicine Treatment During Gout Flare [NCT03933007]Phase 488 participants (Anticipated)Interventional2019-09-10Recruiting
Phase 1, Partially-Blind, Placebo Controlled Randomized, Combined SAD With Food Effect Cohort and MAD and DDI Study to Evaluate Safety, Tolerability, PK and PK Interaction Between TBA-7371 With Midazolam and Bupropion in Healthy Subjects. [NCT03199339]Phase 174 participants (Actual)Interventional2017-08-29Completed
ROle of Dexmedetomidine in Modifying Immune Paralysis In Patient With Septic Shock: Randomized Controlled Trial (RODIS Trial) [NCT03989609]Phase 224 participants (Actual)Interventional2019-06-20Completed
An Open-label Drug Interaction Study in Healthy Subjects to Evaluate the Effect of Oral Doses of JNJ-54175446 on the Inhibition of Cytochrome P450 CYP3A4, CYP2C9, CYP1A2 and CYP2D6 Activity and the Induction of CYP2B6 and CYP2C19 Activity Using a Multiple [NCT03058419]Phase 116 participants (Actual)Interventional2017-03-14Completed
Measurement of Midazolam Levels in Follicular Fluid and Correlation of Midazolam Levels in Follicular Fluid and Oocyte Quality, Fertilization Rate, Embryo Development Pattern and Euploid Status [NCT03049293]Early Phase 130 participants (Actual)Interventional2017-06-20Terminated(stopped due to Difficulty in recruiting participants)
A Phase 1 Open-Label Study to Evaluate the Interaction Potential Between AT 527 and Midazolam in Healthy Adult Subjects [NCT04865445]Phase 124 participants (Actual)Interventional2021-04-22Completed
Diclofenac Premedication, as the Effect of Preemptive Analgesia After Post-thoracotomy Chest and Shoulder Pain, as Well as the Changes of the Postoperative Breathing Function Values, a Randomized, Controlled, Prospective Trial [NCT02445599]Phase 43 participants (Actual)Interventional2014-04-30Completed
Nasal Inhalation of Sevoflurane Versus Midazolm,Ketamine and Propofol For Pediatric Undergoing Upper Gastrointestinal Endoscopy [NCT05474937]74 participants (Anticipated)Interventional2022-06-01Recruiting
Perineural Versus Intravenous Midazolam in Patients Undergoing Forearm Orthopedic Surgeries Using Supraclavicular Brachial Plexus Block [NCT03185351]Phase 290 participants (Actual)Interventional2017-06-14Completed
A Phase I, Multi-center, Open Label, Drug-drug Interaction Study to Assess the Effect of Ceritinib on the Pharmacokinetics of Warfarin and Midazolam Administered as a Two-drug Cocktail in Patients With ALK-positive Advanced Tumors Including Non-small Cell [NCT02422589]Phase 133 participants (Actual)Interventional2015-10-23Completed
A 4-Part Phase 1 Study to Evaluate the Effect of GDC-0853 on the Pharmacokinetics of Midazolam, Rosuvastatin, and Simvastatin and the Effect of Itraconazole on the Pharmacokinetics of GDC-0853 [NCT03174041]Phase 163 participants (Actual)Interventional2017-04-18Completed
An Open Label, 2-Period Study to Assess the Effect of Entinostat on the Pharmacokinetics of Midazolam in Healthy Adult Subjects [NCT03187015]Phase 126 participants (Actual)Interventional2017-05-23Completed
Evaluation and Validation of Metabolic Markers for the Assessment of CYP3A Activity and Prediction of Drug-drug Interaction in Korean Healthy Subjects [NCT02328443]Phase 124 participants (Actual)Interventional2014-01-31Completed
A Phase I, Open-label, Fixed-sequence, Crossover, Drug-drug Interaction Study to Investigate the Inhibition Potential of KL1333 on CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, and CYP3A4 in Healthy Subjects [NCT04643249]Phase 114 participants (Actual)Interventional2020-11-10Completed
Pharmacokinetics-pharmacodynamics of Morphine With or Without Midazolam Administered by Continuous Infusion in Neonatal Intensive Care [NCT05371886]180 participants (Anticipated)Interventional2023-04-01Recruiting
A Single-center, Double-blind, Parallel-group, Randomized, Placebo-controlled, Multiple-ascending Oral Dose Study to Investigate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of ACT-709478 in Healthy Subjects [NCT03165097]Phase 146 participants (Actual)Interventional2017-07-07Completed
Ketamine for Relapse Prevention in Recurrent Depressive Disorder: a Randomised, Controlled, Pilot Trial: the KINDRED Trial [NCT02661061]Phase 19 participants (Actual)Interventional2015-12-31Terminated(stopped due to Inadequate recruitment)
Pharmacovigilance in Gerontopsychiatric Patients [NCT02374567]Phase 3407 participants (Actual)Interventional2015-01-31Terminated
A Phase I, Open-Label Study to Assess the Effects of PRC-4016 (Icosabutate) on the Pharmacokinetics of Midazolam, Omeprazole, Flurbiprofen and Simvastatin in Healthy Male/Female Subjects [NCT02367937]Phase 116 participants (Actual)Interventional2014-08-31Completed
An Open-label Crossover Trial Assessing the Value of Dabigatran in a Drug Interaction Cocktail in Healthy Young Volunteers [NCT02361619]Phase 116 participants (Actual)Interventional2015-02-28Completed
A Phase I, Multi-center Study to Determine the Effect of Fluzoparib on Pharmacokinetics of Caffeine, S-Warfarin, Omeprazole, Midazolam, Repaglinide and Bupropion in Patients With Recurrent Ovarian Cancer [NCT04718740]Phase 133 participants (Actual)Interventional2021-06-25Completed
A Phase 1, Open-label Study in Healthy Female Subjects to Investigate the Effect of JNJ-56136379 at Steady-state on the Single-dose Pharmacokinetics of Ethinylestradiol and Drospirenone (Oral Contraceptive) and on the Single-dose Pharmacokinetics of Midaz [NCT03111511]Phase 118 participants (Actual)Interventional2017-03-27Completed
A Non-Randomized, Open-Label, Three-Part, Drug-Drug Interaction Study to Evaluate the Effects of EDP-938 on the Pharmacokinetics of Tacrolimus, Dabigatran, Rosuvastatin and Midazolam in Healthy Subjects [NCT04498741]Phase 189 participants (Actual)Interventional2020-07-08Completed
Safety, Tolerability and Pharmacokinetics of Multiple Rising Oral Doses of BI 474121 in Young and Elderly Healthy Male and Female Subjects (Double-blind, Randomised, Placebo-controlled, Parallel Group Design) and Evaluation of Midazolam Interaction in You [NCT04537897]Phase 160 participants (Actual)Interventional2020-10-06Completed
Improving Sedation of Children Undergoing Procedures in the Emergency Department: Evaluation of Different Dosages and Routes of Administration of the Sedative Midazolam [NCT00675909]180 participants (Actual)Interventional2006-11-30Completed
A Double-Blind, Placebo-Controlled, Single and Multiple Ascending Dose Study to Investigate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of JNJ-61803534 and an Open-Label Study to Evaluate the Effect of JNJ-61803534 on the Pharmacokine [NCT03139500]Phase 147 participants (Actual)Interventional2017-05-17Terminated(stopped due to Terminated due to nonclinical findings)
A Multi-centre, Open Label, Parallel Group Trial to Evaluate the Pharmacokinetic Interactions Between BI 207127 (600 mg t.i.d. or 600 mg b.i.d.) and BI 201335 (120 mg q.d.) Given in Combination With Ribavirin for 24 Weeks, and Their Combined Effect on the [NCT01525628]Phase 172 participants (Actual)Interventional2012-04-30Completed
The Effect of Cranial Electro Therapy Stimulation in Reducing Perioperative Anxiety for Patients Undergoing First Eye Cataract Surgery [NCT00928772]Phase 4115 participants (Actual)Interventional2009-07-31Terminated(stopped due to Lack of efficacy)
Does the Administration of Preop Midazolam Assist in Maintaining Blood Glucose Norms in Non-diabetic Patient During the Perioperative Period [NCT01641653]Phase 460 participants (Actual)Interventional2011-06-30Completed
A Phase 1 Study of an Oral p38 MAPK Inhibitor in Patients With Advanced Cancer [NCT01393990]Phase 189 participants (Actual)Interventional2008-09-04Completed
Randomized, Placebo-controlled, Double-blind, Parallel Group Study to Investigate Safety, Tolerability and Pharmacokinetics of Increasing Multiple Oral Doses of BAY2328065 Including the CYP3A4 Induction Potential of BAY2328065 and Randomized Cross-over In [NCT04027192]Phase 150 participants (Actual)Interventional2019-07-31Completed
Ketamine vs. Midazolam: Testing Rapid Relief of Suicide Risk in Depression [NCT01700829]Phase 482 participants (Actual)Interventional2012-06-30Completed
Remifentanil Only vs. Combination Group Midazolam + Meperidine During Elective Colonoscopy [NCT01693185]Phase 460 participants (Actual)Interventional2012-12-31Completed
Comparison of the Effect of Adding Midazolam Versus Fentanyl to Intrathecal Levobupivacaine in Patients Undergoing Caesarean Section [NCT03824314]Phase 180 participants (Actual)Interventional2019-05-01Completed
Randomized, Cross-over Study Evaluating the Effect of Sedation on Pain Relief After Diagnostic Injections [NCT01472835]73 participants (Actual)Interventional2011-03-31Completed
The Median Effective Dose of Midazolam Oral Solution for Preoperative Hypnosis in Non-Elderly Adults in the Preoperative Room: An Up-and-Down Sequential Allocation Trial [NCT06018207]40 participants (Anticipated)Interventional2023-08-31Not yet recruiting
Single-dose Ketamine to Reduce Pain Severity, Depressive Symptoms and the Need for Opiates Both During and After Emergency Department Care [NCT03436121]Phase 2/Phase 30 participants (Actual)Interventional2019-12-31Withdrawn(stopped due to Ketamine shortage during the funding period of the trial)
A Randomized, Double-Blind (Sponsor Unblinded), Placebo-Controlled Study to Evaluate the Safety, Tolerability and Pharmacokinetics of Orally Administered VH4004280 in Healthy Participants [NCT05163522]Phase 173 participants (Actual)Interventional2021-12-13Completed
The Effect of Lormetazepam Versus Midazolam in Critically Ill Patients on Hospital Mortality: a Retrospective Cohort Trial [NCT04408911]3,314 participants (Actual)Observational2006-01-01Completed
Phase IV, Open-Label, Safety Study Evaluating the Use of Dexmedetomidine in Pediatric Subjects Undergoing Procedure-Type Sedation [NCT01519167]Phase 491 participants (Actual)Interventional2012-10-31Completed
A Randomised Controlled Trial of Pediatric Sedation for Dental Treatment Using Oral Midazolam or Placebo [NCT01795222]Phase 418 participants (Actual)Interventional2012-03-31Completed
A Phase 1 Study to Evaluate the Potential Pharmacokinetic Interaction Between Entrectinib and Midazolam in Cancer Patients [NCT03330990]Phase 115 participants (Actual)Interventional2017-11-14Completed
Ketamine-Midazolam Versus Morphine-Midazolam for Continous Patient Sedation in Intensive Care Units in Uganda. A Randomised Controlled Trial. [NCT03407404]Phase 2/Phase 3124 participants (Actual)Interventional2017-10-22Terminated(stopped due to Futility)
Regional Anesthesia Versus General Anesthesia in Patients Undergoing Laparoscopic Gynecological Surgery [NCT03830086]28 participants (Actual)Interventional2019-02-07Completed
Daily Interruption of Sedation Versus Non Sedation in Mechanically Ventilated Respiratory Failure Patients [NCT03406936]100 participants (Actual)Interventional2016-08-20Completed
A Comparison of Midazolam and Zolpidem as Oral Premedication in Children [NCT02096900]Phase 386 participants (Actual)Interventional2014-07-21Completed
Effect of Remimazolam Use During Perioperative Period on Brain Waves and Postoperative Recovery Indicators [NCT04601350]80 participants (Actual)Interventional2020-11-01Completed
Comparison of Effects of Intravenous Midazolam and Ketamine on Emergence Agitation : a Randomized Controlled Trial [NCT02256358]68 participants (Actual)Interventional2013-01-31Completed
Ultrasonographic Thyrohyoid Distance Measurement for Prediction of Difficult Intubation and Ultrasonographic Prediction of Pediatric Endotracheal Tube Size [NCT03013036]150 participants (Anticipated)Interventional2013-02-28Recruiting
Effect of Intranasal Midazolam Versus Ketamine Midazolam Combination as a Premedication in Children Undergoing Tonsillectomy and Adenoidectomy on the Occurrence of Postoperative Respiratory Adverse Events: a Double-blind, Randomized Controlled Trial [NCT06122948]Phase 3200 participants (Anticipated)Interventional2023-09-10Recruiting
A Phase 1 Open-Label Drug-Drug Interaction Study Between ABBV-903 and Midazolam [NCT05895266]Phase 124 participants (Actual)Interventional2023-06-23Completed
Comparative Study Between Usage of NIV Versus MV for One Hour After Fulfillment of Weaning Criteria From Ventilation on Re-intubation in Post-traumatic ARDS [NCT04402320]300 participants (Actual)Observational [Patient Registry]2019-04-10Completed
Coronary Angiography THerapeutic Virtual Reality: Investigating the Effect of Virtual Reality on Procedural Anxiety, Pain and Vasospasm [NCT03490903]0 participants (Actual)Interventional2018-06-01Withdrawn(stopped due to No patients enrolled)
An Open-label, Fixed Sequence, Drug-drug Interaction Study in Healthy Subjects to Evaluate the Effect of GLPG4716 on the Pharmacokinetics of Midazolam, a Sensitive Index Substrate of CYP3A4, and to Assess the Effect of Food on the Pharmacokinetics of GLPG [NCT05030857]Phase 119 participants (Actual)Interventional2021-09-08Completed
A Single-center, Non-randomized, Open-lable, Self-controlled Clinical Trial to Evaluate JAB-21822 Drug-drug Interactions in Healthy Subjects [NCT06162169]Phase 166 participants (Anticipated)Interventional2023-11-25Recruiting
A Multi-Part, Phase 1 Study With Randomized, Double-Blind, Sponsor-Open, Placebo-Controlled, Single- And Multiple-Dose Escalation To Evaluate The Safety, Tolerability, And Pharmacokinetics Of PF-07976016 In Healthy Adult Participants [NCT06106009]Phase 1146 participants (Anticipated)Interventional2023-10-27Recruiting
An Open-label Phase 1 Study to Evaluate Drug-Drug Interactions of Agents Co-Administered With Encorafenib and Binimetinib in Patients With BRAF V600-mutant Unresectable or Metastatic Melanoma or Other Advanced Solid Tumors [NCT03864042]Phase 156 participants (Actual)Interventional2018-01-02Active, not recruiting
Optimal Volumes of Administration for Intranasal Midazolam in Children [NCT01948908]Phase 299 participants (Actual)Interventional2013-06-30Completed
A Single Dose of Etomidate During Rapid Sequence Induction in Trauma Patients Causes Significant Adrenocortical Insufficiency: A Prospective Randomized Study [NCT00462644]30 participants (Actual)Interventional2006-02-28Completed
The Effect of Midazolam on Dexamethasone-induced Perineal Pruritus [NCT04326738]Early Phase 190 participants (Actual)Interventional2020-01-16Completed
Repeated Ketamine Infusions for Treatment-Resistant Bipolar Disorder: A Randomized, Double-blind, Midazolam-controlled, Phase II Clinical Trial [NCT05004896]Phase 2100 participants (Anticipated)Interventional2022-04-30Recruiting
Midazolam Versus Dexamethasone as an Adjuvant to Local Anesthetics in the Ultrasound Guided Hydrodissection of Median Nerve for Treatment of Carpal Tunnel Syndrome Patients [NCT04527770]134 participants (Actual)Interventional2020-09-01Completed
Preemptive Analgesia for Post Tonsillectomy Pain With IV Morphine in Children [NCT02995304]60 participants (Anticipated)Interventional2016-12-31Not yet recruiting
Investigation of Antidepressant Efficacy of Oral Ketamine Treatment [NCT02992496]Phase 260 participants (Anticipated)Interventional2017-04-24Recruiting
A Single-Dose Study to Investigate the Pharmacokinetics of MK-7655 in Subjects With Impaired Renal Function [NCT01275170]Phase 149 participants (Actual)Interventional2011-01-28Completed
Dexmedetomidine vs. Midazolam for Facilitating Extubation in Medical and Surgical ICU Patients: A Randomized, Double-Blind Study [NCT00744380]23 participants (Actual)Interventional2008-08-31Completed
Investigating Rapid Anti-Suicidal Ideation Effects of Intravenous (IV) Ketamine in Hospitalized Patients [NCT01507181]Phase 424 participants (Actual)Interventional2012-01-31Completed
Efficacy and Safety Profiles of Sedation With Propofol Combined With Intravenous Midazolam and Meperidine Versus Intravenous Midazolam and Meperidine for Ambulatory Endoscopic Retrograde-cholangiopancreatography(ERCP). [NCT01709422]Phase 4140 participants (Actual)Interventional2010-06-30Completed
Remifentanil Target Controlled Infusion Versus Standard of Care for Conscious Sedation During US-guided Transbronchial Needle Aspiration (EBUS-TBNA): a Randomized, Prospective, Control Study [NCT06033729]30 participants (Actual)Interventional2021-09-20Completed
A Randomised, Double Blinded, Placebo-controlled Single and Multiple Ascending Dose Study of Orally Administered RV299 to Evaluate Safety, Tolerability, Pharmacokinetics and Food Effect in Healthy Adult Participants [NCT06033612]Phase 150 participants (Actual)Interventional2021-11-12Completed
A Multiple-Dose Study to Evaluate the Effects of Steady-State Tedizolid Phosphate Administration on the Pharmacokinetics and Safety of a Single Dose of Midazolam and Rosuvastatin [NCT02477514]Phase 118 participants (Actual)Interventional2015-06-30Completed
Flucloxacillin as an Inducer of CYP-enzymes [NCT04840641]Phase 114 participants (Actual)Interventional2021-03-25Completed
A Multi-Center, Open-Label, Dose Escalation, Phase 1 Study of Oral LGH447 in Patients With Relapsed and/or Refractory Multiple Myeloma [NCT01456689]Phase 179 participants (Actual)Interventional2012-04-25Completed
The Combination of Adductor Canal Block and Periarticular Injection. A Novel Technique for Patients Undergoing Total Knee Replacement (ACB PAI) [NCT02292082]Phase 4111 participants (Actual)Interventional2014-11-30Completed
Intranasal Midazolam in Children as a Pre-Operative Sedative [NCT02314546]Phase 415 participants (Actual)Interventional2011-12-31Completed
A PHASE 1 STUDY TO EVALUATE THE EFFECTS OF MULTIPLE DOSES OF LY3537982 ON THE SINGLE-DOSE PHARMACOKINETICS OF MIDAZOLAM, DIGOXIN, AND ROSUVASTATIN IN HEALTHY ADULT SUBJECTS [NCT06111521]Phase 156 participants (Anticipated)Interventional2023-10-27Not yet recruiting
Ketamine for The Rapid Treatment of Major Depression and Alcohol Use Disorder [NCT02461927]Phase 1/Phase 265 participants (Actual)Interventional2015-01-01Completed
Phase 4, Prospective, Randomized, Double-blinded, Placebo-controlled Study Comparing Propofol vs. Midazolam Plus Propofol for Nonanesthesiologist Targeted Moderate Sedation in Outpatient Colonoscopy [NCT01428882]Phase 4135 participants (Actual)Interventional2011-06-30Completed
IM Ketamine vs Midazolam for Suicidal ER Patients [NCT04640636]Phase 490 participants (Anticipated)Interventional2021-01-02Active, not recruiting
Tablet-based Interactive Distraction for the Management of Preoperative Anxiety in Children: A Randomized Controlled Trial [NCT03531359]112 participants (Anticipated)Interventional2018-07-04Recruiting
Ketamine as an Adjunctive Therapy for Major Depression - A Randomised Controlled Trial: [KARMA-Dep (2)] [NCT04939649]Phase 3104 participants (Anticipated)Interventional2021-09-13Recruiting
A Phase 1 Safety, Tolerability, Pharmacokinetic, Placebo-Controlled and Open-Label Study of Escalating Single and Multiple Oral Doses, Drug-Drug Interaction, Relative Bioavailability, Food Effect, and Effect on Elderly Subjects of TAK-915 in Healthy Subje [NCT02461160]Phase 188 participants (Actual)Interventional2015-05-12Completed
The Efficacy and the Safety of Dexmedetomidine Sedation on the PICU Patients-A Randomized, Controlled Study. [NCT02296073]Phase 4120 participants (Anticipated)Interventional2014-12-31Not yet recruiting
Nebulized Midazolam vs. Oral Midazolam as a Sedative Premedication in Pediatric Anesthesia: A Randomized Comparative Study [NCT04760041]72 participants (Actual)Interventional2021-03-01Completed
Determination of the Effects of Change in Anxiety Level on Pain Perception in Patients Who Present to Emergency Department Due to Acute Pain: a Double Blind, Randomized, Controlled Trial [NCT03420911]180 participants (Actual)Interventional2013-06-30Completed
Efficacy of Midazolam Addition to Local Anesthetic in Peribulbar Block. Randomized, Controlled Trial [NCT03397069]90 participants (Actual)Interventional2018-01-01Completed
Usefulness of Bispectal Index (BIS) on Depth of Sedation With Dexmedetomidine, Propofol and Midazolam During Spinal Anesthesia : a Prospective Randomized Study [NCT03399019]45 participants (Anticipated)Interventional2016-09-05Recruiting
A Phase 1, Open-label, Fixed-sequence Design Study To Assess The Effect Of Multiple Dose Administration Of Pf-06751979 On The Single Dose Pharmacokinetics Of Oral Midazolam In Healthy Adult Subjects [NCT03126721]Phase 112 participants (Actual)Interventional2017-04-18Completed
Bispectral Index Monitoring of Sedation Depth During Flexible Bronchoscopy: With or Without Fentanyl . [NCT03395093]500 participants (Actual)Interventional2016-07-21Active, not recruiting
Evaluating of Oral Propranolol Effect on Managing Anxiety of Dental Extractions in Children: A Randomized Controlled Clinical Trial [NCT03388957]60 participants (Actual)Interventional2018-07-30Completed
Effect of Use of Propofol Versus Use of Midazolam as Sedative Agent in Patients With Liver Cirrhosis Presented for Lower Gastrointestinal Endoscopy, Randomised Controlled Trial [NCT03388151]Phase 3100 participants (Anticipated)Interventional2016-04-01Recruiting
Effects and Mechanism of Pretreatment With Dexmedetomidine to Etomidate Induce Myoclonus During General Anesthesia Induction Period [NCT02518789]Phase 4132 participants (Anticipated)Interventional2015-09-30Not yet recruiting
Open-label, Randomized, Fixed Sequence Cross-over Study With Five Parallel Treatment Arms and Three Treatment Periods to Quantify the Drug-drug Interactions of Two Rifampicin Dose Strengths on Four Progestins and a Fixed Progestin-ethinylestradiol Combina [NCT03353857]Phase 168 participants (Actual)Interventional2017-11-29Completed
An Open-label, Healthy Subject, Two-part Study to Assess the Effect of Verapamil on Systemic Exposure of EP395 (Part A), and to Assess the Effect of EP395 on Systemic Exposure of Midazolam and Digoxin (Part B) [NCT06118684]Phase 136 participants (Anticipated)Interventional2023-10-23Recruiting
A Phase 1, Single-Center, Open-Label, Fixed-Sequence Study to Evaluate the Effect of DC-806 on the Single Dose Pharmacokinetics of CYP450 Enzyme and Transporter Substrates in Healthy Participants [NCT06092931]Phase 128 participants (Anticipated)Interventional2023-10-16Active, not recruiting
A Multicenter, Single-Arm, Open-Label Study to Evaluate the Immunogenicity and Pharmacokinetics of BIIB019, Daclizumab High Yield Process (DAC HYP), Prefilled Syringe Administered by Subcutaneous Injection in Subjects With Relapsing-Remitting Multiple Scl [NCT01462318]Phase 3133 participants (Actual)Interventional2011-11-30Completed
Etomidate With Meperidine vs Midazolam With Meperidine for Sedation During Endodscopic Retrograde Cholangiopancreatogram (ERCP) [NCT02027311]Phase 463 participants (Actual)Interventional2013-04-30Completed
A Drug-Drug Interaction Study to Evaluate the Effect of Ibrutinib on the Pharmacokinetics of Oral Contraceptives, CYP2B6, and CYP3A4 Substrates in Female Subjects With B Cell Malignancy [NCT03301207]Phase 125 participants (Actual)Interventional2017-10-20Completed
A Phase 2, Two-arm Multicenter, Open-Label Study to Determine the Efficacy and the Safety of Two Different Dose Regimens of a Pan-FGFR Tyrosine Kinase Inhibitor JNJ-42756493 in Subjects With Metastatic or Surgically Unresectable Urothelial Cancer With FGF [NCT02365597]Phase 2239 participants (Actual)Interventional2015-04-22Active, not recruiting
A Phase I Study to Evaluate the Effect of Repeated Oral Doses of Delafloxacin on the Pharmacokinetics of a Single Oral Dose of Midazolam in Healthy Subjects [NCT02505997]Phase 122 participants (Actual)Interventional2015-06-30Completed
The Effects of Different Anesthetics on Functional Connectivity in Volunteers and Patients With Brain Tumor (ACTION) [NCT03343873]240 participants (Anticipated)Interventional2017-04-01Recruiting
A Double Blind, Randomised, Multicentre, Active Controlled, Parallel-group, Phase III Trial to Evaluate the Efficacy, Safety and Pharmacokinetics of Intravenous Clonidine (Hydrochloride) Compared to Midazolam for Sedation in Children From Birth to Less Th [NCT02509273]Phase 328 participants (Actual)Interventional2016-05-31Terminated(stopped due to lack of recruitment)
Core Temperature Variations During Midazolam vs Propofol Sedation for Neuraxial Anesthesia [NCT02502877]27 participants (Actual)Interventional2015-07-31Completed
Comparison of Remifentanil and Dexmedetomidine for Monitored Anaesthesia Care [NCT02476981]75 participants (Actual)Interventional2012-08-31Completed
A Single-center, Open-label, Phase I Drug-drug Interaction Clinical Study to Investigate the Effect of SKLB1028 on the Pharmacokinetics of Midazolam in Healthy Subjects [NCT05070195]Phase 114 participants (Actual)Interventional2021-06-07Completed
A PHASE 1, OPEN-LABEL, CROSS-OVER, FIXED SEQUENCE STUDY TO EVALUATE THE EFFECT OF MULTIPLE DOSES OF DS-1971A ON THE SINGLE DOSE PHARMACOKINETICS OF PROBE SUBSTRATES FOR CYP2B6, CYP2C8, CYP2C9, CYP2C19 AND CYP3A4 ENZYMES IN HEALTHY MALE AND FEMALE SUBJECTS [NCT02473627]Phase 118 participants (Actual)Interventional2015-05-31Completed
Preoperative Ketamine as a Strategy to Decrease Perioperative Depression During the Perioperative Period: a Randomized Active Controlled Pilot Study [NCT04220125]Phase 40 participants (Actual)Interventional2022-09-01Withdrawn(stopped due to No enrollment)
Rapid Agitation Control With Ketamine in the Emergency Department (RACKED): a Randomized Controlled Trial [NCT03375671]Phase 281 participants (Actual)Interventional2018-05-29Completed
The Effect of High Dose Rifampicin on the Activity of Cytochrome P450 Enzymes and P-glycoprotein in Patients With Pulmonary Tuberculosis: a Cocktail Phenotyping Study [NCT04525235]Phase 125 participants (Actual)Interventional2021-01-07Completed
A Phase 1, Four-part, Fixed-sequence, Open-label Study to Evaluate the Effect of Multiple Doses of CC-90001 on the Pharmacokinetics of Omeprazole, Midazolam, Warfarin, Rosuvastatin, Metformin, Digoxin, and Nintedanib in Healthy Adult Subjects [NCT03363815]Phase 156 participants (Actual)Interventional2017-12-04Completed
COVID-19: A PHASE 1, OPEN-LABEL, 3-TREATMENT, 6-SEQUENCE, 3-PERIOD CROSSOVER STUDY TO ESTIMATE THE EFFECT OF PF-07321332/RITONAVIR AND RITONAVIR ON THE PHARMACOKINETICS OF MIDAZOLAM IN HEALTHY PARTICIPANTS. [NCT05032950]Phase 112 participants (Actual)Interventional2021-09-17Completed
A Pilot Phase 1, Randomized, Single-Dose, 6-Sequences, 3-Period, Crossover Bioavailability Study of MELT-100 (Midazolam and Ketamine Sublingual Tablet) and Intravenous Midazolam or Ketamine in Healthy Volunteers [NCT04485702]Phase 117 participants (Actual)Interventional2020-07-20Completed
A Randomized Controlled Trial of Intranasal Fentanyl in Combination With Midazolam Versus Midazolam Alone for Analgesia and Anxiolysis During Pediatric Facial Laceration Repair [NCT04745260]100 participants (Anticipated)Interventional2021-03-01Not yet recruiting
A Study Evaluating the Safety and Efficacy of Remimazolam (CNS 7056) Compared to Placebo and Midazolam in ASA III and IV Patients Undergoing Colonoscopy [NCT02532647]Phase 379 participants (Actual)Interventional2015-11-30Completed
Randomized Controlled Trial of Repeated-Dose Intravenous Ketamine for PTSD [NCT02397889]Phase 2/Phase 330 participants (Actual)Interventional2015-05-18Completed
Double Blinded Randomized Controlled Trial of Intranasal Dexmedetomidine Versus Intranasal Midazolam as Anxiolysis Prior to Pediatric Laceration Repair in the Emergency Department [NCT02168439]Phase 440 participants (Actual)Interventional2014-06-30Completed
A Prospective, Double-blind, Randomized, Placebo and Active Controlled, Multi-center, Parallel Group Study Comparing Remimazolam to Placebo, With an Additional Open-label Arm For Midazolam, in Patients Undergoing a Colonoscopy [NCT02290873]Phase 3461 participants (Actual)Interventional2015-03-30Completed
A Phase III Study Evaluating the Efficacy and Safety of Remimazolam (CNS 7056) Compared to Placebo and Midazolam in Patients Undergoing Bronchoscopy [NCT02296892]Phase 3446 participants (Actual)Interventional2015-04-30Completed
Double-Blind, Placebo-Controlled Trial of Ketamine Therapy in Treatment-Resistant Depression (TRD) [NCT01920555]Phase 299 participants (Actual)Interventional2014-12-31Completed
[information is prepared from clinicaltrials.gov, extracted Sep-2024]

Trial Outcomes

TrialOutcome
NCT00326612 (7) [back to overview]Number of Patients Needed to be Seen or Treated in the Emergency Department for Their Seizure and Use of Study Medication.
NCT00326612 (7) [back to overview]Number of Patients That Were Admitted to the Hospital After Their Seizure and Use of Study Medication.
NCT00326612 (7) [back to overview]Number of Patients Who Had a Repeat Seizure Within 12 Hours After Their Seizure Who Used Study Medication
NCT00326612 (7) [back to overview]Number of Patients Who Needed Additional Medication to Treat the Seizure in the Emergency Department Within 24 Hours
NCT00326612 (7) [back to overview]Respiratory Depression Requiring Intubation
NCT00326612 (7) [back to overview]Respiratory Depression Requiring Oxygen at Discharge From the Emergency Department.
NCT00326612 (7) [back to overview]Length of Seizure After Study Medication Administration
NCT00441792 (2) [back to overview]Mortality
NCT00441792 (2) [back to overview]Length of Stay
NCT00462644 (7) [back to overview]Change in Baseline Cortisol
NCT00462644 (7) [back to overview]Intensive Care Unit (ICU) Length of Stay
NCT00462644 (7) [back to overview]Cortisol Level 60 Minutes After Cortisol Stimulating Test (CST)
NCT00462644 (7) [back to overview]Number of Deaths
NCT00462644 (7) [back to overview]Postintubation Cortisol (Baseline Cortisol Level)
NCT00462644 (7) [back to overview]Ventilator Days
NCT00462644 (7) [back to overview]Hospital Length of Stay
NCT00467779 (44) [back to overview]Stage 2A: Accumulation Ratio of Cobimetinib at Steady State
NCT00467779 (44) [back to overview]Stage 2A: Apparent Clearance of Cobimetinib at Steady State
NCT00467779 (44) [back to overview]Stage 2A: AUC 0-24/D of Cobimetinib at Steady State
NCT00467779 (44) [back to overview]Stage 2A: Cmax of Cobimetinib at Steady State
NCT00467779 (44) [back to overview]Stage 1A: Apparent Clearance of Cobimetinib at Steady State
NCT00467779 (44) [back to overview]Stage 1A: Accumulation Ratio of Cobimetinib at Steady State
NCT00467779 (44) [back to overview]Stage 1: Tmax of Cobimetinib at Steady State
NCT00467779 (44) [back to overview]Stage 2A: Half-Life of Cobimetinib at Steady State
NCT00467779 (44) [back to overview]Stage 2A: Tmax of Cobimetinib at Steady State
NCT00467779 (44) [back to overview]Stage III: AUC 0-inf of Dextromethorphan
NCT00467779 (44) [back to overview]Stage III: AUC0-24 of Midazolam
NCT00467779 (44) [back to overview]Stage III: AUC0-inf of Midazolam
NCT00467779 (44) [back to overview]Stage III: Cmax of Dextromethorphan
NCT00467779 (44) [back to overview]Stage III: Cmax of Midazolam
NCT00467779 (44) [back to overview]Stage III: AUC 0-24 of Dextromethorphan
NCT00467779 (44) [back to overview]Stage 1: Time to Maximum Concentration (Tmax) of Cobimetinib at Day 1, Cycle 1
NCT00467779 (44) [back to overview]Stage 1: Maximum Tolerated Dose (MTD) of Cobimetinib in 21/7 Schedule
NCT00467779 (44) [back to overview]Stage 1: Maximum Observed Concentration (Cmax) of Cobimetinib at Day 1, Cycle 1
NCT00467779 (44) [back to overview]Stage 1: Half-Life (t1/2) of Cobimetinib at Steady State
NCT00467779 (44) [back to overview]Stage 1: Cmax of Cobimetinib at Steady State
NCT00467779 (44) [back to overview]Stage 1: AUC 0-24/D of Cobimetinib at Steady State
NCT00467779 (44) [back to overview]Stage 1: AUC 0-24 of Cobimetinib at Steady State
NCT00467779 (44) [back to overview]Stage 1: Area Under the Plasma Cobimetinib Concentration Curve From Time 0 to 24 Hours (AUC 0-24) Day 1, Cycle 1
NCT00467779 (44) [back to overview]Stage 1: Apparent Clearance of Cobimetinib at Steady State
NCT00467779 (44) [back to overview]Stage 1A: AUC 0-24 of Cobimetinib at Cycle 1 Day 1
NCT00467779 (44) [back to overview]Stage 1: Accumulation Ratio of Cobimetinib at Steady State
NCT00467779 (44) [back to overview]Stage 1 and 1A: Number of Participants With Dose Limiting Toxicities (DLTs)
NCT00467779 (44) [back to overview]Stage 2: AUC 0-24 of Cobimetinib at Steady State
NCT00467779 (44) [back to overview]Stage 2: AUC 0-24/D of Cobimetinib at Steady State
NCT00467779 (44) [back to overview]Stage 2: Cmax of Cobimetinib at Cycle 1 Day 1
NCT00467779 (44) [back to overview]Stage 2: Tmax of Cobimetinib at Cycle 1 Day 1
NCT00467779 (44) [back to overview]Stage 2: Tmax of Cobimetinib at Steady State
NCT00467779 (44) [back to overview]Stage 1A: AUC 0-24/D of Cobimetinib at Steady State
NCT00467779 (44) [back to overview]Stage 2:AUC 0-24 of Cobimetinib at Cycle 1 Day 1
NCT00467779 (44) [back to overview]Stage 1A: AUC 0-24 of Cobimetinib at Steady State
NCT00467779 (44) [back to overview]Stage 2: Apparent Clearance of Cobimetinib at Steady State
NCT00467779 (44) [back to overview]Stage 2:Half-Life of Cobimetinib at Steady State
NCT00467779 (44) [back to overview]Stage 1A: Cmax of Cobimetinib at Cycle 1 Day 1
NCT00467779 (44) [back to overview]Stage 1A: Cmax of Cobimetinib at Steady State
NCT00467779 (44) [back to overview]Stage 1A: MTD of Cobimetinib in 14/14 Schedule
NCT00467779 (44) [back to overview]Stage 1A: t1/2 of Cobimetinib at Steady State
NCT00467779 (44) [back to overview]Stage 1A: Tmax of Cobimetinib at Cycle 1 Day 1
NCT00467779 (44) [back to overview]Stage 1A: Tmax of Cobimetinib at Steady State
NCT00467779 (44) [back to overview]Stage 2: Accumulation Ratio of Cobimetinib at Steady State
NCT00578214 (14) [back to overview]Patient Anxiety at 60 and 120 Minutes
NCT00578214 (14) [back to overview]Patient Cognitive Function at Baseline and 60 Minutes
NCT00578214 (14) [back to overview]Heart Rate at 60 Minutes
NCT00578214 (14) [back to overview]Patient Alertness at Baseline
NCT00578214 (14) [back to overview]Patient Anxiety at Baseline
NCT00578214 (14) [back to overview]Patient Cognitive Function at 120 Minutes
NCT00578214 (14) [back to overview]Pulse Oximetry at 30 Minutes
NCT00578214 (14) [back to overview]Pulse Oximetry at 60 Minutes
NCT00578214 (14) [back to overview]Heart Rate at 30 Minutes
NCT00578214 (14) [back to overview]Respiratory Rate at 60 Minutes
NCT00578214 (14) [back to overview]Blood Pressure at 30 Minutes
NCT00578214 (14) [back to overview]Blood Pressure at 60 Minutes
NCT00578214 (14) [back to overview]Patient Alertness at 60 and 120 Minutes
NCT00578214 (14) [back to overview]Respiratory Rate at 30 Minutes
NCT00581139 (8) [back to overview]Post Anesthesia Care Unit (PACU) IV Fluid
NCT00581139 (8) [back to overview]Visual Analogue Pain Scale (VAS) 24 Hour After Surgery
NCT00581139 (8) [back to overview]Percentage of Children Not Exhibiting Negative Behaviors, Fear, or Anxiety (Perfect Induction, 0)
NCT00581139 (8) [back to overview]Percentage of Children Arriving to PACU in Deep Sleep
NCT00581139 (8) [back to overview]Percentage of Children Arriving to PACU Awake
NCT00581139 (8) [back to overview]Percent of Children Crying During Induction
NCT00581139 (8) [back to overview]Modified Yale Preoperative Anxiety Scale
NCT00581139 (8) [back to overview]Heart Rate in the General Clinical Research Unit (GCRC)
NCT00641563 (2) [back to overview]Amplitudes (in Micro Volts) of Acoustic Event Related Potentials (Time-locked Amplitudes in the Electroencephalogram 100 Milliseconds After the Acoustic Stimulus, Averaged Over 40 Stimuli)Awake and at 3 Different Drug-induced Sedation Levels
NCT00641563 (2) [back to overview]BIS-Index Awake and 3 Sedation Levels (RS 2/3/4)
NCT00646646 (1) [back to overview]Dynamic Eye Movement Measures
NCT00652028 (9) [back to overview]Number of Subjects Who Received Rescue Medication for Sedation (Midazolam) and Analgesics (Fentanyl)
NCT00652028 (9) [back to overview]Volume of Steady State Distribution (Vss)
NCT00652028 (9) [back to overview]Terminal Elimination Half-life (t1/2)
NCT00652028 (9) [back to overview]Clearance (CL)
NCT00652028 (9) [back to overview]Plasma Concentration at Steady State (Css)
NCT00652028 (9) [back to overview]Observed Peak Plasma Concentration
NCT00652028 (9) [back to overview]Level of Sedation Based on Average Ramsay Sedation Scale (RSS) Score
NCT00652028 (9) [back to overview]Area Under the Concentration-time Curve From Time Zero to the Time of the Last Measurable Concentration (AUC0-t)
NCT00652028 (9) [back to overview]Area Under the Concentration-time Curve From Time Zero to the Time Infinity (AUC0-∞)
NCT00675909 (5) [back to overview]Time From Study Drug Administration to Start of Procedure
NCT00675909 (5) [back to overview]Duration of Procedure
NCT00675909 (5) [back to overview]Nurse Rating of Sedation
NCT00675909 (5) [back to overview]Physician Rating of Sedation
NCT00675909 (5) [back to overview]Change in CHEOPS Score Measured Level of Sedation From Baseline (Presentation in ED, Before Sedation) to Start of Procedure (Laceration Repair).
NCT00741468 (1) [back to overview]Plasma AUC Ratio of Day 1 and Day 8
NCT00744380 (8) [back to overview]Duration of Study Drug Administration
NCT00744380 (8) [back to overview]ICU Experiences by Administering ICU Stressful Experiences Questionnaire (ICU-SEQ)
NCT00744380 (8) [back to overview]The Quality of Sedation (Assessed by the Riker Sedation-Agitation Score) and Analgesia (Assessed by the Pain Assessment Behavioral Score)
NCT00744380 (8) [back to overview]Sedation-related Adverse Effects
NCT00744380 (8) [back to overview]Hospital Anxiety and Depression Scale (HADS) Score
NCT00744380 (8) [back to overview]Time From Study Drug Initiation to Tracheal Extubation
NCT00744380 (8) [back to overview]Manifestations of Acute Stress Disorder by Impact of Event Scale - Revised (IES-R)
NCT00744380 (8) [back to overview]Cumulative Doses of Conventional Sedatives and Analgesics
NCT00749203 (4) [back to overview]Quick Inventory of Depressive Symptomatology - Self Report (QIDS-SR)
NCT00749203 (4) [back to overview]Montgomery-Asberg Depression Rating Scale (MADRS)
NCT00749203 (4) [back to overview]Impact of Event Scale - Revised (IES-R)
NCT00749203 (4) [back to overview]Clinician-Administered PTSD Scale (CAPS)
NCT00768430 (1) [back to overview]MADRS
NCT00785486 (4) [back to overview]The Area Under the the Concentration Time Curve From Zero to Tau (0-8hrs) for Qualaquin (Quinine) AUC Tau Before and After Midazolam
NCT00785486 (4) [back to overview]Area Under the Concentration Time Curve From Zero to Infinity (AUC Inf) for Midazolam and 1 Hydroxy Midazolam Before (Day 1) and After (Day 10) Qualaquin (Quinine).
NCT00785486 (4) [back to overview]Maximum Serum Concentration (Cmax)
NCT00785486 (4) [back to overview]Area Under the Concentration Time Curve From Zero to T (AUC 0-t) for Midazolam and 1-hydroxy Midazolam at Baseline and With Qualaquin (Quinine) at Steady State.
NCT00789815 (8) [back to overview]The Number of Participants With Any Hypotension Event During Flexible Bronchoscopy
NCT00789815 (8) [back to overview]The Global Tolerance for Flexible Bronchoscopy by Verbal Analogus Scale
NCT00789815 (8) [back to overview]Patients Willing Return if Repeated Bronchoscopy is Indicated.
NCT00789815 (8) [back to overview]The Number of Participants Causing Any Procedure Interference by the Patients' Movement During Flexible Bronchoscocopy
NCT00789815 (8) [back to overview]The Recovery Time to Ambulation
NCT00789815 (8) [back to overview]The Number of Participants Causing Any Procedure Interference by Cough
NCT00789815 (8) [back to overview]The Number of Participants With Any Hypoxemia Event During Flexible Bronchoscopy
NCT00789815 (8) [back to overview]The Recovery Time to Orientation
NCT00853333 (1) [back to overview]Pain Rating Change
NCT00869440 (3) [back to overview]Time to Fully Alert
NCT00869440 (3) [back to overview]Time to Ready for Discharge
NCT00869440 (3) [back to overview]Success Rates of the Procedure
NCT00875550 (6) [back to overview]Time to Successful Extubation
NCT00875550 (6) [back to overview]Absolute Time on Study Drug That the Subject is in a UMSS Range of 1 to 3 While Intubated
NCT00875550 (6) [back to overview]Absolute Time on Study Drug That the Subject is Out of the Target Sedation Range (UMSS <1 or >3) While Intubated
NCT00875550 (6) [back to overview]Percentage of Subjects That do Not Require Rescue Midazolam (MDZ) for Sedation Based on Achieving and Maintaining a Target University of Michigan Sedation Scale (UMSS) Score of 1 to 3 While Intubated.
NCT00875550 (6) [back to overview]Time to First Dose of Rescue Medication for Sedation and Analgesia
NCT00875550 (6) [back to overview]Total Amount of Rescue Medication Required for Sedation and Analgesia While Intubated
NCT00894465 (2) [back to overview]Anxiety Score From the Modified Yale Preoperative Anxiety Scale
NCT00894465 (2) [back to overview]Anxiety Score From the State-Trait Anxiety Inventory
NCT00928772 (4) [back to overview]Eye Discomfort Perception During Cataract Surgery Under Topical Anesthesia
NCT00928772 (4) [back to overview]Heart Rate During Cataract Surgery Under Topical Anesthesia
NCT00928772 (4) [back to overview]Mean Arterial Pressure During the Cataract Surgery Under Topical Anesthesia
NCT00928772 (4) [back to overview]Anxiety During Cataract Surgery Under Topical Anesthesia
NCT00952653 (10) [back to overview]Midazolam Area Under the Plasma Concentration-time Profile From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) Following Midazolam Alone and When Coadministered With DVS SR
NCT00952653 (10) [back to overview]Midazolam Maximum Observed Plasma Concentration (Cmax) Following Midazolam Alone and When Coadministered With DVS SR
NCT00952653 (10) [back to overview]Midazolam Terminal Half-life (t 1/2) Following Midazolam Alone and When Coadministered With DVS SR
NCT00952653 (10) [back to overview]Midazolam Time to Cmax (Tmax) Following Midazolam Alone and When Coadministered With DVS SR
NCT00952653 (10) [back to overview]1-Hydroxy-Midazolam (Analyte) Time to Cmax (Tmax) Following Midazolam Alone and When Coadministered With DVS SR
NCT00952653 (10) [back to overview]1-Hydroxy-Midazolam (Analyte) Area Under the Plasma Concentration-time Profile From Time 0 Extrapolated to Infinite Time (AUCinf) Following Midazolam Alone and When Coadministered With DVS SR
NCT00952653 (10) [back to overview]1-Hydroxy-Midazolam (Analyte) Area Under the Plasma Concentration-time Profile From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) Following Midazolam Alone and When Coadministered With DVS SR
NCT00952653 (10) [back to overview]1-Hydroxy-Midazolam (Analyte) Maximum Observed Plasma Concentration (Cmax) Following Midazolam Alone and When Coadministered With DVS SR
NCT00952653 (10) [back to overview]Midazolam Area Under the Plasma Concentration-time Profile From Time 0 Extrapolated to Infinite Time (AUCinf) Following Midazolam Alone and When Coadministered With DVS SR
NCT00952653 (10) [back to overview]1-Hydroxy-Midazolam (Analyte) Terminal Half-life (t 1/2) Following Midazolam Alone and When Coadministered With DVS SR
NCT00990821 (1) [back to overview]Area Under the Plasma-Time Curve (AUC[0 to Infinity]) for Aprepitant and MK-0517 for Study Part V
NCT01017237 (24) [back to overview]Heart Rate
NCT01017237 (24) [back to overview]Heart Rate
NCT01017237 (24) [back to overview]Bispectral Index Score (BIS)
NCT01017237 (24) [back to overview]Amnesia: Lack of Recall One Day After Surgery of The Picture That Was Shown Prior to Sedation.
NCT01017237 (24) [back to overview]Respiratory Parameters: End-tidal Carbon Dioxide
NCT01017237 (24) [back to overview]Respiratory Parameters: End-tidal Carbon Dioxide
NCT01017237 (24) [back to overview]Respiratory Parameters: Oxyhemoglobin Saturation
NCT01017237 (24) [back to overview]Amnesia: Lack of Picture Recall at Surgery End Time.
NCT01017237 (24) [back to overview]Respiratory Parameters: Oxyhemoglobin Saturation
NCT01017237 (24) [back to overview]Respiratory Parameters: Respiratory Rate
NCT01017237 (24) [back to overview]Amnesia: Lack of Recall One Day After Surgery of The Picture That Was Shown Following Dexmedetomidine Infusion Plus Midazolam.
NCT01017237 (24) [back to overview]Surgeon Satisfaction With Sedation Technique
NCT01017237 (24) [back to overview]Amnesia: Lack of Picture Recall Following Dexmedetomidine Infusion Plus Midazolam.
NCT01017237 (24) [back to overview]Amnesia: Lack of Picture Recall Shown 15 Minutes Into Surgery
NCT01017237 (24) [back to overview]Ramsey Sedation Scale Score
NCT01017237 (24) [back to overview]Primary Title: Amnesia: Lack of Recall One Day After Surgery of The Picture That Was Shown 30 Minutes Into Surgery.
NCT01017237 (24) [back to overview]Amnesia: Lack of Picture Recall Shown 30 Minutes Into Surgery
NCT01017237 (24) [back to overview]Amnesia: Lack of Picture Recall Shown Prior to Sedation.
NCT01017237 (24) [back to overview]Amnesia: Lack of Recall One Day After Surgery of The Picture That Was Shown 15 Minutes Into Surgery.
NCT01017237 (24) [back to overview]Amnesia: Lack of Recall One Day After Surgery of The Picture That Was Shown at Surgery End Time.
NCT01017237 (24) [back to overview]Patient Satisfaction With Sedation Technique
NCT01017237 (24) [back to overview]Mean Arterial Blood Pressure
NCT01017237 (24) [back to overview]Mean Arterial Blood Pressure
NCT01017237 (24) [back to overview]Respiratory Parameters: Respiratory Rate
NCT01059929 (12) [back to overview]Days in Hospital
NCT01059929 (12) [back to overview]Days in ICU
NCT01059929 (12) [back to overview]Days on Ventilator
NCT01059929 (12) [back to overview]Mortality
NCT01059929 (12) [back to overview]Number of Adverse Medication Effects
NCT01059929 (12) [back to overview]Drug Efficacy According to Richmond Agitation Sedation Scale (RASS) Score
NCT01059929 (12) [back to overview]Number of Patients Requiring Midazolam
NCT01059929 (12) [back to overview]Number of Patients Requiring Fentanyl
NCT01059929 (12) [back to overview]Number of Patients Completing Mobility Milestones
NCT01059929 (12) [back to overview]Number of Participants With ICU Complications
NCT01059929 (12) [back to overview]Number of Patients Completing Activities of Daily Living
NCT01059929 (12) [back to overview]Proportion of Days With Delirium
NCT01145222 (3) [back to overview]Time to Ready for Discharge
NCT01145222 (3) [back to overview]Success Rates of the Procedure
NCT01145222 (3) [back to overview]Time to Fully Alert
NCT01158820 (8) [back to overview]Total Midazolam
NCT01158820 (8) [back to overview]Endoscopist Satisfaction
NCT01158820 (8) [back to overview]Patient Satisfaction
NCT01158820 (8) [back to overview]Total Fentanyl
NCT01158820 (8) [back to overview]Desaturation (Cumulative)
NCT01158820 (8) [back to overview]Conversion to General Anesthesia
NCT01158820 (8) [back to overview]Decreased Minute Ventilation
NCT01158820 (8) [back to overview]Desaturation (Longest)
NCT01159262 (9) [back to overview]Weight-adjusted Total Amount (Per kg) of Rescue Medication Morphine Given for Analgesia During Dexmedetomidine Infusion (Among Who Used)
NCT01159262 (9) [back to overview]Weight-adjusted Total Amount (Per kg) of Rescue Medication Midazolam Given for Sedation During Dexmedetomidine Infusion (Among Who Used)
NCT01159262 (9) [back to overview]Total Amount of Rescue Medication Morphine Given for Sedation During Dexmedetomidine Infusion (Among Who Used)
NCT01159262 (9) [back to overview]Total Amount of Rescue Medication Midazolam Given for Sedation During Dexmedetomidine Infusion (Among Who Used)
NCT01159262 (9) [back to overview]Total Amount of Rescue Medication Fentanyl Given for Sedation During Dexmedetomidine Infusion (Among Who Used)
NCT01159262 (9) [back to overview]Time to Successful Extubation in DEX-exposed Subjects
NCT01159262 (9) [back to overview]Percentage of Subjects Who Received Rescue Medication Midazolam for Sedation During Dexmedetomidine Infusion
NCT01159262 (9) [back to overview]Weight-adjusted Total Amount (Per kg) of Rescue Medication Fentanyl Given for Analgesia During Dexmedetomidine Infusion (Among Who Used)
NCT01159262 (9) [back to overview]Percentage of Subjects Who Received Rescue Medication for Analgesia During Dexmedetomidine Infusion
NCT01162486 (3) [back to overview]Number of Participants With Grade 2 or Higher Adverse Events Over the Course of the 26 Day Trial
NCT01162486 (3) [back to overview]Pharmacokinetics (AUC of RPT Over 24 Hours Post-dose)
NCT01162486 (3) [back to overview]Midazolam, AUC Over 12 Hours Post-dose
NCT01188551 (2) [back to overview]FLACC Behavioral Pain Assessment Scale Scores
NCT01188551 (2) [back to overview]Recovery From General Anesthesia
NCT01195103 (1) [back to overview]Percentage of Participants Achieving Sedation Within 4 Minutes
NCT01209832 (6) [back to overview]Tasisulam Pharmacokinetics: Area Under the Concentration-Time Curve Above the Albumin Corrected Threshold (AUCalb)
NCT01209832 (6) [back to overview]Tasisulam Pharmacokinetics: Maximum Concentration (Cmax)
NCT01209832 (6) [back to overview]Number of Participants With Tumor Response
NCT01209832 (6) [back to overview]Midazolam Pharmacokinetics: Maximum Concentration (Cmax)
NCT01209832 (6) [back to overview]Midazolam Pharmacokinetics: Area Under the Concentration-Time Curve From Time Zero to the Last Time Point With Measurable Concentrations (AUC 0-tlast)
NCT01209832 (6) [back to overview]Midazolam Pharmacokinetics: Area Under the Concentration-Time Curve From Time Zero to Infinity (AUC 0-infinity)
NCT01221727 (11) [back to overview]Ratio of Pharmcokinetic (PK) Area Under the Concentration Time Curve (AUC) Parameter Estimates Between Day 16 (Midazolam With the Presence of Denosumab) and Day 1 (Midazolam Only)
NCT01221727 (11) [back to overview]Ratio of PK AUC Parameter Estimates Between Day 16 (Midazolam Only) and Day 1(Midazolam Only)
NCT01221727 (11) [back to overview]Summary of Serum C-Telopeptide Concentration
NCT01221727 (11) [back to overview]Summary of Serum Denosumab Concentration
NCT01221727 (11) [back to overview]Estimates of Inter- and Intra-subject Variability for the PK AUC Parameters for Midazolam Only Group
NCT01221727 (11) [back to overview]Estimates of Inter- and Intra-subject Variability for the PK AUC Parameters for Midazolam With Denosumab Group
NCT01221727 (11) [back to overview]Estimates of Inter- and Intra-subject Variability for PK Maximum Observed Plasma Concentration (Cmax) Parameter for Midazolam With Denosumab Group
NCT01221727 (11) [back to overview]Estimates of Inter- and Intra-subject Variability for PK Cmax Parameter for Midazolam Only Group
NCT01221727 (11) [back to overview]Summary of Percent Change From Baseline to Day 16 for Serum C-Telopeptide Concentration
NCT01221727 (11) [back to overview]Ratio of PK Cmax Parameter Estimates Between Day 16 (Midazolam With the Presence of Denosumab) and Day 1 (Midazolam Only)
NCT01221727 (11) [back to overview]Ratio of PK Cmax Parameter Estimates Between Day 16 (Midazolam Only) and Day 1(Midazolam Only)
NCT01275170 (27) [back to overview]Part 1: Tmax of Cilastin in Combination With MK-7655
NCT01275170 (27) [back to overview]Part 1: Predicted Clearance (CLpred) of MK-7655 in Combination With PRIMAXIN®
NCT01275170 (27) [back to overview]Part 1: Ceoi of Cilastin in Combination With MK-7655
NCT01275170 (27) [back to overview]Part 1: VZpred of Cilastin in Combination With MK-7655
NCT01275170 (27) [back to overview]Part 1: Renal Clearance (CLR) of MK-7655 in Urine
NCT01275170 (27) [back to overview]Part 1: Tmax of Imipenem in Combination With MK-7655
NCT01275170 (27) [back to overview]Part 1: AUC0-inf of Cilastin in Combination With MK-7655
NCT01275170 (27) [back to overview]Part 2: Plasma AUC0-∞ of Midazolam as a Probe Substrate of Cytochrome P450 Enzyme (CYP)3A4
NCT01275170 (27) [back to overview]Part 1: Area Under the Plasma Concentration-time Curve From Dosing to Infinity (AUC0-inf) of MK-7655 in Combination With PRIMAXIN®
NCT01275170 (27) [back to overview]Part 1: Apparent t½ of Imipenem in Combination With MK-7655
NCT01275170 (27) [back to overview]Part 1: Concentration at End of Infusion (Ceoi) of MK-7655 in Combination With PRIMAXIN®
NCT01275170 (27) [back to overview]Part 1: Apparent t½ of Cilastin in Combination With MK-7655
NCT01275170 (27) [back to overview]Part 1: VZpred of Imipenem in Combination With MK-7655
NCT01275170 (27) [back to overview]Part 2: Plasma AUC0-∞ of Caffeine as a Probe Substrate of Cytochrome P450 Enzyme (CYP)1A2
NCT01275170 (27) [back to overview]Part 1: Apparent Plasma Half-life (t½) of MK-7655 in Combination With PRIMAXIN®
NCT01275170 (27) [back to overview]Part 2: Plasma AUC0-∞ of Omeprazole as a Probe Substrate of Cytochrome P450 Enzyme (CYP)2C19
NCT01275170 (27) [back to overview]Dialysis Clearance (CLD) of MK-7655 in Participants With End-stage Renal Diseases Requiring Hemodialysis (ESRD/HD)
NCT01275170 (27) [back to overview]Extraction Coefficient of MK-7655 in Participants With End-stage Renal Diseases Requiring Hemodialysis (ESRD/HD)
NCT01275170 (27) [back to overview]Part 1: CLR of Imipenem in Urine
NCT01275170 (27) [back to overview]Part 1: CLR of Cilastin in Urine
NCT01275170 (27) [back to overview]Part 1: CLpred of Imipenem in Combination With MK-7655
NCT01275170 (27) [back to overview]Part 1: AUC0-inf of Imipenem in Combination With MK-7655
NCT01275170 (27) [back to overview]Part 1: CLpred of Cilastin in Combination With MK-7655
NCT01275170 (27) [back to overview]Part 1: Predicted Volume of Distribution During the Terminal Phase (VZpred) of MK-7655 in Combination With PRIMAXIN®
NCT01275170 (27) [back to overview]Part 1: Time of Maximum Plasma Concentration (Tmax) of MK-7655 in Combination With PRIMAXIN®
NCT01275170 (27) [back to overview]Part 1: Ceoi of Imipenem in Combination With MK-7655
NCT01275170 (27) [back to overview]Parts 1 and 2: Percentage of Participants With ≥1 Adverse Events (AEs)
NCT01309360 (6) [back to overview]Onset Time.
NCT01309360 (6) [back to overview]Number of Participants With Objective Adverse Events as a Measure of Safety and Tolerability
NCT01309360 (6) [back to overview]Number of Participants With Subjective Adverse Events as a Measure of Safety and Tolerability.
NCT01309360 (6) [back to overview]Maximum Concentrations of Methemoglobin
NCT01309360 (6) [back to overview]Number of Participants With Complete Motor Blocks
NCT01309360 (6) [back to overview]Number of Participants With Complete Sensory Block
NCT01315158 (7) [back to overview]Number of Participants Who Experience Symptoms of Nausea and Vomiting Will be Compared Between the Two Groups
NCT01315158 (7) [back to overview]Predictors of Sedation Related Complications as Measured by the Number of Participants Who Experience Hypoxemia (Defined as a Pulse Oximetry <90% for Any Duration)
NCT01315158 (7) [back to overview]Predictors of Sedation Related Complications as Measured by the Incidences of Hypotension (Defined as Systolic Blood Pressure of Less Than 90mmHg or a Decrease of More Than 25% From Baseline)
NCT01315158 (7) [back to overview]Predictors of Sedation Related Complications as Measured by Hypopnea/Apnea (Defined as Fewer Than 6 Breaths/Minute Based on Capnography)
NCT01315158 (7) [back to overview]Predictors of Sedation Related Complications as Measured by Early Procedure Termination for an Alternative Sedation Related Complication
NCT01315158 (7) [back to overview]Number of Participants Who Experience Other Sedation Related Complications
NCT01315158 (7) [back to overview]Number of Participants Who Experience Airway Maneuvers
NCT01333059 (3) [back to overview]Duration of Mechanical Ventilation Days
NCT01333059 (3) [back to overview]Hospital Length of Stay
NCT01333059 (3) [back to overview]PICU Length of Stay
NCT01361217 (2) [back to overview]AUC of Dextromethorphan, Midazolam and Omeprazole in the Presence of Fluoxetine
NCT01361217 (2) [back to overview]Lovastatin AUC in the Presence of Fluoxetine
NCT01371110 (2) [back to overview]Percentage of Patients Who Meet Response and Remission
NCT01371110 (2) [back to overview]Change in Yale-Brown Obsessive Compulsive Scale (Y-BOCCS) Rating OCD Symptom Severity From Baseline to 24-hours After Ketamine Administration
NCT01390220 (4) [back to overview]Participants With Seizure(s) >10 Minutes to 4 Hours After Administration of the Double-blind Dose
NCT01390220 (4) [back to overview]Participants Who Met the Criteria for Treatment Success After Administration of the Double-blind Dose in the Comparative Phase (CP)
NCT01390220 (4) [back to overview]Occurrence of Seizure With a Start Time >10 Minutes After Administration of the Double-blind Dose
NCT01390220 (4) [back to overview]Time to Next Seizure With a Start Time >10 Minutes After Administration of the Double-blind Dose
NCT01393990 (6) [back to overview]PK: Maximum Plasma Concentration (Cmax) of LY2228820
NCT01393990 (6) [back to overview]PK: Area Under the Concentration-Time Curve From Time Zero to 8 Hours (AUC0-8) of LY2228820
NCT01393990 (6) [back to overview]Recommended Dose for Phase 2 Studies
NCT01393990 (6) [back to overview]Percentage of Participants With Best Overall Response [Complete Response (CR)+Partial Response (PR)+Stable Disease (SD)]
NCT01393990 (6) [back to overview]Number of Participants With Clinically Significant Effects (Physical Assessments and Safety Lab Tests)
NCT01393990 (6) [back to overview]Pharmacodynamics (PD): Number of Participants With Greater Than 50% Inhibition of p38 Mitogen-Activated Protein Kinase (MAPK) Activity on Day 1
NCT01428882 (4) [back to overview]Duration of Recovery After the Endoscopic Procedure
NCT01428882 (4) [back to overview]Level of Sedation Throughout the Entire Procedure
NCT01428882 (4) [back to overview]Rate of Patients and Physician Satisfaction With Sedation
NCT01428882 (4) [back to overview]Rate of Sedation-related Complications During the Procedure and the Recovery Phases
NCT01462318 (14) [back to overview]Intensive PK Sub-study: Minimum Concentrations (Cmin) of DAC HYP
NCT01462318 (14) [back to overview]Intensive PK Sub-study: Elimination Half-life (t½) of DAC HYP
NCT01462318 (14) [back to overview]Intensive PK Sub-study: Apparent Volume of Distribution (V/F) of DAC HYP
NCT01462318 (14) [back to overview]Intensive PK Sub-study: Apparent Clearance (CL/F) of DAC HYP
NCT01462318 (14) [back to overview]Number of Participants With Anti-DAC HYP Binding Antibodies (ADAbs): Electrochemiluminescent (ECL) Anti-Drug Antibody (ADA) Assay
NCT01462318 (14) [back to overview]TP-DI Sub-study: CL/F of Each Probe Drug
NCT01462318 (14) [back to overview]TP-DI Sub-study: Omeprazole/Hydroxyomeprazole Concentration Ratio at 2 Hours Post-omeprazole Dosing
NCT01462318 (14) [back to overview]TP-DI Sub-study: Dextromethorphan to Dextrorphan Urine Concentration Ratio
NCT01462318 (14) [back to overview]TP-DI Sub-study: Cmax of Each Probe Drug
NCT01462318 (14) [back to overview]TP-DI Sub-study: Area-Under-the-Curve From Zero to Infinity (AUCinf) of Each Probe Drug
NCT01462318 (14) [back to overview]Number of Participants With Anti-DAC HYP Neutralizing Antibodies (NAbs): ECL ADA Assay
NCT01462318 (14) [back to overview]Intensive PK Sub-study: Time to Reach Maximum Concentration (Tmax) of DAC HYP
NCT01462318 (14) [back to overview]Intensive PK Sub-study: Cmax of DAC HYP
NCT01462318 (14) [back to overview]Intensive PK Sub-study: Area-Under-the-Curve From Start to End of the Dosing Interval (AUCtau) of DAC HYP
NCT01472835 (5) [back to overview]Satisfaction
NCT01472835 (5) [back to overview]Pain Score
NCT01472835 (5) [back to overview]Pain Score
NCT01472835 (5) [back to overview]Oswestry Disability Index
NCT01472835 (5) [back to overview]Procedure-related Pain Score
NCT01488045 (3) [back to overview]Physician Perceptions (Absolute Value)
NCT01488045 (3) [back to overview]Patient Satisfaction Scores (Absolute Value)
NCT01488045 (3) [back to overview]Patient Pain & Discomfort Rating (Absolute Value)
NCT01507181 (8) [back to overview]The Young Mania Rating Scale (YMRS)
NCT01507181 (8) [back to overview]The Clinician-Administered Dissociative States Scale (CADSS)
NCT01507181 (8) [back to overview]Montgomery-Asberg Depression Rating Scale (MADRS)
NCT01507181 (8) [back to overview]Change in Beck Scale for Suicidal Ideation (BSSI)
NCT01507181 (8) [back to overview]Suicidality Item of the MADRS (MADRS-SI)
NCT01507181 (8) [back to overview]Change in Beck Scale for Suicidal Ideation (BSSI)
NCT01507181 (8) [back to overview]The Brief Psychiatric Rating Scale (BPRS)
NCT01507181 (8) [back to overview]Patient Rated Inventory of Side Effects (PRISE)
NCT01508455 (5) [back to overview]Time Spent With a Total N-PASS Score >3 During DEX Infusion
NCT01508455 (5) [back to overview]Percent of Subjects Requiring Rescue Midazolam for Sedation
NCT01508455 (5) [back to overview]Incidence of Rescue Medication (Fentanyl or Morphine) Use for Analgesia During DEX Infusion
NCT01508455 (5) [back to overview]Amount of Rescue Medication for Analgesia During DEX Infusion
NCT01508455 (5) [back to overview]Time to Successful Extubation
NCT01519167 (10) [back to overview]Number of Subjects Who Were Adequately Sedated at Least 80% of Time
NCT01519167 (10) [back to overview]Number of Subjects Who Had Success in Sedation
NCT01519167 (10) [back to overview]Frequency of Midazolam Required for Sedation
NCT01519167 (10) [back to overview]Number of Subjects Who Have Undergone Procedures Without Artificial Ventilation or Intervention
NCT01519167 (10) [back to overview]Frequency of Fentanyl Use for Analgesia
NCT01519167 (10) [back to overview]Number of Subjects Not Receiving Rescue Midazolam
NCT01519167 (10) [back to overview]Time to First Dose of Rescue Midazolam From Start of Dexmedetomidine Infusion
NCT01519167 (10) [back to overview]Total Amount of Rescue Analgesia (Fentanyl)
NCT01519167 (10) [back to overview]Total Amount of Rescue Sedation (Midazolam)
NCT01519167 (10) [back to overview]Number of Subjects Converted to Alternative Sedation or Anesthetic Therapy Due to Failure of Treatment of Study Drug and Rescue Medication
NCT01525628 (24) [back to overview]Cmax of Midazolam
NCT01525628 (24) [back to overview]Cmax of Tolbutamide
NCT01525628 (24) [back to overview]AUC 0-6hr of Deleobuvir Reduction Metabolite CD 6168
NCT01525628 (24) [back to overview]AUC 0-6hr of Deleobuvir Metabolite Acyl-glucuronide (BI 208333)
NCT01525628 (24) [back to overview]AUC 0-6hr of Deleobuvir (BI 207127)
NCT01525628 (24) [back to overview]Area Under the Concentration-time Curve (AUC) of Faldaprevir (BI 201335) From 0 to 24 Hours
NCT01525628 (24) [back to overview]Number of Participants With Sustained Virological Response (SVR12)
NCT01525628 (24) [back to overview]AUC 0-6hr of Deleobuvir Metabolite CD 6168 ag (Acylglucuronide)
NCT01525628 (24) [back to overview]Cmax of Deleobuvir Reduction Metabolite CD 6168
NCT01525628 (24) [back to overview]AUC 0-infinity of 1-OH-Midazolam (1-hydroxy-midazolam)
NCT01525628 (24) [back to overview]AUC 0-infinity of Caffeine
NCT01525628 (24) [back to overview]AUC 0-infinity of Midazolam
NCT01525628 (24) [back to overview]AUC 0-infinity of Tolbutamide
NCT01525628 (24) [back to overview]Cmax of Faldaprevir (BI 201335)
NCT01525628 (24) [back to overview]C24hr of Faldaprevir (BI 201335)
NCT01525628 (24) [back to overview]C6hr of Deleobuvir (BI 207127)
NCT01525628 (24) [back to overview]C6hr of Deleobuvir Metabolite Acyl-glucuronide (BI 208333)
NCT01525628 (24) [back to overview]C6hr of Deleobuvir Metabolite CD 6168 ag (Acylglucuronide)
NCT01525628 (24) [back to overview]C6hr of Deleobuvir Reduction Metabolite CD 6168
NCT01525628 (24) [back to overview]Cmax of 1-OH-Midazolam (1-hydroxy-midazolam)
NCT01525628 (24) [back to overview]Cmax of Caffeine
NCT01525628 (24) [back to overview]Cmax of Deleobuvir (BI 207127)
NCT01525628 (24) [back to overview]Cmax of Deleobuvir Metabolite Acyl-glucuronide (BI 208333)
NCT01525628 (24) [back to overview]Cmax of Deleobuvir Metabolite CD 6168 ag (Acylglucuronide)
NCT01535937 (2) [back to overview]Number of Participants With Cocaine Use/Drop Out
NCT01535937 (2) [back to overview]Abstinence
NCT01641653 (3) [back to overview]Percent Intra-op Blood Glucose Level of 140mg/dL or Less
NCT01641653 (3) [back to overview]Glucose Level Percent Change From Pre-op to Maximum Glucose Level
NCT01641653 (3) [back to overview]Maximum Perioperative Blood Glucose Level of 30 Minute Interval Measurements
NCT01643616 (3) [back to overview]Success Rate Without Supplementation
NCT01643616 (3) [back to overview]Success Rate With Supplementation
NCT01643616 (3) [back to overview]Time Until Readiness for Surgery (Minutes)
NCT01691690 (3) [back to overview]FLACC Pain Score Greater Than or Equal to 4
NCT01691690 (3) [back to overview]Time of First Opioid Analgesia in PACU
NCT01691690 (3) [back to overview]Analgesics Administered After Arrival to Inpatient Ward and Number of Participants Requiring Each
NCT01693185 (6) [back to overview]The Recovery Time
NCT01693185 (6) [back to overview]Patient's Distress Score
NCT01693185 (6) [back to overview]Participants Assumed to Feel Frequent Pain
NCT01693185 (6) [back to overview]Indigence of Patient's Recall
NCT01693185 (6) [back to overview]Endoscopist Satisfaction
NCT01693185 (6) [back to overview]Bispectra Lindex Score
NCT01700829 (3) [back to overview]Change in Scale for Suicidal Ideation
NCT01700829 (3) [back to overview]Neuropsychological Effects
NCT01700829 (3) [back to overview]Saliva Cortisol Awakening Response (CAR).
NCT01709422 (2) [back to overview]Procedure Related Time
NCT01709422 (2) [back to overview]Cardiovascular Adverse Events.
NCT01766050 (36) [back to overview]Time of Maximum Observed Plasma Concentration (Tmax) of the Inje Cocktail Components (Midazolam, Losartan, Omeprazole, Dextromethorphan, and Caffeine) With and Without Coadministration of Belatacept - PK Evaluable Population
NCT01766050 (36) [back to overview]T-HALF of Inje Cocktail Component Metabolites (1'-Hydroxy-Midazolam, E-3174, 5-Hydroxyomeprazole, Dextrorphan, and Paraxanthine) With and Without the Coadministration of Belatacept - PK Evaluable Population
NCT01766050 (36) [back to overview]Ratio of Paraxanthine AUC(0-T) to Caffeine AUC(0-T) and Paraxanthine AUC (INF) to Caffeine AUC (INF), Corrected for Molecular Weight [MR_AUC(0-T) and MR_AUC (INF)] With and Without Coadministration of Belatacept - PK Evaluable Population
NCT01766050 (36) [back to overview]Ratio of E-3174 AUC(0-T) to Losartan AUC(0-T) and E3174 AUC (INF) to Losartan AUC (INF) Corrected for Molecular Weight [MR_AUC(0-T), MR_AUC(INF)] With and Without Coadministration of Belatacept - PK Evaluable Population
NCT01766050 (36) [back to overview]Ratio of 5-Hydroxyomeprazole AUC(0-T) to Omeprazole AUC(0-T) and 5-Hydroxyomeprazole AUC(INF) to Omeprazole AUC(INF) , Corrected for Molecular Weight [MR_AUC(0-T), MR_AUC(INF)] With and Without Coadministration of Belatacept - PK Evaluable Population
NCT01766050 (36) [back to overview]Ratio of 5-Dextrorphan AUC(0-T) to Dextromethorphan AUC(0-T) and 5-Dextrorphan AUC(INF) to Dextromethorphan AUC(INF), Corrected for Molecular Weight [MR_AUC(0-T), MR_AUC (INF)] With and Without Coadministration of Belatacept - PK Evaluable Population
NCT01766050 (36) [back to overview]Plasma Half-Life (T-HALF) of the Inje Cocktail Components (Midazolam, Losartan, Omeprazole, Dextromethorphan, and Caffeine) With and Without Coadministration of Belatacept - PK Evaluable Population
NCT01766050 (36) [back to overview]Number of Participants With Marked Serum Chemistry Laboratory Abnormalities - All Treated Participants
NCT01766050 (36) [back to overview]Number of Participants With Marked Hematology and Urinalysis Laboratory Abnormalities - All Treated Participants
NCT01766050 (36) [back to overview]Number of Participants With Adverse Events (AEs), Serious AEs (SAEs), Deaths, and AEs Leading to Discontinuation - All Treated Participants
NCT01766050 (36) [back to overview]Apparent Total Body Clearance (CLT/F) of the Inje Cocktail Components (Midazolam, Losartan, Omeprazole, Dextromethorphan and Caffeine) With and Without Coadministration of Belatacept - PK Evaluable Population
NCT01766050 (36) [back to overview]Adjusted Geometric Mean AUC (0-T) and AUC (INF) of Omeprazole With and Without the Coadministration of Belatacept - Pharmacokinetic (PK) Evaluable Population
NCT01766050 (36) [back to overview]Adjusted Geometric Mean AUC (0-T) and AUC (INF) of Losartan With and Without the Coadministration of Belatacept - Pharmacokinetic (PK) Evaluable Population
NCT01766050 (36) [back to overview]Mean Change From Baseline in Heart Rate at Study Discharge (Day 46±2 Days)
NCT01766050 (36) [back to overview]Ratio of 5-Dextrorphan (Cmax) to Dextromethorphan (Cmax), Corrected for Molecular Weight (MR_Cmax) With and Without Coadministration of Belatacept - PK Evaluable Population
NCT01766050 (36) [back to overview]Ratio of 5-Hydroxyomeprazole (Cmax) to Omeprazole (Cmax), Corrected for Molecular Weight (MR_Cmax) With and Without Coadministration of Belatacept - PK Evaluable Population
NCT01766050 (36) [back to overview]Ratio of E-3174 (Cmax) to Losartan (Cmax), Corrected for Molecular Weight (MR_Cmax) With and Without Coadministration of Belatacept - PK Evaluable Population
NCT01766050 (36) [back to overview]Ratio of Paraxanthine (Cmax) to Caffeine (Cmax), Corrected for Molecular Weight (MR_Cmax) With and Without Coadministration of Belatacept - PK Evaluable Population
NCT01766050 (36) [back to overview]Adjusted Geometric Mean Cmax of Caffeine With and Without the Coadministration of Belatacept - PK Evaluable Population
NCT01766050 (36) [back to overview]Adjusted Geometric Mean AUC (0-T) and AUC (INF) of Dextromethorphan With and Without the Coadministration of Belatacept - PK Evaluable Population
NCT01766050 (36) [back to overview]Adjusted Geometric Mean Cmax of Dextromethorphan With and Without the Coadministration of Belatacept - PK Evaluable Population
NCT01766050 (36) [back to overview]Adjusted Geometric Mean Cmax of Losartan With and Without the Coadministration of Belatacept - PK Evaluable Population
NCT01766050 (36) [back to overview]AUC(0-T) of Inje Cocktail Component Metabolites (1'-Hydroxy-Midazolam, E-3174, 5-Hydroxyomeprazole, Dextrorphan, and Paraxanthine) With and Without Coadministration of Belatacept - PK Evaluable Population
NCT01766050 (36) [back to overview]Adjusted Geometric Mean Maximum Drug Concentration (Cmax) of Midazolam With and Without the Coadministration of Belatacept - Pharmacokinetic (PK) Evaluable Population
NCT01766050 (36) [back to overview]Tmax of Inje Cocktail Component Metabolites (1'-Hydroxy-Midazolam, E-3174, 5-Hydroxyomeprazole, Dextrorphan, and Paraxanthine) With and Without the Coadministration of Belatacept - PK Evaluable Population
NCT01766050 (36) [back to overview]Ratio of 1'-Hydroxy-Midazolam AUC(0-T) to Midazolam AUC(0-T) and 1'-Hydroxy-Midazolam AUC(INF) to Midazolam AUC(INF), Corrected for Molecular Weight [MR_AUC(0-T), MR_AUC (INF)] With and Without Coadministration of Belatacept - PK Evaluable Population
NCT01766050 (36) [back to overview]AUC(INF) of Inje Cocktail Component Metabolites (1'-Hydroxy-Midazolam, E-3174, 5-Hydroxyomeprazole, Dextrorphan, and Paraxanthine) With and Without Coadministration of Belatacept - PK Evaluable Population
NCT01766050 (36) [back to overview]Mean Change From Baseline in Systolic and Diastolic Blood Pressure at Study Discharge (Day 46±2 Days)
NCT01766050 (36) [back to overview]Number of Participants With Out-of-Range Electrocardiogram Intervals - All Treated Participants
NCT01766050 (36) [back to overview]Adjusted Geometric Mean Area Under the Concentration Time Curve (AUC) From Zero to Last Concentration (0-T) and AUC Extrapolated to Infinity (INF) of Midazolam With and Without the Coadministration of Belatacept - Pharmacokinetic (PK) Evaluable Population
NCT01766050 (36) [back to overview]Cmax of Inje Cocktail Metabolites (1'-Hydroxy-Midazolam, E-3174, 5-Hydroxyomeprazole, Dextrorphan, and Paraxanthine) With and Without Coadministration of Belatacept - PK Evaluable Population
NCT01766050 (36) [back to overview]Mean Change From Baseline in Sitting Heart Rate - All Treated Participants
NCT01766050 (36) [back to overview]Ratio of 1'-Hydroxy-Midazolam (Cmax) to Midazolam (Cmax), Corrected for Molecular Weight (MR_Cmax) With and Without Coadministration of Belatacept - PK Evaluable Population
NCT01766050 (36) [back to overview]Adjusted Geometric Mean AUC (0-T) and AUC (INF) of Caffeine With and Without the Coadministration of Belatacept - PK Evaluable Population
NCT01766050 (36) [back to overview]Mean Change From Baseline in Sitting Systolic and Diastolic Blood Pressure - All Treated Participants
NCT01766050 (36) [back to overview]Adjusted Geometric Mean Cmax of Omeprazole With and Without the Coadministration of Belatacept - Pharmacokinetic (PK) Evaluable Population
NCT01769586 (1) [back to overview]Number of Patients Who Achieve Adequate Sedation to Allow Colonoscopy (Defined as MOAA/S ≤3)
NCT01830881 (20) [back to overview]Subject Perception of Pain and Anxiety Post Procedure
NCT01830881 (20) [back to overview]Subject Perception of Pain and Anxiety Upon Entering Procedure Room
NCT01830881 (20) [back to overview]Subject Satisfaction With Pain and Anxiety 1-3 Days Post Procedure
NCT01830881 (20) [back to overview]Subject's Correct Identification of Receiving Midazolam or Placebo
NCT01830881 (20) [back to overview]Number of Participants With Need for Additional Postoperative Pain Medication
NCT01830881 (20) [back to overview]Patient Satisfaction With Pain and Anxiety 30 Minutes Postoperatively
NCT01830881 (20) [back to overview]Subject Vital Signs (Heart Rate) 30 Minutes Postprocedure
NCT01830881 (20) [back to overview]State-Trait Anxiety Inventory for Anxiety at Baseline
NCT01830881 (20) [back to overview]Subject Perception of Pain and Anxiety During Uterine Aspiration
NCT01830881 (20) [back to overview]Subject Sleepiness 30 Minutes Postprocedure
NCT01830881 (20) [back to overview]Subject Perception of Pain During Cervical Dilation
NCT01830881 (20) [back to overview]Subject Nausea 30 Minutes Postprocedure
NCT01830881 (20) [back to overview]Subject Extent of Amnesia
NCT01830881 (20) [back to overview]Subject Anticipated Perception of Pain and Anxiety During Uterine Aspiration at Baseline
NCT01830881 (20) [back to overview]Subject Vital Signs (Heart Rate)
NCT01830881 (20) [back to overview]Subject Vital Signs (Oxygenation Saturation)
NCT01830881 (20) [back to overview]Subject Extent of Amnesia Using Amnesia Score
NCT01830881 (20) [back to overview]Subject Extent of Sedation
NCT01830881 (20) [back to overview]Subject Vital Signs (Oxygenation Saturation) 30 Minutes Postprocedure
NCT01830881 (20) [back to overview]Subject Perception of Anxiety With Patient Positioning Procedure
NCT01845441 (3) [back to overview]Maintenance of Optimal Sedation Target in Both Groups.
NCT01845441 (3) [back to overview]Preserved Neurological Examination.
NCT01845441 (3) [back to overview]Numbers of Patient Movements (Events) That Delay or Adversely Affect the Procedure Performance and Safety.
NCT01920555 (10) [back to overview]Clinical Global Impressions-Improvement (CGI-I) Scale
NCT01920555 (10) [back to overview]Clinical Global Impressions-Severity (CGI-S)
NCT01920555 (10) [back to overview]Clinical Positive Affect Scale (CPAS)
NCT01920555 (10) [back to overview]Clinician-Administered Dissociative States Scale (CADSS) Scores During Infusion
NCT01920555 (10) [back to overview]Hamilton Rating Scale for Depression - 6 Items
NCT01920555 (10) [back to overview]Montgomery-Asberg Depression Rating Scale (MADRS)
NCT01920555 (10) [back to overview]Number of Participants Reporting Suicidal Ideation/Behavior on the Columbia Suicide Severity Rating Scale (C-SSRS)
NCT01920555 (10) [back to overview]Number of Participants With Abnormal and Clinically Significant CBC and Chemistry Labs by Treatment
NCT01920555 (10) [back to overview]Snaith-Hamilton Pleasure-Scale (SHAPS)
NCT01920555 (10) [back to overview]Symptoms of Depression Questionnaire (SDQ)
NCT01944293 (2) [back to overview]Change in Systolic Blood Pressure
NCT01944293 (2) [back to overview]Change in Suicidal Ideation Measured With the Beck Scale for Suicidal Ideation
NCT01948908 (3) [back to overview]Observational Scale of Behavioral Distress - Revised
NCT01948908 (3) [back to overview]Number of Patients With Physicians Who Were Satisfied or Very Satisfied With Ease of Medication Administration
NCT01948908 (3) [back to overview]Median Time (Minutes) After Administration of Intranasal Midazolam Until Patient Achieves Minimal Sedation
NCT01976845 (3) [back to overview]Produces Amnesia(Memory Recall)
NCT01976845 (3) [back to overview]Scores on the Verbal Rating Scale For Anxiety
NCT01976845 (3) [back to overview]Scores on the Verbal Rating Scale For Sleepiness (Sedation)
NCT01989169 (3) [back to overview]Area Under the Concentration-time Curve From Time Zero to the Time of the Last Measureable Concentration (AUClast) of Midazolam
NCT01989169 (3) [back to overview]Area Under the Plasma Concentration-time Curve (AUC) From Time Zero to Infinity (AUCinf) of Midazolam
NCT01989169 (3) [back to overview]Maximum Plasma Concentration (Cmax) of Midazolam
NCT02014558 (70) [back to overview]Duration of CR (DCR)
NCT02014558 (70) [back to overview]Duration of CR (DCR)
NCT02014558 (70) [back to overview]Duration of CRc (DCRc)
NCT02014558 (70) [back to overview]Duration of CRc (DCRc)
NCT02014558 (70) [back to overview]Duration of CRi (DCRi)
NCT02014558 (70) [back to overview]Duration of CRi (DCRi)
NCT02014558 (70) [back to overview]Duration of CRp (DCRp)
NCT02014558 (70) [back to overview]Duration of Response
NCT02014558 (70) [back to overview]Duration of Response
NCT02014558 (70) [back to overview]Event Free Survival (EFS)
NCT02014558 (70) [back to overview]Fraction of Drug Excreted Into Urine in Percentage (%Ae) of Cephalexin Administered With and Without Gilteritinib
NCT02014558 (70) [back to overview]Leukemia Free Survival (LFS)
NCT02014558 (70) [back to overview]Leukemia Free Survival (LFS)
NCT02014558 (70) [back to overview]Maximum Concentration (Cmax) After Single and Multiple Doses of Gilteritinib
NCT02014558 (70) [back to overview]Number of Participants With Adverse Events (AEs)
NCT02014558 (70) [back to overview]Number of Participants With Dose Limiting Toxicities (DLTs)
NCT02014558 (70) [back to overview]Overall Survival (OS)
NCT02014558 (70) [back to overview]Percentage of Participants Who Achieved Transfusion Conversion
NCT02014558 (70) [back to overview]Percentage of Participants Who Achieved Transfusion Maintenance
NCT02014558 (70) [back to overview]Percentage of Participants Who Achieved Transfusion Maintenance
NCT02014558 (70) [back to overview]Percentage of Participants With Best Response
NCT02014558 (70) [back to overview]Percentage of Participants With Complete Remission (CR) During the First 2 Cycles
NCT02014558 (70) [back to overview]Percentage of Participants With Composite CR (CRc)
NCT02014558 (70) [back to overview]Percentage of Participants With CR During Treatment
NCT02014558 (70) [back to overview]Percentage of Participants With CR With Incomplete Hematological Recovery (CRi)
NCT02014558 (70) [back to overview]Percentage of Participants With CR With Incomplete Platelet Recovery (CRp)
NCT02014558 (70) [back to overview]Percentage of Participants With Partial Remission (PR)
NCT02014558 (70) [back to overview]Renal Clearance (CLr) of Cephalexin in Administered With and Without Gilteritinib
NCT02014558 (70) [back to overview]T1/2 of Cephalexin Administered With and Without Gilteritinib
NCT02014558 (70) [back to overview]Time to Best Response (TTBR)
NCT02014558 (70) [back to overview]Time to Best Response (TTBR)
NCT02014558 (70) [back to overview]Time to CR (TTCR)
NCT02014558 (70) [back to overview]Time to CR (TTCR)
NCT02014558 (70) [back to overview]Time to CRc (TTCRc)
NCT02014558 (70) [back to overview]Time to CRc (TTCRc)
NCT02014558 (70) [back to overview]Time to CRi (TTCRi)
NCT02014558 (70) [back to overview]Time to CRi (TTCRi)
NCT02014558 (70) [back to overview]Time to CRp (TTCRp)
NCT02014558 (70) [back to overview]Time to Observed Cmax (Tmax) After Single and Multiple Doses of Gilteritinib
NCT02014558 (70) [back to overview]Time to Response (TTR)
NCT02014558 (70) [back to overview]Time to Response (TTR)
NCT02014558 (70) [back to overview]Tmax of 1-Hydroxymidazolam After Administration of Midazolam With and Without Gilteritinib
NCT02014558 (70) [back to overview]Tmax of Cephalexin Administered With and Without Gilteritinib
NCT02014558 (70) [back to overview]Tmax of Midazolam Administered With and Without Gilteritinib
NCT02014558 (70) [back to overview]Cmax of Midazolam Administered With and Without Gilteritinib
NCT02014558 (70) [back to overview]Accumulation Ratio After Multiple Doses of Gilteritinib
NCT02014558 (70) [back to overview]AUC24 of Gilteritinib in Co-administration With Voriconazole
NCT02014558 (70) [back to overview]AUClast of Gilteritinib in Co-administration With Voriconazole
NCT02014558 (70) [back to overview]Cmax of Gilteritinib in Co-administration With Voriconazole
NCT02014558 (70) [back to overview]Duration of CR/CRh (DCRCRh)
NCT02014558 (70) [back to overview]Duration of CRh (DCRh)
NCT02014558 (70) [back to overview]Percentage of Participants With Complete Remission and Complete Remission With Partial Hematologic Recovery (CR/CRh)
NCT02014558 (70) [back to overview]Percentage of Participants With Complete Remission With Partial Hematologic Recovery (CRh)
NCT02014558 (70) [back to overview]Terminal Elimination Half-life (t1/2) After Multiple Doses of Gilteritinib
NCT02014558 (70) [back to overview]Time to Best CR/CRh (TTBCRCRh)
NCT02014558 (70) [back to overview]Time to First CR/CRh (TTFCRCRh)
NCT02014558 (70) [back to overview]Tmax of Gilteritinib in Co-administration With Voriconazole
NCT02014558 (70) [back to overview]Amount of Drug Excreted in Urine (Aelast) of Cephalexin Administered With and Without Gilteritinib
NCT02014558 (70) [back to overview]Apparent Total Systemic Clearance After Single or Multiple Extravascular Dosing (CL/F) of Cephalexin Administered With and Without Gilteritinib
NCT02014558 (70) [back to overview]Apparent Volume of Distribution During the Terminal Elimination Phase After Single Extravascular Dosing (Vz/F) of Cephalexin Administered With and Without Gilteritinib
NCT02014558 (70) [back to overview]Area Under the Concentration-time Curve From the Time of Dosing Extrapolated to Time Infinity (AUCinf) of Cephalexin Administered With and Without Gilteritinib
NCT02014558 (70) [back to overview]Area Under the Concentration-time Curve From the Time of Dosing to the Last Measurable Concentration (AUClast) After Single and Multiple Doses of Gilteritinib
NCT02014558 (70) [back to overview]Area Under the Concentration-time Curve Over the 24-Hour Dosing Interval (AUC24) After Single and Multiple Doses of Gilteritinib
NCT02014558 (70) [back to overview]AUC24 of Metabolite 1-Hydroxymidazolam After Administration of Midazolam With and Without Gilteritinib
NCT02014558 (70) [back to overview]AUC24 of Midazolam Administered With and Without Gilteritinib
NCT02014558 (70) [back to overview]AUClast of 1-Hydroxymidazolam After Administration of Midazolam With and Without Gilteritinib
NCT02014558 (70) [back to overview]AUClast of Cephalexin Administered With and Without Gilteritinib
NCT02014558 (70) [back to overview]AUClast of Midazolam Administered With and Without Gilteritinib
NCT02014558 (70) [back to overview]Cmax of 1-Hydroxymidazolam After Administration of Midazolam With and Without Gilteritinib
NCT02014558 (70) [back to overview]Cmax of Cephalexin Administered With and Without Gilteritinib
NCT02027311 (2) [back to overview]Number of Intervention
NCT02027311 (2) [back to overview]Event of Hypoxia
NCT02062177 (3) [back to overview]Patient's Satisfaction (Visual Analog Scale) About Sedation Before Discharge
NCT02062177 (3) [back to overview]Endoscopist's Satisfaction (Visual Analog Scale) About Sedation
NCT02062177 (3) [back to overview]Patient's Satisfaction (Visual Analog Scale) About Sedation 24-72 Hours After Procedure
NCT02096900 (3) [back to overview]Modified Yale Preoperative Anxiety Scale (mYPAS) Score at Separation (mYPAS2) Based on Baseline (mYPAS1) Score.
NCT02096900 (3) [back to overview]Patient Anxiety at the Time of Separation
NCT02096900 (3) [back to overview]Parental/Caregiver Anxiety Assessed Using the Validated State-Trait Anxiety Inventory for Adults (STAI)
NCT02129426 (4) [back to overview]Percent Change in Blood Pressure From Baseline
NCT02129426 (4) [back to overview]Percent Change in Heart Rate From Baseline
NCT02129426 (4) [back to overview]The Number of Participants With Adverse Recovery-related Behaviors During Sedation Recovery
NCT02129426 (4) [back to overview]The Number of Participants With Hypotension and/or Bradycardia During Sedation and Recovery (Generally 2-3 Hours)
NCT02161185 (1) [back to overview]Number of Participants With Death, Serious Adverse Events, Treatment Emergent Adverse Events (TEAEs) Leading to Discontinuation
NCT02164929 (8) [back to overview]Time to First Ingestion of Solid Food
NCT02164929 (8) [back to overview]Time to First Bowel Movement
NCT02164929 (8) [back to overview]Quality of Recovery
NCT02164929 (8) [back to overview]Postoperative Opioid Consumption
NCT02164929 (8) [back to overview]Pain Scores
NCT02164929 (8) [back to overview]Opioid Related Side Effects
NCT02164929 (8) [back to overview]Number of Epidural-related Side Effects
NCT02164929 (8) [back to overview]Length of Stay
NCT02168439 (6) [back to overview]VAS for Anxiety as Completed by Caregiver and Observer
NCT02168439 (6) [back to overview]mYPAS Scores at Other Time Points
NCT02168439 (6) [back to overview]Anxiolysis Satisfaction
NCT02168439 (6) [back to overview]Procedure Completion
NCT02168439 (6) [back to overview]Need for Procedural Sedation
NCT02168439 (6) [back to overview]mYPAS Score as Completed by Researchers to Assess Anxiety
NCT02206776 (1) [back to overview]Number of Patients Who Met and Exceeded Response Criteria of Yale-Brown Obsessive-Compulsive Scale.
NCT02250703 (1) [back to overview]University of Michigan Sedation Scale
NCT02256358 (1) [back to overview]Emergence Agitation
NCT02290873 (4) [back to overview]Time to Fully Alert
NCT02290873 (4) [back to overview]Time to Start of Procedure
NCT02290873 (4) [back to overview]Success Rates of the Procedure
NCT02290873 (4) [back to overview]Time to Ready for Discharge
NCT02292082 (11) [back to overview]Patient Outcome Questionnaire (painOUT) Most Pain for 0-24 Hours Postoperatively
NCT02292082 (11) [back to overview]Patient Outcome Questionnaire (painOUT) Least Pain for 24-48 Hours Postoperatively
NCT02292082 (11) [back to overview]Patient Outcome Questionnaire (painOUT) Least Pain for 0-24 Hours Postoperatively
NCT02292082 (11) [back to overview]Opioid Consumption Postoperative Day (POD) 1
NCT02292082 (11) [back to overview]Opioid Consumption POD2
NCT02292082 (11) [back to overview]Time to Meet Physical Therapy Discharge Criteria
NCT02292082 (11) [back to overview]NRS Pain Score With Movement POD2
NCT02292082 (11) [back to overview]Knee Society Score (KSS) at 6 Weeks Postoperatively
NCT02292082 (11) [back to overview]Hospital Length of Stay
NCT02292082 (11) [back to overview]Patient Outcome Questionnaire (painOUT) Most Pain for 24-48 Hours Postoperatively
NCT02292082 (11) [back to overview]Numerical Rating Scale (NRS) Pain Scores With Ambulation Postoperative Day 1
NCT02296892 (4) [back to overview]Number of Participants With a Successful Procedure
NCT02296892 (4) [back to overview]Time to Start of Procedure
NCT02296892 (4) [back to overview]Time to Fully Alert
NCT02296892 (4) [back to overview]Time to Ready for Discharge
NCT02314546 (7) [back to overview]Parental Observed Behavioral Distress Score
NCT02314546 (7) [back to overview]Time From Administration to Discharge
NCT02314546 (7) [back to overview]Sedation Scale Score
NCT02314546 (7) [back to overview]Sedation Scale Score
NCT02314546 (7) [back to overview]Verbal Complaint
NCT02314546 (7) [back to overview]Verbal Complaints
NCT02314546 (7) [back to overview]RN Observed Behavioral Distress Score
NCT02356705 (4) [back to overview]Time to Discharge
NCT02356705 (4) [back to overview]Observational Distress Score at 1 Minute (Blinded Study Nurse Assessment)
NCT02356705 (4) [back to overview]Number of Participants With Nosebleeds From Time of Drug Administration to Discharge Home
NCT02356705 (4) [back to overview]Observational Distress Score 5 Min (Blinded Study Nurse Assessmnet)
NCT02360280 (4) [back to overview]Time From Post-infusion Response to Occurrence of Relapse Defined as <50% of Baseline MADRS Score
NCT02360280 (4) [back to overview]Remission Defined as MADRS Score Equal or Less Than 9
NCT02360280 (4) [back to overview]Change From Baseline in Montgomery-Asberg Depression Rating Scale (MADRS) Score After 12 Days of Treatment
NCT02360280 (4) [back to overview]Antidepressant Response Defined as >50% Decrease in MADRS Baseline Score
NCT02365597 (19) [back to overview]Main Study: Progression-free Survival (PFS)
NCT02365597 (19) [back to overview]Main Study: Plasma Concentration of Erdafitinib at 2 Hours (C2h)
NCT02365597 (19) [back to overview]Main Study: Plasma Concentration of Erdafitinib at 4 Hours (C4h)
NCT02365597 (19) [back to overview]Drug-Drug Interaction (DDI) Substudy: Area Under the Plasma Concentration Versus Time Curve From Time 0 to the Infinite Time (AUC[0-Infinity]) of Midazolam Alone or in Combination With Erdafitinib
NCT02365597 (19) [back to overview]Drug-Drug Interaction (DDI) Substudy: Area Under the Plasma Concentration Versus Time Curve From Time 0 to the Infinite Time (AUC[0-Infinity]) of 1-OH-Midazolam (Midazolam Metabolite) Alone or in Combination With Erdafitinib
NCT02365597 (19) [back to overview]Drug-Drug Interaction (DDI) Substudy: Area Under the Plasma Concentration Versus Time Curve From Time 0 to the Infinite Time (AUC[0-Infinity]) of Metformin Alone or in Combination With Erdafitinib
NCT02365597 (19) [back to overview]Drug-Drug Interaction (DDI) Substudy: Area Under the Plasma Concentration Versus Time Curve From Time 0 to the Time of the Last Measurable Concentration (AUC[0-last]) of 1-OH-Midazolam (Midazolam Metabolite) Alone or in Combination With Erdafitinib
NCT02365597 (19) [back to overview]Drug-Drug Interaction (DDI) Substudy: Area Under the Plasma Concentration Versus Time Curve From Time 0 to the Time of the Last Measurable Concentration (AUC[0-last]) of Metformin Alone or in Combination With Erdafitinib
NCT02365597 (19) [back to overview]Drug-Drug Interaction (DDI) Substudy: Area Under the Plasma Concentration Versus Time Curve From Time 0 to the Time of the Last Measurable Concentration (AUC[0-last]) of Midazolam Alone or in Combination With Erdafitinib
NCT02365597 (19) [back to overview]Drug-Drug Interaction (DDI) Substudy: Maximum Observed Plasma Concentration (Cmax) of 1-OH-Midazolam (Midazolam Metabolite) Alone or in Combination With Erdafitinib
NCT02365597 (19) [back to overview]Drug-Drug Interaction (DDI) Substudy: Maximum Observed Plasma Concentration (Cmax) of Metformin Alone or in Combination With Erdafitinib
NCT02365597 (19) [back to overview]Drug-Drug Interaction (DDI) Substudy: Maximum Observed Plasma Concentration (Cmax) of Midazolam Alone or in Combination With Erdafitinib
NCT02365597 (19) [back to overview]Drug-Drug Interaction (DDI) Substudy: Time to Reach the Maximum Observed Plasma Concentration (Tmax) of 1-OH-Midazolam (Midazolam Metabolite) Alone or in Combination With Erdafitinib
NCT02365597 (19) [back to overview]Drug-Drug Interaction (DDI) Substudy: Time to Reach the Maximum Observed Plasma Concentration (Tmax) of Metformin Alone or in Combination With Erdafitinib
NCT02365597 (19) [back to overview]Drug-Drug Interaction (DDI) Substudy: Time to Reach the Maximum Observed Plasma Concentration (Tmax) of Midazolam Alone or in Combination With Erdafitinib
NCT02365597 (19) [back to overview]Main Study: Duration of Response (DoR)
NCT02365597 (19) [back to overview]Main Study: Overall Survival
NCT02365597 (19) [back to overview]Main Study: Percentage of Participants With Best (Overall) Objective Response
NCT02365597 (19) [back to overview]Main Study: Percentage of Participants With Treatment-emergent Adverse Event (TEAEs)
NCT02370615 (17) [back to overview]Number of Participants With TEAEs Related to Vital Signs
NCT02370615 (17) [back to overview]Number of Participants With Clinically Significant Change From Baseline in Continuous Pulse Oximetry (SpO2) in Cohort 2
NCT02370615 (17) [back to overview]Cmax: Maximum Observed Plasma Concentration for Midazolam and 1'Hydroxymidazolam in Cohort 2
NCT02370615 (17) [back to overview]Cmax: Maximum Observed Plasma Concentration for Digoxin in Cohort 2
NCT02370615 (17) [back to overview]Number of Participants With TEAEs Related to Body Weight
NCT02370615 (17) [back to overview]Cmax: Maximum Observed Plasma Concentration for TAK 272F and TAK 272-Metabolite (M-I) in Cohort 1
NCT02370615 (17) [back to overview]Urinary Excretion Ratio of Digoxin From 0 to 48 Hours Postdose in Cohort 2
NCT02370615 (17) [back to overview]AUC(0-inf): Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for Midazolam and 1'Hydroxymidazolam in Cohort 2
NCT02370615 (17) [back to overview]AUC(0-inf): Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK 272F and TAK 272-M-I in Cohort 1
NCT02370615 (17) [back to overview]Number of Participants Who Had Clinically Significant Changes From Baseline in 12-lead Electrocardiograms
NCT02370615 (17) [back to overview]AUC(0-tlqc): Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration for Midazolam and 1'Hydroxymidazolam in Cohort 2
NCT02370615 (17) [back to overview]AUC(0-tlqc): Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK 272F and TAK 272-M-I in Cohort 1
NCT02370615 (17) [back to overview]Cumulative Urinary Excretion Ratio of TAK 272F and TAK 272-M-I From 0 to 72 Hours Postdose in Cohort 1
NCT02370615 (17) [back to overview]Number of Participants With TEAEs Categorized Into Investigations System Organ Class (SOC) Related to Chemistry, Hematology or Urinalysis
NCT02370615 (17) [back to overview]AUC(0-tlqc): Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration for Digoxin in Cohort 2
NCT02370615 (17) [back to overview]AUC(0-inf): Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for Digoxin in Cohort 2
NCT02370615 (17) [back to overview]Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs)
NCT02396537 (1) [back to overview]Discomfort With Intranasal Midazolam Administration
NCT02397889 (6) [back to overview]The Impact of Event Scale - Revised (IES-R)
NCT02397889 (6) [back to overview]Clinician-Administered PTSD Scale for DSM-5 (CAPS-5)
NCT02397889 (6) [back to overview]Montgomery Asberg Depression Rating Scale (MADRS)
NCT02397889 (6) [back to overview]Montgomery Asberg Depression Rating Scale (MADRS)
NCT02397889 (6) [back to overview]Number of Participants With Patient-Rated Inventory of Side Effects (PRISE)
NCT02397889 (6) [back to overview]Quick Inventory of Depression Symptomatology - Self-Report (QIDS-SR)
NCT02403635 (20) [back to overview]Number of Participants With Serious and Non-Serious Adverse Events
NCT02403635 (20) [back to overview]Area Under Concentration-Time Curve up to Last Non-zero Value (AUC0-tn) of Midazolam
NCT02403635 (20) [back to overview]Peak Plasma Concentration (Cmax) of Midazolam
NCT02403635 (20) [back to overview]Peak Plasma Concentration (Cmax) of ASP2151
NCT02403635 (20) [back to overview]Peak Plasma Concentration (Cmax) of 1-hydroxymidazolam
NCT02403635 (20) [back to overview]Area Under Concentration-Time Curve up to Last Non-zero Value (AUC0-tn) of 1-hydroxymidazolam
NCT02403635 (20) [back to overview]Half-life (t1/2) of Midazolam
NCT02403635 (20) [back to overview]Area Under Concentration-Time Curve Extrapolated to Infinite Time (AUC0-∞) of Midazolam
NCT02403635 (20) [back to overview]Half-life (t1/2) of ASP2151
NCT02403635 (20) [back to overview]Area Under Concentration-Time Curve Extrapolated to Infinite Time (AUC0-∞) of ASP2151
NCT02403635 (20) [back to overview]Apparent Total Body Clearance (CL/F) of Midazolam
NCT02403635 (20) [back to overview]Area Under Concentration-Time Curve Over the Dosing Interval (AUC0-tau) of ASP2151
NCT02403635 (20) [back to overview]Time of Peak Concentration (Tmax) of Midazolam
NCT02403635 (20) [back to overview]Apparent Total Body Clearance (CL/F) of ASP2151
NCT02403635 (20) [back to overview]Trough Plasma Concentration (Ctrough) of ASP2151
NCT02403635 (20) [back to overview]Apparent Volume of Distribution (Vd/F) of ASP2151
NCT02403635 (20) [back to overview]Time of Peak Concentration (Tmax) of ASP2151
NCT02403635 (20) [back to overview]Half-life (t1/2) of 1-hydroxymidazolam
NCT02403635 (20) [back to overview]Apparent Volume of Distribution (Vd/F) of Midazolam
NCT02403635 (20) [back to overview]Time of Peak Concentration (Tmax) of 1-hydroxymidazolam
NCT02406261 (6) [back to overview]Number of Participants With One or More Serious Adverse Events(s) Considered by the Investigator to be Related to Study Drug Administration
NCT02406261 (6) [back to overview]PK Profile for Midazolam: AUC(0-∞) Oral and IV Dose
NCT02406261 (6) [back to overview]PK Profile for Donepezil: AUC(0-∞)
NCT02406261 (6) [back to overview]PK Profile for Simvastatin: AUC(0-∞)
NCT02406261 (6) [back to overview]Pharmacokinetic (PK): Area Under the Curve Zero to Infinity (AUC[0-∞]) for LY3314814
NCT02406261 (6) [back to overview]Number of Participants Experiencing Suicidal Ideation or Suicidal Behavior Based on Columbia-Suicide Severity Rating Scale (C-SSRS)
NCT02414932 (2) [back to overview]Completion Rate for Randomised Treatment
NCT02414932 (2) [back to overview]Depression Relapse Rate
NCT02419547 (1) [back to overview]Number of Participants Who Had Inducible Ventricular Tachycardia Under General Anesthesia.
NCT02439164 (4) [back to overview]Task Completing Time Change Between Sedation and Baseline Measured by 9-hole Peg Test
NCT02439164 (4) [back to overview]Mean Arterial Blood Pressure (MAP) as a Measure of Physiological Change
NCT02439164 (4) [back to overview]Heart Rate as a Measure of Physiological Change
NCT02439164 (4) [back to overview]Number of Participants With OAA/S=4 After Sedation
NCT02461160 (33) [back to overview]AUClast: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-915
NCT02461160 (33) [back to overview]AUClast: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-915 and TAK-915 Metabolite M-I in BA/FE Cohort
NCT02461160 (33) [back to overview]CL/F: Apparent Clearance for TAK-915
NCT02461160 (33) [back to overview]Cmax: Maximum Observed Plasma Concentration for Midazolam Alone (Day 1) and in the Presence of TAK-915 (Day 16) in DDI Cohort
NCT02461160 (33) [back to overview]Cmax: Maximum Observed Plasma Concentration for TAK-915
NCT02461160 (33) [back to overview]Cmax: Maximum Observed Plasma Concentration for TAK-915 and TAK-915 Metabolite M-I in BA/FE Cohort
NCT02461160 (33) [back to overview]Fraction of Drug Excreted in Urine (Fe) for TAK-915
NCT02461160 (33) [back to overview]Percentage of Participants With Markedly Abnormal Values of 12-Lead Electrocardiogram (ECG) Parameters
NCT02461160 (33) [back to overview]Percentage of Participants With Markedly Abnormal Vital Sign Measurements
NCT02461160 (33) [back to overview]Ratio of TAK-915 Metabolite Cmax to TAK-915 Cmax in SRD and MRD Cohorts
NCT02461160 (33) [back to overview]Renal Clearance (CLr) for TAK-915
NCT02461160 (33) [back to overview]Terminal Elimination Half-life (t1/2) for TAK-915
NCT02461160 (33) [back to overview]Terminal Elimination Half-life (t1/2) for TAK-915 and TAK-915 Metabolite M-I in BA/FE Cohort
NCT02461160 (33) [back to overview]Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-915
NCT02461160 (33) [back to overview]Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-915 and TAK-915 Metabolite M-I in BA/FE Cohort
NCT02461160 (33) [back to overview]Total Amount of Drug Excreted in Urine (Ae) for TAK-915
NCT02461160 (33) [back to overview]λz: Terminal Elimination Rate Constant for TAK-915 and TAK-915 Metabolite M-I in BA/FE Cohort
NCT02461160 (33) [back to overview]AUC(0-24): Area Under the Plasma Concentration-Time Curve From Time 0 to 24 Hours Postdose for TAK-915 on Day 1 in DDI Cohort
NCT02461160 (33) [back to overview]AUC(0-24) for Midazolam After Single Dose (Day 1)/AUC(0-24) for Midazolam After 7 Daily Doses of TAK-915 (Day 16) in DDI Cohort
NCT02461160 (33) [back to overview]Time Dependency Assessment From AUC(0-24) After Last Dose for TAK-915 on Day 14 in MRD Cohorts Compared to AUC(0-inf) After a Single Dose on Day 1
NCT02461160 (33) [back to overview]Apparent Volume of Distribution (Vz/F) for TAK-915
NCT02461160 (33) [back to overview]AUC(0-tau): Area Under the Plasma Concentration-Time Curve From Time 0 to Time Tau Over a Dosing Interval Where Tau is the Length of the Dosing Interval for TAK-915 in DDI Cohort
NCT02461160 (33) [back to overview]AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-915
NCT02461160 (33) [back to overview]AUC(0-24): Area Under the Plasma Concentration-Time Curve From Time 0 to 24 Hours Postdose for Midazolam Alone (Day 1) and in the Presence of TAK-915 (Day 16) in DDI Cohort
NCT02461160 (33) [back to overview]AUC(0-24): Area Under the Plasma Concentration-Time Curve From Time 0 to 24 Hours Postdose for TAK-915
NCT02461160 (33) [back to overview]AUC(0-inf): Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-915 and TAK-915 Metabolite M-I in BA/FE Cohort
NCT02461160 (33) [back to overview]Cmax: Maximum Observed Plasma Concentration for TAK-915 on Day 1 in DDI Cohort
NCT02461160 (33) [back to overview]Percentage of Participants Who Experience at Least One Treatment Emergent Adverse Event (TEAE)
NCT02461160 (33) [back to overview]Percentage of Participants With Markedly Abnormal Safety Laboratory Tests
NCT02461160 (33) [back to overview]Rac(AUC): Accumulation Ratios Between Day 14 AUC(0-24) and Day 1 AUC(0-24) for TAK-915
NCT02461160 (33) [back to overview]Rac(Cmax): Accumulation Ratios Between Day 14 Cmax and Day 1 Cmax for TAK-915
NCT02461160 (33) [back to overview]Ratio of TAK-915 Metabolite Area Under the Plasma Concentration-Time Curve From Time 0 to Time Tau Over a Dosing Interval [AUC(0-tau)] Where Tau is the Length of the Dosing Interval to TAK-915 AUC(0-tau) in MRD Cohorts
NCT02461160 (33) [back to overview]Ratio of TAK-915 Metabolite AUC(0-inf) to TAK-915 AUC(0-inf) in SRD Cohorts
NCT02486328 (6) [back to overview]Mean Arterial Pressure
NCT02486328 (6) [back to overview]Heart Rate
NCT02486328 (6) [back to overview]Change in Visual Analogue Scale Scores From the Baseline
NCT02486328 (6) [back to overview]Peripheral Oxygen Saturation
NCT02486328 (6) [back to overview]Change in Cognitive Function
NCT02486328 (6) [back to overview]Change in Cognitive Function
NCT02494180 (7) [back to overview]Clinical Pregnancy Rate
NCT02494180 (7) [back to overview]Ongoing Pregnancy Rate
NCT02494180 (7) [back to overview]Patient's Satisfaction on Pain Relief
NCT02494180 (7) [back to overview]Pain Level After Oocyte Retrieval
NCT02494180 (7) [back to overview]Pain Level During Oocyte Retrieval
NCT02494180 (7) [back to overview]Patient's Satisfaction on Oocyte Retrieval
NCT02494180 (7) [back to overview]Percentage of Participants With Side Effects by Type
NCT02506673 (13) [back to overview]Request of Sedation/Termination of AVA
NCT02506673 (13) [back to overview]Number of Providers That Were Satisfied With Their Experience With the Audio-visual Aids
NCT02506673 (13) [back to overview]Skin Conductance Response
NCT02506673 (13) [back to overview]Beats Per Minute (BPM)
NCT02506673 (13) [back to overview]Narcotic Consumption
NCT02506673 (13) [back to overview]Number of Participants With Complications
NCT02506673 (13) [back to overview]Pain Numerical Rating Scale (NRS) Levels
NCT02506673 (13) [back to overview]Number of Patients Who Requested Additional Sedation
NCT02506673 (13) [back to overview]Respiratory Rate
NCT02506673 (13) [back to overview]State-Trait Anxiety Inventory Questionnaire (STAI)
NCT02506673 (13) [back to overview]Systolic and Diastolic Blood Pressure
NCT02506673 (13) [back to overview]Client Satisfaction Questionnaire (CSQ-8)
NCT02506673 (13) [back to overview]Heidelberg Peri-anaesthetic Questionnaire
NCT02515890 (1) [back to overview]Memory Testing
NCT02522377 (5) [back to overview]Montreal Cognitive Assessment (MOCA) at Last Infusion
NCT02522377 (5) [back to overview]Montgomery Asberg Depression Rating Scale (MADRS) at Last Infusion
NCT02522377 (5) [back to overview]Hopkins Verbal Learning Test - Revised (HVLT-R) at Last Infusion
NCT02522377 (5) [back to overview]Hamilton Depression Rating Scale (HAMD-17) at Last Infusion
NCT02522377 (5) [back to overview]Controlled Oral Word Association Test (COWAT) at Last Infusion
NCT02532647 (3) [back to overview]Time to Fully Alert
NCT02532647 (3) [back to overview]Time to Start of Procedure
NCT02532647 (3) [back to overview]Success Rates of the Procedure
NCT02556606 (6) [back to overview]Change in Systolic Blood Pressure (Millimeters of Mercury, mm Hg)
NCT02556606 (6) [back to overview]Change in Resting-state Quantitative Electroencephalography (EEG) Frontal Gamma Band Power (Log of Microvolt Squared)
NCT02556606 (6) [back to overview]Change in Diastolic Blood Pressure (Millimeters of Mercury, mm Hg)
NCT02556606 (6) [back to overview]Change in Clinician-Administered Dissociative States Scale (CADSS)
NCT02556606 (6) [back to overview]Percentage of Patients With Continuation From Day 7 to Day 28 Post-infusion of at Least a 50% Improvement in MADRS
NCT02556606 (6) [back to overview]Percentage of Participants Demonstrating at Least a 50% Reduction on Montgomery-Asberg Depression Rating Scale Scores
NCT02579928 (1) [back to overview]Montgomery-Asberg Depression Rating Scale Score 1 Day After Infusion
NCT02618772 (14) [back to overview]Guardian/Parent's Prediction is Respect to Intervention Drug
NCT02618772 (14) [back to overview]Length of Procedure (Mins)
NCT02618772 (14) [back to overview]Per-Protocol: Modified Yale Preoperative Anxiety Score (mYPAS)
NCT02618772 (14) [back to overview]Per-Protocol: State Trait Anxiety Inventory (STAI)
NCT02618772 (14) [back to overview]Physician's Prediction is Respect to Intervention Drug
NCT02618772 (14) [back to overview]Time That the Participant Remained in Hospital After Procedure (Mins)
NCT02618772 (14) [back to overview]Intention to Treat (ITT): State Trait Anxiety Inventory (STAI)
NCT02618772 (14) [back to overview]Intention to Treat (ITT): Dartmouth Operative Conditions Scale
NCT02618772 (14) [back to overview]Intention to Treat (ITT): Modified Yale Preoperative Anxiety Score (mYPAS)
NCT02618772 (14) [back to overview]Per-Protocol: Dartmouth Operative Conditions Scale
NCT02618772 (14) [back to overview]Per-Protocol: Faces Pain Scale-Revised/ FLACC Scale
NCT02618772 (14) [back to overview]Intention to Treat (ITT): Faces Pain Scale-Revised/ FLACC Scale
NCT02618772 (14) [back to overview]Per-Protocol: Modified Yale Preoperative Anxiety Score (mYPAS)
NCT02618772 (14) [back to overview]Intention to Treat (ITT): Modified Yale Preoperative Anxiety Score (mYPAS)
NCT02619799 (6) [back to overview]Onset of Motor Blockade
NCT02619799 (6) [back to overview]Onset of Sensory Blockade
NCT02619799 (6) [back to overview]Perioperative Side Effects
NCT02619799 (6) [back to overview]Duration of Motor Blockade
NCT02619799 (6) [back to overview]Duration of Postoperative Analgesia
NCT02619799 (6) [back to overview]Duration of Sensory Blockade
NCT02661061 (2) [back to overview]Completion Rate for Randomised Treatment Phase
NCT02661061 (2) [back to overview]Depression Relapse Rate During Treatment and Follow-up Phase
NCT02679781 (1) [back to overview]Behavior During Dental Treatment
NCT02683707 (4) [back to overview]Single Time-point Platelet Reactivity Using Verify Now
NCT02683707 (4) [back to overview]Patient Self-reported Pain
NCT02683707 (4) [back to overview]Platelet Reactivity Using Light Transmission Aggregometry
NCT02683707 (4) [back to overview]Ticagrelor Pharmacokinetics
NCT02686164 (3) [back to overview]Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
NCT02686164 (3) [back to overview]AUC(0-24): Area Under the Concentration-time Curve From Time Zero to 24 Hours Postdose for Midazolam and 1'-Hydroxymidazolam
NCT02686164 (3) [back to overview]Cmax: Maximum Observed Plasma Concentration for Midazolam and 1'-Hydroxymidazolam
NCT02688088 (14) [back to overview]Pharmacokinetics: Maximum Concentration (Cmax) of Caffeine
NCT02688088 (14) [back to overview]Pharmacokinetics: Maximum Concentration (Cmax) of Dextromethorphan
NCT02688088 (14) [back to overview]Pharmacokinetics: Maximum Concentration (Cmax) of Midazolam
NCT02688088 (14) [back to overview]Pharmacokinetics: Maximum Concentration (Cmax) S-Warfarin
NCT02688088 (14) [back to overview]Mean Change From Baseline at 24 Hours in Systolic and Diastolic Blood Pressure in Period 1
NCT02688088 (14) [back to overview]Mean Change From Baseline at 24 Hours in Systolic and Diastolic Blood Pressure in Period 2
NCT02688088 (14) [back to overview]Mean Change From Baseline at 24 Hours in Systolic and Diastolic Blood Pressure in Period 2
NCT02688088 (14) [back to overview]Pharmacokinetics: Area Under the Concentration Versus Time Curve [AUC(0-infinity)] of S-Warfarin
NCT02688088 (14) [back to overview]Mean Change From Baseline at 24 Hours in Pulse Rate in Period 1
NCT02688088 (14) [back to overview]Mean Change From Baseline at 24 Hours in Pulse Rate in Period 2
NCT02688088 (14) [back to overview]Mean Change From Baseline at 24 Hours in Pulse Rate in Period 2
NCT02688088 (14) [back to overview]Pharmacokinetics: Area Under the Concentration Versus Time Curve [AUC(0-infinity)] of Caffeine
NCT02688088 (14) [back to overview]Pharmacokinetics: Area Under the Concentration Versus Time Curve [AUC(0-infinity)] of Dextromethorphan
NCT02688088 (14) [back to overview]Pharmacokinetics: Area Under the Concentration Versus Time Curve [AUC(0-infinity)] of Midazolam
NCT02727998 (2) [back to overview]Change in Beck Depression Inventory (BDI-II)
NCT02727998 (2) [back to overview]Change in PTSD Symptoms
NCT02856698 (3) [back to overview]Length of Hospital Stay
NCT02856698 (3) [back to overview]Number of Participants That Required Invasive Mechanical Ventilation
NCT02856698 (3) [back to overview]In-hospital Mortality
NCT02903407 (13) [back to overview]Number of Participants With Bradycardia
NCT02903407 (13) [back to overview]In Hospital Mortality
NCT02903407 (13) [back to overview]Intensive Care Unit Length of Stay
NCT02903407 (13) [back to overview]Number of Days Alive During Admission and Free From Delirium or Coma
NCT02903407 (13) [back to overview]Number of Days From Decision to Extubate to True Extubation
NCT02903407 (13) [back to overview]Number of Participants Requiring Reintubation
NCT02903407 (13) [back to overview]Number of Participants With Increased Vasopressor Requirement
NCT02903407 (13) [back to overview]Number of Ventilator Days
NCT02903407 (13) [back to overview]Pain Management
NCT02903407 (13) [back to overview]Number of Participants With Delirium
NCT02903407 (13) [back to overview]Percentage of Time at Goal Sedation
NCT02903407 (13) [back to overview]Time From Withdrawal of Sedation to ICU Discharge
NCT02903407 (13) [back to overview]Hospital Length of Stay
NCT02993471 (10) [back to overview]Pharmacokinetics (PK): Maximum Observed Drug Concentration (Cmax) of CYP450 Substrate-Omeprazole and Its Metabolite 5-Hydroxyomeprazole
NCT02993471 (10) [back to overview]Pharmacokinetics (PK): Maximum Observed Drug Concentration (Cmax) of CYP450 Substrate-Caffeine
NCT02993471 (10) [back to overview]Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Zero to 48 Hours (AUC[0-48h]) of CYP450 Substrate-Caffeine
NCT02993471 (10) [back to overview]Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Zero to Infinity (AUC[0-∞]) of CYP450 Substrate-Dextromethorphan
NCT02993471 (10) [back to overview]Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Zero to Infinity (AUC[0-∞]) of CYP450 Substrate-Midazolam
NCT02993471 (10) [back to overview]Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Zero to Infinity (AUC[0-∞]) of CYP450 Substrate-Warfarin
NCT02993471 (10) [back to overview]Pharmacokinetics (PK): Maximum Observed Drug Concentration (Cmax) of CYP450 Substrate-Dextromethorphan
NCT02993471 (10) [back to overview]Pharmacokinetics (PK): Maximum Observed Drug Concentration (Cmax) of CYP450 Substrate-Warfarin
NCT02993471 (10) [back to overview]Pharmacokinetics (PK): Maximum Observed Drug Concentration (Cmax) of Cytochrome P450 (CYP450) Substrate-Midazolam
NCT02993471 (10) [back to overview]Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Zero to Infinity (AUC[0-∞]) of CYP450 Substrate-Omeprazole and Its Metabolite 5-Hydroxyomeprazole
NCT02996591 (16) [back to overview]Postoperative Discomfort and Needs (Post-op Pain, Sore Throat, Back Pain, Nausea, Cold, Hunger, Thirst)
NCT02996591 (16) [back to overview]Cognitive Recovery on POD1
NCT02996591 (16) [back to overview]Cognitive Recovery at 2 Hours Post-operative
NCT02996591 (16) [back to overview]Incidence of Transient Neurologic Symptoms
NCT02996591 (16) [back to overview]Back Pain on POD1
NCT02996591 (16) [back to overview]Time Until Patient is Ready for Discharge From Post-Anesthesia Care Unit (PACU) to Home.
NCT02996591 (16) [back to overview]Numerical Rating Scale Pain Scores at 2 Hours Postop
NCT02996591 (16) [back to overview]Postoperative Discomfort and Needs (Post-op Pain, Sore Throat, Back Pain, Nausea, Cold, Hunger, Thirst)
NCT02996591 (16) [back to overview]Postoperative Discomfort and Needs (Post-op Pain, Sore Throat, Back Pain, Nausea, Cold, Hunger, Thirst)
NCT02996591 (16) [back to overview]Opioid-Related Symptom Distress Scale (ORSDS) Score
NCT02996591 (16) [back to overview]Opioid Consumption Through First Postoperative Day. Measured in mg OME
NCT02996591 (16) [back to overview]Opioid Consumption
NCT02996591 (16) [back to overview]Numerical Rating Scale Pain Scores on Postoperative Day (POD) 1
NCT02996591 (16) [back to overview]Assessment of Patient Blinding to Group Assignment
NCT02996591 (16) [back to overview]Nausea Intensity
NCT02996591 (16) [back to overview]Numerical Rating Scale (NRS) Pain Scores at 1 Hour Postop
NCT03054103 (4) [back to overview]Measure of Comfort (See Link to Study Protocol for Scale)
NCT03054103 (4) [back to overview]PACU Length of Stay
NCT03054103 (4) [back to overview]Eye Mobility During Surgery (See Link to Study Protocol for Scale)
NCT03054103 (4) [back to overview]Nausea
NCT03054844 (6) [back to overview]Parental Satisfaction
NCT03054844 (6) [back to overview]Procedural Distress, Cry Duration
NCT03054844 (6) [back to overview]Procedural Distress, FLACC
NCT03054844 (6) [back to overview]Procedural Distress, OSBD-R
NCT03054844 (6) [back to overview]Provider Satisfaction
NCT03054844 (6) [back to overview]Procedural Pain
NCT03069677 (6) [back to overview]Evaluation of Difficulties in Communication From Provider to Patient and Patient to Provider
NCT03069677 (6) [back to overview]Block Times
NCT03069677 (6) [back to overview]Change in STAI-6 Scores From Post to Pre.
NCT03069677 (6) [back to overview]Patient Satisfaction Scores of the Experience During Procedure
NCT03069677 (6) [back to overview]Provider Satisfaction Scores of the Experience During Procedure
NCT03069677 (6) [back to overview]Anxiety Levels
NCT03078946 (2) [back to overview]The C-reactive Protein (CRP) Quantitative Titer Daily as Part of the Routine Clinical Care as a Prognostic Factor for Delirium (mg/L)
NCT03078946 (2) [back to overview]The Incidence of Delirium (Number of Patients (in Digits))
NCT03084536 (5) [back to overview]Change in Quality of Life as Measured by the Veterans RAND12 Questionnaire Mental Health Summary Measure
NCT03084536 (5) [back to overview]Change in Quality of Life as Measured by the Veterans RAND12 Questionnaire Physical Health Summary Measure
NCT03084536 (5) [back to overview]Interference as Measured by the Brief Pain Inventory (BPI) at 1 Year
NCT03084536 (5) [back to overview]Worst Pain as Measured by the Brief Pain Inventory (BPI) at 1 Year
NCT03084536 (5) [back to overview]Average Pain as Measured by the Brief Pain Inventory (BPI) at 1 Year
NCT03085563 (3) [back to overview]Patient/Parent and Provider Satisfaction With Sedation and Anxiolytic/Sedative.
NCT03085563 (3) [back to overview]Adverse Events.
NCT03085563 (3) [back to overview]ED Length of Stay After Intranasal Midazolam or Nitrous Oxide Administration
NCT03246724 (5) [back to overview]Surgeon Satisfaction
NCT03246724 (5) [back to overview]Surgical Complication Rates
NCT03246724 (5) [back to overview]Patient Satisfaction
NCT03246724 (5) [back to overview]Number of Participants Requiring Additional Anesthesia Intervention
NCT03246724 (5) [back to overview]Anesthesiologist/Certified Registered Nurse Anesthetist (CRNA) Satisfaction
NCT03255824 (12) [back to overview]Reaction to Administration of Local Anesthesia
NCT03255824 (12) [back to overview]Postoperative Recovery Time - Time to Discharge
NCT03255824 (12) [back to overview]Postoperative Recovery Time - Duration of Procedure
NCT03255824 (12) [back to overview]Postoperative Recovery Time - Ambulation
NCT03255824 (12) [back to overview]Patient Satisfaction
NCT03255824 (12) [back to overview]Hemodynamic Stability - Heart Rate
NCT03255824 (12) [back to overview]Respiratory Depression - Respiratory Rate
NCT03255824 (12) [back to overview]Respiratory Events Requiring Intervention
NCT03255824 (12) [back to overview]Surgeon Satisfaction - Survey
NCT03255824 (12) [back to overview]Cooperation Scale
NCT03255824 (12) [back to overview]Hemodynamic Stability - Blood Pressure
NCT03255824 (12) [back to overview]Respiratory Depression - Oxygen Saturation
NCT03256162 (7) [back to overview]The Brief Psychiatric Rating Scale (BPRS)
NCT03256162 (7) [back to overview]The Clinician-Administered Dissociative States Scale (CADSS)
NCT03256162 (7) [back to overview]The Quick Inventory of Depressive Symptoms, Self-report Version (QIDS-SR16)
NCT03256162 (7) [back to overview]The Patient-Rated Inventory of Side Effects (PRISE)
NCT03256162 (7) [back to overview]Young Mania Rating Scale (YMRS; Mood Item)
NCT03256162 (7) [back to overview]The Hamilton Rating Scale for Depression-24 Item Version (HRSD-24)
NCT03256162 (7) [back to overview]The Montreal Cognitive Assessment (MoCA)
NCT03279978 (5) [back to overview]Area Under the Concentration-time Curve of the Analyte BI 730357 in Plasma Over a Uniform Dosing Interval Tau After Administration of the First Dose (AUCtau,1)
NCT03279978 (5) [back to overview]Area Under the Concentration-time Curve of BI 730357 in Plasma at Steady State Over a Uniform Dosing Interval τ (AUCτ,ss) After Last Dose Administration.
NCT03279978 (5) [back to overview]Maximum Measured Concentration of the Analyte BI 730357 in Plasma at Steady State Over a Uniform Dosing Interval τ After the Last Dose (Cmax,ss)
NCT03279978 (5) [back to overview]Number of Subjects With Drug-related Adverse Events (AEs)
NCT03279978 (5) [back to overview]Maximum Measured Concentration of the Analyte BI 730357 in Plasma After Administration of the First Dose (Cmax)
NCT03284307 (5) [back to overview]Effect of Study Drug on Ability to Form Implicit Memory
NCT03284307 (5) [back to overview]Effect of Study Drug on Ability to Correctly Identify Images
NCT03284307 (5) [back to overview]Effect of Study Drug on Ability to Correctly Identify Shapes/Images
NCT03284307 (5) [back to overview]Number of Instances of Disconnected Conscious Experience (Dreaming) vs Connected Conscious Experience (Awareness of External World).
NCT03284307 (5) [back to overview]Occipital Delta Power Spectral Density by Conscious State and Study Group.
NCT03291288 (14) [back to overview]Pharmacokinetic Analysis: Area Under the Curve to the Last Observable Concentration (AUClast) for Pexidartinib and ZAAD-1006a Metabolite
NCT03291288 (14) [back to overview]Pharmacokinetic Analysis: Area Under the Curve to the Last Observable Concentration (AUClast) for Midazolam
NCT03291288 (14) [back to overview]Pharmacokinetic Analysis: Time to Maximum Concentration (Tmax) for Tolbutamide
NCT03291288 (14) [back to overview]Pharmacokinetic Analysis: Area Under the Curve to the Last Observable Concentration (AUClast) for Midazolam Metabolite, 1-Hydroxy Midazolam
NCT03291288 (14) [back to overview]Overall Summary of Treatment-emergent Adverse Events
NCT03291288 (14) [back to overview]Pharmacokinetic Analysis: Area Under the Curve to the Last Observable Concentration (AUClast) for Tolbutamide
NCT03291288 (14) [back to overview]Pharmacokinetic Analysis: Maximum Concentration (Cmax) for Midazolam
NCT03291288 (14) [back to overview]Pharmacokinetic Analysis: Maximum Concentration (Cmax) for Midazolam Metabolite, 1-Hydroxy Midazolam
NCT03291288 (14) [back to overview]Pharmacokinetic Analysis: Maximum Concentration (Cmax) for Tolbutamide
NCT03291288 (14) [back to overview]Pharmacokinetic Analysis: Metabolite to Parent Ratio (MPR) for Midazolam
NCT03291288 (14) [back to overview]Pharmacokinetic Analysis: Time to Maximum Concentration (Tmax) for Midazolam
NCT03291288 (14) [back to overview]Pharmacokinetic Analysis: Time to Maximum Concentration (Tmax) for Midazolam Metabolite, 1-Hydroxy Midazolam
NCT03291288 (14) [back to overview]Pharmacokinetic Analysis: Time to Maximum Concentration (Tmax) for Pexidartinib and ZAAD-1006a Metabolite
NCT03291288 (14) [back to overview]Pharmacokinetic Analysis: Maximum Concentration (Cmax) for Pexidartinib and ZAAD-1006a Metabolite
NCT03311841 (18) [back to overview]Apparent Plasma Terminal Half-life (t1/2) Post-dose Period 1
NCT03311841 (18) [back to overview]Effect of Rifampin on t1/2 Post-dose Period 2
NCT03311841 (18) [back to overview]Effect of Rifampin on Tmax Post-dose Period 2
NCT03311841 (18) [back to overview]Effect of Rifampin on Vz/F Post-dose Period 2
NCT03311841 (18) [back to overview]Maximum Plasma Concentration (Cmax) Post-dose Period 1
NCT03311841 (18) [back to overview]Plasma Concentration at 24 Hours (C24) Post-dose Period 1
NCT03311841 (18) [back to overview]Time to Maximum Plasma Concentration (Tmax) Post-dose Period 1
NCT03311841 (18) [back to overview]Effect of Rifampin on AUC0-last Post-dose Period 2
NCT03311841 (18) [back to overview]Effect of Rifampin on AUC0-inf Post-dose Period 2
NCT03311841 (18) [back to overview]Effect of Rifampin on AUC0-24 Post-dose Period 2
NCT03311841 (18) [back to overview]Area Under the Plasma Concentration-time Curve From Time 0 to Last (AUC0-last) Post-dose Period 1
NCT03311841 (18) [back to overview]Area Under the Plasma Concentration-time Curve From Time 0 to Infinity (AUC0-inf) Post-dose Period 1
NCT03311841 (18) [back to overview]Area Under the Plasma Concentration-time Curve From Time 0 to 24 Hours (AUC0-24) Post-dose Period 1
NCT03311841 (18) [back to overview]Apparent Volume of Distribution During the Terminal Phase (Vz/F) Post-dose Period 1
NCT03311841 (18) [back to overview]Apparent Clearance After Extravascular Administration (CL/F) Post-dose Period 1
NCT03311841 (18) [back to overview]Effect of Rifampin on CL/F Post-dose Period 2
NCT03311841 (18) [back to overview]Effect of Rifampin on Cmax Post-dose Period 2
NCT03311841 (18) [back to overview]Effect of Rifampin on C24 Post-dose Period 2
NCT03325712 (7) [back to overview]Maximum Measured Concentration of Midazolam in Plasma (Cmax) After the First and Last Dose
NCT03325712 (7) [back to overview]Area Under the Concentration-time Curve of Midazolam in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz) After the First and Last Dose
NCT03325712 (7) [back to overview]Percentage of Participants With Drug-related Adverse Events
NCT03325712 (7) [back to overview]Maximum Measured Concentration of BI 705564 in Plasma at Steady State Over a Uniform Dosing Interval τ (Cmax,ss) After the Administration of the Last Dose
NCT03325712 (7) [back to overview]Maximum Measured Concentration of BI 705564 in Plasma (Cmax) After the Administration of the First Dose
NCT03325712 (7) [back to overview]Area Under the Concentration-time Curve of BI 705564 in Plasma Over a Uniform Dosing Interval τ After Administration of the First Dose (AUCτ,1)
NCT03325712 (7) [back to overview]Area Under the Concentration-time Curve of BI 705564 in Plasma at Steady State Over a Uniform Dosing Interval τ (AUCτ,ss) After the Administration of the Last Dose
NCT03336450 (15) [back to overview]Safety: Number of Participants With Aspiration Pneumonia Reported as Treatment Emergent Adverse Events (TEAEs)
NCT03336450 (15) [back to overview]Safety: Number of Participants With Buccal Irritation Reported as Treatment Emergent Adverse Events (TEAEs)
NCT03336450 (15) [back to overview]Safety: Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters Reported as TEAEs
NCT03336450 (15) [back to overview]Safety: Number of Participants With Clinically Significant Change in Electrocardiogram (ECG) Reported as TEAEs
NCT03336450 (15) [back to overview]Safety: Number of Participants With Clinically Significant Change in Vital Signs Reported as TEAEs
NCT03336450 (15) [back to overview]Safety: Number of Participants With Respiratory Depression
NCT03336450 (15) [back to overview]Safety: Number of Participants With Treatment-emergent Adverse Events (TEAEs)
NCT03336450 (15) [back to overview]Efficacy: Number of Participants Who Had Sustained Absence of Seizure Activity for at Least 1, 4, and 6 Hours
NCT03336450 (15) [back to overview]Efficacy: Time to Recovery of Consciousness
NCT03336450 (15) [back to overview]Efficacy: Time to Resolution of Seizures (Convulsions)
NCT03336450 (15) [back to overview]Safety: Number of Participants Analyzed for Sedation or Agitation Measured by the Riker Sedation-Agitation Scale
NCT03336450 (15) [back to overview]Safety: Percentage of Participants With Normal Oxygen Saturation Values Collected During Hospital Setting
NCT03336450 (15) [back to overview]Efficacy: Number of Participants With Therapeutic Success
NCT03336450 (15) [back to overview]Efficacy: Percentage of Participants Who Failed to Respond to Treatment With SHP615
NCT03336450 (15) [back to overview]Efficacy: Percentage of Participants Who Required Additional Anticonvulsant Medication for Ongoing Status Epilepticus (SE) 10 Minutes After Administration of SHP615
NCT03336645 (19) [back to overview]Time at Maximum Concentration (Tmax) of SHP615 in Plasma
NCT03336645 (19) [back to overview]Number of Participants With Time to Recovery of Consciousness
NCT03336645 (19) [back to overview]Number of Participants With Time to Resolution of Seizures (Convulsions)
NCT03336645 (19) [back to overview]Number of Participants With Respiratory Depression
NCT03336645 (19) [back to overview]Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
NCT03336645 (19) [back to overview]Percentage of Participants Who Failed to Respond to the Treatment With SHP615
NCT03336645 (19) [back to overview]Percentage of Participants Who Required Additional Anticonvulsant Medication for Ongoing Status Epilepticus (SE)
NCT03336645 (19) [back to overview]Change From Baseline in Riker Sedation-Agitation Scale at 24 Hours Post-dose
NCT03336645 (19) [back to overview]Percentage of Participants Who Had Sustained Absence of Seizure Activity for at Least 1, 4 and 6 Hours
NCT03336645 (19) [back to overview]Percentage of Participants With Response Rate
NCT03336645 (19) [back to overview]Area Under the Concentration-time Curve From Time Zero to 180 Minutes (AUC0-180) of SHP615 in Plasma
NCT03336645 (19) [back to overview]Area Under the Concentration-time Curve From Time Zero to 60 Minutes (AUC0-60) of SHP615 in Plasma
NCT03336645 (19) [back to overview]Area Under the Concentration-time Curve From Time Zero to Infinity (AUC0-inf) of SHP615 in Plasma
NCT03336645 (19) [back to overview]Change From Baseline in Oxygen Saturation Percentage at 24 Hours Post-dose
NCT03336645 (19) [back to overview]Area Under the Concentration-time Curve From Time Zero to 10 Minutes (AUC0-10) of SHP615 in Plasma
NCT03336645 (19) [back to overview]Concentration of SHP615 in Plasma at 10 Minutes (C10)
NCT03336645 (19) [back to overview]Elimination Half-life (T1/2) of SHP615 in Plasma
NCT03336645 (19) [back to overview]Maximum Plasma Concentration (Cmax) of SHP615
NCT03336645 (19) [back to overview]Number of Participants With Aspiration Pneumonia Reported as Treatment Emergent Adverse Events (TEAEs)
NCT03357393 (7) [back to overview]Patients' Satisfaction Using a Likert-type Scale
NCT03357393 (7) [back to overview]Quality of Recovery (QoR-23)
NCT03357393 (7) [back to overview]Assessment of Self-rated Patient Questionaries' Using S-PSR
NCT03357393 (7) [back to overview]Bronchoscopist Evaluation Using a Likert-type Scale
NCT03357393 (7) [back to overview]Discharge Assessment Using PADSS After 2 Hours Number of Patients Reaching PADSS Score 10 After 2 Hours
NCT03357393 (7) [back to overview]Level of Sedation Using the Observer's Assessment of Alertness/Sedation (OAA/S) Scale
NCT03357393 (7) [back to overview]Number of Participants With Interventions Performed
NCT03395314 (18) [back to overview]Change in Brief Psychiatric Rating Scale (BPRS) Total Scores
NCT03395314 (18) [back to overview]Change in Beck Depression Inventory Score
NCT03395314 (18) [back to overview]Change in Beck Suicide Scale Total Score
NCT03395314 (18) [back to overview]Change in Behavior in the Economic Trust Game - Cooperation
NCT03395314 (18) [back to overview]Change in Brief Pain Inventory Score - Intensity
NCT03395314 (18) [back to overview]Change in Adverse Events
NCT03395314 (18) [back to overview]Change in Brief Pain Inventory Score - Interference
NCT03395314 (18) [back to overview]Change in Preferred Distance in Stop-distance Paradigm (SDP)
NCT03395314 (18) [back to overview]Change in Beck Anxiety Inventory Score
NCT03395314 (18) [back to overview]Change in Clinician-Administered Dissociative States Scale (CADSS) Score
NCT03395314 (18) [back to overview]Change in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score
NCT03395314 (18) [back to overview]Change in Social Adjustment Scale Self Report (SAS-SR) Short Version Score
NCT03395314 (18) [back to overview]Change in Suicidal Thoughts as Measured by Item 10 on the Montgomery-Asberg Depression Scale (MADRS)
NCT03395314 (18) [back to overview]Change in 'Reading the Mind in the Eyes' Test (RMET) Score
NCT03395314 (18) [back to overview]Change in Suicidality as Measured by Item-12 on the Quick Inventory of Depressive Symptomatology (QIDS SR-16)
NCT03395314 (18) [back to overview]Change in Suicidality as Measured by the Columbia Suicide Severity Rating Scale (C-SSRS)
NCT03395314 (18) [back to overview]Change in Zanarini Rating Scale for Borderline Personality Disorder
NCT03395314 (18) [back to overview]Change in Suicidality as Measured by Item 9 on Beck Depression Inventory
NCT03420742 (3) [back to overview]Part A, Cmax: Maximum Observed Plasma Concentration for Midazolam
NCT03420742 (3) [back to overview]Part A, AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for Midazolam
NCT03420742 (3) [back to overview]Part A, Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for Midazolam
NCT03493698 (7) [back to overview]PK of Inarigivir After Single and Multiple Oral Doses in Healthy Subjects (AUC)
NCT03493698 (7) [back to overview]PK of Inarigivir After Single and Multiple Oral Doses in Healthy Subjects (Cmax)
NCT03493698 (7) [back to overview]Number of Participants With Clinical Relevant Clinical Laboratory, Vital Signs, 12-lead ECG, or Physical Examination
NCT03493698 (7) [back to overview]Effect of Steady-state Oral Inarigivir on the Single Dose Pharmacokinetics (PK) of Oral Midazolam in Healthy Subjects (Cmax)
NCT03493698 (7) [back to overview]Effect of Steady-state Oral Inarigivir on the Single Dose Pharmacokinetics (PK) of Oral Midazolam in Healthy Subjects (AUC0-t)
NCT03493698 (7) [back to overview]Effect of Steady-state Oral Inarigivir on the Single Dose Pharmacokinetics (PK) of Oral Midazolam in Healthy Subjects (AUC0-inf )
NCT03493698 (7) [back to overview]PK of Inarigivir After Single and Multiple Oral Doses in Healthy Subjects (AUC)
NCT03500289 (6) [back to overview]Change in Daily Fatigue Severity Score
NCT03500289 (6) [back to overview]Change in Epworth Sleepiness Scale Score
NCT03500289 (6) [back to overview]Change in Fatigue Severity Scale (FSS) Score
NCT03500289 (6) [back to overview]Change in Beck Depression Inventory (BDI) Score
NCT03500289 (6) [back to overview]Change in Quality of Life in Neurological Disorders (NeuroQol) Fatigue Item Bank Score
NCT03500289 (6) [back to overview]Change in Modified Fatigue Impact Scale (MFIS) Score
NCT03528512 (6) [back to overview]Nurse and Physician Satisfaction
NCT03528512 (6) [back to overview]Change in Vitals
NCT03528512 (6) [back to overview]Pain Scores During Laceration Repair
NCT03528512 (6) [back to overview]Proportion of Children With Maximum Sedation Score
NCT03528512 (6) [back to overview]Rates of Failure
NCT03528512 (6) [back to overview]Sedation Score
NCT03628339 (13) [back to overview]Number of Participants With Clinically Significant Changes in Vital Signs
NCT03628339 (13) [back to overview]Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious TEAEs and TEAEs Leading to Death
NCT03628339 (13) [back to overview]Maximum Observed Plasma Concentration (Cmax) of Midazolam
NCT03628339 (13) [back to overview]Area Under the Plasma Concentration-Time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of Midazolam Metabolite (1-Hydroxymidazolam)
NCT03628339 (13) [back to overview]Area Under the Plasma Concentration-Time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of Midazolam
NCT03628339 (13) [back to overview]Area Under Plasma Concentration-time Curve From Time Zero to Last Sampling Time (Tlast) at Which the Concentration is at or Above the Lower Limit of Quantification (AUC0-t) of Midazolam Metabolite (1-Hydroxymidazolam)
NCT03628339 (13) [back to overview]Area Under Plasma Concentration-time Curve From Time Zero to Last Sampling Time (Tlast) at Which the Concentration is at or Above the Lower Limit of Quantification (AUC0-t) of Midazolam
NCT03628339 (13) [back to overview]Time to Reach Maximum Plasma Concentration (Tmax) of Midazolam and Midazolam Metabolite (1-Hydroxymidazolam)
NCT03628339 (13) [back to overview]Maximum Observed Plasma Concentration (Cmax) of Midazolam Metabolite (1-Hydroxymidazolam)
NCT03628339 (13) [back to overview]Metabolic Ratio of Midazolam and Midazolam Metabolite (1-hydroxymidazolam)
NCT03628339 (13) [back to overview]Number of Participants With Clinically Significant Changes in 12-Lead Electrocardiogram (ECG)
NCT03628339 (13) [back to overview]Number of Participants With Clinically Significant Changes in Laboratory Values
NCT03628339 (13) [back to overview]Elimination Half Life (t1/2) of Midazolam and Midazolam Metabolite (1-Hydroxymidazolam)
NCT03806270 (5) [back to overview]Heart Rate-2
NCT03806270 (5) [back to overview]Heart Rate-1
NCT03806270 (5) [back to overview]Heart Rate-3
NCT03806270 (5) [back to overview]Number of Observed Oculocardiac Reflex(OCR)
NCT03806270 (5) [back to overview]Number of Orbital Muscles of the Participants With Different Considerations Taken With Respect to the Treatment of OCR
NCT03813121 (1) [back to overview]Side Effects
NCT03889756 (2) [back to overview]Tolerability of a Multiple-dosing Ketamine Infusion Paradigm (2 Infusions Per Week for 3 Weeks) Compared to Midazolam in Adolescents With Treatment Resistant Depression
NCT03889756 (2) [back to overview]Efficacy of a Multiple-dosing Ketamine Infusion Paradigm (2 Infusions Per Week for 3 Weeks) Compared to Midazolam in Adolescents With Treatment Resistant Depression Using the Children's Depression Rating Scale (CDRS)
NCT03988907 (20) [back to overview]Part 2: AUClast of Midazolam Metabolite (1-Hydroxy Midazolam) Alone and in Combination With Risdiplam
NCT03988907 (20) [back to overview]Part 2: Cmax of Risdiplam and M1 Risdiplam Following Multiple Oral Doses
NCT03988907 (20) [back to overview]Part 2: Maximum Observed Plasma Concentration (Cmax) of Midazolam Alone and in Combination With Risdiplam
NCT03988907 (20) [back to overview]Part 2: AUClast of Risdiplam and M1 Risdiplam Following Multiple Oral Doses
NCT03988907 (20) [back to overview]Part 2: Cmax of Midazolam Metabolite (1-Hydroxy Midazolam) Alone and in Combination With Risdiplam
NCT03988907 (20) [back to overview]Part 2: Percentage of Participants With Adverse Events After Midazolam Administration Alone and in Combination With Risdiplam
NCT03988907 (20) [back to overview]Part 2: Maximum Observed Plasma Concentration (Cmax) of Midazolam Alone and in Combination With Risdiplam
NCT03988907 (20) [back to overview]Part 2: Cmax of Midazolam Metabolite (1-Hydroxy Midazolam) Alone and in Combination With Risdiplam
NCT03988907 (20) [back to overview]Part 2: AUCtau of Risdiplam and M1 Risdiplam Following Multiple Oral Doses
NCT03988907 (20) [back to overview]Part 1: Cmax of Risdiplam and M1 Risdiplam Following Multiple Oral Doses
NCT03988907 (20) [back to overview]Part 2: Area Under the Concentration-Time Curve From Time Zero Extrapolated to Infinity (AUCinf) of Midazolam Alone and in Combination With Risdiplam
NCT03988907 (20) [back to overview]Part 2: Area Under the Concentration-Time Curve From Time Zero Extrapolated to Infinity (AUCinf) of Midazolam Alone and in Combination With Risdiplam
NCT03988907 (20) [back to overview]Part 2: Area Under the Plasma Concentration-Time Curve From Time Zero to the Time of Last Quantifiable Concentration (AUClast) of Midazolam Alone and in Combination With Risdiplam
NCT03988907 (20) [back to overview]Part 2: Area Under the Plasma Concentration-Time Curve From Time Zero to the Time of Last Quantifiable Concentration (AUClast) of Midazolam Alone and in Combination With Risdiplam
NCT03988907 (20) [back to overview]Part 2: AUCinf of Midazolam Metabolite (1-Hydroxy Midazolam) Alone and in Combination With Risdiplam
NCT03988907 (20) [back to overview]Part 2: AUCinf of Midazolam Metabolite (1-Hydroxy Midazolam) Alone and in Combination With Risdiplam
NCT03988907 (20) [back to overview]Part 2: AUClast of Midazolam Metabolite (1-Hydroxy Midazolam) Alone and in Combination With Risdiplam
NCT03988907 (20) [back to overview]Part 1: AUClast of Risdiplam and M1 Risdiplam Following Multiple Oral Doses
NCT03988907 (20) [back to overview]Part 1: Area Under the Plasma Concentration-Time Curve From Time Zero to the End of the Dosing Interval (AUCtau) of Risdiplam and Its Metabolite (M1) Following Multiple Oral Doses
NCT03988907 (20) [back to overview]Part 1 and Part 2: Percentage of Participants With Adverse Events After Administration of Multiple Doses of Risdiplam
NCT04068948 (1) [back to overview]Number of Participants With Successful Sedation
NCT04147715 (50) [back to overview]Part 1: Maximum Plasma Concentration (Cmax) of S-648414
NCT04147715 (50) [back to overview]Part 1: Mean Residence Time (MRT) of S-648414
NCT04147715 (50) [back to overview]Part 1: Renal Clearance (CLR) of S-648414
NCT04147715 (50) [back to overview]Part 1: Terminal Elimination Half-life (t1/2,z) of S-648414
NCT04147715 (50) [back to overview]Part 1: Terminal Elimination Rate Constant (λz) of S-648414
NCT04147715 (50) [back to overview]Part 1: Time to Maximum Plasma Concentration (Tmax) of S-648414
NCT04147715 (50) [back to overview]Part 2: Apparent Total Clearance (CL/F) of S-648414 Following Multiple-dose Administration
NCT04147715 (50) [back to overview]Part 2: Apparent Volume of Distribution in the Terminal Elimination Phase (Vz/F) of S-648414 Following Multiple-dose Administration
NCT04147715 (50) [back to overview]Part 2: Area Under the Concentration-time Curve From Time Zero to Infinity (AUC0-inf) of Midazolam
NCT04147715 (50) [back to overview]Part 1: Apparent Volume of Distribution in the Terminal Elimination Phase (Vz/F) of S-648414
NCT04147715 (50) [back to overview]Part 2: Area Under the Concentration-time Curve From Time Zero to the Last Quantifiable Concentration After Dosing (AUC0-last) for Midazolam
NCT04147715 (50) [back to overview]Part 2: Fraction of S-648414 Dose Excreted in Urine Over the Dosing Interval (Feu0- τ) Following Multiple-dose Administration
NCT04147715 (50) [back to overview]Part 1: Apparent Total Clearance (CL/F) of S-648414
NCT04147715 (50) [back to overview]Part 1: Area Under the Concentration-time Curve From Time Zero to Infinity (AUC0-inf) of S-648414
NCT04147715 (50) [back to overview]Part 1: Area Under the Concentration-time Curve From Time Zero to the Last Quantifiable Concentration After Dosing (AUC0-last) of S-648414
NCT04147715 (50) [back to overview]Part 1: Fraction of S-648414 Dose Excreted in Urine From 0 to 96 Hours Postdose (Feu0-96)
NCT04147715 (50) [back to overview]Parts 1: Change From Baseline in Heart Rate (HR)
NCT04147715 (50) [back to overview]Part 3: Number of Participants With Treatment-emergent Adverse Events
NCT04147715 (50) [back to overview]Part 2: Time to Maximum Plasma Concentration (Tmax) of S-648414 Following Single and Multiple-dose Administration
NCT04147715 (50) [back to overview]Part 2: Number of Participants With Treatment-emergent Adverse Events
NCT04147715 (50) [back to overview]Part 2: Maximum Plasma Concentration (Cmax) of S-648414 Following Single and Multiple-dose Administration
NCT04147715 (50) [back to overview]Part 2: Area Under the Concentration-time Curve Over the Dosing Interval τ (AUC0-τ) of S-648414 Following Single and Multiple-dose Administration
NCT04147715 (50) [back to overview]Part 1: Placebo-corrected Change From Baseline in QRS Duration
NCT04147715 (50) [back to overview]Part 1: Placebo-corrected Change From Baseline in PR Interval
NCT04147715 (50) [back to overview]Part 1: Placebo-corrected Change From Baseline in Heart Rate
NCT04147715 (50) [back to overview]Part 1: Placebo-corrected Change From Baseline in Fridericia's Corrected QT Interval
NCT04147715 (50) [back to overview]Part 1: Number of Participants With Treatment-emergent Changes for T-wave Morphology and U-wave Presence
NCT04147715 (50) [back to overview]Part 1: Number of Participants With Treatment-emergent Adverse Events (TEAEs)
NCT04147715 (50) [back to overview]Part 1: Number of Participants With Recorded Outlier Values for QTcF, HR, PR, and QRS
NCT04147715 (50) [back to overview]Part 1: Change From Baseline in QRS Interval
NCT04147715 (50) [back to overview]Part 1: Change From Baseline in PR Interval
NCT04147715 (50) [back to overview]Part 1: Change From Baseline in Fridericia's Corrected QT Interval (QTcF)
NCT04147715 (50) [back to overview]Part 3: Time to Maximum Plasma Concentration (Tmax) of S-648414
NCT04147715 (50) [back to overview]Part 3: Time to Maximum Plasma Concentration (Tmax) of Dolutegravir
NCT04147715 (50) [back to overview]Part 3: Plasma Concentration of S-648414 at the End of the Dosing Interval τ (Cτ)
NCT04147715 (50) [back to overview]Part 3: Plasma Concentration of Dolutegravir at the End of the Dosing Interval τ (Cτ)
NCT04147715 (50) [back to overview]Part 3: Maximum Plasma Concentration (Cmax) of S-648414
NCT04147715 (50) [back to overview]Part 3: Maximum Plasma Concentration (Cmax) of Dolutegravir
NCT04147715 (50) [back to overview]Part 3: Area Under the Concentration-time Curve Over the Dosing Interval τ (AUC0-τ) for S-648414
NCT04147715 (50) [back to overview]Part 3: Area Under the Concentration-time Curve Over the Dosing Interval τ (AUC0-τ) for Dolutegravir
NCT04147715 (50) [back to overview]Part 3: Apparent Total Clearance (CL/F) of S-648414
NCT04147715 (50) [back to overview]Part 3: Apparent Total Clearance (CL/F) of Dolutegravir
NCT04147715 (50) [back to overview]Part 2: Time to Maximum Plasma Concentration of Midazolam
NCT04147715 (50) [back to overview]Part 2: Terminal Elimination Rate Constant for Midazolam
NCT04147715 (50) [back to overview]Part 2: Terminal Elimination Rate Constant (λz) of S-648414 Following Multiple-dose Administration
NCT04147715 (50) [back to overview]Part 2: Terminal Elimination Half-life for Midazolam
NCT04147715 (50) [back to overview]Part 2: Terminal Elimination Half-life (t1/2,z) of S-648414 Following Multiple-dose Administration
NCT04147715 (50) [back to overview]Part 2: Renal Clearance (CLR) of S-648414 Following Multiple-dose Administration
NCT04147715 (50) [back to overview]Part 2: Mean Residence Time for Midazolam
NCT04147715 (50) [back to overview]Part 2: Maximum Plasma Concentration (Cmax) of Midazolam
NCT04173962 (9) [back to overview]Change in Positive and Negative Affect Scale (PANAS)
NCT04173962 (9) [back to overview]Change in Visual Analog Scale: Stressed (VAS-Stressed)
NCT04173962 (9) [back to overview]Change in The Profile of Mood States - Bipolar Version (POMS - Bi) Composed-Anxious Subscale
NCT04173962 (9) [back to overview]Change in Systolic Blood Pressure
NCT04173962 (9) [back to overview]Change in Salivary Cortisol
NCT04173962 (9) [back to overview]Change in Salivary Alpha-amylase Level
NCT04173962 (9) [back to overview]Change in Heart Rate
NCT04173962 (9) [back to overview]Change in Diastolic Blood Pressure
NCT04173962 (9) [back to overview]Change in Beck Anxiety Inventory (BAI)
NCT04378426 (1) [back to overview]Improvement in the Severity of PTSD as Measured by the Clinician Administered PTSD Scale DSM5 (CAPS-5)
NCT04392011 (7) [back to overview]Mitragynine Half Life
NCT04392011 (7) [back to overview]Midazolam and Dextromethorphan Cmax
NCT04392011 (7) [back to overview]Midazolam and Dextromethorphan Half-life
NCT04392011 (7) [back to overview]Dextromethorphan Area Under the Concentration vs. Time Curve (AUC)
NCT04392011 (7) [back to overview]Mitragynine Cmax
NCT04392011 (7) [back to overview]Mitragynine Area Under the Concentration vs. Time Curve (AUC)
NCT04392011 (7) [back to overview]Midazolam Area Under the Concentration vs. Time Curve (AUC)
NCT04425902 (171) [back to overview]Treatment C: Change From Baseline in Erythrocytes
NCT04425902 (171) [back to overview]Treatment C: Change From Baseline in Erythrocytes Mean Corpuscular Hemoglobin
NCT04425902 (171) [back to overview]Treatment C: Change From Baseline in Erythrocytes Mean Corpuscular Volume
NCT04425902 (171) [back to overview]Treatment C: Change From Baseline in Glucose, Carbon Dioxide, Cholesterol, Triglycerides, Anion Gap, Calcium, Chloride, Phosphate, Potassium, Sodium, Urea
NCT04425902 (171) [back to overview]Treatment C: Change From Baseline in Hematocrit
NCT04425902 (171) [back to overview]Treatment C: Change From Baseline in Hemoglobin
NCT04425902 (171) [back to overview]Treatment C: Change From Baseline in Oral Temperature
NCT04425902 (171) [back to overview]Treatment C: Change From Baseline in Platelet Count, Leukocyte Count, Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils
NCT04425902 (171) [back to overview]Treatment C: Change From Baseline in Pulse Rate
NCT04425902 (171) [back to overview]Treatment C: Change From Baseline in Respiratory Rate
NCT04425902 (171) [back to overview]Treatment C: Change From Baseline in SBP and DBP
NCT04425902 (171) [back to overview]Treatment C: Change From Baseline in Urate, Creatinine, Bilirubin, Direct Bilirubin
NCT04425902 (171) [back to overview]Treatment A: Change From Baseline in Urate, Creatinine, Bilirubin, Direct Bilirubin
NCT04425902 (171) [back to overview]Treatment A: Change From Baseline in SBP and DBP
NCT04425902 (171) [back to overview]Treatment A: Change From Baseline in Glucose, Carbon Dioxide, Cholesterol, Triglycerides, Anion Gap, Calcium, Chloride, Phosphate, Potassium, Sodium, Urea
NCT04425902 (171) [back to overview]Treatment A: Change From Baseline in ECG Parameters: PR Interval, QRS Duration, QT Interval, QTcF
NCT04425902 (171) [back to overview]Treatment A: Change From Baseline in Creatine Kinase, Lactate Dehydrogenase, ALT, ALP, AST, Gamma-glutamyl Transferase
NCT04425902 (171) [back to overview]Treatment A: Change From Baseline in Amylase, Lipase
NCT04425902 (171) [back to overview]Treatment A: Change From Baseline in Albumin, Globulin, Protein
NCT04425902 (171) [back to overview]Treatment A: Absolute Values of Urate, Creatinine, Bilirubin, Direct Bilirubin
NCT04425902 (171) [back to overview]Treatment A: Absolute Values of Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)
NCT04425902 (171) [back to overview]Treatment A: Absolute Values of Respiratory Rate
NCT04425902 (171) [back to overview]Treatment A: Absolute Values of Pulse Rate
NCT04425902 (171) [back to overview]Treatment A: Absolute Values of Platelet Count, Leukocyte Count, Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils
NCT04425902 (171) [back to overview]Treatment A: Absolute Values of Oral Temperature
NCT04425902 (171) [back to overview]Treatment A: Absolute Values of Hemoglobin
NCT04425902 (171) [back to overview]Treatment A: Absolute Values of Hematocrit
NCT04425902 (171) [back to overview]Treatment A: Absolute Values of Glucose, Carbon Dioxide, Cholesterol, Triglycerides, Anion Gap, Calcium, Chloride, Phosphate, Potassium, Sodium, Urea
NCT04425902 (171) [back to overview]Treatment A: Absolute Values of Erythrocytes Mean Corpuscular Volume
NCT04425902 (171) [back to overview]Treatment A: Absolute Values of Erythrocytes Mean Corpuscular Hemoglobin
NCT04425902 (171) [back to overview]Treatment A: Absolute Values of Erythrocytes
NCT04425902 (171) [back to overview]Treatment A: Absolute Values of Creatine Kinase, Lactate Dehydrogenase, Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST), Gamma-glutamyl Transferase
NCT04425902 (171) [back to overview]Treatment A: Absolute Values of Amylase, Lipase
NCT04425902 (171) [back to overview]Treatment A: Absolute Values of Albumin, Globulin, Protein
NCT04425902 (171) [back to overview]Treatment A: Absolute Values for Electrocardiogram (ECG) Parameters: PR Interval, QRS Duration, QT Interval, Corrected QT Interval Using Fridericia's Formula (QTcF)
NCT04425902 (171) [back to overview]Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
NCT04425902 (171) [back to overview]Treatment C: Tmax for GSK3640254
NCT04425902 (171) [back to overview]Treatment C: t1/2 for GSK3640254
NCT04425902 (171) [back to overview]Treatment C: Plasma Concentration at the End of the Dosing Interval (Ctau) for GSK3640254
NCT04425902 (171) [back to overview]Treatment C: Cmax for GSK3640254
NCT04425902 (171) [back to overview]Treatment C: AUC(0-t) for GSK3640254
NCT04425902 (171) [back to overview]Treatment C: AUC From Time Zero to the End of the Dosing Interval at Steady State (AUC[0-tau]) for GSK3640254
NCT04425902 (171) [back to overview]Treatment B: Change From Baseline in Respiratory Rate
NCT04425902 (171) [back to overview]Treatment B: Change From Baseline in Pulse Rate
NCT04425902 (171) [back to overview]Treatment B: Change From Baseline in Oral Temperature
NCT04425902 (171) [back to overview]Treatment B: Change From Baseline in Hemoglobin
NCT04425902 (171) [back to overview]Treatment B: Change From Baseline in Hematocrit
NCT04425902 (171) [back to overview]Treatment B: Change From Baseline in Erythrocytes Mean Corpuscular Volume
NCT04425902 (171) [back to overview]Treatment B: Change From Baseline in Erythrocytes Mean Corpuscular Hemoglobin
NCT04425902 (171) [back to overview]Treatment B: Change From Baseline in Erythrocytes
NCT04425902 (171) [back to overview]Treatment A: Change From Baseline in Respiratory Rate
NCT04425902 (171) [back to overview]Treatment A: Change From Baseline in Pulse Rate
NCT04425902 (171) [back to overview]Treatment A: Change From Baseline in Oral Temperature
NCT04425902 (171) [back to overview]Treatment A: Change From Baseline in Hemoglobin
NCT04425902 (171) [back to overview]Treatment A: Change From Baseline in Hematocrit
NCT04425902 (171) [back to overview]Treatment A: Change From Baseline in Erythrocytes Mean Corpuscular Volume
NCT04425902 (171) [back to overview]Treatment A: Change From Baseline in Erythrocytes Mean Corpuscular Hemoglobin
NCT04425902 (171) [back to overview]Treatment A: Change From Baseline in Erythrocytes
NCT04425902 (171) [back to overview]Tmax for Pravastatin
NCT04425902 (171) [back to overview]Tmax for Omeprazole
NCT04425902 (171) [back to overview]Tmax for Montelukast
NCT04425902 (171) [back to overview]Tmax for Midazolam
NCT04425902 (171) [back to overview]Tmax for Metoprolol
NCT04425902 (171) [back to overview]Tmax for Flurbiprofen
NCT04425902 (171) [back to overview]Tmax for Digoxin
NCT04425902 (171) [back to overview]Tmax for Alpha-hydroxymetoprolol
NCT04425902 (171) [back to overview]Tmax for 5-hydroxyomeprazole
NCT04425902 (171) [back to overview]Tmax for 36-hydroxymontelukast
NCT04425902 (171) [back to overview]Tmax for 1-hydroxymidazolam
NCT04425902 (171) [back to overview]Time to Cmax (Tmax) for Caffeine
NCT04425902 (171) [back to overview]t1/2 for Pravastatin
NCT04425902 (171) [back to overview]t1/2 for Omeprazole
NCT04425902 (171) [back to overview]t1/2 for Montelukast
NCT04425902 (171) [back to overview]t1/2 for Midazolam
NCT04425902 (171) [back to overview]t1/2 for Metoprolol
NCT04425902 (171) [back to overview]t1/2 for Flurbiprofen
NCT04425902 (171) [back to overview]t1/2 for Digoxin
NCT04425902 (171) [back to overview]t1/2 for Alpha-hydroxymetoprolol
NCT04425902 (171) [back to overview]t1/2 for 5-hydroxyomeprazole
NCT04425902 (171) [back to overview]t1/2 for 36-hydroxymontelukast
NCT04425902 (171) [back to overview]t1/2 for 1-hydroxymidazolam
NCT04425902 (171) [back to overview]Ratio of Cmax of Alpha-hydroxymetoprolol to Metoprolol
NCT04425902 (171) [back to overview]Ratio of Cmax of 5-hydroxyomeprazole to Omeprazole
NCT04425902 (171) [back to overview]Ratio of Cmax of 36-hydroxymontelukast to Montelukast
NCT04425902 (171) [back to overview]Ratio of Cmax of 1-hydroxymidazolam to Midazolam
NCT04425902 (171) [back to overview]Ratio of AUC(0-infinity) of Alpha-hydroxymetoprolol to Metoprolol
NCT04425902 (171) [back to overview]Ratio of AUC(0-infinity) of 5-hydroxyomeprazole to Omeprazole
NCT04425902 (171) [back to overview]Ratio of AUC(0-infinity) of 36-hydroxymontelukast to Montelukast
NCT04425902 (171) [back to overview]Ratio of AUC(0-infinity) of 1-hydroxymidazolam to Midazolam
NCT04425902 (171) [back to overview]Apparent Terminal Phase Half-life (t1/2) for Caffeine
NCT04425902 (171) [back to overview]Area Under the Plasma Concentration-time Curve (AUC) From Time Zero to Time t (AUC[0-t]) for Caffeine
NCT04425902 (171) [back to overview]Treatment A: Change From Baseline in Platelet Count, Leukocyte Count, Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils
NCT04425902 (171) [back to overview]AUC From Time Zero Extrapolated to Infinity (AUC[0-infinity]) for Caffeine
NCT04425902 (171) [back to overview]AUC(0-infinity) for 1-hydroxymidazolam
NCT04425902 (171) [back to overview]AUC(0-infinity) for 36-hydroxymontelukast
NCT04425902 (171) [back to overview]AUC(0-infinity) for 5-hydroxyomeprazole
NCT04425902 (171) [back to overview]AUC(0-infinity) for Alpha-hydroxymetoprolol
NCT04425902 (171) [back to overview]AUC(0-infinity) for Digoxin
NCT04425902 (171) [back to overview]AUC(0-infinity) for Flurbiprofen
NCT04425902 (171) [back to overview]AUC(0-infinity) for Metoprolol
NCT04425902 (171) [back to overview]AUC(0-infinity) for Midazolam
NCT04425902 (171) [back to overview]AUC(0-infinity) for Montelukast
NCT04425902 (171) [back to overview]Treatment B: Absolute Values of Erythrocytes Mean Corpuscular Volume
NCT04425902 (171) [back to overview]Treatment B: Absolute Values of Erythrocytes Mean Corpuscular Hemoglobin
NCT04425902 (171) [back to overview]Treatment B: Absolute Values of Erythrocytes
NCT04425902 (171) [back to overview]Treatment B: Absolute Values of Creatine Kinase, Lactate Dehydrogenase, ALT, ALP, AST, Gamma-glutamyl Transferase
NCT04425902 (171) [back to overview]Treatment B: Absolute Values of Amylase, Lipase
NCT04425902 (171) [back to overview]Treatment B: Absolute Values of Albumin, Globulin, Protein
NCT04425902 (171) [back to overview]Treatment B: Absolute Values for ECG Parameters: PR Interval, QRS Duration, QT Interval, QTcF Interval
NCT04425902 (171) [back to overview]AUC(0-infinity) for Omeprazole
NCT04425902 (171) [back to overview]AUC(0-infinity) for Pravastatin
NCT04425902 (171) [back to overview]AUC(0-t) for 1-hydroxymidazolam
NCT04425902 (171) [back to overview]AUC(0-t) for 36-hydroxymontelukast
NCT04425902 (171) [back to overview]AUC(0-t) for 5-hydroxyomeprazole
NCT04425902 (171) [back to overview]AUC(0-t) for Alpha-hydroxymetoprolol
NCT04425902 (171) [back to overview]AUC(0-t) for Digoxin
NCT04425902 (171) [back to overview]AUC(0-t) for Flurbiprofen
NCT04425902 (171) [back to overview]AUC(0-t) for Metoprolol
NCT04425902 (171) [back to overview]AUC(0-t) for Midazolam
NCT04425902 (171) [back to overview]AUC(0-t) for Montelukast
NCT04425902 (171) [back to overview]AUC(0-t) for Omeprazole
NCT04425902 (171) [back to overview]AUC(0-t) for Pravastatin
NCT04425902 (171) [back to overview]Cmax for 1-hydroxymidazolam
NCT04425902 (171) [back to overview]Cmax for 36-hydroxymontelukast
NCT04425902 (171) [back to overview]Cmax for 5-hydroxyomeprazole
NCT04425902 (171) [back to overview]Cmax for Alpha-hydroxymetoprolol
NCT04425902 (171) [back to overview]Cmax for Digoxin
NCT04425902 (171) [back to overview]Cmax for Flurbiprofen
NCT04425902 (171) [back to overview]Cmax for Metoprolol
NCT04425902 (171) [back to overview]Cmax for Midazolam
NCT04425902 (171) [back to overview]Cmax for Montelukast
NCT04425902 (171) [back to overview]Treatment B: Absolute Values of Glucose, Carbon Dioxide, Cholesterol, Triglycerides, Anion Gap, Calcium, Chloride, Phosphate, Potassium, Sodium, Urea
NCT04425902 (171) [back to overview]Treatment B: Absolute Values of Hematocrit
NCT04425902 (171) [back to overview]Treatment B: Absolute Values of Hemoglobin
NCT04425902 (171) [back to overview]Treatment B: Absolute Values of Oral Temperature
NCT04425902 (171) [back to overview]Treatment B: Absolute Values of Platelet Count, Leukocyte Count, Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils
NCT04425902 (171) [back to overview]Treatment B: Absolute Values of Pulse Rate
NCT04425902 (171) [back to overview]Treatment B: Absolute Values of Respiratory Rate
NCT04425902 (171) [back to overview]Treatment B: Absolute Values of SBP and DBP
NCT04425902 (171) [back to overview]Cmax for Omeprazole
NCT04425902 (171) [back to overview]Cmax for Pravastatin
NCT04425902 (171) [back to overview]Maximum Observed Plasma Concentration (Cmax) for Caffeine
NCT04425902 (171) [back to overview]Treatment B: Absolute Values of Urate, Creatinine, Bilirubin, Direct Bilirubin
NCT04425902 (171) [back to overview]Treatment B: Change From Baseline in Albumin, Globulin, Protein
NCT04425902 (171) [back to overview]Treatment B: Change From Baseline in Amylase, Lipase
NCT04425902 (171) [back to overview]Treatment B: Change From Baseline in Creatine Kinase, Lactate Dehydrogenase, ALT, ALP, AST, Gamma-glutamyl Transferase
NCT04425902 (171) [back to overview]Treatment B: Change From Baseline in ECG Parameters: PR Interval, QRS Duration, QT Interval, QTcF
NCT04425902 (171) [back to overview]Treatment B: Change From Baseline in Glucose, Carbon Dioxide, Cholesterol, Triglycerides, Anion Gap, Calcium, Chloride, Phosphate, Potassium, Sodium, Urea
NCT04425902 (171) [back to overview]Treatment B: Change From Baseline in Platelet Count, Leukocyte Count, Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils
NCT04425902 (171) [back to overview]Treatment B: Change From Baseline in SBP and DBP
NCT04425902 (171) [back to overview]Treatment B: Change From Baseline in Urate, Creatinine, Bilirubin, Direct Bilirubin
NCT04425902 (171) [back to overview]Treatment C: Absolute Values for ECG Parameters: PR Interval, QRS Duration, QT Interval, QTcF Interval
NCT04425902 (171) [back to overview]Treatment C: Absolute Values of Albumin, Globulin, Protein
NCT04425902 (171) [back to overview]Treatment C: Absolute Values of Amylase, Lipase
NCT04425902 (171) [back to overview]Treatment C: Absolute Values of Creatine Kinase, Lactate Dehydrogenase, ALT, ALP, AST, Gamma-glutamyl Transferase
NCT04425902 (171) [back to overview]Treatment C: Absolute Values of Erythrocytes
NCT04425902 (171) [back to overview]Treatment C: Absolute Values of Erythrocytes Mean Corpuscular Hemoglobin
NCT04425902 (171) [back to overview]Treatment C: Absolute Values of Erythrocytes Mean Corpuscular Volume
NCT04425902 (171) [back to overview]Treatment C: Absolute Values of Glucose, Carbon Dioxide, Cholesterol, Triglycerides, Anion Gap, Calcium, Chloride, Phosphate, Potassium, Sodium, Urea
NCT04425902 (171) [back to overview]Treatment C: Absolute Values of Hematocrit
NCT04425902 (171) [back to overview]Treatment C: Absolute Values of Hemoglobin
NCT04425902 (171) [back to overview]Treatment C: Absolute Values of Oral Temperature
NCT04425902 (171) [back to overview]Treatment C: Absolute Values of Platelet Count, Leukocyte Count, Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils
NCT04425902 (171) [back to overview]Treatment C: Absolute Values of Pulse Rate
NCT04425902 (171) [back to overview]Treatment C: Absolute Values of Respiratory Rate
NCT04425902 (171) [back to overview]Treatment C: Absolute Values of SBP and DBP
NCT04425902 (171) [back to overview]Treatment C: Absolute Values of Urate, Creatinine, Bilirubin, Direct Bilirubin
NCT04425902 (171) [back to overview]Treatment C: Change From Baseline in Albumin, Globulin, Protein
NCT04425902 (171) [back to overview]Treatment C: Change From Baseline in Amylase, Lipase
NCT04425902 (171) [back to overview]Treatment C: Change From Baseline in Creatine Kinase, Lactate Dehydrogenase, ALT, ALP, AST, Gamma-glutamyl Transferase
NCT04425902 (171) [back to overview]Treatment C: Change From Baseline in ECG Parameters: PR Interval, QRS Duration, QT Interval, QTcF
NCT04493931 (139) [back to overview]Cohort 3: Tmax of Gepotidacin in Plasma After the First Dose of 3000 mg (First Dose)
NCT04493931 (139) [back to overview]Cohort 4: AUC(0-t) of Gepotidacin in Plasma Following Two 3000 mg Doses (First Dose + Second Dose)-Fed State
NCT04493931 (139) [back to overview]Cohort 4: AUC(0-t) of Gepotidacin Following Single Dose of 1500 mg in Plasma - Food Effect in Japanese Participants
NCT04493931 (139) [back to overview]Cohort 4: AUC(0-t) of Gepotidacin Following Single Dose of 1500 mg in Plasma
NCT04493931 (139) [back to overview]Cohort 4: AUC(0-infinity) of Gepotidacin Following Single Dose of 1500 mg in Plasma - Food Effect in Japanese Participants
NCT04493931 (139) [back to overview]Cohort 4: AUC(0-infinity) of Gepotidacin Following Single Dose of 1500 mg in Plasma
NCT04493931 (139) [back to overview]Cohort 4: AUC(0-48) of Gepotidacin in Urine Following Two 3000 mg Doses-Fed State
NCT04493931 (139) [back to overview]Cohort 4: AUC(0-48) of Gepotidacin in Plasma Following Two 3000 mg Doses (First Dose + Second Dose)-Fed State
NCT04493931 (139) [back to overview]Cohort 4: AUC(0-48) of Gepotidacin Following Single Dose of 1500 mg Under Fed Condition in Urine
NCT04493931 (139) [back to overview]Cohort 4: AUC(0-24) of Gepotidacin in Urine Following Two 3000 mg Doses-Fed State
NCT04493931 (139) [back to overview]Cohort 4: AUC(0-24) of Gepotidacin in Plasma Following Two 3000 mg Doses (First Dose + Second Dose)-Fed State
NCT04493931 (139) [back to overview]Cohort 4: AUC(0-24) of Gepotidacin Following Single Dose of 1500 mg Under Fed Condition in Urine
NCT04493931 (139) [back to overview]Cohort 4: AUC From Time 0 (Predose) to Time Tau (AUC[0-tau]) of Gepotidacin in Plasma After the First Dose of 3000 Mg-Fed State
NCT04493931 (139) [back to overview]Cohort 4: Area Under the Concentration-time Curve From Time 0 (Pre-dose) to the Concentration at 48 Hours Post-dose (AUC[0-48]) of Gepotidacin Following Single Dose of 1500 mg in Plasma
NCT04493931 (139) [back to overview]Cohort 4: Area Under the Concentration-time Curve From Time 0 (Pre-dose) to the Concentration at 24 Hours Post-dose (AUC[0-24]) of Gepotidacin Following Single Dose of 1500 mg in Plasma
NCT04493931 (139) [back to overview]Cohort 4: Ae Total of Gepotidacin in Urine Following Two 3000 mg Doses-Fed State
NCT04493931 (139) [back to overview]Cohort 4: Accumulation Ratio Based on Cmax (RoCmax) of Gepotidacin in Plasma After the Second Dose of 3000 mg (Second Dose)-Fed State
NCT04493931 (139) [back to overview]Cohort 4: Accumulation Ratio Based on AUC(0-tau) (RoAUC) of Gepotidacin in Plasma After the Second Dose of 3000 mg (Second Dose)-Fed State
NCT04493931 (139) [back to overview]Cohort 3: Vz/F of Midazolam in Plasma
NCT04493931 (139) [back to overview]Cohort 3: Vz/F of Gepotidacin in Plasma Following Two 3000 mg Doses (First Dose + Second Dose)
NCT04493931 (139) [back to overview]Cohort 3: Vz/F of Digoxin in Plasma
NCT04493931 (139) [back to overview]Cohort 3: Tmax of Midazolam in Plasma
NCT04493931 (139) [back to overview]Cohort 3: Tmax of Gepotidacin in Plasma After the Second Dose of 3000 mg (Second Dose)
NCT04493931 (139) [back to overview]Cohort 3: AUC(0-tau) of Gepotidacin in Plasma After the Second Dose of 3000 mg (Second Dose)
NCT04493931 (139) [back to overview]Cohort 3: Tmax of Digoxin in Plasma
NCT04493931 (139) [back to overview]Cohort 3: Tlag of Midazolam in Plasma
NCT04493931 (139) [back to overview]Cohort 3: Tlag of Gepotidacin in Plasma After the First Dose of 3000 mg (First Dose)
NCT04493931 (139) [back to overview]Cohort 3: Tlag of Digoxin in Plasma
NCT04493931 (139) [back to overview]Cohort 3: T1/2 of Midazolam in Plasma
NCT04493931 (139) [back to overview]Cohort 3: T1/2 of Gepotidacin in Plasma Following Two 3000 mg Doses (First Dose+ Second Dose)
NCT04493931 (139) [back to overview]Cohort 3: T1/2 of Digoxin in Plasma
NCT04493931 (139) [back to overview]Cohort 3: RoCmax of Gepotidacin in Plasma After the Second Dose of 3000 mg (Second Dose)
NCT04493931 (139) [back to overview]Cohort 3: RoAUC of Gepotidacin in Plasma After the Second Dose of 3000 mg (Second Dose)
NCT04493931 (139) [back to overview]Cohort 3: Percentage of the Given Dose of Drug Excreted in Urine (fe%) Following Two 3000 mg Doses of Gepotidacin (First Dose + Second Dose )
NCT04493931 (139) [back to overview]Cohort 3: Minimum Observed Concentration (Cmin) of Digoxin in Plasma
NCT04493931 (139) [back to overview]Cohort 3: Cmin of Midazolam in Plasma
NCT04493931 (139) [back to overview]Cohort 3: Cmax of Midazolam in Plasma
NCT04493931 (139) [back to overview]Cohort 3: Cmax of Gepotidacin in Plasma After the Second Dose of 3000 mg (Second Dose)
NCT04493931 (139) [back to overview]Cohort 3: Cmax of Gepotidacin in Plasma After the First Dose of 3000 mg (First Dose)
NCT04493931 (139) [back to overview]Cohort 3: Cmax of Digoxin in Plasma
NCT04493931 (139) [back to overview]Cohort 3: CLr of Gepotidacin Following Two 3000 mg Doses (First Dose + Second Dose)
NCT04493931 (139) [back to overview]Cohort 3: CL/F of Midazolam in Plasma
NCT04493931 (139) [back to overview]Cohort 3: CL/F of Gepotidacin in Plasma Following Two 3000 mg Doses (First Dose + Second Dose)
NCT04493931 (139) [back to overview]Cohort 3: CL/F of Digoxin in Plasma
NCT04493931 (139) [back to overview]Cohort 3: AUC(0-tau) of Gepotidacin in Urine Following Two 3000 mg Doses (First Dose + Second Dose)
NCT04493931 (139) [back to overview]Cohort 3: AUC(0-tau) of Gepotidacin in Plasma First Dose of 3000 mg (First Dose)
NCT04493931 (139) [back to overview]Cohort 4: AUC(0-tau) of Gepotidacin in Plasma After the Second Dose of 3000 mg (Evening Dose)-Fed State
NCT04493931 (139) [back to overview]Cohort 3: AUC(0-t) of Midazolam in Plasma
NCT04493931 (139) [back to overview]Cohort 3: AUC(0-t) of Gepotidacin in Plasma Following Two 3000 mg Doses (First Dose + Second Dose)
NCT04493931 (139) [back to overview]Cohort 3: AUC(0-t) of Digoxin in Plasma
NCT04493931 (139) [back to overview]Cohort 3: AUC(0-infinity) of Midazolam in Plasma
NCT04493931 (139) [back to overview]Cohort 3: AUC(0-infinity) of Digoxin in Plasma
NCT04493931 (139) [back to overview]Cohort 3: AUC(0-48) of Gepotidacin in Plasma Following Two 3000 mg Doses (First Dose + Second Dose)
NCT04493931 (139) [back to overview]Cohort 4: AUC(0-tau) of Gepotidacin Following Single Dose of 1500 mg Under Fed Condition in Urine
NCT04493931 (139) [back to overview]Cohort 3: AUC(0-24) of Gepotidacin in Plasma Following Two 3000 mg Doses (First Dose + Second Dose)
NCT04493931 (139) [back to overview]Cohort 3: AUC (0-48) of Gepotidacin in Urine Following Two 3000 mg Doses (First Dose + Second Dose)
NCT04493931 (139) [back to overview]Cohort 3: Ae Total of Gepotidacin in Urine Following Two 3000 mg Doses (First Dose + Second Dose )
NCT04493931 (139) [back to overview]Cohort 2: Vz/F of Gepotidacin in Plasma
NCT04493931 (139) [back to overview]Cohort 2: Tmax of Gepotidacin in Plasma
NCT04493931 (139) [back to overview]Cohort 2: T1/2 of Gepotidacin in Plasma
NCT04493931 (139) [back to overview]Cohort 2: Percentage of the Given Dose of Drug Excreted in Urine (fe%) of Gepotidacin
NCT04493931 (139) [back to overview]Cohort 2: Lag Time Before Observation of Drug Concentrations (Tlag) of Gepotidacin in Plasma
NCT04493931 (139) [back to overview]Cohort 2: Cmax of Gepotidacin in Plasma
NCT04493931 (139) [back to overview]Cohort 2: CLr of Gepotidacin
NCT04493931 (139) [back to overview]Cohort 2: CL/F of Gepotidacin in Plasma
NCT04493931 (139) [back to overview]Cohort 2: AUC(0-t) of Gepotidacin in Plasma
NCT04493931 (139) [back to overview]Cohort 2: AUC(0-infinity) of Gepotidacin in Plasma
NCT04493931 (139) [back to overview]Cohort 2: AUC(0-48) of Gepotidacin in Urine
NCT04493931 (139) [back to overview]Cohort 2: AUC(0-48) of Gepotidacin in Plasma
NCT04493931 (139) [back to overview]Cohort 2: AUC(0-24) of Gepotidacin in Urine
NCT04493931 (139) [back to overview]Cohort 2: AUC(0-24) of Gepotidacin in Plasma
NCT04493931 (139) [back to overview]Cohort 2: Ae Total of Gepotidacin in Urine
NCT04493931 (139) [back to overview]Cohort 1: Total Unchanged Drug (Ae Total) of Gepotidacin in Urine
NCT04493931 (139) [back to overview]Cohort 1: Tlag of Gepotidacin in Plasma
NCT04493931 (139) [back to overview]Cohort 1: Time to Reach Maximum Observed Concentration (Tmax) of Gepotidacin in Plasma
NCT04493931 (139) [back to overview]Cohort 1: Terminal Phase Half-life (t1/2) of Gepotidacin in Plasma
NCT04493931 (139) [back to overview]Cohort 1: Renal Clearance (CLr) of Gepotidacin
NCT04493931 (139) [back to overview]Cohort 1: Percentage of the Given Dose of Drug Excreted in Urine (fe%) of Gepotidacin
NCT04493931 (139) [back to overview]Cohort 1: Maximum Observed Concentration (Cmax) of Gepotidacin in Plasma
NCT04493931 (139) [back to overview]Cohort 1: AUC(0-48) of Gepotidacin in Urine
NCT04493931 (139) [back to overview]Cohort 1: AUC(0-48) of Gepotidacin in Plasma
NCT04493931 (139) [back to overview]Cohort 1: AUC(0-24) of Gepotidacin in Urine
NCT04493931 (139) [back to overview]Cohort 1: AUC From Time 0 (Pre-dose) Extrapolated to Infinite Time (AUC[0-infinity]) of Gepotidacin in Plasma
NCT04493931 (139) [back to overview]Cohort 1: AUC (0-24) of Gepotidacin in Plasma
NCT04493931 (139) [back to overview]Cohort 1: Area Under the Concentration-time Curve From Time 0 (Pre-dose) to the Time of the Last Quantifiable Concentration (AUC [0-t]) of Gepotidacin in Plasma
NCT04493931 (139) [back to overview]Cohort 1: Apparent Volume of Distribution (Vz/F) of Gepotidacin in Plasma
NCT04493931 (139) [back to overview]Cohort 1: Apparent Oral Clearance (CL/F) of Gepotidacin in Plasma
NCT04493931 (139) [back to overview]Cohort 4: Number of Participants With Worst Case Hematology Results Relative to Normal Range Post-Baseline Relative to Baseline
NCT04493931 (139) [back to overview]Cohort 4: Number of Participants With Worst Case Urinalysis Results Relative to Normal Range Post-Baseline Relative to Baseline
NCT04493931 (139) [back to overview]Cohort 4: Number of Participants With Worst Case Vital Sign Results Relative to Normal Range Post-Baseline Relative to Baseline
NCT04493931 (139) [back to overview]Cohort 4: CL/F of Gepotidacin in Plasma Following Two 3000 mg Doses (First Dose + Second Dose)-Fed State
NCT04493931 (139) [back to overview]Cohort 4: Number of Participants With Worst Case Clinical Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline
NCT04493931 (139) [back to overview]Cohort 4: Number of Participants With Serious Adverse Events (SAE) and Non-serious Adverse Events (Non-SAE)
NCT04493931 (139) [back to overview]Cohort 4: Number of Participants With Any Increase in Maximum Post-Baseline Electrocardiogram (ECG) Parameter Corrected QT (QTc) Interval
NCT04493931 (139) [back to overview]Cohort 4: Ae(t1-t2) of Gepotidacin in Urine Following Two 3000 mg Doses-Fed State
NCT04493931 (139) [back to overview]Cohort 4: Ae(t1-t2) of Gepotidacin Following Single Dose of 1500 mg Under Fed Condition in Urine
NCT04493931 (139) [back to overview]Cohort 3: Number of Participants With Worst Case Vital Sign Results Relative to Normal Range Post-Baseline Relative to Baseline
NCT04493931 (139) [back to overview]Cohort 3: Number of Participants With Worst Case Urinalysis Results Relative to Normal Range Post-Baseline Relative to Baseline
NCT04493931 (139) [back to overview]Cohort 3: Number of Participants With Worst Case Hematology Results Relative to Normal Range Post-Baseline Relative to Baseline
NCT04493931 (139) [back to overview]Cohort 3: Number of Participants With Worst Case Clinical Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline
NCT04493931 (139) [back to overview]Cohort 3: AUC(0-24) of Gepotidacin in Urine Following Two 3000 mg Doses (First Dose + Second Dose)
NCT04493931 (139) [back to overview]Cohort 4: Ae Total of Gepotidacin Following Single Dose of 1500 mg Under Fed Condition in Urine
NCT04493931 (139) [back to overview]Cohort 3: Number of Participants With SAE and Non-SAE
NCT04493931 (139) [back to overview]Cohort 3: Number of Participants With Any Increase in Maximum Post-Baseline ECG Parameter QTc Interval
NCT04493931 (139) [back to overview]Cohort 3: Amount of Drug Excreted in Urine in a Time Interval (Ae[t1-t2]) of Gepotidacin Following Two 3000 mg Doses (First Dose + Second Dose)
NCT04493931 (139) [back to overview]Cohort 2: Number of Participants With Worst Case Vital Sign Results Relative to Normal Range Post-Baseline Relative to Baseline
NCT04493931 (139) [back to overview]Cohort 2: Number of Participants With Worst Case Urinalysis Results Relative to Normal Range Post-Baseline Relative to Baseline
NCT04493931 (139) [back to overview]Cohort 2: Number of Participants With Worst Case Hematology Results Relative to Normal Range Post-Baseline Relative to Baseline
NCT04493931 (139) [back to overview]Cohort 2: Number of Participants With Worst Case Clinical Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline
NCT04493931 (139) [back to overview]Cohort 2: Number of Participants With SAE and Non-SAE
NCT04493931 (139) [back to overview]Cohort 4: Vz/F of Gepotidacin in Plasma Following Two 3000 mg Doses (First Dose + Second Dose)-Fed State
NCT04493931 (139) [back to overview]Cohort 2: Number of Participants With Any Increase in Maximum Post-Baseline ECG Parameter QTc Interval
NCT04493931 (139) [back to overview]Cohort 2: Ae(t1-t2) of Gepotidacin
NCT04493931 (139) [back to overview]Cohort 1: Number of Participants With Worst Case Vital Sign Results Relative to Normal Range Post-Baseline Relative to Baseline
NCT04493931 (139) [back to overview]Cohort 1: Number of Participants With Worst Case Urinalysis Results Relative to Normal Range Post-Baseline Relative to Baseline
NCT04493931 (139) [back to overview]Cohort 1: Number of Participants With Worst Case Hematology Results Relative to Normal Range Post-Baseline Relative to Baseline
NCT04493931 (139) [back to overview]Cohort 1: Number of Participants With Worst Case Clinical Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline
NCT04493931 (139) [back to overview]Cohort 1: Number of Participants With SAE and Non-SAE
NCT04493931 (139) [back to overview]Cohort 1: Number of Participants With Any Increase in Maximum Post-Baseline ECG Parameter QTc Interval
NCT04493931 (139) [back to overview]Cohort 1: Amount of Drug Excreted in Urine in a Time Interval (Ae[t1-t2]) of Gepotidacin
NCT04493931 (139) [back to overview]Cohort 4: Vz/F of Gepotidacin Following Single Dose of 1500 mg in Plasma
NCT04493931 (139) [back to overview]Cohort 4: Tmax of Gepotidacin in Plasma After the Second Dose of 3000 mg (Second Dose)-Fed State
NCT04493931 (139) [back to overview]Cohort 4: Tmax of Gepotidacin in Plasma After the First Dose of 3000 mg -Fed State
NCT04493931 (139) [back to overview]Cohort 4: Tmax of Gepotidacin Following Single Dose of 1500 mg in Plasma - Food Effect in Japanese Participants
NCT04493931 (139) [back to overview]Cohort 4: Tmax of Gepotidacin Following Single Dose of 1500 mg in Plasma
NCT04493931 (139) [back to overview]Cohort 4: Tlag of Gepotidacin in Plasma After the First Dose of 3000 mg (First Dose)-Fed State
NCT04493931 (139) [back to overview]Cohort 4: Tlag of Gepotidacin Following Single Dose of 1500 mg in Plasma - Food Effect in Japanese Participants
NCT04493931 (139) [back to overview]Cohort 4: T1/2 of Gepotidacin in Plasma Following Two 3000 mg Doses (First Dose + Second Dose )-Fed State
NCT04493931 (139) [back to overview]Cohort 4: T1/2 of Gepotidacin Following Single Dose of 1500 mg in Plasma
NCT04493931 (139) [back to overview]Cohort 4: Percentage of the Given Dose of Drug Excreted in Urine (fe%) of Gepotidacin Following Two 3000 mg Doses-Fed State
NCT04493931 (139) [back to overview]Cohort 4: Percentage of the Given Dose of Drug Excreted in Urine (fe%) for Gepotidacin 1500 mg Under Fed Condition
NCT04493931 (139) [back to overview]Cohort 4: Cmax of Gepotidacin in Plasma After the Second Dose of 3000 mg (Second Dose)-Fed State
NCT04493931 (139) [back to overview]Cohort 4: Cmax of Gepotidacin in Plasma After the First Dose of 3000 mg -Fed State
NCT04493931 (139) [back to overview]Cohort 4: Cmax of Gepotidacin Following Single Dose of 1500 mg in Plasma - Food Effect in Japanese Participants
NCT04493931 (139) [back to overview]Cohort 4: Cmax of Gepotidacin Following Single Dose of 1500 mg in Plasma
NCT04493931 (139) [back to overview]Cohort 4: CLr of Gepotidacin Following Two 3000 mg Dose-Fed State
NCT04493931 (139) [back to overview]Cohort 4: CLr of Gepotidacin Following Single Dose of 1500 mg Under Fed Condition
NCT04493931 (139) [back to overview]Cohort 4: CL/F of Gepotidacin Following Single Dose of 1500 mg in Plasma
NCT04493931 (139) [back to overview]Cohort 4: AUC(0-tau) of Gepotidacin in Urine Following Two 3000 mg Doses-Fed State
NCT04545944 (3) [back to overview]Area Under the Plasma Concentration Versus Time Curve From Time 0 to the Last Quantifiable Concentration (AUC0-t) of Midazolam
NCT04545944 (3) [back to overview]Area Under the Plasma Concentration Versus Time Curve From Time 0 Extrapolated to Infinity (AUC0-inf) of Midazolam
NCT04545944 (3) [back to overview]Maximum Observed Plasma Concentration (Cmax) of Midazolam
NCT04621227 (9) [back to overview]Area Under the Plasma Concentration-time Profile From Time 0 to Last Quantifiable Concentration (AUClast) of Rosuvastatin in Periods 1, 4 and 7
NCT04621227 (9) [back to overview]Number of Participants With Categorical Scores on the Patient Health Questionnaire (PHQ-9)
NCT04621227 (9) [back to overview]Number of Participants With Vital Signs Data Meeting the Pre-defined Categorical Summarization Criteria
NCT04621227 (9) [back to overview]Number of Participants With Treatment-emergent Adverse Events (TEAEs)
NCT04621227 (9) [back to overview]Number of Participants With Positive Response on the Columbia Suicide Severity Rating Scale (C-SSRS)
NCT04621227 (9) [back to overview]Number of Participants With Electrocardiogram (ECG) Data Meeting the Pre-defined Categorical Summarization Criteria
NCT04621227 (9) [back to overview]Change From Baseline in Body Weight
NCT04621227 (9) [back to overview]Number of Participants With Laboratory Abnormalities (Without Regard to Baseline [BL] Abnormality)
NCT04621227 (9) [back to overview]AUClast of Midazolam in Periods 2, 5 and 8
NCT04679948 (8) [back to overview]Area Under the Concentration-time Curve of Midazolam in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-infinity, Midazolam)
NCT04679948 (8) [back to overview]Area Under the Concentration-time Curve of Omeprazole in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-infinity, Omeprazole)
NCT04679948 (8) [back to overview]Area Under the Concentration-time Curve of S-warfarin in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-infinity, S-warfarin)
NCT04679948 (8) [back to overview]Area Under the Concentration-time Curve of Caffeine in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-infinity, Caffeine)
NCT04679948 (8) [back to overview]Maximum Measured Concentration of Omeprazole in Plasma (Cmax, Omeprazole)
NCT04679948 (8) [back to overview]Maximum Measured Concentration of the Caffeine in Plasma (Cmax, Caffeine)
NCT04679948 (8) [back to overview]Maximum Measured Concentration of Midazolam in Plasma (Cmax, Midazolam)
NCT04679948 (8) [back to overview]Maximum Measured Concentration of the S-warfarin in Plasma (Cmax, S-warfarin)
NCT05032950 (14) [back to overview]Apparent Clearance (CL/F) of Midazolam When Administered Alone, With PF-07321332/Ritonavir, and With Ritonavir
NCT05032950 (14) [back to overview]Apparent Volume of Distribution (Vz/F) of Midazolam When Administered Alone, With PF-07321332/Ritonavir, and With Ritonavir
NCT05032950 (14) [back to overview]Area Under the Plasma Concentration-time Profile From Time 0 Extrapolated to Infinity Time (AUCinf) of Midazolam When Administered Alone and With PF-07321332/Ritonavir
NCT05032950 (14) [back to overview]Area Under the Plasma Concentration-time Profile From Time 0 to the Time of the Last Quantifiable Concentration (Clast) (AUClast) of Midazolam When Administered Alone and With PF-07321332/Ritonavir
NCT05032950 (14) [back to overview]AUCinf of Midazolam When Administered Alone and With Ritonavir
NCT05032950 (14) [back to overview]AUClast of Midazolam When Administered Alone and With Ritonavir
NCT05032950 (14) [back to overview]Cmax of Midazolam When Administered Alone and With Ritonavir
NCT05032950 (14) [back to overview]Maximum Plasma Concentration (Cmax) of Midazolam When Administered Alone and With PF-07321332/Ritonavir
NCT05032950 (14) [back to overview]Number of Participants With Vital Signs Abnormalities
NCT05032950 (14) [back to overview]Terminal Half-life (t1/2) of Midazolam When Administered Alone, With PF-07321332/Ritonavir, and With Ritonavir
NCT05032950 (14) [back to overview]Time for Cmax (Tmax) of Midazolam When Administered Alone, With PF-07321332/Ritonavir, and With Ritonavir
NCT05032950 (14) [back to overview]Number of Participants With Electrocardiogram (ECG) Abnormalities
NCT05032950 (14) [back to overview]Number of Participants With Laboratory Abnormalities
NCT05032950 (14) [back to overview]Number of Participants With Treatment-emergent Adverse Events (TEAEs)
NCT05395104 (13) [back to overview]Area Under the Plasma Concentration-time Curve Over the Dosing Interval τ (8 Hours) (AUC0-τ) of Cefiderocol
NCT05395104 (13) [back to overview]Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUC0-last) of Midazolam
NCT05395104 (13) [back to overview]Maximum Observed Plasma Concentration (Cmax) of Midazolam
NCT05395104 (13) [back to overview]Terminal Elimination Half-life (t1/2,z) of Midazolam
NCT05395104 (13) [back to overview]Terminal Elimination Rate Constant (λz) of Midazolam
NCT05395104 (13) [back to overview]Time to Maximum Plasma Concentration (Tmax) of Midazolam
NCT05395104 (13) [back to overview]Area Under the Concentration-time Curve Extrapolated From Time 0 to Infinity (AUC0-inf) of Midazolam
NCT05395104 (13) [back to overview]Apparent Volume of Distribution (Vz/F) of Midazolam
NCT05395104 (13) [back to overview]Apparent Total Clearance (CL/F) of Midazolam
NCT05395104 (13) [back to overview]Tmax of Cefiderocol
NCT05395104 (13) [back to overview]Cmax of Cefiderocol
NCT05395104 (13) [back to overview]CL of Cefiderocol
NCT05395104 (13) [back to overview]Mean Residence Time (MRT) of Midazolam

Number of Patients Needed to be Seen or Treated in the Emergency Department for Their Seizure and Use of Study Medication.

(NCT00326612)
Timeframe: 24 hours

Interventionparticipants (Number)
Intranasal Midazolam21
Rectal Diazepam17

[back to top]

Number of Patients That Were Admitted to the Hospital After Their Seizure and Use of Study Medication.

(NCT00326612)
Timeframe: 24 hours

Interventionparticipants (Number)
Intranasal Midazolam4
Rectal Diazepam3

[back to top]

Number of Patients Who Had a Repeat Seizure Within 12 Hours After Their Seizure Who Used Study Medication

(NCT00326612)
Timeframe: 12 hours

Interventionparticipants (Number)
Intranasal Midazolam1
Rectal Diazepam1

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Number of Patients Who Needed Additional Medication to Treat the Seizure in the Emergency Department Within 24 Hours

(NCT00326612)
Timeframe: 24 hours

Interventionparticipants (Number)
Intranasal Midazolam5
Rectal Diazepam5

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Respiratory Depression Requiring Intubation

Respiratory depression was defined as intubation at Emergency Department discharge. (NCT00326612)
Timeframe: 24 hours

Interventionparticipants (Number)
Intranasal Midazolam1
Rectal Diazepam0

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Respiratory Depression Requiring Oxygen at Discharge From the Emergency Department.

Respiratory depression was defined as requiring oxygen at discharge from the Emergency Department. (NCT00326612)
Timeframe: 24 hours

Interventionparticipants (Number)
Intranasal Midazolam3
Rectal Diazepam1

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Length of Seizure After Study Medication Administration

Length of seizure. (NCT00326612)
Timeframe: 24 hours

InterventionMinutes (Median)
Intranasal Midazolam3.0
Rectal Diazepam4.3

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Mortality

In-hospital mortality. (NCT00441792)
Timeframe: Duration of hospitalization.

Interventionpercentage of patients dying (Number)
Midazolam36
Etomidate43

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Length of Stay

The primary outcome of the study was hospital length of stay. (NCT00441792)
Timeframe: time in days of hospitalization

Interventiondays (Median)
Midazolam9.5
Etomidate7.3

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Change in Baseline Cortisol

change from baseline cortisol (drawn prior to RSI) to 2nd cortisol level (4-6hrs after RSI, but before stim test) (NCT00462644)
Timeframe: 4-6hr after RSI

Interventionmicrograms/dL (Mean)
Etomidate-12.8
Fentanyl-Midazolam1.1

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Intensive Care Unit (ICU) Length of Stay

ICU length of stay in days (NCT00462644)
Timeframe: time from hospital admission to transfer out of ICU to floor bed

Interventiondays (Mean)
Etomidate8.1
Fentanyl-Midazolam3.0

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Cortisol Level 60 Minutes After Cortisol Stimulating Test (CST)

(NCT00462644)
Timeframe: 60 minutes after administration of cotrosyn

Interventionmicrograms/dL (Mean)
Etomidate22.91
Fentanyl-Midazolam39.09

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Number of Deaths

deaths (NCT00462644)
Timeframe: death in hospital

Interventionparticipants (Number)
Etomidate2
Fentanyl-Midazolam0

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Postintubation Cortisol (Baseline Cortisol Level)

cortisol level after randomization and rapid sequence induction (NCT00462644)
Timeframe: postintubation (baseline cortisol level)

Interventionmicrograms/dL (Mean)
Etomidate18.2
Fentanyl-Midazolam27.9

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Ventilator Days

(NCT00462644)
Timeframe: time from intubation to extubation

Interventiondays (Mean)
Etomidate6.3
Fentanyl-Midazolam1.5

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Hospital Length of Stay

days from admission to hospital discharge (NCT00462644)
Timeframe: time to hospital discharge in days

Interventiondays (Mean)
Etomidate13.9
Fentanyl-Midazolam6.4

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Stage 2A: Accumulation Ratio of Cobimetinib at Steady State

Accumulation Ratio AUC0-24 is ratio of AUC on Day 20: Day 1. (NCT00467779)
Timeframe: Stage 2A: Pre-dose & 0.5, 1, 1.5, 2, 3, 4, 6 hours post-dose on Cycle 1 Day 14, 24 hours post Cycle 1 Day 14 dose (Cycle 1 Day 15), and between Cycle 1 Days 26-28

Interventionratio (Mean)
Stage 2A Cohort 30 - Cobimetinib 100 mg (Expansion) (14/14)2.3

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Stage 2A: Apparent Clearance of Cobimetinib at Steady State

Apparent clearance is the plasma clearance of absorbed drug. (NCT00467779)
Timeframe: Stage 2A: Pre-dose & 0.5, 1, 1.5, 2, 3, 4, 6 hours post-dose on Cycle 1 Day 14, 24 hours post Cycle 1 Day 14 dose (Cycle 1 Day 15), and between Cycle 1 Days 26-28

InterventionL/hr (Mean)
Stage 2A Cohort 30 - Cobimetinib 100 mg (Expansion) (14/14)11.8

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Stage 2A: AUC 0-24/D of Cobimetinib at Steady State

AUC 0-24/D is the dose normalized truncated AUC over a 24-hour sampling interval. (NCT00467779)
Timeframe: Stage 2A: Pre-dose & 0.5, 1, 1.5, 2, 3, 4, 6 hours post-dose on Cycle 1 Day 14, 24 hours post Cycle 1 Day 14 dose (Cycle 1 Day 15), and between Cycle 1 Days 26-28

Interventionh*ng/mL (Mean)
Stage 2A Cohort 30 - Cobimetinib 100 mg (Expansion) (14/14)84.8

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Stage 2A: Cmax of Cobimetinib at Steady State

Cmax is the maximum plasma concentration achieved following the Day 20 dose in Stage 2A. (NCT00467779)
Timeframe: Stage 2A: Pre-dose & 0.5, 1, 1.5, 2, 3, 4, 6 hours post-dose on Cycle 1 Day 14, 24 hours post Cycle 1 Day 14 dose (Cycle 1 Day 15), and between Cycle 1 Days 26-28

Interventionng/mL (Geometric Mean)
Stage 2A Cohort 30 - Cobimetinib 100 mg (Expansion) (14/14)315.0

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Stage 1A: Apparent Clearance of Cobimetinib at Steady State

Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood. Apparent clearance was calculated only for participants who had a quantifiable AUC 0-24 in steady state. (NCT00467779)
Timeframe: Stage 1A: Pre-dose & 0.5, 1, 1.5, 2, 3, 4, 6 hours post-dose on Cycle 1 Day 14, 24, 48, 72 hours post Cycle 1 Day 14 dose (Cycle 1 Day 15, 16, and 17, respectively)

InterventionL/hr (Mean)
Stage 1A Cohort 01A - Cobimetinib 60 mg (14/14)25.1
Stage 1A Cohort 02A - Cobimetinib 80 mg (14/14)14.9
Stage 1A Cohort 03A - Cobimetinib 100 mg (14/14)21.9
Stage 1A Cohort 04A - Cobimetinib 125 mg (14/14)6.9

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Stage 1A: Accumulation Ratio of Cobimetinib at Steady State

Accumulation Ratio: AUC0-24 at steady state divided by AUC0-24 on Cycle 1 Day 1. It was calculated only for participants who had a quantifiable AUC 0-24 at steady state. (NCT00467779)
Timeframe: Stage 1A: Pre-dose & 0.5, 1, 1.5, 2, 3, 4, 6 hours post-dose on Cycle 1 Day 1, 14, 24, 48, 72 hours post Cycle 1 Day 14 dose (Cycle 1 Day 15, 16, and 17, respectively)

Interventionratio (Mean)
Stage 1A Cohort 01A - Cobimetinib 60 mg (14/14)2.32
Stage 1A Cohort 02A - Cobimetinib 80 mg (14/14)3.14
Stage 1A Cohort 03A - Cobimetinib 100 mg (14/14)2.6
Stage 1A Cohort 04A - Cobimetinib 125 mg (14/14)5.15

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Stage 1: Tmax of Cobimetinib at Steady State

Tmax is defined as the time to reach Cmax during stage 1 in steady state. Steady state was reached when overall intake of cobimetinib was in dynamic equilibrium with its elimination. (NCT00467779)
Timeframe: Stage 1: Pre-dose & 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12-18 hours post-dose on Cycle 1 Day 21, 24, 48, and 72 hours post Cycle 1 Day 21 dose (Cycle 1 Day 22, 23, and 24, respectively)

Interventionhours (Median)
Stage 1 Cohort 01 - Cobimetinib 0.05 mg/kg (21/7)4.0
Stage 1 Cohort 02 - Cobimetinib 0.10 mg/kg (21/7)1.0
Stage 1 Cohort 03 - Cobimetinib 0.20 mg/kg (21/7)2.25
Stage 1 Cohort 04 - Cobimetinib 10 mg (21/7)4.0
Stage 1 Cohort 05 - Cobimetinib 20 mg (21/7)3.0
Stage 1 Cohort 06 - Cobimetinib 40 mg (21/7)2.0
Stage 1 Cohort 07 - Cobimetinib 60 mg (21/7)3.0
Stage 1 Cohort 08 - Cobimetinib 80 mg (21/7)2.5

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Stage 2A: Half-Life of Cobimetinib at Steady State

(NCT00467779)
Timeframe: Stage 2A: Pre-dose & 0.5, 1, 1.5, 2, 3, 4, 6 hours post-dose on Cycle 1 Day 14, 24 hours post Cycle 1 Day 14 dose (Cycle 1 Day 15), and between Cycle 1 Days 26-28

Interventionhours (Median)
Stage 2A Cohort 30 - Cobimetinib 100 mg (Expansion) (14/14)42.7

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Stage 2A: Tmax of Cobimetinib at Steady State

Tmax is defined as the time to reach Cmax during stage 2A in steady state. (NCT00467779)
Timeframe: Stage 2A: Pre-dose & 0.5, 1, 1.5, 2, 3, 4, 6 hours post-dose on Cycle 1 Day 14, 24 hours post Cycle 1 Day 14 dose (Cycle 1 Day 15), and between Cycle 1 Days 26-28

Interventionhours (Median)
Stage 2A Cohort 30 - Cobimetinib 100 mg (Expansion) (14/14)3.0

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Stage III: AUC 0-inf of Dextromethorphan

AUC0-inf is AUC from time 0 to infinity and was calculated both in presence Cycle 1 Day 15) and absence (Cycle 1 Day 1) of cobimetinib. (NCT00467779)
Timeframe: Stage III: Predose, 0.5, 1, 1.5, 2, 4, 6, 8, and 24 hours after dextromethorphan administration on Days 1 and 15 of Cycle 1

Interventionh*ng/mL (Geometric Mean)
With cobimetinib - Cycle 1 Day 15 (n=13)Without cobimetinib - Cycle 1 Day1 (n=19)
Stage 3 Cohort 40 - Cobimetinib+Midazolam+Dextromethorphan29.118.9

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Stage III: AUC0-24 of Midazolam

AUC0-24 is the area under the plasma drug concentration curve over a 24-hour sampling interval and was calculated both in the presence (Cycle 1 Day 15) and absence (CXycle 1 Day 1) of cobimetinib. (NCT00467779)
Timeframe: Stage III: Predose, 0.5, 1, 1.5, 2, 4, 6, 8, and 24 hours after dextromethorphan administration on Days 1 and 15 of Cycle 1

Interventionh*ng/mL (Geometric Mean)
With cobimetinib - Cycle 1 Day 15 (n=14)Without cobimetinib - Cycle 1 Day 1 (n=11)
Stage 3 Cohort 40 - Cobimetinib+Midazolam+Dextromethorphan33.033.4

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Stage III: AUC0-inf of Midazolam

AUC0-inf is the AUC from time 0 to infinity and was calculated both in the presence (Cycle 1 Day 15) and absence (Cycle 1 Day 1) of cobimetinib. (NCT00467779)
Timeframe: Stage III: Predose, 0.5, 1, 1.5, 2, 4, 6, 8, and 24 hours after dextromethorphan administration on Days 1 and 15 of Cycle 1

Interventionh*ng/mL (Geometric Mean)
With cobimetinib - Cycle 1 Day 15 (n=17)Without cobimetinib Cycle 1 Day 1 (n=19)
Stage 3 Cohort 40 - Cobimetinib+Midazolam+Dextromethorphan34.935.7

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Stage III: Cmax of Dextromethorphan

Cmax is defined as maximum observed plasma concentration and was determined both in the presence (Cycle 1 Day 15) and absence of cobimetinib (Cycle 1 Day 1). (NCT00467779)
Timeframe: Stage III: Predose, 0.5, 1, 1.5, 2, 4, 6, 8, and 24 hours after dextromethorphan administration on Days 1 and 15 of Cycle 1

Interventionng/mL (Geometric Mean)
With cobimetinib - Cycle 1 Day 15(n=17)Without cobimetinib - Cycle 1 Day 1 (n=20)
Stage 3 Cohort 40 - Cobimetinib+Midazolam+Dextromethorphan3.443.16

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Stage III: Cmax of Midazolam

Cmax is the maximum observed plasma concentration and was calculated both in the presence (Cycle 1 Day 15) and absence (Cycle 1 Day 1) of cobimetinib. (NCT00467779)
Timeframe: Stage III: Predose, 0.5, 1, 1.5, 2, 4, 6, 8, and 24 hours after dextromethorphan administration on Days 1 and 15 of Cycle 1

Interventionng/mL (Geometric Mean)
With cobimetinib - Cycle 1 Day15 (n=17)Without cobimetinib - Cycle 1 Day 1(n=20)
Stage 3 Cohort 40 - Cobimetinib+Midazolam+Dextromethorphan11.510.9

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Stage III: AUC 0-24 of Dextromethorphan

AUC0-24 is the area under the plasma drug concentration curve over a 24-hour sampling interval and was determined both in presence (Cycle 1 Day 15) and absence (Cycle 1 Day 1) of cobimetinib. (NCT00467779)
Timeframe: Stage III: Predose, 0.5, 1, 1.5, 2, 4, 6, 8, and 24 hours after dextromethorphan administration on Days 1 and 15 of Cycle 1

Interventionh*ng/mL (Geometric Mean)
With cobimetinib - Cycle 1 Day 1 (n=17)Without cobimetinib - Cycle 1 Day1 (n=19)
Stage 3 Cohort 40 - Cobimetinib+Midazolam+Dextromethorphan24.825.8

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Stage 1: Time to Maximum Concentration (Tmax) of Cobimetinib at Day 1, Cycle 1

Tmax is defined as the time to reach Cmax during stage 1 at Day 1 Cycle 1. (NCT00467779)
Timeframe: Stage 1: Pre-dose & 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12-18 hours post-dose on Cycle 1 Day 1 and pre-dose on Cycle 1 Day 2

Interventionhours (Median)
Stage 1 Cohort 01 - Cobimetinib 0.05 mg/kg (21/7)2.0
Stage 1 Cohort 02 - Cobimetinib 0.10 mg/kg (21/7)1.0
Stage 1 Cohort 03 - Cobimetinib 0.20 mg/kg (21/7)1.5
Stage 1 Cohort 04 - Cobimetinib 10 mg (21/7)3.0
Stage 1 Cohort 05 - Cobimetinib 20 mg (21/7)4.0
Stage 1 Cohort 06 - Cobimetinib 40 mg (21/7)2.5
Stage 1 Cohort 07 - Cobimetinib 60 mg (21/7)2.0
Stage 1 Cohort 08 - Cobimetinib 80 mg (21/7)2.0

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Stage 1: Maximum Tolerated Dose (MTD) of Cobimetinib in 21/7 Schedule

"AEs were graded according to the NCI-CTCAE v3.0. A DLT was determined from clinical findings during the Study Treatment Period (Cycle 1, Days 1). MTD was defined as the dose at which no DLTs were observed. DLT was defined as either of the following occurring during the Study Treatment Period. The occurrence of a drug-related AE that, in the opinion of the CRC, was of potential clinical significance such that further dose escalation would expose participants in higher dose cohorts to risk of irreversible medical harm or require medical treatment to avoid irreversible medical harm or non-hematologic toxicity~Grade 3 or 4 events, including Grade 3 nausea and/or vomiting and/or Grade 3 diarrhea, despite prophylaxis and/or treatment Hematologic toxicity~Grade 4 thrombocytopenia~Grade 4 neutropenia of greater than or equal to (≥) 4 days' duration~Grade 4 neutropenia of any duration with fever or documented infection" (NCT00467779)
Timeframe: Stage 1: Days 1 to 28 of Cycle 1

Interventionmilligrams (mg) (Number)
Stage 1 All Cohorts (21/7)60

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Stage 1: Maximum Observed Concentration (Cmax) of Cobimetinib at Day 1, Cycle 1

Cmax is defined as the maximum plasma concentration achieved after administration of cobimetinib on Day 1, Cycle 1 in Stage 1 and was measured as nanograms per milliliter (ng/mL). (NCT00467779)
Timeframe: Stage 1: Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12-18 hours post-dose on Cycle 1 Day 1 and pre-dose on Cycle 1 Day 2

Interventionng/mL (Geometric Mean)
Stage 1 Cohort 01 - Cobimetinib 0.05 mg/kg (21/7)4.51
Stage 1 Cohort 02 - Cobimetinib 0.10 mg/kg (21/7)6.92
Stage 1 Cohort 03 - Cobimetinib 0.20 mg/kg (21/7)18.3
Stage 1 Cohort 04 - Cobimetinib 10 mg (21/7)18.8
Stage 1 Cohort 05 - Cobimetinib 20 mg (21/7)30.8
Stage 1 Cohort 06 - Cobimetinib 40 mg (21/7)71.7
Stage 1 Cohort 07 - Cobimetinib 60 mg (21/7)163.0
Stage 1 Cohort 08 - Cobimetinib 80 mg (21/7)261.0

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Stage 1: Half-Life (t1/2) of Cobimetinib at Steady State

t1/2 is the half-life of cobimetinib measured over the terminal phase by noncompartmental analysis in stage 1 in steady state. (NCT00467779)
Timeframe: Stage 1: Pre-dose & 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12-18 hours post-dose on Cycle 1 Day 21, 24, 48, and 72 hours post Cycle 1 Day 21 dose (Cycle 1 Day 22, 23, and 24, respectively)

Interventionhours (Median)
Stage 1 Cohort 01 - Cobimetinib 0.05 mg/kg (21/7)80.0
Stage 1 Cohort 02 - Cobimetinib 0.10 mg/kg (21/7)64.0
Stage 1 Cohort 03 - Cobimetinib 0.20 mg/kg (21/7)47.8
Stage 1 Cohort 04 - Cobimetinib 10 mg (21/7)66.0
Stage 1 Cohort 05 - Cobimetinib 20 mg (21/7)50.5
Stage 1 Cohort 06 - Cobimetinib 40 mg (21/7)41.3
Stage 1 Cohort 07 - Cobimetinib 60 mg (21/7)51.3
Stage 1 Cohort 08 - Cobimetinib 80 mg (21/7)60.0

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Stage 1: Cmax of Cobimetinib at Steady State

Cmax is defined as the maximum plasma concentration achieved after administration of cobimetinib in Stage 1 and was measured at steady state in ng/mL. (NCT00467779)
Timeframe: Stage 1: Pre-dose & 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12-18 hours post-dose on Cycle 1 Day 21, 24, 48, and 72 hours post Cycle 1 Day 21 dose (Cycle 1 Day 22, 23, and 24, respectively)

Interventionng/mL (Mean)
Stage 1 Cohort 01 - Cobimetinib 0.05 mg/kg (21/7)13.5
Stage 1 Cohort 02 - Cobimetinib 0.10 mg/kg (21/7)19.8
Stage 1 Cohort 03 - Cobimetinib 0.20 mg/kg (21/7)28.7
Stage 1 Cohort 04 - Cobimetinib 10 mg (21/7)53.0
Stage 1 Cohort 05 - Cobimetinib 20 mg (21/7)54.7
Stage 1 Cohort 06 - Cobimetinib 40 mg (21/7)341.0
Stage 1 Cohort 07 - Cobimetinib 60 mg (21/7)401.0
Stage 1 Cohort 08 - Cobimetinib 80 mg (21/7)641.0

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Stage 1: AUC 0-24/D of Cobimetinib at Steady State

AUC 0-24/D is the dose normalized truncated AUC over a 24-hour sampling interval. (NCT00467779)
Timeframe: Stage 1: Pre-dose & 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12-18 hours post-dose on Cycle 1 Day 21, 24, 48, and 72 hours post Cycle 1 Day 21 dose (Cycle 1 Day 22, 23, and 24, respectively)

Interventionng*hr/mL/mg (Mean)
Stage 1 Cohort 01 - Cobimetinib 0.05 mg/kg (21/7)62.4
Stage 1 Cohort 02 - Cobimetinib 0.10 mg/kg (21/7)34
Stage 1 Cohort 03 - Cobimetinib 0.20 mg/kg (21/7)28.2
Stage 1 Cohort 04 - Cobimetinib 10 mg (21/7)76.3
Stage 1 Cohort 05 - Cobimetinib 20 mg (21/7)44.3
Stage 1 Cohort 06 - Cobimetinib 40 mg (21/7)134
Stage 1 Cohort 07 - Cobimetinib 60 mg (21/7)104
Stage 1 Cohort 08 - Cobimetinib 80 mg (21/7)132

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Stage 1: AUC 0-24 of Cobimetinib at Steady State

The area under the AUC0-24 for steady state in stage 1 was calculated with the measured data points from the time of administration of cobimetinib up to 24 h after administration by the trapezoidal formula. AUC 0-24 is the truncated AUC over a 24-hour sampling interval. The concentration-time curve is the result of time points of blood sampling and its measured concentration of free cobimetinib in the blood samplings. (NCT00467779)
Timeframe: Stage 1: Pre-dose & 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12-18 hours post-dose on Cycle 1 Day 21, 24, 48, and 72 hours post Cycle 1 Day 21 dose (Cycle 1 Day 22, 23, and 24, respectively)

Interventionh*ng/mL (Mean)
Stage 1 Cohort 01 - Cobimetinib 0.05 mg/kg (21/7)202.0
Stage 1 Cohort 02 - Cobimetinib 0.10 mg/kg (21/7)288.0
Stage 1 Cohort 03 - Cobimetinib 0.20 mg/kg (21/7)411.0
Stage 1 Cohort 04 - Cobimetinib 10 mg (21/7)763.0
Stage 1 Cohort 05 - Cobimetinib 20 mg (21/7)886.0
Stage 1 Cohort 06 - Cobimetinib 40 mg (21/7)5370.0
Stage 1 Cohort 07 - Cobimetinib 60 mg (21/7)6250.0
Stage 1 Cohort 08 - Cobimetinib 80 mg (21/7)10500.0

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Stage 1: Area Under the Plasma Cobimetinib Concentration Curve From Time 0 to 24 Hours (AUC 0-24) Day 1, Cycle 1

The area under the concentrations-time curve (AUC0-24) was calculated with the measured data points from the time of administration of cobimetinib up to 24 h after administration by the trapezoidal formula. AUC 0-24 is the truncated AUC over a 24-hour sampling interval. The concentration-time curve is the result of time points of blood sampling and its measured concentration of free cobimetinib in the blood samples. AUC is measured as hours times nanograms per milliliter (h*ng/mL). (NCT00467779)
Timeframe: Stage 1: Pre-dose & 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12-18 hours post-dose on Cycle 1 Day 1, pre-dose on Cycle 1 Day 2

Interventionh*ng/mL (Geometric Mean)
Stage 1 Cohort 01 - Cobimetinib 0.05 mg/kg (21/7)56.2
Stage 1 Cohort 02 - Cobimetinib 0.10 mg/kg (21/7)68.0
Stage 1 Cohort 03 - Cobimetinib 0.20 mg/kg (21/7)203.0
Stage 1 Cohort 04 - Cobimetinib 10 mg (21/7)242.0
Stage 1 Cohort 05 - Cobimetinib 20 mg (21/7)440.0
Stage 1 Cohort 06 - Cobimetinib 40 mg (21/7)785.0
Stage 1 Cohort 07 - Cobimetinib 60 mg (21/7)1620.0
Stage 1 Cohort 08 - Cobimetinib 80 mg (21/7)3060.0

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Stage 1: Apparent Clearance of Cobimetinib at Steady State

Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood. Apparent clearance was calculated only for participants who had a quantifiable AUC 0-24 in steady state. (NCT00467779)
Timeframe: Stage 1: Pre-dose & 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12-18 hours post-dose on Cycle 1 Day 21, 24, 48, and 72 hours post Cycle 1 Day 21 dose (Cycle 1 Day 22, 23, and 24, respectively)

InterventionLiters per hour (L/hr) (Mean)
Stage 1 Cohort 01 - Cobimetinib 0.05 mg/kg (21/7)22.4
Stage 1 Cohort 02 - Cobimetinib 0.10 mg/kg (21/7)34.0
Stage 1 Cohort 03 - Cobimetinib 0.20 mg/kg (21/7)37.1
Stage 1 Cohort 04 - Cobimetinib 10 mg (21/7)13.5
Stage 1 Cohort 05 - Cobimetinib 20 mg (21/7)22.6
Stage 1 Cohort 06 - Cobimetinib 40 mg (21/7)14.0
Stage 1 Cohort 07 - Cobimetinib 60 mg (21/7)11.8
Stage 1 Cohort 08 - Cobimetinib 80 mg (21/7)11.6

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Stage 1A: AUC 0-24 of Cobimetinib at Cycle 1 Day 1

AUC0-24 for stage 1A was calculated on Day 1 with the measured data points from the time of administration of cobimetinib up to 24 h after administration by the trapezoidal formula. AUC 0-24 is the truncated AUC over a 24-hour sampling interval. The concentration-time curve is the result of time points of blood sampling and its measured concentration of free cobimetinib in the blood samplings. (NCT00467779)
Timeframe: Stage 1A: Pre-dose & 0.5, 1, 1.5, 2, 3, 4, 6 hours post-dose on Cycle 1 Day 1, pre-dose on Cycle 1 Day 2

Interventionh*ng/mL (Mean)
Stage 1A Cohort 01A - Cobimetinib 60 mg (14/14)1140
Stage 1A Cohort 02A - Cobimetinib 80 mg (14/14)2130
Stage 1A Cohort 03A - Cobimetinib 100 mg (14/14)4020
Stage 1A Cohort 04A - Cobimetinib 125 mg (14/14)7190

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Stage 1: Accumulation Ratio of Cobimetinib at Steady State

Accumulation Ratio: AUC0-24 at steady state divided by AUC0-24 on Cycle 1 Day 1. It was calculated only for participants who had a quantifiable AUC 0-24 at steady state. (NCT00467779)
Timeframe: Stage 1: Pre-dose & 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12-18 hours post-dose on Cycle 1 Day 1, Day 21, 24, 48, and 72 hours post Cycle 1 Day 21 dose (Cycle 1 Day 22, 23, and 24, respectively)

Interventionratio (Mean)
Stage 1 Cohort 01 - Cobimetinib 0.05 mg/kg (21/7)3.56
Stage 1 Cohort 02 - Cobimetinib 0.10 mg/kg (21/7)3.66
Stage 1 Cohort 03 - Cobimetinib 0.20 mg/kg (21/7)2.65
Stage 1 Cohort 04 - Cobimetinib 10 mg (21/7)3.23
Stage 1 Cohort 05 - Cobimetinib 20 mg (21/7)2.96
Stage 1 Cohort 06 - Cobimetinib 40 mg (21/7)3.61
Stage 1 Cohort 07 - Cobimetinib 60 mg (21/7)2.87
Stage 1 Cohort 08 - Cobimetinib 80 mg (21/7)3.26

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Stage 1 and 1A: Number of Participants With Dose Limiting Toxicities (DLTs)

"Adverse events (AE) were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) v3.0. DLT was defined as either of the following occurring during the Study Treatment Period. The occurrence of a drug-related AE that, in the opinion of the cohort review committee (CRC), was of potential clinical significance such that further dose escalation would expose participants in higher dose cohorts to risk of irreversible medical harm or require medical treatment to avoid irreversible medical harm or non-hematologic toxicity~Grade 3 or 4 events, including Grade 3 nausea and/or vomiting and/or Grade 3 diarrhea, despite prophylaxis and/or treatment Hematologic toxicity~Grade 4 thrombocytopenia~Grade 4 neutropenia of greater than or equal to (≥) 4 days' duration~Grade 4 neutropenia of any duration with fever or documented infection" (NCT00467779)
Timeframe: Stage 1 and 1A: Days 1 to 28 of Cycle 1

Interventionparticipants (Number)
Stage 1 Cohort 01 - Cobimetinib 0.05 mg/kg (21/7)0
Stage 1 Cohort 02 - Cobimetinib 0.10 mg/kg (21/7)0
Stage 1 Cohort 03 - Cobimetinib 0.20 mg/kg (21/7)0
Stage 1 Cohort 04 - Cobimetinib 10 mg (21/7)0
Stage 1 Cohort 05 - Cobimetinib 20 mg (21/7)0
Stage 1 Cohort 06 - Cobimetinib 40 mg (21/7)1
Stage 1 Cohort 07 - Cobimetinib 60 mg (21/7)1
Stage 1 Cohort 08 - Cobimetinib 80 mg (21/7)2
Stage 1A Cohort 01A - Cobimetinib 60 mg (14/14)0
Stage 1A Cohort 02A - Cobimetinib 80 mg (14/14)0
Stage 1A Cohort 03A - Cobimetinib 100 mg (14/14)0
Stage 1A Cohort 04A - Cobimetinib 125 mg (14/14)2

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Stage 2: AUC 0-24 of Cobimetinib at Steady State

The area under the AUC0-24 for steady state in stage 2 was calculated with the measured data points from the time of administration of cobimetinib up to 24 h after administration by the trapezoidal formula. AUC 0-24 is the truncated AUC over a 24-hour sampling interval. The concentration-time curve is the result of time points of blood sampling and its measured concentration of free cobimetinib in the blood samplings. (NCT00467779)
Timeframe: Stage 2: Pre-dose & 0.5, 1, 1.5, 2, 3, 4, 6 hours post-dose on Cycle 1 Day 21, 24 hours post Cycle 1 Day 21 dose (Cycle 1 Day 22), and between Cycle 1 Days 26-28

Interventionh*ng/mL (Geometric Mean)
Stage 2 Cohort 20 - Cobimetinib 60 mg (Expansion) (21/7)10200.0

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Stage 2: AUC 0-24/D of Cobimetinib at Steady State

AUC 0-24/D is the dose normalized truncated AUC over a 24-hour sampling interval. (NCT00467779)
Timeframe: Stage 2: Pre-dose & 0.5, 1, 1.5, 2, 3, 4, 6 hours post-dose on Cycle 1 Day 21, 24 hours post Cycle 1 Day 21 dose (Cycle 1 Day 22), and between Cycle 1 Days 26-28

Interventionh*ng/mL (Geometric Mean)
Stage 2 Cohort 20 - Cobimetinib 60 mg (Expansion) (21/7)102.0

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Stage 2: Cmax of Cobimetinib at Cycle 1 Day 1

Cmax is defined as the maximum plasma concentration achieved after administration of cobimetinib in Stage 2 and was measured in ng/mL. (NCT00467779)
Timeframe: Stage 2: Pre-dose & 0.5, 1, 1.5, 2, 3, 4, 6 hours post-dose on Cycle 1 Day 1, pre-dose on Cycle 1 Day 2

Interventionng/mL (Geometric Mean)
Stage 2 Cohort 20 - Cobimetinib 60 mg (Expansion) (21/7)184.0

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Stage 2: Tmax of Cobimetinib at Cycle 1 Day 1

Tmax is defined as the time to reach Cmax during stage 2 on Day 1. (NCT00467779)
Timeframe: Stage 2: Pre-dose & 0.5, 1, 1.5, 2, 3, 4, 6 hours post-dose on Cycle 1 Day 1, pre-dose on Cycle 1 Day 2

Interventionhours (Median)
Stage 2 Cohort 20 - Cobimetinib 60 mg (Expansion) (21/7)3.0

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Stage 2: Tmax of Cobimetinib at Steady State

Tmax is defined as the time to reach Cmax during stage 2 in steady state. (NCT00467779)
Timeframe: Stage 2: Pre-dose & 0.5, 1, 1.5, 2, 3, 4, 6 hours post-dose on Cycle 1 Day 21, 24 hours post Cycle 1 Day 21 dose (Cycle 1 Day 22), and between Cycle 1 Days 26-28

Interventionhours (Median)
Stage 2 Cohort 20 - Cobimetinib 60 mg (Expansion) (21/7)4.0

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Stage 1A: AUC 0-24/D of Cobimetinib at Steady State

AUC 0-24/D is the dose normalized truncated AUC over a 24-hour sampling interval. (NCT00467779)
Timeframe: Stage 1A: Pre-dose & 0.5, 1, 1.5, 2, 3, 4, 6 hours post-dose on Cycle 1 Day 14, 24, 48, 72 hours post Cycle 1 Day 14 dose (Cycle 1 Day 15, 16, and 17, respectively)

Interventionng*hr/mL/mg (Mean)
Stage 1A Cohort 01A - Cobimetinib 60 mg (14/14)49.8
Stage 1A Cohort 02A - Cobimetinib 80 mg (14/14)84.2
Stage 1A Cohort 03A - Cobimetinib 100 mg (14/14)115.0
Stage 1A Cohort 04A - Cobimetinib 125 mg (14/14)172.0

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Stage 2:AUC 0-24 of Cobimetinib at Cycle 1 Day 1

The area under the AUC0-24 on Day 1 in stage 2 was calculated with the measured data points from the time of administration of cobimetinib up to 24 h after administration by the trapezoidal formula. AUC 0-24 is the truncated AUC over a 24-hour sampling interval. The concentration-time curve is the result of time points of blood sampling and its measured concentration of free cobimetinib in the blood samplings. (NCT00467779)
Timeframe: Stage 2: Pre-dose & 0.5, 1, 1.5, 2, 3, 4, 6 hours post-dose on Cycle 1 Day 1, pre-dose on Cycle 1 Day 2

Interventionh*ng/mL (Geometric Mean)
Stage 2 Cohort 20 - Cobimetinib 60 mg (Expansion) (21/7)3060.0

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Stage 1A: AUC 0-24 of Cobimetinib at Steady State

The area under the AUC0-24 for steady state in stage 1A was calculated with the measured data points from the time of administration of cobimetinib up to 24 h after administration by the trapezoidal formula. AUC 0-24 is the truncated AUC over a 24-hour sampling interval. The concentration-time curve is the result of time points of blood sampling and its measured concentration of free cobimetinib in the blood samplings. (NCT00467779)
Timeframe: Stage 1A: Pre-dose & 0.5, 1, 1.5, 2, 3, 4, 6 hours post-dose on Cycle 1 Day 14, 24, 48, 72 hours post Cycle 1 Day 14 dose (Cycle 1 Day 15, 16, and 17, respectively)

Interventionh*ng/mL (Mean)
Stage 1A Cohort 01A - Cobimetinib 60 mg (14/14)2990.0
Stage 1A Cohort 02A - Cobimetinib 80 mg (14/14)6740.0
Stage 1A Cohort 03A - Cobimetinib 100 mg (14/14)11500.0
Stage 1A Cohort 04A - Cobimetinib 125 mg (14/14)21500.0

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Stage 2: Apparent Clearance of Cobimetinib at Steady State

Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood. Apparent clearance was calculated only for participants who had a quantifiable AUC 0-24 in steady state. (NCT00467779)
Timeframe: Stage 2: Pre-dose & 0.5, 1, 1.5, 2, 3, 4, 6 hours post-dose on Cycle 1 Day 21, 24 hours post Cycle 1 Day 21 dose (Cycle 1 Day 22), and between Cycle 1 Days 26-28

InterventionL/hr (Mean)
Stage 2 Cohort 20 - Cobimetinib 60 mg (Expansion) (21/7)9.8

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Stage 2:Half-Life of Cobimetinib at Steady State

T1/2 half-life of cobimetinib measured over the terminal phase by noncompartmental analysis. (NCT00467779)
Timeframe: Stage 2: Pre-dose & 0.5, 1, 1.5, 2, 3, 4, 6 hours post-dose on Cycle 1 Day 21, 24 hours post Cycle 1 Day 21 dose (Cycle 1 Day 22), and between Cycle 1 Days 26-28

Interventionhours (Median)
Stage 2 Cohort 20 - Cobimetinib 60 mg (Expansion) (21/7)53.4

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Stage 1A: Cmax of Cobimetinib at Cycle 1 Day 1

Cmax is defined as the maximum plasma concentration achieved after administration of cobimetinib on on Day 1 in Stage 1A and was measured as ng/mL. (NCT00467779)
Timeframe: Stage 1A: Pre-dose & 0.5, 1, 1.5, 2, 3, 4, 6 hours post-dose on Cycle 1 Day 1, pre-dose on Cycle 1 Day 2

Interventionng/mL (Mean)
Stage 1A Cohort 01A - Cobimetinib 60 mg (14/14)78.4
Stage 1A Cohort 02A - Cobimetinib 80 mg (14/14)167.0
Stage 1A Cohort 03A - Cobimetinib 100 mg (14/14)258.0
Stage 1A Cohort 04A - Cobimetinib 125 mg (14/14)533.0

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Stage 1A: Cmax of Cobimetinib at Steady State

Cmax is defined as the maximum plasma concentration achieved after administration of cobimetinib in Stage 1A and was measured in steady state as ng/mL. (NCT00467779)
Timeframe: Stage 1A: Pre-dose & 0.5, 1, 1.5, 2, 3, 4, 6 hours post-dose on Cycle 1 Day 14, 24, 48, 72 hours post Cycle 1 Day 14 dose (Cycle 1 Day 15, 16, and 17, respectively)

Interventionng/mL (Mean)
Stage 1A Cohort 01A - Cobimetinib 60 mg (14/14)180.0
Stage 1A Cohort 02A - Cobimetinib 80 mg (14/14)494.0
Stage 1A Cohort 03A - Cobimetinib 100 mg (14/14)640.0
Stage 1A Cohort 04A - Cobimetinib 125 mg (14/14)1160.0

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Stage 1A: MTD of Cobimetinib in 14/14 Schedule

"AEs were graded according to NCI-CTCAE v3.0. A DLT was the basis for determining MTD in Stage 1A participants. The participants of Stage 1A are dose-escalation cohorts, starting at the MTD of the 21/7 schedule, were treated on a 14/14 schedule to determine the MTD. A DLT was defined as either of the following occurring during the Study Treatment Period:~Occurrence of a drug-related AE that, in the opinion of the CRC, was of potential clinical significance such that further dose escalation would expose participants to risk of irreversible medical harm; Nonhematologic toxicity: Grade 3 or 4 events, including Grade 3 nausea and/or vomiting and/or Grade 3 diarrhea, despite prophylaxis and/or treatment; Hematologic toxicity: Grade 4 thrombocytopenia. Grade 4 neutropenia of more than 4 days' duration; Grade 4 neutropenia of any duration with fever or documented infection. AEs (Grade 3 or higher) for which a clinical cause unrelated to cobimetinib was evident was not considered DLTs." (NCT00467779)
Timeframe: Stage 1A: Days 1 to 28 of Cycle 1

Interventionmg (Number)
Stage 1A - All Cohorts (14/14)100

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Stage 1A: t1/2 of Cobimetinib at Steady State

t1/2 is the half-life of cobimetinib measured over the terminal phase by noncompartmental analysis in stage 1A in steady state. (NCT00467779)
Timeframe: Stage 1A: Pre-dose & 0.5, 1, 1.5, 2, 3, 4, 6 hours post-dose on Cycle 1 Day 14, 24, 48, 72 hours post Cycle 1 Day 14 dose (Cycle 1 Day 15, 16, and 17, respectively)

Interventionhours (Median)
Stage 1A Cohort 01A - Cobimetinib 60 mg (14/14)59.4
Stage 1A Cohort 02A - Cobimetinib 80 mg (14/14)44.1
Stage 1A Cohort 03A - Cobimetinib 100 mg (14/14)51.6
Stage 1A Cohort 04A - Cobimetinib 125 mg (14/14)47.7

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Stage 1A: Tmax of Cobimetinib at Cycle 1 Day 1

Tmax is defined as the time to reach Cmax during stage 1A at Day 1. (NCT00467779)
Timeframe: Stage 1A: Pre-dose & 0.5, 1, 1.5, 2, 3, 4, 6 hours post-dose on Cycle 1 Day 1, pre-dose on Cycle 1 Day 2

Interventionhours (Median)
Stage 1A Cohort 01A - Cobimetinib 60 mg (14/14)3.0
Stage 1A Cohort 02A - Cobimetinib 80 mg (14/14)4.0
Stage 1A Cohort 03A - Cobimetinib 100 mg (14/14)3.5
Stage 1A Cohort 04A - Cobimetinib 125 mg (14/14)2.5

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Stage 1A: Tmax of Cobimetinib at Steady State

Tmax is defined as the time to reach Cmax during stage 1A in steady state. (NCT00467779)
Timeframe: Stage 1A: Pre-dose & 0.5, 1, 1.5, 2, 3, 4, 6 hours post-dose on Cycle 1 Day 14, 24, 48, 72 hours post Cycle 1 Day 14 dose (Cycle 1 Day 15, 16, and 17, respectively)

Interventionhours (Median)
Stage 1A Cohort 01A - Cobimetinib 60 mg (14/14)2.0
Stage 1A Cohort 02A - Cobimetinib 80 mg (14/14)2.0
Stage 1A Cohort 03A - Cobimetinib 100 mg (14/14)3
Stage 1A Cohort 04A - Cobimetinib 125 mg (14/14)6

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Stage 2: Accumulation Ratio of Cobimetinib at Steady State

Accumulation ratio is AUC0-24 at steady state divided by AUC0-24 on Cycle 1 Day 1. It was calculated only for participants who had a quantifiable AUC 0-24 at steady state. (NCT00467779)
Timeframe: Stage 2: Pre-dose & 0.5, 1, 1.5, 2, 3, 4, 6 hours post-dose on Cycle 1 Day 21, 24 hours post Cycle 1 Day 21 dose (Cycle 1 Day 22), and between Cycle 1 Days 26-28

Interventionratio (Geometric Mean)
Stage 2 Cohort 20 - Cobimetinib 60 mg (Expansion) (21/7)2.5

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Patient Anxiety at 60 and 120 Minutes

A 10-point visual analog scale (VAS) was used to measure anxiety. The patients marked on the scale their feeling of anxiety. The lowest value possible was 0 (no anxiety) and the highest value possible was 10 (highest possible anxiety). (NCT00578214)
Timeframe: 60 and 120 minutes after drug administration

,,
Interventionunits on a scale (Mean)
60 min patient anxiety120 min patient anxiety
Placebo0.80.4
Prospective Midazolam1.00.8
Randomized Midazolam0.10.2

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Patient Cognitive Function at Baseline and 60 Minutes

Cognitive function was measured by the Mini-Mental State Examination (MMSE), a brief 30 point questionnaire test. The scores can range from 0 (low cognitive function) to 30 (high cognitive function). (NCT00578214)
Timeframe: baseline (prior to drug administration) and 60 minutes after drug administration

,,
Interventionunits on a scale (Mean)
Baseline Cognitive Function60 min Cognitive Function
Placebo29.329.4
Prospective Midazolam29.224.3
Randomized Midazolam28.922.9

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Heart Rate at 60 Minutes

(NCT00578214)
Timeframe: 60 minutes after drug administration

Interventionheart beats per minute (Mean)
Randomized Midazolam60.3
Placebo61.4
Prospective Midazolam69.6

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Patient Alertness at Baseline

A 10-point visual analog scale (VAS) was used to measure alertness. The patients marked on the scale their feeling of alertness. The lowest value possible was 0 (awake) and the highest value possible was 10 (barely awake). (NCT00578214)
Timeframe: Baseline (prior to drug administration)

Interventionunits on a scale (Mean)
Randomized Midazolam0.2
Placebo0.2
Prospective Midazolam0.2

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Patient Anxiety at Baseline

A 10-point visual analog scale (VAS) was used to measure anxiety. The patients marked on the scale their feeling of anxiety. The lowest value possible was 0 (no anxiety) and the highest value possible was 10 (highest possible anxiety). (NCT00578214)
Timeframe: Baseline (prior to drug administration)

Interventionunits on a scale (Mean)
Randomized Midazolam1.3
Placebo1.4
Prospective Midazolam3.4

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Patient Cognitive Function at 120 Minutes

Cognitive function was measured by the Mini-Mental State Examination (MMSE), a brief 30 point questionnaire test. The scores can range from 0 (low cognitive function) to 30 (high cognitive function). (NCT00578214)
Timeframe: 120 minutes after drug administration

Interventionunits on a scale (Mean)
Randomized Midazolam26.0
Placebo29.2
Prospective Midazolam27.5

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Pulse Oximetry at 30 Minutes

Pulse oximetry measures the oxygenation of a patient's hemoglobin. A sensor is placed on the patient's finger. Light at red and infrared wavelengths is passed sequentially through the patient to a photodetector. The changing absorbance at each of the two wavelengths is measured, allowing determination of the absorbance. The color of the blood provides a measure of oxygenation (the percentage of hemoglobin molecules bound with oxygen molecules). A healthy young person will probably have an oxygen saturation of 95-99%. (NCT00578214)
Timeframe: 30 minutes after drug administration

Interventionpercentage of oxygenation (Mean)
Randomized Midazolam94.5
Placebo95.6
Prospective Midazolam95.6

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Pulse Oximetry at 60 Minutes

Pulse oximetry measures the oxygenation of a patient's hemoglobin. A sensor is placed on the patient's finger. Light at red and infrared wavelengths is passed sequentially through the patient to a photodetector. The changing absorbance at each of the two wavelengths is measured, allowing determination of the absorbance. The color of the blood provides a measure of oxygenation (the percentage of hemoglobin molecules bound with oxygen molecules). A healthy young person will probably have an oxygen saturation of 95-99%. (NCT00578214)
Timeframe: 60 minutes after drug administration

Interventionpercentage of oxygenation (Mean)
Randomized Midazolam94.5
Placebo96.4
Prospective Midazolam95.5

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Heart Rate at 30 Minutes

(NCT00578214)
Timeframe: 30 minutes after drug administration

Interventionheart beats per minute (Mean)
Randomized Midazolam61.7
Placebo64.3
Prospective Midazolam72.1

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Respiratory Rate at 60 Minutes

(NCT00578214)
Timeframe: 60 minutes after drug administration

Interventionbreaths per minute (Mean)
Randomized Midazolam20.6
Placebo16.3
Prospective Midazolam16.8

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Blood Pressure at 30 Minutes

(NCT00578214)
Timeframe: 30 minutes after drug administration

,,
Interventionmm Hg (Mean)
30 min Systolic Blood Pressure30 min Diastolic Blood Pressure
Placebo125.968.4
Prospective Midazolam118.563.2
Randomized Midazolam121.467.1

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Blood Pressure at 60 Minutes

(NCT00578214)
Timeframe: 60 minutes after drug administration

,,
Interventionmm Hg (Mean)
60 min systolic blood pressure60 min diastolic blood pressure
Placebo131.969.5
Prospective Midazolam113.561.5
Randomized Midazolam120.165.3

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Patient Alertness at 60 and 120 Minutes

A 10-point visual analog scale (VAS) was used to measure alertness. The patients marked on the scale their feeling of alertness. The lowest value possible was 0 (awake) and the highest value possible was 10 (barely awake). (NCT00578214)
Timeframe: 60 and 120 minutes after drug administration

,,
Interventionunits on a scale (Mean)
60 min patient alertness120 min patient alertness
Placebo0.70.5
Prospective Midazolam5.13.4
Randomized Midazolam3.72.1

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Respiratory Rate at 30 Minutes

(NCT00578214)
Timeframe: 30 minutes after drug administration

Interventionbreaths per minute (Mean)
Randomized Midazolam19.4
Placebo16.1
Prospective Midazolam16.2

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Post Anesthesia Care Unit (PACU) IV Fluid

Total IV fluid per kg in PACU (NCT00581139)
Timeframe: Post Anesthesia Care Unit up to 2 hours

InterventionmL/Kg (Mean)
Standard of Care13.18
Pre-medication16.85
Parental Presence During Induction of Anesthesia18.78
Parental Presence During Induction of Anesthesia PLUS Premedic22.21

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Visual Analogue Pain Scale (VAS) 24 Hour After Surgery

"Parent-ranted child pain on the Visual Analogue Scale. The VAS for pain is a unidimensional measure of pain presented in a horizontal line from 0-100. A higher score indicates greater pain intensity.~0-4= no pain/anxiety, 5-44= mild pain/anxiety, 45-74 = moderate pain/anxiety, 75-100 = severe pain/anxiety." (NCT00581139)
Timeframe: 24 Hours after surgery

InterventionScore on Visual Analogue Scale (Mean)
Standard of Care34.13
Pre-medication35.93
Parental Presence During Induction of Anesthesia38.30
Parental Presence During Induction of Anesthesia PLUS Premedic47.02

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Percentage of Children Not Exhibiting Negative Behaviors, Fear, or Anxiety (Perfect Induction, 0)

"A total score is the number of categories checked (1-10). A perfect induction is when a patient does not exhibit negative behaviors, fear, or anxiety. A perfect score would be 0.~icc 1 = Crying, tears in eyes~icc 2 = Turns head away from mask~icc 3 = Verbal refusal, says no~icc 4 = Verbalization indicating fear or worry, Where's mommy? or Will it hurt?~icc 5 = Pushes mask away with hands, pushes nurse/anesthesiologist with hands/feet~icc 6 = Covers mouth/nose with hands/arms or buries face~icc 7 = Hysterical crying, may scream~icc8 = Kicks/flails legs/arms, arches back, and/or general struggling~icc9 = Requires physical restraint~icc10 = Complete passivity either rigid or limp~icc 0 = Perfect induction" (NCT00581139)
Timeframe: Induction, up to 10 minutes

InterventionPercentage of Participants (Number)
Standard of Care68
Pre-medication83
Parental Presence During Induction of Anesthesia62
Parental Presence During Induction of Anesthesia PLUS Premedic86

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Percentage of Children Arriving to PACU in Deep Sleep

Whether child arrived to PACU awake Emergence of 2 // whether child arrived to PACU in deep sleep (NCT00581139)
Timeframe: Arrival at PACU, after surgery up to 20 minutes

InterventionPercentage of Participants (Number)
Standard of Care45
Pre-medication68
Parental Presence During Induction of Anesthesia46
Parental Presence During Induction of Anesthesia PLUS Premedic67

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Percentage of Children Arriving to PACU Awake

Whether child arrived to PACU awake Emergence of 1 // whether child arrived to PACU awake (NCT00581139)
Timeframe: Arrival at PACU, after surgery up to 20 minutes

InterventionPercentage of participants (Number)
Standard of Care55
Pre-medication32
Parental Presence During Induction of Anesthesia32
Parental Presence During Induction of Anesthesia PLUS Premedic33

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Percent of Children Crying During Induction

Children who were crying/ had tears in their eyes during induction. (NCT00581139)
Timeframe: Induction, up to 10 minutes

InterventionPercentage of Participants (Number)
Standard of Care32
Pre-medication17
Parental Presence During Induction of Anesthesia38
Parental Presence During Induction of Anesthesia PLUS Premedic14

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Modified Yale Preoperative Anxiety Scale

"The Modified Yale Preoperative Anxiety Scale (mYPAS) is the current criterion standard for assessing child anxiety during induction of anesthesia and has been used in >100 studies. This observational instrument covers 5 items and is typically administered at 4 perioperative time points. Minimum value is 23.33 and maximum value is 100. Scores below 30 are considered low anxiety. Score of 30 or more is considered high anxiety." (NCT00581139)
Timeframe: Day of surgery

InterventionScore on mYPAS scale (Mean)
Standard of Care41.59
Pre-medication37.44
Parental Presence During Induction of Anesthesia46.17
Parental Presence During Induction of Anesthesia PLUS Premedic33.65

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Heart Rate in the General Clinical Research Unit (GCRC)

Heart rate was measured in the GCRC by the nurse hours 0 through 6 after Surgery (NCT00581139)
Timeframe: Hour 0-6 after surgery

Interventionbeats per minute (Mean)
Standard of Care96.75
Pre-medication95.13
Parental Presence During Induction of Anesthesia97.39
Parental Presence During Induction of Anesthesia PLUS Premedic104.55

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BIS-Index Awake and 3 Sedation Levels (RS 2/3/4)

BIS-Index is a dimensionless value ranging from 0-100, indicating fully awake at 100 and a flat-line electroencephalogram at 0. Standard anesthesia creates a BIS-Index range 40-60. The scale is ordinal, not interval. BIS Index is calculated from the EEG by a proprietary algorithm (Aspect Medical Inc.) (NCT00641563)
Timeframe: awake and 3 sedation levels (RS 2/3/4) 20 min each

,
InterventionUnits on a scale (Mean)
awakesedation level RS 2sedation level RS 3sedation level RS 4
Dex/Remi92.584.569.551.4
Mida/Remi93.784.773.268.9

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Dynamic Eye Movement Measures

Change in Eye Movements Parameters (NCT00646646)
Timeframe: baseline to Sedation State (approx. 1 hr)

Intervention(degrees/second) (Mean)
Dexmedetomidine-25
Midazolam-115
Propofol-90
Placebo10

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Number of Subjects Who Received Rescue Medication for Sedation (Midazolam) and Analgesics (Fentanyl)

Number of subjects who received rescue medication for Sedation (Midazolam) and analgesics (Fentanyl) while intubated during Treatment Period (NCT00652028)
Timeframe: During the treatment period (Approximately 24 hours)

,,,
Interventionparticipants (Number)
MidazolamFentanyl
Dose Level 1712
Dose Level 2710
Dose Level 3513
Dose Level 438

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Volume of Steady State Distribution (Vss)

Volume of steady state distribution (Vss) for Dexmedetomidine (NCT00652028)
Timeframe: ≤30 min prior to start of loading dose (LD); 5 min before finishing LD; 0.5,1,2 & 4-6 hrs after start of maintenance infusion (MI); 30 min prior to end of MI (within 24 hrs of start of MI); 10 min after end of MI and 0.5,1,2,4 & 10 hrs after end of MI.

InterventionLitre (Mean)
Dose Level 156.808
Dose Level 235.246
Dose Level 332.789
Dose Level 443.652

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Terminal Elimination Half-life (t1/2)

Terminal elimination half-life (t1/2) for Dexmedetomidine (NCT00652028)
Timeframe: ≤30 min prior to start of loading dose (LD); 5 min before finishing LD; 0.5,1,2 & 4-6 hrs after start of maintenance infusion (MI); 30 min prior to end of MI (within 24 hrs of start of MI); 10 min after end of MI and 0.5,1,2,4 & 10 hrs after end of MI.

Interventionhour (Mean)
Dose Level 11.546
Dose Level 21.743
Dose Level 32.045
Dose Level 42.145

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Clearance (CL)

Clearance (CL) for Dexmedetomidine (NCT00652028)
Timeframe: ≤30 min prior to start of loading dose (LD); 5 min before finishing LD; 0.5,1,2 & 4-6 hrs after start of maintenance infusion (MI); 30 min prior to end of MI (within 24 hrs of start of MI); 10 min after end of MI and 0.5,1,2,4 & 10 hrs after end of MI.

InterventionLitre/hour (Mean)
Dose Level 132.208
Dose Level 220.268
Dose Level 318.565
Dose Level 422.199

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Plasma Concentration at Steady State (Css)

Plasma concentration at steady state (Css) for Dexmedetomidine (NCT00652028)
Timeframe: ≤30 min prior to start of loading dose (LD); 5 min before finishing LD; 0.5,1,2 & 4-6 hrs after start of maintenance infusion (MI); 30 min prior to end of MI (within 24 hrs of start of MI); 10 min after end of MI and 0.5,1,2,4 & 10 hrs after end of MI.

Interventionpicograms per milliliter (Mean)
Dose Level 1402.026
Dose Level 2539.848
Dose Level 31347.284
Dose Level 42827.144

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Observed Peak Plasma Concentration

Observed peak plasma concentration (Cmax) for Dexmedetomidine (NCT00652028)
Timeframe: ≤30 min prior to start of the loading dose (LD); 5 min before finishing the LD; 0.5,1,2&4 to 6 hrs after start of maintenance infusion (MI); 30 min prior to end of MI (24 hrs of start of MI); 10 min after end of MI and 0.5,1,2,4&10 hrs after end of MI.

Interventionpicograms per milliliter (Mean)
Dose Level 1480.437
Dose Level 2847.691
Dose Level 33385.569
Dose Level 43090.939

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Level of Sedation Based on Average Ramsay Sedation Scale (RSS) Score

"RSS Score range from 1 to 6:~Patient is anxious and agitated or restless, or both.~Patient is cooperative, orientated and tranquil.~Patient responds to command only.~Patient exhibits brisk response to light glabellar (between the eyebrows) tap or loud auditory stimulus.~Patient exhibits a sluggish response to light glabellar tap or loud auditory stimulus.~Patient exhibits no response to stimulus." (NCT00652028)
Timeframe: Prior to loading (Baseline), 5 and 10 min during the load, at start of maintenance infusion and every 15 min for 1 hour, hourly during the maintenance period, before and within 5 min after midazolam or fentanyl dose during the dexmedetomidine infusion.

Interventionunits on a scale (Mean)
Dose Level 12.4
Dose Level 22.8
Dose Level 32.4
Dose Level 44.0

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Area Under the Concentration-time Curve From Time Zero to the Time of the Last Measurable Concentration (AUC0-t)

Area under the concentration-time curve from time zero to the time of the last measurable concentration (AUC0-t) for Dexmedetomidine (NCT00652028)
Timeframe: ≤30 min prior to start of loading dose (LD); 5 min before finishing LD; 0.5,1,2 & 4-6 hrs after start of maintenance infusion (MI); 30 min prior to end of MI (within 24 hrs of start of MI); 10 min after end of MI and 0.5,1,2,4 & 10 hrs after end of MI.

Interventionpicograms*hr/mL (Mean)
Dose Level 12681.332
Dose Level 26460.576
Dose Level 316992.540
Dose Level 428531.864

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Area Under the Concentration-time Curve From Time Zero to the Time Infinity (AUC0-∞)

Area under the concentration-time curve from time zero to the time infinity (AUC0-∞) for Dexmedetomidine (NCT00652028)
Timeframe: ≤30 min prior to start of the loading dose (LD); 5 min before finishing the LD; 0.5,1,2&4 to 6 hrs after start of maintenance infusion (MI); 30 min prior to end of MI (24 hrs of start of MI); 10 min after end of MI and 0.5,1,2,4&10 hrs after end of MI.

Interventionpicograms*hr/mL (Mean)
Dose Level 13153.518
Dose Level 26673.163
Dose Level 317300.539
Dose Level 428970.541

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Time From Study Drug Administration to Start of Procedure

(NCT00675909)
Timeframe: Time from study drug administration to start of procedure up to 68 minutes

Interventionminutes (Median)
Oral Midazolam34
Intranasal Midazolam28
Buccal Midazolam32

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Duration of Procedure

(NCT00675909)
Timeframe: Duration of procedure up to 40 minutes

Interventionminutes (Median)
Oral Midazolam12
Intranasal Midazolam12
Buccal Midazolam10

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Nurse Rating of Sedation

Range is 0-10. Higher is associated with nurse impression that sedation is better. (NCT00675909)
Timeframe: After the procedure nurse was asked about their impression of the level of sedation.

Interventionunits on a scale (Median)
Oral Midazolam6.8
Intranasal Midazolam7.7
Buccal Midazolam7.6

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Physician Rating of Sedation

Range is 0-10. Higher is associated with physician impression that sedation is better. (NCT00675909)
Timeframe: Physician was asked after the procedure was done about their impression of sedation.

Interventionunits on a scale (Median)
Oral Midazolam6.7
Intranasal Midazolam8.1
Buccal Midazolam7.1

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Change in CHEOPS Score Measured Level of Sedation From Baseline (Presentation in ED, Before Sedation) to Start of Procedure (Laceration Repair).

"Modified CHEOPS (Children's Hospital of Eastern Ontario Pain Scale)assessment used to score sedation.~Scale range is 0-10 with 0 meaning no pain and 4 or greater meaning pain. Scale is determined by assessing Facial Expression (0-2), Cry (0-3), Child Verbal (0-2) and Movements (0-3)." (NCT00675909)
Timeframe: Baseline (presentation, before sedation) in ED to start of procedure (laceration repair).

InterventionScores on a scale (Median)
Oral Midazolam2
Intranasal Midazolam2
Buccal Midazolam1

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Plasma AUC Ratio of Day 1 and Day 8

"Assessment of the drug-drug interactions of Proellex® (CDB-4124) with cytochrome P450 isoenzymes CYP1A2, 2C9, 2C19, 2D6, and 3A4 in healthy female subjects administered 50 mg Proellex® once daily (QD). The Day 8 AUC was compared to the Day 1 AUC to determine inhibition.~For CYP1A2 the plasma paraxanthine/caffeine MR ratio (metabolic ratio) was used. For CYP2D6 the MR ratio of dextromethorphan/dextrorphan was used." (NCT00741468)
Timeframe: 8 days

InterventionRatio of geometric means Day 8 to Day 1 (Mean)
CYP1A21.093
CYP2C91.029
CYP2C191.104
CYP2D61.914
CYP3A42.245

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Duration of Study Drug Administration

(NCT00744380)
Timeframe: Duration of ICU stay, up to 24 weeks

Interventiondays (Median)
Midazolam3
Dexmedetomidine3.5

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ICU Experiences by Administering ICU Stressful Experiences Questionnaire (ICU-SEQ)

"The ICU-SEQ assesses patient recall of their ICU experience. The ICU-SEQ assesses both psychological (e.g. fearfulness, anxiety) and physical (e.g. pain, difficulty breathing) perceptions of ICU patients who have received mechanical ventilation. It consists of 29 potentially stressful experiences with seven items specifically addressing the endotracheal tube. The extent that patients are bothered by each item is scored on a five point scale: 0 = not at all, 1 = a little bit, 2 = moderately, 3 = quite a bit, and 4 = extremely. The cumulative score is an integer interpreted as interval data with higher scores indicating greater stressful experiences associated with the ICU. The minimum score is 0 and the maximum score possible is 116." (NCT00744380)
Timeframe: Duration of hospital stay, up to 24 weeks

Interventionunits on a scale (Median)
Midazolam8.5
Dexmedetomidine18.5

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The Quality of Sedation (Assessed by the Riker Sedation-Agitation Score) and Analgesia (Assessed by the Pain Assessment Behavioral Score)

The Riker sedation-agitation score (range 1-7) and PABS (range 0-10) are assessed hourly by the bedside nurse. Riker scores assess restlessness and cooperation. Riker scores of 5 - 7 indicate agitation, 3 - 4 represent adequate sedation and 1 - 2 represent excessive sedation. PABS assessments include domains of restlessness, muscle tone, vocalization, consolability, and facial expressions. PABS assessments of 0 represent no pain, 1 - 3 represent mild pain, 4 - 6 represent moderate pain, and ≥ 7 represent severe pain. (NCT00744380)
Timeframe: Duration of ICU stay, for up to 24 weeks

,
Interventionpercentage of assessments while on study (Number)
Riker score 1-2 while on study drugRiker score 3-4 while on study drugRiker score 5-7 while on study drugPain score > 3 while on study drug
Dexmedetomidine4.171.227.121.4
Midazolam5.484.16.613.3

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Hospital Anxiety and Depression Scale (HADS) Score

The HADS consists of 14 questions, seven for anxiety and seven for depression. Each item is scored from 0 to 3, with a cut-off cumulative score of 11 for both subscales indicative of anxiety or depression. This scoring tool has been used for 30 years, possesses excellent reliability and validity, and avoids reliance conditions that are also common somatic symptoms of illness such fatigue, insomnia, and hypersomnia. The maximum score for each subscale is 21 with a maximum possible cumulative score of 42. The minimum score for each subscale is 0. The minimum cumulative score is 0 (NCT00744380)
Timeframe: Duration of hospital stay, up to 24 weeks

,
Interventionunits on a scale (Mean)
AnxietyDepression
Dexmedetomidine64
Midazolam36

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Time From Study Drug Initiation to Tracheal Extubation

(NCT00744380)
Timeframe: Duration of ICU stay, for up to 24 weeks

Interventiondays (Median)
Midazolam2.9
Dexmedetomidine3.4

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Manifestations of Acute Stress Disorder by Impact of Event Scale - Revised (IES-R)

"The IES-R evaluates subjective distress caused by traumatic events and assesses manifestations of post-traumatic stress disorder (PTSD) or acute stress disorder. It is not diagnostic but possesses excellent reliability and validity for manifestations of PTSD. The IES-R has three subscales (eight items on intrusion, eight items on avoidance, and six items on hyperarousal). Each item is scored on a four point scale: 0 = not at all, 1 = a little bit, 2 = moderately often, 3 = quite a bit, and 4 = extremely often. The total score of each subscale may be averaged and a cumulative score of 30 is indicative of the presence of PTSD. The maximum score for each subscale is 32 for intrusion, 32 for avoidance, and 24 for hyperarousal. The minimum cumulative score is 0 and the maximum cumulative score possible is 88." (NCT00744380)
Timeframe: Duration of hospital stay, up to 24 weeks

Interventionunits on a scale (Mean)
Midazolam13
Dexmedetomidine36

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Cumulative Doses of Conventional Sedatives and Analgesics

(NCT00744380)
Timeframe: Duration of ICU stay, for up to 24 weeks

,
Interventionmg (Median)
Open-label midazolam while on study drugAll midazolam whil eon study drugAll fentanyl while on study drug
Dexmedetomidine65.365.34.1
Midazolam29126.95.4

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Quick Inventory of Depressive Symptomatology - Self Report (QIDS-SR)

Self-report questionnaire measuring depressive symptoms. Each item is rated 0 (no depression) to 3 (severe depression). The total score ranges from 0-27. (NCT00749203)
Timeframe: 24 hours after first infusion

Interventionunits on a scale (Mean)
Ketamine12.4
Midazolam11.3

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Montgomery-Asberg Depression Rating Scale (MADRS)

Clinician-administered questionnaire measuring depressive symptoms. The MADRS-S has 10-items which are based on mood symptoms over the past 7 days. Each items is scored 0 (normal) to 6 (severe depression) with overall score ranges from 0 (normal) to 60 (severe depression). Mean difference between baseline and 2 weeks. (NCT00749203)
Timeframe: 24 hours after first infusion

Interventionunits on a scale (Mean)
Ketamine12.6
Midazolam10.1

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Impact of Event Scale - Revised (IES-R)

"A 22-item self-report questionnaire measuring PTSD symptoms. Items are rated on a 5-point scale ranging from 0 (not at all) to 4 (extremely). The IES-R yields a total score ranging from 0 (not at all) to 88 (extremely)" (NCT00749203)
Timeframe: 7 days after first infusion

Interventionunits on a scale (Mean)
Ketamine25.76
Midazolam36.32

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Clinician-Administered PTSD Scale (CAPS)

Clinician-administered structured interview measuring PTSD symptoms. frequency score - scale 0 = none of the time to 4 = most or all of the time intensity score - scale 0 = none to 4 = extreme To meet criteria for a symptom, a patient must meet criteria in both frequency and intensity score for each item. Frequency and intensity and then combined to form a single severity score. 30 questions scale, with total score ranging from 0 to 240. (NCT00749203)
Timeframe: 7 days after first infusion

Interventionunits on a scale (Mean)
Ketamine54
Midazolam65.69

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MADRS

Montgomery-Asberg Depression Rating Scale, each of the ten items can be scored from 0 (absence of symptoms to 6 most severe) and has a total score range of 0-60. A lower score on a MADRS indicates a less severe depression. (NCT00768430)
Timeframe: 24 hours post-infusion

Interventionunits on a scale (Mean)
Ketamine14.77
Midazolam22.72

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The Area Under the the Concentration Time Curve From Zero to Tau (0-8hrs) for Qualaquin (Quinine) AUC Tau Before and After Midazolam

Qualaquin (quinine) - AUC tau alone at steady state (day 9) and in the presence of coadministered midazolam 2 mg (day 10) over the dosing interval (0 - 8 hours), as calculated by the linear trapezoidal method. (NCT00785486)
Timeframe: Days 9 and 10 at 0, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 7, and 7.917 hours

Interventionng•h/mL (Mean)
Qualaquin (Quinine) Alone30455.4
Qualaquin (Quinine) With Midazolam30568.7

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Area Under the Concentration Time Curve From Zero to Infinity (AUC Inf) for Midazolam and 1 Hydroxy Midazolam Before (Day 1) and After (Day 10) Qualaquin (Quinine).

AUC inf for Midazolam and hydroxy-midazolam on day 1 (midazolam alone) and day 10 (midazolam with steady state Qualaquin(quinine)- the sum of AUC0-t plus the ratio of the last measured plasma concentration to the elimination rate constant to determine whether a significant drug interaction occurs between midazolam and quinine (NCT00785486)
Timeframe: Days 1 and 10 at 0.167, 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 3, 4, 6, 7.917, 12, 15 and 24 hours

Interventionng·h/mL (Mean)
Midazolam - Midazolam Alone31.324
1-Hydroxy-Midazolam - Midazolam Alone11.669
Midazolam - Midazolam With Qualaquin (Quinine)28.771
1-Hydroxy-Midazolam -Midazolam With Qualaquin (Quinine)11.447

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Maximum Serum Concentration (Cmax)

Maximum serum concentration(Cmax) (NCT00785486)
Timeframe: Day 1 (Midazolam Alone), Day 9 (Qualaquin (quinine) Alone), Day 10 Midazolam with Qualaquin (quinine)

Interventionng/ml (Mean)
Midazolam - Midazolam Alone12.0435
1-Hydroxy-Midazolam - Midazolam Alone4.6907
Quinine - Qualaquin(Quinine) Alone4432.4089
Midazolam - Midazolam With Qualaquin(Quinine)12.5585
1-Hydroxy-Midazolam -Midazolam With Qualaquin(Quinine)4.8605
Quinine - Qualaquin (Quinine) With Midazolam4399.7690

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Area Under the Concentration Time Curve From Zero to T (AUC 0-t) for Midazolam and 1-hydroxy Midazolam at Baseline and With Qualaquin (Quinine) at Steady State.

Area under the concentration time curve(AUC 0-t) calculated by the linear trapezoidal method from time 0 to 24 hours, for Midazolam and 1-hydroxy-midazolam on day 1 (midazolam alone) and day 10 (midazolam with Qualaquin -(quinine) at steady state to determine if a significant drug interaction occurs between midazolam and quinine (NCT00785486)
Timeframe: Days 1 and 10 at 0.167, 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 3, 4, 6, 7.917, 12, 15 and 24 hours

Interventionng•h/mL (Mean)
Midazolam - Midazolam Alone30.076
1-Hydroxy-Midazolam - Midazolam Alone10.780
Midazolam - Midazolam With Qualaquin (Quinine)27.242
1-Hydroxy-Midazolam -Midazolam With Qualaquin (Quinine)10.454

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The Number of Participants With Any Hypotension Event During Flexible Bronchoscopy

The event of hypotension: when the systolic blood pressure (SBP) was less than 90mmHg with any duration. (NCT00789815)
Timeframe: From the time when bronchoscope introducing patients' nose or mouth to the time when bronchoscope leaving patients' nose or mouth

Interventionparticipants (Number)
BIS-guided Propofol Infusion18
Clinical-judged Midazolam Administration11

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The Global Tolerance for Flexible Bronchoscopy by Verbal Analogus Scale

The global tolerance of the entire procedure was evaluated on a 10-point verbal analogous scale (VAS, 0: no bother, 10: worst intolerable). (NCT00789815)
Timeframe: After patients recovered orientation and before they leaved the scope room.

Interventionunits on a scale (Median)
BIS-guided Propofol Infusion0
Clinical-judged Midazolam Administration0

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Patients Willing Return if Repeated Bronchoscopy is Indicated.

"Patients were asked their willingness to return for another FB if needed by means of a five-point scale (definitely not, probably not, unsure, probably would, and definitely would return). Both probably would, and definitely would return were defined as patients agreed to return." (NCT00789815)
Timeframe: After patients recovered orientation and before they leaved the scope room.

Interventionparticipants (Number)
BIS-guided Propofol Infusion171
Clinical-judged Midazolam Administration169

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The Number of Participants Causing Any Procedure Interference by the Patients' Movement During Flexible Bronchoscocopy

"Procedure interference by patients' movement was when the bronchoscopist had to stop the procedure temporarily and our assistant had to hold down the irritant patient" (NCT00789815)
Timeframe: From the time when bronchoscope introducing patients' nose or mouth to the time when bronchoscope leaving patients' nose or mouth

Interventionparticipants (Number)
BIS-guided Propofol Infusion33
Clinical-judged Midazolam Administration90

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The Recovery Time to Ambulation

The recovery time to ambulation defined as the time between finishing flexible bronchoscopy to the moment when patients could walk without assistance. (NCT00789815)
Timeframe: After the bronchoscopy

InterventionMinutes (Mean)
BIS-guided Propofol Infusion30.0
Clinical-judged Midazolam Administration55.7

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The Number of Participants Causing Any Procedure Interference by Cough

"Procedure interference by cough was when the bronchoscopist had to stop the procedure temporarily and additional xylocaine spray and/or alfentanil had to be given to stop the cough." (NCT00789815)
Timeframe: From the time when bronchoscope introducing patients' nose or mouth to the time when bronchoscope leaving patients' nose or mouth

Interventionparticipants (Number)
BIS-guided Propofol Infusion73
Clinical-judged Midazolam Administration110

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The Number of Participants With Any Hypoxemia Event During Flexible Bronchoscopy

The hypoxemia event is defined as that when the oxyhemoglobin (SpO2) was less than 90% with any duration during the flexible bronchoscopy. (NCT00789815)
Timeframe: From the time when bronchoscope introducing patients' nose or mouth to the time when bronchoscope leaving patients' nose or mouth

Interventionparticipants (Number)
BIS-guided Propofol Infusion97
Clinical-judged Midazolam Administration88

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The Recovery Time to Orientation

The time to orientation defined as the time between finishing flexible bronchoscopy to the moment when patients could open their eyes spontaneously, could recall their date of birth, and perform a finger-nose test correctly (NCT00789815)
Timeframe: After the bronchoscope leaving patients' nose or mouth to the time patients returned orientation

Interventionminutes (Mean)
BIS-guided Propofol Infusion11.7
Clinical-judged Midazolam Administration30.0

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Pain Rating Change

"Mechanical Slide Algometer (www.decisionaidsonline.com), Range: No Pain Sensation (1) to Most Intense Sensation Imaginable (10) 10 point scale.~Change Time Points: Baseline (no sedation), Sedation. Same Day Intervention." (NCT00853333)
Timeframe: Sedation

Interventionunits on a scale (Least Squares Mean)
Dexmedetomidine-0.253
Midazolam0.762
Propofol-0.346

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Time to Fully Alert

Time to first of 3 consecutive Modified Observer's Assessment of Alertness/Sedation (MOAA/S) scores of 5 following study drug administration in patients who underwent the endoscopy procedure (NCT00869440)
Timeframe: From study drug administration until fully alert criteria are reached

Interventionminutes (Mean)
1: CNS 7056 0.10 mg/kg11
2: CNS 7056 0.15 mg/kg13.4
3: CNS 7056 0.20 mg/kg12.1
4: Midazolam 0.075 mg/kg17.2

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Time to Ready for Discharge

Time to first of 3 consecutive Aldrete scores ≥9 after the end endoscopy procedure (NCT00869440)
Timeframe: From the end of the endoscopy procedure up to 120 minutes or until 3 consecutive Aldrete scores of ≥9 are reached, whichever occurs first

Interventionminutes (Mean)
1: CNS 7056 0.10 mg/kg14
2: CNS 7056 0.15 mg/kg12.8
3: CNS 7056 0.20 mg/kg11.8
4: Midazolam 0.075 mg/kg17.2

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Success Rates of the Procedure

Success of the procedure is a composite endpoint consisting of: MOAA/S scores ≤4 on three consecutive measurements after administration of study drug AND completion of the endoscopy procedure AND no requirement for rescue sedative medication AND no requirement for manual or mechanical ventilation (NCT00869440)
Timeframe: From start of study drug injection to patient discharge

InterventionParticipants (Count of Participants)
1: CNS 7056 0.10 mg/kg8
2: CNS 7056 0.15 mg/kg14
3: CNS 7056 0.20 mg/kg16
4: Midazolam 0.075 mg/kg11

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Time to Successful Extubation

(NCT00875550)
Timeframe: 6 to 24 hours

InterventionHours (Median)
Dexmedetomidine Low Dose23.8
Dexmedetomidine High Dose20.5

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Absolute Time on Study Drug That the Subject is in a UMSS Range of 1 to 3 While Intubated

(NCT00875550)
Timeframe: 6 to 24 hours

InterventionHours (Median)
Dexmedetomidine Low Dose17.2
Dexmedetomidine High Dose17.3

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Absolute Time on Study Drug That the Subject is Out of the Target Sedation Range (UMSS <1 or >3) While Intubated

(NCT00875550)
Timeframe: 6 to 24 hours

Interventionhours (Median)
Dexmedetomidine Low Dose1.0
Dexmedetomidine High Dose0.7

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Percentage of Subjects That do Not Require Rescue Midazolam (MDZ) for Sedation Based on Achieving and Maintaining a Target University of Michigan Sedation Scale (UMSS) Score of 1 to 3 While Intubated.

"Clinical Score Level of Sedation 0 Awake/Alert~Minimally Sedated: Tired/sleepy, appropriate response to verbal conversation and/or sounds.~Moderately Sedated: Somnolent/sleeping, easily aroused with light tactile stimulation.~Deeply sedated: Deep sleep, arousable only with significant physical stimulation.~Unarousable" (NCT00875550)
Timeframe: 6 to 24 hours

InterventionPercentage of subjects (Number)
Dexmedetomidine Low Dose44.6
Dexmedetomidine High Dose54.3

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Time to First Dose of Rescue Medication for Sedation and Analgesia

(NCT00875550)
Timeframe: 6 to 24 hours

InterventionHours (Median)
Dexmedetomidine Low Dose1.6
Dexmedetomidine High Dose2.0

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Total Amount of Rescue Medication Required for Sedation and Analgesia While Intubated

(NCT00875550)
Timeframe: 6 to 24 hours

,
InterventionMilligram (Mean)
MidazolamFentanylMorphine
Dexmedetomidine High Dose1.24144.3671.141
Dexmedetomidine Low Dose2.22145.2251.446

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Anxiety Score From the Modified Yale Preoperative Anxiety Scale

The modified Yale preoperative scale consists of 5 categories (activity, vocalizations, emotional expressivity, state of apparent arousal, and use of parents). Four of the five categories are scored between 1-4 points and one of the categories is scored from 1-6 points. The scores are divided by their number of possible points in their respective category and multiplied by 20 to get the final anxiety score which ranges from 20 to 100. Low numbers represent low anxiety and higher numbers represent high anxiety. (NCT00894465)
Timeframe: Waiting room, before catheterization, and after catheterization

,
Interventionunits on a scale (Mean)
Waiting RoomBefore catheterizationAfter catheterization
Placebo25.7257.5581.39
Versed30.8044.5179.01

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Anxiety Score From the State-Trait Anxiety Inventory

The State-Trait anxiety inventory is consists of 20 questions on a 4-point force-choice Likert-type response scales (scores 0 - 3). The 20 questions are summed together for final score. The score can range from 0 to 60 with higher scores representing higher levels of anxiety. This questionnaire was used to evaluate the anxiety level of the parents of the children who randomized to versed or placebo. (NCT00894465)
Timeframe: At the time of the procedure

,
Interventionunits on a scale (Mean)
MothersFathers
Placebo11.725.00
Versed10.0713.54

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Eye Discomfort Perception During Cataract Surgery Under Topical Anesthesia

VAS from 0 to 10 with 10 being maximal discomfort percieved (NCT00928772)
Timeframe: during cataract surgery up to 30 minutes

Interventionunits on a scale (Mean)
Alpha-Stim Intervention2.58
Sham Alpha-Stim With Midazolam2.66
Placebo2.79

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Heart Rate During Cataract Surgery Under Topical Anesthesia

(NCT00928772)
Timeframe: during cataract surgery up to 30 minutes

InterventionBeats per minute (Mean)
Alpha-Stim Intervention64.6
Sham Alpha-Stim With Midazolam65.4
Placebo67.9

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Mean Arterial Pressure During the Cataract Surgery Under Topical Anesthesia

(NCT00928772)
Timeframe: during cataract surgery up to 30 minutes

InterventionmmHg (Mean)
Alpha-Stim Intervention99.5
Sham Alpha-Stim With Midazolam99.8
Placebo104.5

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Anxiety During Cataract Surgery Under Topical Anesthesia

Anxiety was accessed via VAS from 0 to 10 with 10 being the most anxious. (NCT00928772)
Timeframe: during the cataract surgery up to30 minutes

Interventionunits on a scale (Mean)
Alpha-Stim Intervention3.19
Sham Alpha-Stim With Midazolam2.96
Placebo4.10

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Midazolam Area Under the Plasma Concentration-time Profile From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) Following Midazolam Alone and When Coadministered With DVS SR

(NCT00952653)
Timeframe: Period 1 / Day 1 and Period 2 / Day 6: 0, 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16, and 24 hours following dosing

Interventionng*hr/mL (Geometric Mean)
Midazolam 4 mg (Period 1)52.85
DVS SR 50 mg, Midazolam 4 mg (Period 2)38.11

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Midazolam Maximum Observed Plasma Concentration (Cmax) Following Midazolam Alone and When Coadministered With DVS SR

Cmax measured as nanograms per milliliters (ng/mL). (NCT00952653)
Timeframe: Period 1 / Day 1 and Period 2 / Day 6: 0, 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16, and 24 hours following dosing

Interventionng/mL (Geometric Mean)
Midazolam 4 mg (Period 1)21.20
DVS SR 50 mg, Midazolam 4 mg (Period 2)18.24

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Midazolam Terminal Half-life (t 1/2) Following Midazolam Alone and When Coadministered With DVS SR

(NCT00952653)
Timeframe: Period 1 / Day 1 and Period 2 / Day 6: 0, 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16, and 24 hours following dosing

Interventionhr (Mean)
Midazolam 4 mg (Period 1)5.320
DVS SR 50 mg, Midazolam 4 mg (Period 2)4.648

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Midazolam Time to Cmax (Tmax) Following Midazolam Alone and When Coadministered With DVS SR

(NCT00952653)
Timeframe: Period 1 / Day 1 and Period 2 / Day 6: 0, 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16, and 24 hours following dosing

Interventionhr (Median)
Midazolam 4 mg (Period 1)0.517
DVS SR 50 mg, Midazolam 4 mg (Period 2)0.500

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1-Hydroxy-Midazolam (Analyte) Time to Cmax (Tmax) Following Midazolam Alone and When Coadministered With DVS SR

(NCT00952653)
Timeframe: Period 1 / Day 1 and Period 2 / Day 6: 0, 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16, and 24 hours following dosing

Interventionhr (Median)
Midazolam 4 mg (Period 1)1.00
DVS SR 50 mg, Midazolam 4 mg (Period 2)0.500

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1-Hydroxy-Midazolam (Analyte) Area Under the Plasma Concentration-time Profile From Time 0 Extrapolated to Infinite Time (AUCinf) Following Midazolam Alone and When Coadministered With DVS SR

1-Hydroxy-Midazolam is an analyte of Midazolam. (NCT00952653)
Timeframe: Period 1 / Day 1 and Period 2 / Day 6: 0, 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16, and 24 hours following dosing

Interventionng*hr/mL (Geometric Mean)
Midazolam 4 mg (Period 1)36.87
DVS SR 50 mg, Midazolam 4 mg (Period 2)30.74

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1-Hydroxy-Midazolam (Analyte) Area Under the Plasma Concentration-time Profile From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) Following Midazolam Alone and When Coadministered With DVS SR

(NCT00952653)
Timeframe: Period 1 / Day 1 and Period 2 / Day 6: 0, 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16, and 24 hours following dosing

Interventionng*hr/mL (Geometric Mean)
Midazolam 4 mg (Period 1)37.09
DVS SR 50 mg, Midazolam 4 mg (Period 2)32.42

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1-Hydroxy-Midazolam (Analyte) Maximum Observed Plasma Concentration (Cmax) Following Midazolam Alone and When Coadministered With DVS SR

(NCT00952653)
Timeframe: Period 1 / Day 1 and Period 2 / Day 6: 0, 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16, and 24 hours following dosing

Interventionng/mL (Geometric Mean)
Midazolam 4 mg (Period 1)14.93
DVS SR 50 mg, Midazolam 4 mg (Period 2)15.10

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Midazolam Area Under the Plasma Concentration-time Profile From Time 0 Extrapolated to Infinite Time (AUCinf) Following Midazolam Alone and When Coadministered With DVS SR

AUCinf measured as nanograms multiplied by hours divided by milliliters (ng*hr/mL). (NCT00952653)
Timeframe: Period 1 / Day 1 and Period 2 / Day 6: 0, 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16, and 24 hours following dosing

Interventionng*hr/mL (Geometric Mean)
Midazolam 4 mg (Period 1)54.69
DVS SR 50 mg, Midazolam 4 mg (Period 2)39.45

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1-Hydroxy-Midazolam (Analyte) Terminal Half-life (t 1/2) Following Midazolam Alone and When Coadministered With DVS SR

(NCT00952653)
Timeframe: Period 1 / Day 1 and Period 2 / Day 6: 0, 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16, and 24 hours following dosing

Interventionhr (Mean)
Midazolam 4 mg (Period 1)5.396
DVS SR 50 mg, Midazolam 4 mg (Period 2)4.616

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Area Under the Plasma-Time Curve (AUC[0 to Infinity]) for Aprepitant and MK-0517 for Study Part V

AUC (0-inf) is the area under the plasma concentration-time curve from time zero extrapolated to infinite time. The AUC(0-inf) bioequivalence was evaluated for single doses of 100 and 115 mg MK-0517 PS80, IV and that of an oral 125-mg capsule of aprepitant. Period I to IV populations are not included in the outcome analysis because those were formulation and dose-finding/dose confirmation arms. (NCT00990821)
Timeframe: Up to 72 Hours Post Dose

Interventionng*hr/mL (Least Squares Mean)
Aprepitant (125 mg)29215
MK-0517 (100 mg)24961
MK-0517 (115 mg)31724

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Heart Rate

Per EKG monitor (NCT01017237)
Timeframe: Duration of surgery

InterventionBeats per minute (Mean)
Dex Plus Midazolam75
Dex Plus Midazolam and Ketamine85.6

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Heart Rate

Heart rate per EKG monitor (NCT01017237)
Timeframe: Prior to sedation

InterventionBeats per minute (Mean)
Dex Plus Midazolam66.8
Dex Plus Midazolam and Ketamine71.4

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Bispectral Index Score (BIS)

Bispectral Index (BIS) measures level of consciousness by algorithmic analysis of the patient's electroencephalogram (EEG) during anesthesia and sedation. The BIS can range from 0 (equivalent to EEG silence) to 100 (equivalent to fully awake and alert). A BIS value of 40-60 indicates an adequate general anesthesia state. (NCT01017237)
Timeframe: During surgery duration.

Interventionunits on a scale (Mean)
Dex Plus Midazolam75.1
Dex Plus Midazolam and Ketamine82.6

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Amnesia: Lack of Recall One Day After Surgery of The Picture That Was Shown Prior to Sedation.

Lack of recall of picture shown indicates presence of amnesia the day following surgery. (NCT01017237)
Timeframe: One day after surgery

Interventionpercentage of patients (Number)
Dexmedetomidine Plus Midazolam0
Dexmedetomidine Plus Midazolam and Ketamine0

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Respiratory Parameters: End-tidal Carbon Dioxide

Measured by capnography at nares (NCT01017237)
Timeframe: Duration of surgery

InterventionmmHg (Mean)
Dex Plus Midazolam36.9
Dex Plus Midazolam and Ketamine38.2

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Respiratory Parameters: End-tidal Carbon Dioxide

Measured via capnography at nares (NCT01017237)
Timeframe: Immediately prior to sedation

InterventionmmHg (Mean)
Dex Plus Midazolam39.4
Dex Plus Midazolam and Ketamine36.2

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Respiratory Parameters: Oxyhemoglobin Saturation

Oxyhemoglobin saturation per pule oximeter (NCT01017237)
Timeframe: Immediately prior to surgery

InterventionPercent oxyhemoglobin saturation (Mean)
Dex Plus Midazolam98
Dex Plus Midazolam and Ketamine98

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Amnesia: Lack of Picture Recall at Surgery End Time.

Lack of recall of picture shown indicates presence of amnesia (NCT01017237)
Timeframe: Day of surgery prior to discharge

Interventionpercentage of patients (Number)
Dexmedetomidine Plus Midazolam83
Dexmedetomidine Plus Midazolam and Ketamine100

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Respiratory Parameters: Oxyhemoglobin Saturation

Oxyhemoglobin saturation per pulse oximetry (NCT01017237)
Timeframe: During surgical procedure

InterventionPercent oxyhemoglobin saturation (Mean)
Dex Plus Midazolam98
Dex Plus Midazolam and Ketamine98

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Respiratory Parameters: Respiratory Rate

Rate of respirations (NCT01017237)
Timeframe: During surgical procedure

InterventionBreaths per Minute (Mean)
Dex Plus Midazolam15
Dex Plus Midazolam and Ketamine19

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Amnesia: Lack of Recall One Day After Surgery of The Picture That Was Shown Following Dexmedetomidine Infusion Plus Midazolam.

Inability to recall picture shown at this time indicates presence of amnesia on the day following surgery. (NCT01017237)
Timeframe: One day after surgery

Interventionpercentage of patients (Number)
Dexmedetomidine Plus Midazolam100
Dexmedetomidine Plus Midazolam and Ketamine100

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Surgeon Satisfaction With Sedation Technique

Numerical value on scale of 1-5 from Very dissatisfied (1) to Extremely satisfied (5) (NCT01017237)
Timeframe: After surgery completed: day of surgery, within 15 minutes

Interventionunits on a scale (Mean)
Dex Plus Midazolam4.0
Dex Plus Midazolam and Ketamine3.2

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Amnesia: Lack of Picture Recall Following Dexmedetomidine Infusion Plus Midazolam.

Percentage of patients unable to recall picture (NCT01017237)
Timeframe: Day of Surgery prior to discharge

Interventionpercentage of patients (Number)
Dexmedetomidine Plus Midazolam100
Dexmedetomidine Plus Midazolam and Ketamine100

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Amnesia: Lack of Picture Recall Shown 15 Minutes Into Surgery

Lack of recall of picture shown at this time indicates presence of amnesia (NCT01017237)
Timeframe: Day of Surgery prior to discharge

Interventionpercentage of patients (Number)
Dexmedetomidine Plus Midazolam100
Dexmedetomidine Plus Midazolam and Ketamine100

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Ramsey Sedation Scale Score

Rating of depth of sedation by sedationist. Scale 1 - 6, 1 being widw awake and 6 being non-responsive (NCT01017237)
Timeframe: During surgical procedure

Interventionunits on a scale (Mean)
Dex Plus Midazolam3.2
Dex Plus Midazolam and Ketamine3.5

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Primary Title: Amnesia: Lack of Recall One Day After Surgery of The Picture That Was Shown 30 Minutes Into Surgery.

Lack of recall of picture shown indicates presence of amnesia on day following surgery. (NCT01017237)
Timeframe: One day after surgery

Interventionpercentage of patients (Number)
Dexmedetomidine Plus Midazolam83
Dexmedetomidine Plus Midazolam and Ketamine100

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Amnesia: Lack of Picture Recall Shown 30 Minutes Into Surgery

Lack of recall of picture shown indicates presence of amnesia (NCT01017237)
Timeframe: Day of Surgery prior to discharge

Interventionpercentage of patients (Number)
Dexmedetomidine Plus Midazolam83
Dexmedetomidine Plus Midazolam and Ketamine100

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Amnesia: Lack of Picture Recall Shown Prior to Sedation.

Subjects were shown pictures of familiar objects prior to sedation, after the bolus dose of dexmedetomidine was administered, at 15 minutes and 30 minutes into the surgery and at the end of surgery. Subjects were shown a page containing multiple pictures to evaluate whether they could remember any of them. No recall demonstrating the presence of amnesia during that portion of the procedure. This process was repeated the day following surgery (NCT01017237)
Timeframe: Day of surgery prior to discharge

Interventionpercentage of participants (Number)
Dexmedetomidine Plus Midazolam0
Dexmedetomidine Plus Midazolam and Ketamine0

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Amnesia: Lack of Recall One Day After Surgery of The Picture That Was Shown 15 Minutes Into Surgery.

Lack of recall of picture demonstrates presence of amnesia on day following surgery (NCT01017237)
Timeframe: One day after surgery

Interventionpercentage of patients (Number)
Dexmedetomidine Plus Midazolam100
Dexmedetomidine Plus Midazolam and Ketamine100

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Amnesia: Lack of Recall One Day After Surgery of The Picture That Was Shown at Surgery End Time.

Lack of recall of picture shown indicates presence of amnesia on day following surgery. (NCT01017237)
Timeframe: One day after surgery

Interventionpercentage of patients (Number)
Dexmedetomidine Plus Midazolam83
Dexmedetomidine Plus Midazolam and Ketamine100

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Patient Satisfaction With Sedation Technique

Rating of how satisfied the patient was with their sedation on a scale of 1-5 with 1 being very dissatisfied and 5 being extremely satisfied (NCT01017237)
Timeframe: after completion of surgery (within 15 minutes)

Interventionunits on a scale (Mean)
Dex Plus Midazolam4.7
Dex Plus Midazolam and Ketamine4.8

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Mean Arterial Blood Pressure

Measured using automated blood pressure monitor (NCT01017237)
Timeframe: During duration of surgery

InterventionmmHg (Mean)
Dex Plus Midazolam93.8
Dex Plus Midazolam and Ketamine95.9

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Mean Arterial Blood Pressure

Blood pressure per automated monitor (NCT01017237)
Timeframe: Immediately prior to surgery

InterventionmmHg (Mean)
Dex Plus Midazolam96.2
Dex Plus Midazolam and Ketamine96.4

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Respiratory Parameters: Respiratory Rate

Respirations per minute (NCT01017237)
Timeframe: Immediately prior to sedation

InterventionBreaths per Minute (Mean)
Dex Plus Midazolam15
Dex Plus Midazolam and Ketamine17.2

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Days in Hospital

(NCT01059929)
Timeframe: 60 days from enrollment

Interventiondays (Median)
Dexmedetomidine14.33
Propofol12.96

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Days in ICU

(NCT01059929)
Timeframe: 60 days from enollment

Interventiondays (Median)
Dexmedetomidine6.39
Propofol5.61

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Days on Ventilator

(NCT01059929)
Timeframe: 60 days from enrollment

Interventiondays (Median)
Dexmedetomidine3.85
Propofol4.05

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Mortality

(NCT01059929)
Timeframe: 28 days from enrollment

InterventionParticipants (Count of Participants)
Dexmedetomidine8
Propofol12

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Number of Adverse Medication Effects

(NCT01059929)
Timeframe: duration of infusion of study medication up to 28 days

Interventionnumber of events (Number)
Dexmedetomidine0
Propofol0

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Drug Efficacy According to Richmond Agitation Sedation Scale (RASS) Score

Richmond Agitation Sedation Scale (RASS). This is a validated scale that measures level of sedation. The scale ranges from -5 to +4. -5 refers to a state where one is unarousable, +4 refers to a state where one is combative. The median and inter-quartile range over all daily assessments will be provided. (NCT01059929)
Timeframe: Daily up to day 28

Interventionscore on a scale (Median)
Dexmedetomidine-1
Propofol-1.6

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Number of Patients Requiring Midazolam

(NCT01059929)
Timeframe: during infusion of study medication through day 28

InterventionParticipants (Count of Participants)
Dexmedetomidine3
Propofol0

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Number of Patients Requiring Fentanyl

(NCT01059929)
Timeframe: during infusion of study medication up to day 28

InterventionParticipants (Count of Participants)
Dexmedetomidine3
Propofol6

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Number of Patients Completing Mobility Milestones

Milestones: sitting upright independently, standing independently, transfer to chair, marching in place, ambulating independently (NCT01059929)
Timeframe: Daily through day 28

InterventionParticipants (Count of Participants)
Dexmedetomidine7
Propofol6

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Number of Participants With ICU Complications

(NCT01059929)
Timeframe: daily through day 28

InterventionParticipants (Count of Participants)
Dexmedetomidine0
Propofol0

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Number of Patients Completing Activities of Daily Living

activities of daily living: eating, bathing, dressing, grooming, toileting (NCT01059929)
Timeframe: daily through day 28

InterventionParticipants (Count of Participants)
Dexmedetomidine7
Propofol6

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Proportion of Days With Delirium

delirium assessment using CAM-ICU (NCT01059929)
Timeframe: daily up to 28 days

Interventionproportion of days (Median)
Dexmedetomidine0
Propofol.33

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Time to Ready for Discharge

Time of the first of 3 consecutive Aldrete scores ≥ 9 (NCT01145222)
Timeframe: After the Last Injection of Double-Blind Study Medication AND after end of colonoscopy until first of 3 consecutive Aldrete scores ≥ 9

,,,
Interventionminutes (Mean)
After last injectionAfter end of colonoscopy
Midazolam 2.5/1.015.35.5
Remimazolam 5.0/3.0 mg11.33.8
Remimazolam 7.0/2.0 mg12.44.6
Remimazolam 8.0/3.0 mg14.65.0

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Success Rates of the Procedure

Success of the procedure is a composite endpoint consisting of: Modified Observer's Assessment for Alertness/Sedation (MOAA/S) scores ≤4 on three consecutive measurements after administration of study drug AND completion of the endoscopy procedure AND no requirement for rescue sedative medication AND no requirement for manual or mechanical ventilation (NCT01145222)
Timeframe: From start of study drug injection to patient discharge

InterventionParticipants (Count of Participants)
Remimazolam 8.0/3.0 mg37
Remimazolam 7.0/2.0 mg38
Remimazolam 5.0/3.0 mg39
Midazolam 2.5/1.030

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Time to Fully Alert

Time to first of 3 consecutive MOAA/S scores of 5 after the last injection of double-blind study medication (NCT01145222)
Timeframe: From last injection of double-blind study medication until fully alert criteria are reached

Interventionminutes (Mean)
Remimazolam 8.0/3.0 mg13.6
Remimazolam 7.0/2.0 mg11.3
Remimazolam 5.0/3.0 mg13.3
Midazolam 2.5/1.015.2

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Total Midazolam

Total midazolam delivered during procedure (NCT01158820)
Timeframe: Duration of procedure

Interventionmg (Median)
Placebo4.5
Dexmedetomidine and Ketamine2.75

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Endoscopist Satisfaction

Satisfaction rated by 10 point Likert scale (0 = Totally dissatisfied, 10 = Totally satisfied) (NCT01158820)
Timeframe: After the bronchoscopy procedure only

Interventionscore on a scale (Median)
Placebo7
Dexmedetomidine and Ketamine8

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Patient Satisfaction

Satisfaction rated by 10 point Likert scale (0 = Totally dissatisfied, 10 = Totally satisfied) (NCT01158820)
Timeframe: After the bronchoscopy procedure only

Interventionscore on a scale (Median)
Placebo9
Dexmedetomidine and Ketamine10

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Total Fentanyl

Total fentanyl dose delivered during the procedure (NCT01158820)
Timeframe: During the bronchoscopy procedure only, 58.5 minutes average

Interventionµg (Median)
Placebo112.5
Dexmedetomidine and Ketamine68.75

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Desaturation (Cumulative)

Cumulative time below saturation of 90% - the total number of seconds that the pulse oximeter reported a saturation below 90% (NCT01158820)
Timeframe: During the bronchoscopy procedure only, 58.5 minutes average

Interventionseconds (Median)
Placebo39
Dexmedetomidine and Ketamine40

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Conversion to General Anesthesia

Patients in which the procedure could not be completed without conversion to general anesthesia (NCT01158820)
Timeframe: During the bronchoscopy procedure only, 58.5 minutes average

InterventionParticipants (Count of Participants)
Placebo6
Dexmedetomidine and Ketamine1

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Decreased Minute Ventilation

An initial baseline minute ventilation estimate was obtained via calibrated respiratory impedance plethysmography bands. Subsequent minute ventilation was normalized to this value. Values exceeding 100% were excluded from analysis, as these typically reflected a period of hyperpnea subsequent to relief of airway obstruction by chin lift or jaw thrust. (NCT01158820)
Timeframe: During the bronchoscopy procedure only, 58.5 minutes average

Interventionpercentage of baseline (Median)
Placebo0.736
Dexmedetomidine and Ketamine0.764

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Desaturation (Longest)

Longest time below saturation of 90% (the number of seconds elapsed between the start of a period in which the pulse oximeter saturation fell below 90% and the return above 90%) (NCT01158820)
Timeframe: During the bronchoscopy procedure only, 58.5 minutes average

Interventionseconds (Median)
Placebo21
Dexmedetomidine and Ketamine18

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Weight-adjusted Total Amount (Per kg) of Rescue Medication Morphine Given for Analgesia During Dexmedetomidine Infusion (Among Who Used)

(NCT01159262)
Timeframe: During study drug administration (6 to 24 hours)

Interventionmilligram/Kg (Mean)
Dexmedetomidine 0.1 mcg/kg0.125
Dexmedetomidine 0.2 mcg/kg0.109

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Weight-adjusted Total Amount (Per kg) of Rescue Medication Midazolam Given for Sedation During Dexmedetomidine Infusion (Among Who Used)

(NCT01159262)
Timeframe: During study drug administration (6 to 24 hours)

Interventionmilligrams/Kg (Mean)
Dexmedetomidine 0.05 mcg/kg0.100
Dexmedetomidine 0.1 mcg/kg0.152
Dexmedetomidine 0.2 mcg/kg0.318

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Total Amount of Rescue Medication Morphine Given for Sedation During Dexmedetomidine Infusion (Among Who Used)

(NCT01159262)
Timeframe: During study drug administration (6 to 24 hours)

Interventionmilligram (Mean)
Dexmedetomidine 0.1 mcg/kg0.275
Dexmedetomidine 0.2 mcg/kg0.400

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Total Amount of Rescue Medication Midazolam Given for Sedation During Dexmedetomidine Infusion (Among Who Used)

(NCT01159262)
Timeframe: During Study drug administration (6 to 24 hours)

InterventionMilligram (Mean)
Dexmedetomidine 0.05 mcg/kg.360
Dexmedetomidine 0.1 mcg/kg.500
Dexmedetomidine 0.2 mcg/kg1.125

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Total Amount of Rescue Medication Fentanyl Given for Sedation During Dexmedetomidine Infusion (Among Who Used)

(NCT01159262)
Timeframe: During study drug administration (6 to 24 hours)

InterventionMicrogram (Mean)
Dexmedetomidine 0.05 mcg/kg10.808
Dexmedetomidine 0.1 mcg/kg5.667
Dexmedetomidine 0.2 mcg/kg9.522

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Time to Successful Extubation in DEX-exposed Subjects

(NCT01159262)
Timeframe: From start of DEX administration to extubation of each subject up to 7 days post-infusion

Interventionhour (Median)
Dexmedetomidine 0.05 mcg/kg22.9
Dexmedetomidine 0.1 mcg/kg49.3
Dexmedetomidine 0.2 mcg/kg23.7

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Percentage of Subjects Who Received Rescue Medication Midazolam for Sedation During Dexmedetomidine Infusion

(NCT01159262)
Timeframe: During study drug administration (6 to 24 hours)

Interventionpercentage of subjects (Number)
Dexmedetomidine 0.05 mcg/kg7.1
Dexmedetomidine 0.1 mcg/kg7.1
Dexmedetomidine 0.2 mcg/kg25

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Weight-adjusted Total Amount (Per kg) of Rescue Medication Fentanyl Given for Analgesia During Dexmedetomidine Infusion (Among Who Used)

(NCT01159262)
Timeframe: During study drug administration (6 to 24 hours)

Interventionmicrogram/Kg (Mean)
Dexmedetomidine 0.05 mcg/kg5.137
Dexmedetomidine 0.1 mcg/kg1.863
Dexmedetomidine 0.2 mcg/kg2.725

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Percentage of Subjects Who Received Rescue Medication for Analgesia During Dexmedetomidine Infusion

(NCT01159262)
Timeframe: During Study drug administration (6 to 24 hours)

Interventionpercentage of subjects (Number)
Dexmedetomidine 0.05 mcg/kg35.7
Dexmedetomidine 0.1 mcg/kg35.7
Dexmedetomidine 0.2 mcg/kg75

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Number of Participants With Grade 2 or Higher Adverse Events Over the Course of the 26 Day Trial

Number of Participants with Grade 2 or higher adverse events over 26 days (NCT01162486)
Timeframe: 26 days

InterventionParticipants (Count of Participants)
Rifampin Control1
RPT 10
RPT 21
RPT 31
RPT 40

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Pharmacokinetics (AUC of RPT Over 24 Hours Post-dose)

To determine and compare the steady-state pharmacokinetics and dose linearity of escalating daily doses of rifapentine in dose cohorts of 5 mg/kg, 10 mg/kg, 15 mg/kg and 20 mg/kg in healthy volunteers after a single dose (Day 2) or multiple doses (Day 15) (NCT01162486)
Timeframe: days: 2, 15

,,,
Intervention(mcg*h/ml) (Median)
RPT AUC, Day 2 single doseRPT AUC, Day 15 multiple dose
RPT 1128218
RPT 2242330
RPT 3363560
RPT 4403483

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Midazolam, AUC Over 12 Hours Post-dose

To compare and describe, the pharmacokinetics of single-dose midazolam alone (Day 1) versus midazolam co-administered with either steady-state rifapentine at multiple daily doses (5, 10, 15, and 20 mg/kg) or rifampin at 10 mg/kg daily (Day 15) (NCT01162486)
Timeframe: days: 1, 15

,,,,
Interventionng*h/ml (Median)
AUC 0-12 Midazolam alone (Day 1)AUC 0-12 Midazolam with RIF (Day 15)
Rifampin Control15126.9
RPT 115014.2
RPT 211410.2
RPT 320414.0
RPT 417311.7

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FLACC Behavioral Pain Assessment Scale Scores

"FLACC Behavioral Pain Assessment Scale: each of the five categories (F) Face, (L) Legs, (A) Activity, (C) Cry, (C) Consolability is scored from 0-2, which results in a total score between 0 and 10.~0 = Relaxed and comfortable 1-3 = Mild discomfort 4-6 = Moderate pain 7-10 = Severe discomfort or pain or both" (NCT01188551)
Timeframe: 30 mins. post-op

Interventionunits on a scale (Mean)
Dexmedetomidine w/ Midazolam5
Fentanyl w/ Midazolam3
Dexmedetomidine w/o Midazolam1
Fentanyl w/o Midazolam2

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Recovery From General Anesthesia

Post-anesthesia recovery score: Aldrete The Aldrete scoring system takes into account the patient's ability to move, respiration, circulation, consciousness, and oxygen saturation. A maximum of two points are awarded in each category and a score of 9 or 10 is required for discharge. (NCT01188551)
Timeframe: 30 mins. post-op

Interventionunits on a scale (Mean)
Dexmedetomidine w/ Midazolam8.67
Fentanyl w/ Midazolam9
Dexmedetomidine w/o Midazolam9.25
Fentanyl w/o Midazolam9.5

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Percentage of Participants Achieving Sedation Within 4 Minutes

"Percentage of patients achieving a Modified Observer's Assessment of Alertness/Sedation Scale score less than or equal to 4, and the block procedure initiated, within 4 minutes of the administration of the first bolus of study drug. The Modified Observer's Assessment of Alertness/Sedation Scale ranges from 0 (does not respond to deep stimulus) to 6 (agitated). The score of 4 equals lethargic response to name spoken in normal tone." (NCT01195103)
Timeframe: approximately 4 minutes after administration of first bolus of study drug

Interventionpercentage of participants (Number)
10 mg/kg Lusedra100
6.5 mg/kg Lusedra50
Placebo + Midazolam40

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Tasisulam Pharmacokinetics: Area Under the Concentration-Time Curve Above the Albumin Corrected Threshold (AUCalb)

Tasisulam is highly bound to albumin. AUCalb is a surrogate measure of exposure to unbound (free) tasisulam. (NCT01209832)
Timeframe: Period 2: Predose, preinfusion start, 1, 1.75, 2 (post end of infusion), 2.5, 3, 4, 6, 8, 24, 48, 72, 120, 168, and 336 hours.

Interventionhour*micrograms/milliliter (h*mcg/mL) (Geometric Mean)
Tasisulam5840

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Tasisulam Pharmacokinetics: Maximum Concentration (Cmax)

(NCT01209832)
Timeframe: Period 2: Predose, preinfusion start, 1, 1.75, 2 (post end of infusion), 2.5, 3, 4, 6, 8, 24, 48, 72, 120, 168, and 336 hours.

Interventionmicrograms per milliliter (mcg/mL) (Geometric Mean)
Tasisulam358

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Number of Participants With Tumor Response

Number of participants with tumor response = number of participants with complete response (CR) + number of participants with partial response (PR), as classified by the investigators according to the Response Evaluation Criteria In Solid Tumors (RECIST) guidelines. CR is disappearance of all target and non-target lesions; PR is ≥30% decrease in sum of longest diameter of target lesions. (NCT01209832)
Timeframe: Baseline to Day 15 of Maintenance Period up to 3 months

InterventionParticipants (Count of Participants)
Midazolam + Tasisulam0

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Midazolam Pharmacokinetics: Maximum Concentration (Cmax)

(NCT01209832)
Timeframe: Period 1 and 2: Predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 7, 9, 11, 24, 48, and 72 hours post-dose.

Interventionnanograms per milliliter (ng/mL) (Geometric Mean)
Midazolam9.07
Midazolam + Tasisulam9.48

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Midazolam Pharmacokinetics: Area Under the Concentration-Time Curve From Time Zero to the Last Time Point With Measurable Concentrations (AUC 0-tlast)

(NCT01209832)
Timeframe: Period 1 and 2: Predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 7, 9, 11, 24, 48, and 72 hours post-dose.

Interventionnanograms*hour per milliliter (ng*h/mL) (Geometric Mean)
Midazolam25.9
Midazolam + Tasisulam22.5

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Midazolam Pharmacokinetics: Area Under the Concentration-Time Curve From Time Zero to Infinity (AUC 0-infinity)

(NCT01209832)
Timeframe: Period 1 and 2: Predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 7, 9, 11, 24, 48, and 72 hours post-dose.

Interventionnanograms*hour per milliliter (ng*h/mL) (Geometric Mean)
Midazolam27.0
Midazolam + Tasisulam22.8

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Ratio of Pharmcokinetic (PK) Area Under the Concentration Time Curve (AUC) Parameter Estimates Between Day 16 (Midazolam With the Presence of Denosumab) and Day 1 (Midazolam Only)

The ratio and confidence interval are calculated based on natural log scale data and converted back to the original scale. (NCT01221727)
Timeframe: From day 1 pre-dose to 24 hours post-dose and from day 16 pre-dose to 24 hours post-dose

Interventionunitless (Least Squares Mean)
AUC (0-t)AUC (0-inf)
Midazolam With Denosumab1.101.12

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Ratio of PK AUC Parameter Estimates Between Day 16 (Midazolam Only) and Day 1(Midazolam Only)

The ratio and confidence interval are calculated based on natural log scale data and converted back to the original scale. (NCT01221727)
Timeframe: From day 1 pre-dose to 24 hours post-dose and from day 16 pre-dose to 24 hours post-dose

Interventionunitless (Least Squares Mean)
AUC (0-t)AUC (0-inf)
Midazolam Only0.980.98

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Summary of Serum C-Telopeptide Concentration

This table summarizes serum C-Telopeptide (sCTX) concentration raw values for Midazolam with Denosumab group. (NCT01221727)
Timeframe: Baseline (day 2 pre-dose) to day 16

Interventionng/mL (Median)
Baseline (day 2 pre-dose)Day 16Change from baseline to Day 16
Midazolam With Denosumab0.46550.0606-0.4079

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Summary of Serum Denosumab Concentration

This table summarizes serum Denosumab for Midazolam with Denosumab group. The Lower Limit Of Quantification (LLOQ) is 20 ng/mL. On Day 2 (pre-dose), the true value is below LLOQ, and is treated as 0 in the analysis. (NCT01221727)
Timeframe: Baseline (day 2 pre-dose) to day 16

Interventionng/mL (Median)
Day 2 (Pre-dose)Day 16 (0hr)Day 17 (24hr)
Midazolam With Denosumab058205500

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Estimates of Inter- and Intra-subject Variability for the PK AUC Parameters for Midazolam Only Group

AUC Subject denotes the inter-subject variability, while AUC Residual denotes the intra-subject variability. (NCT01221727)
Timeframe: From day 1 pre-dose to 24 hours post-dose and from day 16 pre-dose to 24 hours post-dose

Interventionng*hr/mL (Mean)
AUC (0-t) Subject: Inter-subjectAUC (0-t) Residual: Intra-subjectAUC (0-inf) Subject: Inter-subjectAUC (0-inf) Residual: Intra-subject
Midazolam Only0.270.030.310.03

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Estimates of Inter- and Intra-subject Variability for the PK AUC Parameters for Midazolam With Denosumab Group

AUC Subject denotes the inter-subject variability, while AUC Residual denotes the intra-subject variability (NCT01221727)
Timeframe: From day 1 pre-dose to 24 hours post-dose and from day 16 pre-dose to 24 hours post-dose

Interventionng*hr/mL (Mean)
AUC (0-t) Subject: Inter-subjectAUC (0-t) Residual: Intra-subjectAUC (0-inf) Subject: Inter-subjectAUC (0-inf) Residual: Intra-subject
Midazolam With Denosumab0.190.070.210.08

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Estimates of Inter- and Intra-subject Variability for PK Maximum Observed Plasma Concentration (Cmax) Parameter for Midazolam With Denosumab Group

Cmax Subject denotes the inter-subject variability, while Cmax Residual denotes the intra-subject variability (NCT01221727)
Timeframe: From day 1 pre-dose to 24 hours post-dose and from day 16 pre-dose to 24 hours post-dose

Interventionng/mL (Mean)
Cmax Subject: Inter-subjectCmax Residual: Intra-subject
Midazolam With Denosumab0.150.07

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Estimates of Inter- and Intra-subject Variability for PK Cmax Parameter for Midazolam Only Group

Cmax Subject denotes the inter-subject variability, while Cmax Residual denotes the intra-subject variability. (NCT01221727)
Timeframe: From day 1 pre-dose to 24 hours post-dose and from day 16 pre-dose to 24 hours post-dose

Interventionng/mL (Mean)
Cmax Subject: Inter-subjectCmax Residual: Intra-subject
Midazolam Only0.230.06

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Summary of Percent Change From Baseline to Day 16 for Serum C-Telopeptide Concentration

This table summarizes percent change from baseline to day 16 for serum C-Telopeptide (sCTX) concentration raw values for Midazolam with Denosumab group. (NCT01221727)
Timeframe: Baseline (day 2 pre-dose) to day 16

Interventionpercentage (Median)
Midazolam With Denosumab-87.52

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Ratio of PK Cmax Parameter Estimates Between Day 16 (Midazolam With the Presence of Denosumab) and Day 1 (Midazolam Only)

The ratio and confidence interval are calculated based on natural log scale data and converted back to the original scale. (NCT01221727)
Timeframe: From day 1 pre-dose to 24 hours post-dose and from day 16 pre-dose to 24 hours post-dose

Interventionunitless (Least Squares Mean)
Midazolam With Denosumab1.11

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Ratio of PK Cmax Parameter Estimates Between Day 16 (Midazolam Only) and Day 1(Midazolam Only)

The ratio and confidence interval are calculated based on natural log scale data and converted back to the original scale. (NCT01221727)
Timeframe: From day 1 pre-dose to 24 hours post-dose and from day 16 pre-dose to 24 hours post-dose

Interventionunitless (Least Squares Mean)
Midazolam Only1.05

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Part 1: Tmax of Cilastin in Combination With MK-7655

Tmax is the time at which the highest plasma drug concentration was observed. (NCT01275170)
Timeframe: Predose and 0.08, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4.5, 6, 8, 10, and 14 hours postdose

Interventionhours (Median)
Panel A: Mild Renal Impairment0.50
Panel B: Healthy Controls to Panel A0.50
Panel C: Moderate Renal Impairment0.49
Panel D: Healthy Controls to Panel C0.48
Panel E: Severe Renal Impairment0.48
Panel F: Healthy Controls to Panel E0.48
Panel G: ESRD/HD Period 1 Postdialysis0.48
Panel H: Healthy Controls to Panel G0.48
Panel G: ESRD/HD Period 2 Predialysis0.48

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Part 1: Predicted Clearance (CLpred) of MK-7655 in Combination With PRIMAXIN®

CLpred is the predicted apparent total body clearance of drug. (NCT01275170)
Timeframe: Predose and 0.08, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4.5, 6, 8, 10, and 14 hours postdose

InterventionmL/min (Geometric Mean)
Panel A: Mild Renal Impairment81.3
Panel B: Healthy Controls to Panel A133
Panel C: Moderate Renal Impairment52.1
Panel D: Healthy Controls to Panel C114
Panel E: Severe Renal Impairment25.3
Panel F: Healthy Controls to Panel E123
Panel G: ESRD/HD Period 1 Postdialysis14.4
Panel H: Healthy Controls to Panel G135
Panel G: ESRD/HD Period 2 Predialysis76.6

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Part 1: Ceoi of Cilastin in Combination With MK-7655

Cilastin is 1 of the 2 constituents of PRIMAXIN®. Ceoi is the observed plasma drug concentration at the end of IV infusion. (NCT01275170)
Timeframe: At 0.5 hours postdose

InterventionµM (Geometric Mean)
Panel A: Mild Renal Impairment43.4
Panel B: Healthy Controls to Panel A34.8
Panel C: Moderate Renal Impairment48.7
Panel D: Healthy Controls to Panel C42.9
Panel E: Severe Renal Impairment53.3
Panel F: Healthy Controls to Panel E35.8
Panel G: ESRD/HD Period 1 Postdialysis111
Panel H: Healthy Controls to Panel G44.5
Panel G: ESRD/HD Period 2 Predialysis41.7

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Part 1: VZpred of Cilastin in Combination With MK-7655

Cilastin is 1 of the 2 constituents of PRIMAXIN®. VZpred is the predicted volume of distribution during the terminal phase. (NCT01275170)
Timeframe: Predose and 0.08, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4.5, 6, 8, 10, and 14 hours postdose

Interventionliters (L) (Geometric Mean)
Panel A: Mild Renal Impairment19.2
Panel B: Healthy Controls to Panel A23.9
Panel C: Moderate Renal Impairment19.4
Panel D: Healthy Controls to Panel C21.4
Panel E: Severe Renal Impairment16.9
Panel F: Healthy Controls to Panel E21.2
Panel G: ESRD/HD Period 1 Postdialysis15.9
Panel H: Healthy Controls to Panel G21.0
Panel G: ESRD/HD Period 2 Predialysis59.1

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Part 1: Renal Clearance (CLR) of MK-7655 in Urine

CLR represents renal clearance in urine. Urine was collected for 24 hours postdose. (NCT01275170)
Timeframe: Predose to 24 hours postdose

InterventionmL/min (Geometric Mean)
Panel A: Mild Renal Impairment69.8
Panel B: Healthy Controls to Panel A118
Panel C: Moderate Renal Impairment38.4
Panel D: Healthy Controls to Panel C110
Panel E: Severe Renal Impairment22.3
Panel F: Healthy Controls to Panel E107
Panel H: Healthy Controls to Panel G110

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Part 1: Tmax of Imipenem in Combination With MK-7655

Tmax is the time at which the highest plasma drug concentration was observed. (NCT01275170)
Timeframe: Predose and 0.08, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4.5, 6, 8, 10, and 14 hours postdose

Interventionhours (Median)
Panel A: Mild Renal Impairment0.50
Panel B: Healthy Controls to Panel A0.50
Panel C: Moderate Renal Impairment0.49
Panel D: Healthy Controls to Panel C0.48
Panel E: Severe Renal Impairment0.48
Panel F: Healthy Controls to Panel E0.48
Panel G: ESRD/HD Period 1 Postdialysis0.48
Panel H: Healthy Controls to Panel G0.48
Panel G: ESRD/HD Period 2 Predialysis0.48

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Part 1: AUC0-inf of Cilastin in Combination With MK-7655

Cilastin is 1 of the 2 constituents of PRIMAXIN®. AUC0-∞ is a measure of the mean (extrapolated) plasma drug concentration after dosing to infinity. (NCT01275170)
Timeframe: Predose and 0.08, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4.5, 6, 8, 10, and 14 hours postdose

InterventionµM*hr (Geometric Mean)
Panel A: Mild Renal Impairment71.7
Panel B: Healthy Controls to Panel A44.8
Panel C: Moderate Renal Impairment100.0
Panel D: Healthy Controls to Panel C53.6
Panel E: Severe Renal Impairment300
Panel F: Healthy Controls to Panel E53.7
Panel G: ESRD/HD Period 1 Postdialysis777
Panel H: Healthy Controls to Panel G56.5
Panel G: ESRD/HD Period 2 Predialysis205

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Part 2: Plasma AUC0-∞ of Midazolam as a Probe Substrate of Cytochrome P450 Enzyme (CYP)3A4

Midazolam was selected as a substrate of CYP3A4. AUC0-∞ was determined in participants with severe renal impairment and ESRD/HD participants. (NCT01275170)
Timeframe: Predose and 0.5, 1, 2,3, 4, 8, 12, and 24 hours postdose

InterventionµM*hr (Geometric Mean)
Panel E: Severe Renal Impairment0.130
Panel F: Healthy Controls to Panel E0.121
Panel G: ESRD/HD Period 1 Postdialysis0.0681
Panel G: ESRD/HD Period 2 Predialysis0.0700
Panel H: Healthy Controls to Panel G0.114

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Part 1: Area Under the Plasma Concentration-time Curve From Dosing to Infinity (AUC0-inf) of MK-7655 in Combination With PRIMAXIN®

AUC0-∞ is a measure of the mean (extrapolated) plasma drug concentration after dosing to infinity. (NCT01275170)
Timeframe: Predose and 0.08, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4.5, 6, 8, 10, and 14 hours postdose

InterventionµM*hr (Geometric Mean)
Panel A: Mild Renal Impairment73.5
Panel B: Healthy Controls to Panel A45.0
Panel C: Moderate Renal Impairment115
Panel D: Healthy Controls to Panel C52.3
Panel E: Severe Renal Impairment236
Panel F: Healthy Controls to Panel E48.5
Panel G: ESRD/HD Period 1 Postdialysis414
Panel H: Healthy Controls to Panel G44.5
Panel G: ESRD/HD Period 2 Predialysis78.0

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Part 1: Apparent t½ of Imipenem in Combination With MK-7655

Imipenem is 1 of the 2 constituents of PRIMAXIN®. Apparent t½ is the amount of time for the maximum drug concentration to decrease by 50%. (NCT01275170)
Timeframe: Predose and 0.08, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4.5, 6, 8, 10, and 14 hours postdose

Interventionhours (Geometric Mean)
Panel A: Mild Renal Impairment1.54
Panel B: Healthy Controls to Panel A1.24
Panel C: Moderate Renal Impairment2.18
Panel D: Healthy Controls to Panel C1.40
Panel E: Severe Renal Impairment2.78
Panel F: Healthy Controls to Panel E1.32
Panel G: ESRD/HD Period 1 Postdialysis3.24
Panel H: Healthy Controls to Panel G1.21
Panel G: ESRD/HD Period 2 Predialysis3.20

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Part 1: Concentration at End of Infusion (Ceoi) of MK-7655 in Combination With PRIMAXIN®

Ceoi is the observed plasma drug concentration at the end of IV infusion. (NCT01275170)
Timeframe: At 0.5 hours postdose

InterventionµM (Geometric Mean)
Panel A: Mild Renal Impairment22.4
Panel B: Healthy Controls to Panel A20.4
Panel C: Moderate Renal Impairment23.5
Panel D: Healthy Controls to Panel C22.5
Panel E: Severe Renal Impairment23.6
Panel F: Healthy Controls to Panel E18.1
Panel G: ESRD/HD Period 1 Postdialysis53.1
Panel H: Healthy Controls to Panel G22.7
Panel G: ESRD/HD Period 2 Predialysis19.3

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Part 1: Apparent t½ of Cilastin in Combination With MK-7655

Cilastin is 1 of the 2 constituents of PRIMAXIN®. Apparent t½ is the amount of time for the maximum drug concentration to decrease by 50%. (NCT01275170)
Timeframe: Predose and 0.08, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4.5, 6, 8, 10, and 14 hours postdose

Interventionhours (Geometric Mean)
Panel A: Mild Renal Impairment1.43
Panel B: Healthy Controls to Panel A1.08
Panel C: Moderate Renal Impairment2.11
Panel D: Healthy Controls to Panel C1.19
Panel E: Severe Renal Impairment5.08
Panel F: Healthy Controls to Panel E1.09
Panel G: ESRD/HD Period 1 Postdialysis12.2
Panel H: Healthy Controls to Panel G1.14
Panel G: ESRD/HD Period 2 Predialysis12.2

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Part 1: VZpred of Imipenem in Combination With MK-7655

Imipenem is 1 of the 2 constituents of PRIMAXIN®. VZpred is the predicted volume of distribution during the terminal phase. (NCT01275170)
Timeframe: Predose and 0.08, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4.5, 6, 8, 10, and 14 hours postdose

Interventionliters (L) (Geometric Mean)
Panel A: Mild Renal Impairment21.1
Panel B: Healthy Controls to Panel A26.1
Panel C: Moderate Renal Impairment22.3
Panel D: Healthy Controls to Panel C23.4
Panel E: Severe Renal Impairment20.0
Panel F: Healthy Controls to Panel E24.8
Panel G: ESRD/HD Period 1 Postdialysis20.5
Panel H: Healthy Controls to Panel G24.9
Panel G: ESRD/HD Period 2 Predialysis63.3

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Part 2: Plasma AUC0-∞ of Caffeine as a Probe Substrate of Cytochrome P450 Enzyme (CYP)1A2

Caffeine was selected as a substrate of CYP1A2. AUC0-∞ was determined in participants with severe renal impairment and ESRD/HD participants. (NCT01275170)
Timeframe: Predose and 0.5, 1, 2,3, 4, 8, 12, and 24 hours postdose

InterventionµM*hr (Geometric Mean)
Panel E: Severe Renal Impairment336
Panel F: Healthy Controls to Panel E221
Panel G: ESRD/HD Period 1 Postdialysis190
Panel G: ESRD/HD Period 2 Predialysis200
Panel H: Healthy Controls to Panel G300

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Part 1: Apparent Plasma Half-life (t½) of MK-7655 in Combination With PRIMAXIN®

Apparent t½ is the amount of time for the maximum drug concentration to decrease by 50%. (NCT01275170)
Timeframe: Predose and 0.08, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4.5, 6, 8, 10, and 14 hours postdose

Interventionhours (Geometric Mean)
Panel A: Mild Renal Impairment2.63
Panel B: Healthy Controls to Panel A1.75
Panel C: Moderate Renal Impairment4.51
Panel D: Healthy Controls to Panel C2.10
Panel E: Severe Renal Impairment8.65
Panel F: Healthy Controls to Panel E2.00
Panel G: ESRD/HD Period 1 Postdialysis15.6
Panel H: Healthy Controls to Panel G1.79
Panel G: ESRD/HD Period 2 Predialysis10.5

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Part 2: Plasma AUC0-∞ of Omeprazole as a Probe Substrate of Cytochrome P450 Enzyme (CYP)2C19

Omeprazole was selected as a substrate of CYP2C19. AUC0-∞ was determined in participants with severe renal impairment and ESRD/HD participants. (NCT01275170)
Timeframe: Predose and 0.5, 1, 2,3, 4, 8, 12, and 24 hours postdose

InterventionµM*hr (Geometric Mean)
Panel E: Severe Renal Impairment9.10
Panel F: Healthy Controls to Panel E6.20
Panel G: ESRD/HD Period 1 Postdialysis4.56
Panel G: ESRD/HD Period 2 Predialysis4.08
Panel H: Healthy Controls to Panel G5.03

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Dialysis Clearance (CLD) of MK-7655 in Participants With End-stage Renal Diseases Requiring Hemodialysis (ESRD/HD)

The CLD of MK-7655 was determined in ESRD/HD participants for 4.5 hours during HD. The formula for calculating CLD was: CLd = (1-Hct)*QB*[(pre-dialyzer concentration - post-dialyzer concentration) / (pre-dialyzer concentration)] where QB=350 mL/min and Hct=hematocrit. (NCT01275170)
Timeframe: 1, 1.5, 2, 2.5, 3, 3.5, 4, and 4.5 hours postdose

InterventionmL/min (Geometric Mean)
1 hour postdose1.5 hours postdose2 hours postdose2.5 hours postdose3.0 hours postdose3.5 hours postdose4 hours postdose4.5 hours postdose
Panel G: ESRD/HD Period 2 Predialysis172158170166171177204198

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Extraction Coefficient of MK-7655 in Participants With End-stage Renal Diseases Requiring Hemodialysis (ESRD/HD)

The extraction coefficient of MK-7655 was determined in ESRD/HD participants for 4.5 hours during HD. The formula for calculating extraction coefficient was: Extraction Coefficient = ABS[100*(post-dialyzer concentration - pre-dialyzer concentration) / pre-dialyzer concentration]. (NCT01275170)
Timeframe: 1, 1.5, 2, 2.5, 3, 3.5, 4, and 4.5 hours postdose

InterventionExtraction coefficient (Geometric Mean)
1 hour postdose1.5 hours postdose2 hours postdose2.5 hours postdose3.0 hours postdose3.5 hours postdose4 hours postdose4.5 hours postdose
Panel G: ESRD/HD Period 2 Predialysis7367737173768784

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Part 1: CLR of Imipenem in Urine

CLR represents renal clearance in urine. Urine was collected for 24 hours postdose. (NCT01275170)
Timeframe: Predose to 24 hours postdose

InterventionmL/min (Geometric Mean)
Panel A: Mild Renal Impairment75.0
Panel B: Healthy Controls to Panel A115
Panel C: Moderate Renal Impairment41.1
Panel D: Healthy Controls to Panel C109
Panel E: Severe Renal Impairment17.4
Panel F: Healthy Controls to Panel E104
Panel H: Healthy Controls to Panel G99.1

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Part 1: CLR of Cilastin in Urine

CLR represents renal clearance in urine. Urine was collected for 24 hours postdose. (NCT01275170)
Timeframe: Predose to 24 hours postdose

InterventionmL/min (Geometric Mean)
Panel A: Mild Renal Impairment99.4
Panel B: Healthy Controls to Panel A144
Panel C: Moderate Renal Impairment59.6
Panel D: Healthy Controls to Panel C136
Panel E: Severe Renal Impairment24.5
Panel F: Healthy Controls to Panel E140
Panel H: Healthy Controls to Panel G146

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Part 1: CLpred of Imipenem in Combination With MK-7655

Imipenem is 1 of the 2 constituents of PRIMAXIN®. CLpred is the predicted apparent total body clearance of drug. (NCT01275170)
Timeframe: Predose and 0.08, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4.5, 6, 8, 10, and 14 hours postdose

InterventionmL/min (Geometric Mean)
Panel A: Mild Renal Impairment180
Panel B: Healthy Controls to Panel A253
Panel C: Moderate Renal Impairment138
Panel D: Healthy Controls to Panel C211
Panel E: Severe Renal Impairment87.0
Panel F: Healthy Controls to Panel E218
Panel G: ESRD/HD Period 1 Postdialysis62.5
Panel H: Healthy Controls to Panel G194
Panel G: ESRD/HD Period 2 Predialysis195

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Part 1: AUC0-inf of Imipenem in Combination With MK-7655

Imipenem is 1 of the 2 constituents of PRIMAXIN®. AUC0-∞ is a measure of the mean (extrapolated) plasma drug concentration after dosing to infinity. (NCT01275170)
Timeframe: Predose and 0.08, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4.5, 6, 8, 10, and 14 hours postdose

InterventionµM*hr (Geometric Mean)
Panel A: Mild Renal Impairment77.3
Panel B: Healthy Controls to Panel A55.0
Panel C: Moderate Renal Impairment101
Panel D: Healthy Controls to Panel C66.0
Panel E: Severe Renal Impairment160
Panel F: Healthy Controls to Panel E63.8
Panel G: ESRD/HD Period 1 Postdialysis223
Panel H: Healthy Controls to Panel G71.8
Panel G: ESRD/HD Period 2 Predialysis71.2

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Part 1: CLpred of Cilastin in Combination With MK-7655

Cilastin is 1 of the 2 constituents of PRIMAXIN®. CLpred is the predicted apparent total body clearance of drug. (NCT01275170)
Timeframe: Predose and 0.08, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4.5, 6, 8, 10, and 14 hours postdose

InterventionmL/min (Geometric Mean)
Panel A: Mild Renal Impairment162
Panel B: Healthy Controls to Panel A259
Panel C: Moderate Renal Impairment116
Panel D: Healthy Controls to Panel C217
Panel E: Severe Renal Impairment38.7
Panel F: Healthy Controls to Panel E217
Panel G: ESRD/HD Period 1 Postdialysis15.0
Panel H: Healthy Controls to Panel G206
Panel G: ESRD/HD Period 2 Predialysis56.6

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Part 1: Predicted Volume of Distribution During the Terminal Phase (VZpred) of MK-7655 in Combination With PRIMAXIN®

VZpred is the predicted volume of distribution during the terminal phase. (NCT01275170)
Timeframe: Predose and 0.08, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4.5, 6, 8, 10, and 14 hours postdose

Interventionliters (L) (Geometric Mean)
Panel A: Mild Renal Impairment21.4
Panel B: Healthy Controls to Panel A21.6
Panel C: Moderate Renal Impairment22.2
Panel D: Healthy Controls to Panel C21.9
Panel E: Severe Renal Impairment20.1
Panel F: Healthy Controls to Panel E22.4
Panel G: ESRD/HD Period 1 Postdialysis16.2
Panel H: Healthy Controls to Panel G17.0
Panel G: ESRD/HD Period 2 Predialysis55.7

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Part 1: Time of Maximum Plasma Concentration (Tmax) of MK-7655 in Combination With PRIMAXIN®

Tmax is the time at which the highest plasma drug concentration was observed. (NCT01275170)
Timeframe: Predose and 0.08, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4.5, 6, 8, 10, and 14 hours postdose

Interventionhours (Median)
Panel A: Mild Renal Impairment0.50
Panel B: Healthy Controls to Panel A0.50
Panel C: Moderate Renal Impairment0.50
Panel D: Healthy Controls to Panel C0.49
Panel E: Severe Renal Impairment0.48
Panel F: Healthy Controls to Panel E0.48
Panel G: ESRD/HD Period 1 Postdialysis0.48
Panel H: Healthy Controls to Panel G0.48
Panel G: ESRD/HD Period 2 Predialysis0.48

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Part 1: Ceoi of Imipenem in Combination With MK-7655

Imipenem is 1 of the 2 constituents of PRIMAXIN®. Ceoi is the observed plasma drug concentration at the end of IV infusion. (NCT01275170)
Timeframe: At 0.5 hours postdose

InterventionµM (Geometric Mean)
Panel A: Mild Renal Impairment40.7
Panel B: Healthy Controls to Panel A35.3
Panel C: Moderate Renal Impairment45.6
Panel D: Healthy Controls to Panel C42.6
Panel E: Severe Renal Impairment46.9
Panel F: Healthy Controls to Panel E35.5
Panel G: ESRD/HD Period 1 Postdialysis103
Panel H: Healthy Controls to Panel G41.8
Panel G: ESRD/HD Period 2 Predialysis35.9

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Parts 1 and 2: Percentage of Participants With ≥1 Adverse Events (AEs)

An AE is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. (NCT01275170)
Timeframe: Up to 14 days after the last dose of study drug in Part 2 (up to 11 weeks)

InterventionPercentage of Participants (Number)
Panel A: Mild Renal Impairment28.6
Panel C: Moderate Renal Impairment16.7
Panel E: Severe Renal Impairment16.7
Panel G: ESRD/HD Participants33.3
Healthy Matched Controls (Part 1)0.0
Panel E: Severe Renal Impairment (Part 2)33.3
Panel G: ESRD/HD (Part 2)33.3
Healthy Matched Controls (Part 2)0.0

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Onset Time.

Time from beginning of administration of the local anesthetic until complete sensoric block. (NCT01309360)
Timeframe: within 60 minutes after administration of the local anesthetic

Interventionminutes (Mean)
Group A : 40ml Prilocaine 1%18
Group B : 30ml Prilocaine 1%20
Group C : 20ml Prilocaine 1%26

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Number of Participants With Objective Adverse Events as a Measure of Safety and Tolerability

In groups A, B and C was determined the rate of objective clinical signs of increased Met-Hb-levels : drops in oxygen saturation <93% using pulseoximetry or lip cyanosis. (NCT01309360)
Timeframe: Outpatients were followed for the duration of hospital stay, an average of six hours.

Interventionparticipants (Number)
Group A : 40ml Prilocaine 1%13
Group B : 30ml Prilocaine 1%5
Group C : 20ml Prilocaine 1%1

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Number of Participants With Subjective Adverse Events as a Measure of Safety and Tolerability.

In groups A, B and C was determined the rate of subjective clinical signs of increased Met-Hb-Levels : headaches or dizziness, when correlated with the peak-Met-Hb-Level. (NCT01309360)
Timeframe: Outpatients were followed for the duration of hospital stay, an average of six hours.

Interventionparticipants (Number)
Group A : 40ml Prilocaine 1%4
Group B : 30ml Prilocaine 1%0
Group C : 20ml Prilocaine 1%0

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Maximum Concentrations of Methemoglobin

Concentration of Methemoglobin (Met-Hb) was measured using spectrophotometry prior to the anesthesia (baseline value) and then hourly after performing the block until a clear decrease became apparent. The maximum amount was reached in every case two or three hours after administration of the local anesthetic. (NCT01309360)
Timeframe: 0,1,2,3,4 hours post-dose

Interventionpercentage of methemoglobin (Mean)
Group A : 40ml Prilocaine 1%4.7
Group B : 30ml Prilocaine 1%3.7
Group C : 20ml Prilocaine 1%2.4

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Number of Participants With Complete Motor Blocks

To examine the extent of the motor block the manual muscle function test after Vladimir Janda was used. As a complete motor block was defined, when no motion (grade zero after Janda) of muscles innervated by the four blocked nerves (musculocutaneous, median, radial and ulnar nerve) was observed within 60 minutes after administration of the local anesthetic. (NCT01309360)
Timeframe: Within 60 minutes after administration of the local anesthetic

Interventionparticipants (Number)
Group A : 40ml Prilocaine 1%38
Group B : 30ml Prilocaine 1%36
Group C : 20ml Prilocaine 1%32

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Number of Participants With Complete Sensory Block

The number of outpatients with complete sensory block of all 4 nerves (n.musculocutaneous, n.radialis, n.ulnaris,n.medianus) was registrated in each group. (NCT01309360)
Timeframe: 60 minutes after administration of the local anesthetic

Interventionparticipants (Number)
Group A : 40ml Prilocaine 1%38
Group B : 30ml Prilocaine 1%39
Group C : 20ml Prilocaine 1%39

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Number of Participants Who Experience Symptoms of Nausea and Vomiting Will be Compared Between the Two Groups

The number of participants who experience symptoms of nausea and vomiting in the two groups of patients will be recorded. This will be recorded during the follow-up phone call made 24-48 hours after the procedure. (NCT01315158)
Timeframe: 24-48 hours

Interventionparticipants (Number)
Propofol+Benzo/Opioids2
Propofol Alone1

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Number of Participants Who Experience Airway Maneuvers

In high risk patients (meeting at least of 1 of 3 criteria: ASA ≥ 3, BMI ≥ 30, those at risk for OSA) undergoing advanced endoscopy procedures, compare the number of participants who experience airway maneuvers (AMs) when sedated with propofol alone versus propofol in combination with benzodiazepines and opioids. (NCT01315158)
Timeframe: One day (during procedure)

Interventionparticipants (Number)
Propofol+Benzo/Opioids4
Propofol Alone4

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Duration of Mechanical Ventilation Days

Participants will be followed for an expected average of 4 days. The Data Safety Monitoring Group will review the data every 6 months. (NCT01333059)
Timeframe: From date of randomization until the date of discharge from PICU, assessed up to 1 month

Interventiondays (Mean)
Experimental Group10.14
Control Group5.82

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Hospital Length of Stay

Participants will be followed for an expected average of 7 days in PICU and 10 days of hospitalization. This secondary endpoint is to be evaluated every six months. (NCT01333059)
Timeframe: From date of hospital admission to date of hospital discharge, assessed up to 6 weeks

Interventiondays (Mean)
Experimental Group25.21
Control Group20.82

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PICU Length of Stay

Participants will be followed for an expected average of 7 days. This secondary endpoint is to be evaluated every six months. (NCT01333059)
Timeframe: From date of randomization until the date of discharge from PICU, assessed up to 1 month

Interventiondays (Mean)
Experimental Group13.93
Control Group9.82

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AUC of Dextromethorphan, Midazolam and Omeprazole in the Presence of Fluoxetine

Our secondary outcome measure will be the interaction between fluoxetine and each CYP evaluated in the cocktail. A 50% increase in the AUC of caffeine (CYP1A2), dextromethorphan (CYP2D6), omeprazole (CYP2C19) or midazolam (CYP3A4) between treatment and control days is considered clinically significant. The interaction of fluoxetine with caffeine (CYP1A2) will be considered as a negative control for the study. These AUCs will be measured on study day 1 (control day) and study day 18 (NCT01361217)
Timeframe: The secondary outcome will be assessed within 2 months after the last subject is enrolled or at 2 years from the start of study enrollment, which ever is sooner.

Interventionnmol*hr/L (Mean)
caffeine control AUCCaffeine treatment AUCdextromethophan control AUCDextromethorphan treatment AUCOmeprazole control AUComeprazole treatment AUCmidazolam control AUCmidazolam treatment AUC
Midazolam, Caffeine, Omeprazole, Caffeine AUC After Fluoxetine4300043000681850120085003024

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Lovastatin AUC in the Presence of Fluoxetine

Our primary outcome measure will be the interaction of fluoxetine with CYP3A4. A 50% increase in the AUC for lovastatin plus hydroxy-lovastatin acid (the active form of lovastatin) between treatment day 14 (study day 20) and control days (study day 2) is considered clinically significant. (NCT01361217)
Timeframe: The primary outcome will be assessed within 2 months after the last subject is enrolled or at 2 years from the start of study enrollment, which ever is sooner.

Interventionnmol*hr/L (Mean)
Lovastatin AUC After Fluoxetine Dosing170
Lovastatin Before Fluoxetine180

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Percentage of Patients Who Meet Response and Remission

Percentage of patients who meet response (defined as 25% reduction in Y-BOCCS score) and remission (defined as Y-BOCS score ≤10) criteria at 24 hrs post-infusion and durability of efficacy up to two weeks after administration. Assessments will be performed 24, 48 and 72 hrs post-infusion and after 7, 10, and 14 days. (NCT01371110)
Timeframe: up to 14 days

Interventionpercentage of participants (Number)
Ketamine (Randomized Week 1, Cross Over Midazolam Week 3))0
Midazolam (Randomized Wk 1, Cross Over Ketamine Wk 3)50

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Change in Yale-Brown Obsessive Compulsive Scale (Y-BOCCS) Rating OCD Symptom Severity From Baseline to 24-hours After Ketamine Administration

"The primary efficacy outcome is change in the Y-BOCCS rating score on a scale from baseline to 24 hrs post-administration of ketamine.~The 10 Y-BOCCS items are each scored on a four-point scale from 0 = no symptoms to 4 = extreme symptoms. The sum of the first five items is a severity index for obsessions. The sum of the last five an index for compulsions. A translation of total score into an approximate index of overall severity is: 0-7 - subclinical; 8-15 - mild; 16-23 - moderate; 24-31 - severe; 32-40 - extreme." (NCT01371110)
Timeframe: Baseline and 24 Hours

InterventionUnits on a scale (Mean)
Ketamine (Randomized Week 1, Cross Over Midazolam Week 3))-2.98
Midazolam (Randomized Wk 1, Cross Over Ketamine Wk 3)-2.185

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Participants With Seizure(s) >10 Minutes to 4 Hours After Administration of the Double-blind Dose

Participants with recurrence of seizure(s) >10 minutes and up to 4 hours after administration of the double-blind dose in the CP. Participants who received the open-label second dose within 4 hours of administration of the double-blind dose were analyzed as having had a seizure. (NCT01390220)
Timeframe: 4 hours

InterventionParticipants (Count of Participants)
USL261 CP51
Placebo CP40

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Participants Who Met the Criteria for Treatment Success After Administration of the Double-blind Dose in the Comparative Phase (CP)

Treatment Success is defined as achieving both of the following: 1) termination of seizure(s) within 10 minutes after double-blind study drug administration, and 2) no recurrence of seizure(s) beginning 10 minutes after study drug administration to 6 hours after study drug administration. Participants who received the open-label second dose within 6 hours of administration of the double-blind dose were analyzed as having had a seizure. (NCT01390220)
Timeframe: 6 hours

InterventionParticipants (Count of Participants)
USL261 CP72
Placebo CP23

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Occurrence of Seizure With a Start Time >10 Minutes After Administration of the Double-blind Dose

Occurrence of next seizure with a start time >10 minutes and up to 24 hours after administration of the double-blind dose in the CP. Participants who did not have another seizure before the end of the 24-hour observation period were censored at the end of the observation period. Participants administered the open-label second dose who did not have a seizure were censored at the time of the administration. (NCT01390220)
Timeframe: 24 hours

InterventionParticipants (Count of Participants)
USL261 CP50
Placebo CP31

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PK: Maximum Plasma Concentration (Cmax) of LY2228820

(NCT01393990)
Timeframe: Cycle 1, Days 1 and 14: predose, 0.5, 1, 2, 3, 4, 6 and 8 h postdose

,,,,,,,,,,,,,,
Interventionng/mL (Geometric Mean)
Cycle 1 Day 1Cycle 1 Day 14
Part A and Part B: 420 mg LY2228820 Tablets17002230
Part A and Part C: 300 mg LY2228820 Tablets10201400
Part A: 10 mg LY2228820 Capsules14.728.4
Part A: 120 mg LY2228820 Capsules405530
Part A: 160 mg LY2228820 Capsules6061930
Part A: 160 mg LY2228820 Tablets454574
Part A: 20 mg LY2228820 Capsules90.181.4
Part A: 200 mg LY2228820 Capsules6731330
Part A: 200 mg LY2228820 Tablets636963
Part A: 40 mg LY2228820 Capsules144252
Part A: 560 mg LY2228820 Tablets2360NA
Part A: 65 mg LY2228820 Capsules135415
Part A: 90 mg LY2228820 Capsules202208
Part D: 200 mg LY2228820 Tablets7181030
Part D: 300 mg LY2228820 Tablets18101700

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PK: Area Under the Concentration-Time Curve From Time Zero to 8 Hours (AUC0-8) of LY2228820

(NCT01393990)
Timeframe: Cycle 1, Days 1 and 14: predose, 0.5, 1, 2, 3, 4, 6 and 8 h postdose

,,,,,,,,,,,,,,
Interventionnanograms*hour/milliliter (ng*hr/mL) (Geometric Mean)
Cycle 1 Day 1Cycle 1 Day 14
Part A and Part B: 420 mg LY2228820 Tablets578010200
Part A and Part C: 300 mg LY2228820 Tablets34606620
Part A: 10 mg LY2228820 Capsules55.6151
Part A: 120 mg LY2228820 Capsules13101960
Part A: 160 mg LY2228820 Capsules21206000
Part A: 160 mg LY2228820 Tablets17502810
Part A: 20 mg LY2228820 Capsules257372
Part A: 200 mg LY2228820 Capsules25506220
Part A: 200 mg LY2228820 Tablets1720NA
Part A: 40 mg LY2228820 Capsules3751070
Part A: 560 mg LY2228820 Tablets8880NA
Part A: 65 mg LY2228820 Capsules4451300
Part A: 90 mg LY2228820 Capsules707827
Part D: 200 mg LY2228820 Tablets23603810
Part D: 300 mg LY2228820 Tablets45006910

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Percentage of Participants With Best Overall Response [Complete Response (CR)+Partial Response (PR)+Stable Disease (SD)]

Response was defined using Response Evaluation Criteria In Solid Tumors (RECIST, version 1.1) criteria. CR was defined as the disappearance of all target and non-target lesions and normalization of tumor marker level in non-target lesions. PR was defined as having at least a 30% decrease in sum of longest diameter (LD) of target lesions. PD was defined as having at least a 20% increase in the sum of the LD of target lesion and appearance of ≥1 new lesion and/or unequivocal progression of existing nontarget lesions. SD was defined as small changes that did not meet the above criteria taking as reference the smallest sum LD since treatment started. (NCT01393990)
Timeframe: Baseline to study completion (Up to 41 months)

Interventionpercentage of participants (Number)
Part A: 10 mg LY2228820 Capsules25.0
Part A: 20 mg LY2228820 Capsules33.3
Part A: 40 mg LY2228820 Capsules33.3
Part A: 65 mg LY2228820 Capsules33.3
Part A: 90 mg LY2228820 Capsules40.0
Part A: 120 mg LY2228820 Capsules33.3
Part A: 160 mg LY2228820 Capsules66.7
Part A: 200 mg LY2228820 Capsules28.6
Part A: 160 mg Bridge LY222882016.7
Part A: 160 mg LY2228820 Tablets33.3
Part A: 200 mg LY2228820 Tablets33.3
Part A: 300 mg LY2228820 Tablets0.0
Part A: 420 mg LY2228820 Tablets33.3
Part A: 560 mg LY2228820 Tablets0.0
Part B: 420 mg LY2228820 Tablets16.7
Part C: 300 mg LY2228820 Tablets0.0
Part D: 200 mg LY2228820 Tablets0.0
Part D: 300 mg LY2228820 Tablets16.7

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Number of Participants With Clinically Significant Effects (Physical Assessments and Safety Lab Tests)

Data presented are the number of participants who experienced at least one treatment emergent adverse event (TEAE). A TEAE is defined as an event that first occurred or worsened after the administration of at least 1 dose of study drug, regardless of causality. A summary of serious AEs (SAEs) and other non-serious AEs, regardless of causality, is located in the Reported Adverse Events module. (NCT01393990)
Timeframe: Baseline to study completion (Up to 41 months)

InterventionParticipants (Count of Participants)
Part A: 10 mg LY2228820 Capsules1
Part A: 20 mg LY2228820 Capsules3
Part A: 40 mg LY2228820 Capsules2
Part A: 65 mg LY2228820 Capsules3
Part A: 90 mg LY2228820 Capsules1
Part A: 120 mg LY2228820 Capsules1
Part A: 160 mg LY2228820 Capsules1
Part A: 200 mg LY2228820 Capsules5
Part A: 160 mg LY2228820 Bridge4
Part A: 160 mg LY2228820 Tablets1
Part A: 200 mg LY2228820 Tablets3
Part A: 300 mg LY2228820 Tablets3
Part A: 420 mg LY2228820 Tablets3
Part A: 560 mg LY2228820 Tablets4
Part B: 420 mg LY2228820 Tablets18
Part C: 300 mg LY2228820 Tablets7
Part D: 200 mg LY2228820 Tablets3
Part D: 300 mg LY2228820 Tablets6

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Pharmacodynamics (PD): Number of Participants With Greater Than 50% Inhibition of p38 Mitogen-Activated Protein Kinase (MAPK) Activity on Day 1

The effect of LY2228820 on PD biomarker was measured as MAPK-activated protein kinase -2 (MAPKAP-K2) level which is regulated by p38 MAPK activity. Inhibition of p38 MAPK activity will result in lower levels of MAPKAPK-2. (NCT01393990)
Timeframe: Cycle 1 Day 1: predose, 1, 2, 4, and 6 h postdose

InterventionParticipants (Count of Participants)
Part A, C and D: LY2228820 300 mg Tablets14

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Duration of Recovery After the Endoscopic Procedure

"After completion of the procedure, the patient stood in the examination room monitored continuously by a nurse. When patients responded to normal verbal command, they were asked to sit up and were offered a drink. This was considered the early recovery time.~If they were able to stand unassisted by the bed and had stable hemodynamics parameters (saturation>90 % on room air and blood pressure and heart rate within 20 % of baseline), they were transferred to a locker room accompanied by a relative. The discharge criteria included ability to stand unassisted and tolerate clear liquids once dressed. Once a patient met discharge criteria, they were allowed to leave at their own discretion" (NCT01428882)
Timeframe: Up to 1 hour after colonoscopy

,
Interventionminutes (Mean)
Early recovery timeDischarge time
Midazolam Balanced Propofol Sedation6.810.4
Single-agent Propofol Sedation5.39.80

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Level of Sedation Throughout the Entire Procedure

Assessment every two minutes of the level of sedation during the endoscopic procedure, rating it as minimal, moderate or deep. (NCT01428882)
Timeframe: Up to 1 hour after introduction of the colonoscope

,
Interventionparticipants (Number)
Deep sedation at any pointDeep sedation at minute 4Deep sedation at minute 6Deep sedation at minute 8
Midazolam Balanced Propofol Sedation22101210
Single-agent Propofol Sedation9123

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Rate of Patients and Physician Satisfaction With Sedation

"Endoscopists and patients rated their satisfaction with sedation in a 10-cm visual analogue scale after discharge.The patients were contacted 24-48 h after the procedure to answer a questionnaire regarding if they remembered scope insertion or scope removal and willingness to repeat it with a similar protocol and rated their satisfaction and pain perception from 0 to 10. This phone survey was done by the nurse specifically making the measurements in the endoscopy room, who was blinded to the sedation regimen.~For the interpretation of results of the 0-10 point numerical scale, 0 stands for 'extremely dissatisfied with sedation level during the endoscopic procedure', whereas 10 stands for 'extremely satisfied with sedation level during the endoscopic procedure." (NCT01428882)
Timeframe: Up to 1 hour after colonoscopy for endoscopists and up to 48 hours for patients

,
Interventionunits on a scale (Mean)
Endoscopist SatisfactionPatient Satisfaction
Midazolam Balanced Propofol Sedation8.99.8
Single-agent Propofol Sedation8.49.5

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Intensive PK Sub-study: Minimum Concentrations (Cmin) of DAC HYP

(NCT01462318)
Timeframe: Day 141 (Week 20) at pre-dose and 8, 24, 72 and 120 hours post-dose and 7, 10, 14 and 21 days post-dose

Interventionmcg/mL (Mean)
Main Study14.93

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Intensive PK Sub-study: Elimination Half-life (t½) of DAC HYP

(NCT01462318)
Timeframe: Day 141 (Week 20) at pre-dose and 8, 24, 72 and 120 hours post-dose and 7, 10, 14 and 21 days post-dose

Interventionday (Mean)
Main Study21.92

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Intensive PK Sub-study: Apparent Volume of Distribution (V/F) of DAC HYP

(NCT01462318)
Timeframe: Day 141 (Week 20) at pre-dose and 8, 24, 72 and 120 hours post-dose and 7, 10, 14 and 21 days post-dose

InterventionLiters (Mean)
Main Study8.21

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Intensive PK Sub-study: Apparent Clearance (CL/F) of DAC HYP

(NCT01462318)
Timeframe: Day 141 (Week 20) at pre-dose and 8, 24, 72 and 120 hours post-dose and 7, 10, 14 and 21 days post-dose

InterventionL/day (Mean)
Main Study0.27

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Number of Participants With Anti-DAC HYP Binding Antibodies (ADAbs): Electrochemiluminescent (ECL) Anti-Drug Antibody (ADA) Assay

Participants with post-baseline (PB) ADAbs through Week 44, in the treatment period (extends up to 42 days after the last dose during the main study), and in the post-treatment period (43 days after the last dose until the end of the post-treatment period dose). (NCT01462318)
Timeframe: Up to 44 weeks

Interventionparticipants (Number)
PB ADAbs through Week 44=negative; n=113PB ADAbs through Week 44=positive; n=113PB ADAbs in treatment period=negative; n=113PB ADAbs in treatment period=positive; n=113PB ADAbs in post-treatment period=negative; n=110PB ADAbs in post-treatment period=positive; n=110
Main Study783592218921

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TP-DI Sub-study: CL/F of Each Probe Drug

CL/F of each of the following CYP isoenzyme substrates: midazolam (CYP3A), warfarin + vitamin K (CYP2C9), and omeprazole (CYP2C19). (NCT01462318)
Timeframe: Week 43 (7 days prior to DAC HYP administration) and Week 53 (7 days after DAC HYP administration), pre-cocktail dose and at 0.5 and 1, 2, 3, 4, 6, 8, 10 , 24, 48, 72 and 96 hours post-probe drug cocktail administration

InterventionmL/hr (Mean)
Midazolam (Period 1); n=20Midazolam+DAC HYP (Period 2); n=19S-Warfarin (Period 1); n=17S-Warfarin+DAC HYP (Period 2); n=18Omeprazole (Period 1); n=18Omeprazole+DAC HYP (Period 2); n=19
TP-DI Sub-study7625.77298.6565.86541.4641612.441772.4

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TP-DI Sub-study: Omeprazole/Hydroxyomeprazole Concentration Ratio at 2 Hours Post-omeprazole Dosing

(NCT01462318)
Timeframe: Week 43 (7 days prior to DAC HYP administration) and Week 53 (7 days after DAC HYP administration) at 2 hours after probe drug cocktail administration

Interventionratio (Mean)
Omeprazole (Period 1)Omeprazole+ DAC HYP (Period 2)
TP-DI Sub-study2.6731.028

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TP-DI Sub-study: Dextromethorphan to Dextrorphan Urine Concentration Ratio

(NCT01462318)
Timeframe: Week 43 (7 days prior to DAC HYP administration) and Week 53 (7 days after DAC HYP administration), pre-cocktail dose and for 12 hours after probe-drug cocktail administration

Interventionratio (Mean)
Dextromethorphan (Period 1)Dextromethorphan+DAC HYP (Period 2)
TP-DI Sub-study0.424680.48939

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TP-DI Sub-study: Cmax of Each Probe Drug

Cmax of each of the following CYP isoenzyme substrates: midazolam (CYP3A), caffeine (CYP1A2), warfarin + vitamin K (CYP2C9), and omeprazole (CYP2C19). (NCT01462318)
Timeframe: Week 43 (7 days prior to DAC HYP administration) and Week 53 (7 days after DAC HYP administration), pre-cocktail dose and at 0.5 and 1, 2, 3, 4, 6, 8, 10 , 24, 48, 72 and 96 hours post-probe drug cocktail administration

Interventionng/mL (Mean)
Midazolam (Period 1); n=20Midazolam+DAC HYP (Period 2); n=19Caffeine (Period 1); n=20Caffeine+DAC HYP (Period 2); n=19S-Warfarin (Period 1); n=20S-Warfarin+DAC HYP (Period 2); n=19Omeprazole (Period 1); n=19Omeprazole+DAC HYP (Period 2); n=19
TP-DI Sub-study271.05311.214965.05399.5635.65649.74776.95771.16

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TP-DI Sub-study: Area-Under-the-Curve From Zero to Infinity (AUCinf) of Each Probe Drug

AUCinf of each of the following cytochrome P450 (CYP) isoenzyme substrates: midazolam (CYP3A), S-warfarin + vitamin K (CYP2C9), and omeprazole (CYP2C19). The AUC from zero to 12 hours (AUC0-12) was calculated for caffeine (CYP1A2). (NCT01462318)
Timeframe: Week 43 (7 days prior to DAC HYP administration) and Week 53 (7 days after DAC HYP administration), pre-cocktail dose and at 0.5 and 1, 2, 3, 4, 6, 8, 10 , 24, 48, 72 and 96 hours post-probe drug cocktail administration

Interventionhr*ng/mL (Mean)
Midazolam (Period 1) AUCinf; n=20Midazolam+DAC HYP (Period 2) AUCinf; n=19S-warfarin (Period 1) AUCinf; n=17S-warfarin+DAC HYP (Period 2) AUCinf; n=18Omeprazole (Period 1) AUCinf; n=18Omeprazole+DAC HYP (Period 2) AUCinf; n=19Caffeine (Period 1) AUC0-12; n=20Caffeine+DAC HYP (Period 2) AUC0-12; n=20
TP-DI Sub-study786.75816.8719292.919609.32214.51770.035742.437449.2

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Number of Participants With Anti-DAC HYP Neutralizing Antibodies (NAbs): ECL ADA Assay

Participants with PB NAbs through Week 44, in the treatment period (extends up to 42 days after the last dose during the main study), and in the post-treatment period (43 days after the last dose until the end of the post-treatment period dose). (NCT01462318)
Timeframe: Up to 44 weeks

Interventionparticipants (Number)
PB NAbs through Week 44=negative; n=113PB NAbs through Week 44=positive; n=113PB NAbs in treatment period=negative; n=113PB NAbs in treatment period=positive; n=113PB NAbs in post-treatment period=negative; n=110PB NAbs in post-treatment period=positive; n=110
Main Study105810941046

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Intensive PK Sub-study: Time to Reach Maximum Concentration (Tmax) of DAC HYP

(NCT01462318)
Timeframe: Day 1 and Day 141 (Week 20) at pre-dose and 8, 24, 72, and 120 hours post-dose and 7, 10, 14 and 21 days post-dose

Interventionday (Mean)
Day 1 (Week 0); n=25Day 141 (Week 20); n=24
Main Study9.316.41

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Intensive PK Sub-study: Cmax of DAC HYP

(NCT01462318)
Timeframe: Day 1 and Day 141 (Week 20) at pre-dose and 8, 24, 72, and 120 hours post-dose and 7, 10, 14 and 21 days post-dose

Interventionmcg/mL (Mean)
Day 1 (Week 0); n=25Day 141 (Week 20); n=24
Main Study12.6329.07

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Intensive PK Sub-study: Area-Under-the-Curve From Start to End of the Dosing Interval (AUCtau) of DAC HYP

(NCT01462318)
Timeframe: Day 1 and Day 141 (Week 20) at pre-dose and 8, 24, 72, and 120 hours post-dose and 7, 10, 14, and 21 days post-dose

Interventionday*mcg/mL (Mean)
Week 0 (Day 1); n=25Week 20; n=24
Main Study255.25638.10

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Satisfaction

5-point Likert scale. The scale is from 1-5. 1 being very unsatisfied and 5 being very satisfied. (NCT01472835)
Timeframe: 1 day

Interventionunits on a scale (Mean)
Sedation4.0
Control3.6

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Pain Score

pain diary using 0-10 scale, with 0 being no pain and 10 being the worst pain imaginable (NCT01472835)
Timeframe: through 6 hours after injection

Interventionunits on a scale (Mean)
Sedation2.2
Control3.4

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Pain Score

0-10 numerical rating scale (NRS) pain scale. 0 being no pain and 10 being the worst possible pain. (NCT01472835)
Timeframe: 1-month

Interventionunits on a scale (Mean)
Sedation5.1
Control5.6

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Oswestry Disability Index

Measure of functional capacity on a scale ranging from 0% to 100%, with 0% signifying no disability (NCT01472835)
Timeframe: 1-month

Interventionunits on a scale (Mean)
Sedation34.8
Control40.6

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Physician Perceptions (Absolute Value)

Self-reported Physician/Endoscopist perceptions Measured via Visual Analog Scale [0-10] of: Highest pain, Average pain, Difficulty of procedure, Bowel preparation, Patient movement. A score of 0 on the scale=no pain/difficulty, while a score of 10=worst possible pain/difficulty/severity. The higher the score the worse the outcome. (NCT01488045)
Timeframe: Measured via physician survey within 30 minutes after the procedure

,
Interventionscore on a scale (Mean)
Endoscopist rating: Highest PainEndoscopist rating: Average PainEndoscopist rating: Difficulty of ProcedureEndoscopist rating: Bowel preparationEndoscopist rating: Patient Movement
Midazolam/Fentanyl Intervention3.72.15.21.31.6
Propofol Intervention1.30.64.41.41.3

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Patient Satisfaction Scores (Absolute Value)

Measured by the patient using a 100-point Visual Analog Scale (VAS) [0-100%] with higher score indicating higher agreement with the statement/question. Higher agreement scores would indicate higher satisfaction (better outcome). (NCT01488045)
Timeframe: "Survey administered in the recovery room up to 30 minutes following procedure (Recovery room), and a follow-up patient survey was carried out by telephone between 1 and 5 days postprocedure (1-5 d postprocedure)"

,
Interventionscore on a scale (Mean)
Recovery Room: Satisfaction with colonoscopyRecovery Room: Would undergo another colonoscopy with same sedationRecovery Room: Would encourage others to have same sedationRecovery Room: Comfort1-5 d postprocedure: Satisfaction with colonoscopy1-5d postprocedure: Would undergo another colonoscopy with same sedation1-5d postprocedure: Would encourage others to have same sedation1-5d postprocedure: Comfort
Midazolam/Fentanyl Intervention83.979.279.586.179.873.974.584.4
Propofol Intervention98.098.1100.088.898.798.298.294.7

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Patient Pain & Discomfort Rating (Absolute Value)

Self-reported by patient via a Visual Analog Scale [0-10], where 0=no pain, 10=worst possible pain (NCT01488045)
Timeframe: "Survey administered in the recovery room up to 30 minutes following procedure (Recovery room), and a follow-up patient survey was carried out by telephone between 1 and 5 days postprocedure (1-5 d postprocedure)"

,
Interventionscore on a scale (Mean)
Recovery room: patient highest painRecovery room: Average painRecovery room: Average discomfort during recovery1-5d postprocedure: Highest pain1-5d postprocedure: Average pain1-5d postprocedure: Average discomfort during recovery
Midazolam/Fentanyl Intervention2.41.91.21.90.71.7
Propofol Intervention0.20.80.70.160.40.17

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The Young Mania Rating Scale (YMRS)

An 11-item questionnaire, used to assess manic symptoms based on the patient's subjective report of his or her clinical condition. There are four items that are graded on a 0 to 8 scale (irritability, speech, thought content, and disruptive/aggressive behavior), while the remaining seven items are graded on a 0 to 4 scale. The scores from each question are added together to form a total score ranging from 0 to 60, with higher scores indicating a greater severity of symptoms. (NCT01507181)
Timeframe: baseline, 40 minutes post infusion, 240 minutes post infusion

,
Interventionunits on a scale (Mean)
baseline40 minutes post infusion240 minutes post infusion
Ketamine0.00.00.2
Midazolam0.10.30.2

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The Clinician-Administered Dissociative States Scale (CADSS)

The CADSS measures dissociation with higher scores indicating more severe symptoms (scale range 0 - 92). (NCT01507181)
Timeframe: baseline, 40 minutes post infusion and 240 minutes post infusion

,
Interventionunits on a scale (Mean)
baseline40 minutes post infusion240 minutes post infusion
Ketamine1.117.11.2
Midazolam4.03.31.3

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Montgomery-Asberg Depression Rating Scale (MADRS)

The MADRS is a 10-item instrument used for the evaluation of depressive symptoms in adults and for the assessment of any changes to those symptoms. Higher MADRS score indicates more severe depression, and each item yields a score of 0 to 6. The overall score ranges from 0 to 60. (NCT01507181)
Timeframe: up to 7 days post infusion

,
Interventionunits on a scale (Mean)
24 hours48 hours72 hours7 days
Ketamine19.019.320.921.7
Midazolam26.22824.122.2

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Change in Beck Scale for Suicidal Ideation (BSSI)

Change in BSI score at 48 hours following treatment as compared to baseline. Beck Scale is a 21-item self or clinician administered instrumentation used to measure the current intensity of patients' specific attitudes, behaviors and plans to commit suicide. Score range 0-42, with higher score indicating higher intensity. (NCT01507181)
Timeframe: baseline and 48 hours post infusion

Interventionunits on a scale (Mean)
Ketamine8.8
Midazolam15.3

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Suicidality Item of the MADRS (MADRS-SI)

The MADRS-SI ranges from 0 to 6; a score of 2 corresponds to fleeting, passive SI; a score of 4 indicates that SI is frequent with at least moderate intensity but without specific plans or intention; a score of 6 corresponds to active intention and planning for suicide. (NCT01507181)
Timeframe: 24 hours post infusion

Interventionunits on a scale (Mean)
Ketamine1.8
Midazolam3.3

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Change in Beck Scale for Suicidal Ideation (BSSI)

Change in BSI score at 24 hours following treatment as compared to baseline. Beck Scale is a 21-item self or clinician administered instrumentation used to measure the current intensity of patients' specific attitudes, behaviors and plans to commit suicide. Score range 0-42, with higher score indicating higher intensity. (NCT01507181)
Timeframe: baseline and 24 hours post infusion

Interventionunits on a scale (Mean)
Ketamine10.8
Midazolam14.0

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The Brief Psychiatric Rating Scale (BPRS)

The BPRS measures psychomimetic effects with higher scores indicating more severe symptoms (scale range 7 - 49). (NCT01507181)
Timeframe: baseline, 40 minutes post infusion, and 240 minutes post infusion

,
Interventionunits on a scale (Mean)
baseline40 minutes post infusion240 minutes post infusion
Ketamine7.79.98.1
Midazolam7.77.97.0

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Patient Rated Inventory of Side Effects (PRISE)

The PRISE assesses the presence of treatment side effects in nine organ/function systems (gastrointestinal, nervous system, heart, eyes/ears, skin, genital/urinary, sleep, sexual functioning, and other). Data reported in in Adverse Events section. (NCT01507181)
Timeframe: duration of study

Interventionevents (Number)
Ketamine29
Midazolam23

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Time Spent With a Total N-PASS Score >3 During DEX Infusion

The N-PASS score >3 indicates adequately sedated and not manifesting signs of pain/agitation. (NCT01508455)
Timeframe: Predose, loading dose (LD) 5 & 10mins/if LD is 20mins (5, 10, 15 & 20mins); maintenance infusion: 0 min, every 15mins (1st hr); every 30mins (2hrs), then hourly; within 5mins of DEX discontinuation; 5mins pre and post rescue medication

InterventionHours (Mean)
Dexmedetomidine0.44

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Percent of Subjects Requiring Rescue Midazolam for Sedation

(NCT01508455)
Timeframe: During the study drug administration (ie., loading dose 10 or 20 minutes and maintenance infusion minimum of 6 hours up to 24 hours) and during the post drug administration (up to 24 hours).

Interventionpercentage of participants (Number)
Dexmedetomidine0

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Incidence of Rescue Medication (Fentanyl or Morphine) Use for Analgesia During DEX Infusion

(NCT01508455)
Timeframe: During the study drug administration (ie., loading dose 10 or 20 minutes and maintenance infusion minimum of 6 hours up to 24 hours) and during the post drug administration (up to 24 hours).

Interventionparticipant (Number)
Dexmedetomidine1

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Amount of Rescue Medication for Analgesia During DEX Infusion

(NCT01508455)
Timeframe: During the study drug administration (ie., loading dose 10 or 20 minutes and maintenance infusion minimum of 6 hours up to 24 hours) and during the post drug administration (up to 24 hours).

Interventionmcg/kg (Number)
Dexmedetomidine1

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Time to Successful Extubation

(NCT01508455)
Timeframe: From the start of study drug infusion to the study completion/withdrawal (Approximately 48 hours)

InterventionHours (Median)
Dexmedetomidine37.3

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Number of Subjects Who Were Adequately Sedated at Least 80% of Time

Subjects who are adequately sedated (UMSS score of 1 to 3 or NPASS score of -5 to -2) at least 80% of the time sedated with the study drug (NCT01519167)
Timeframe: During the treatment period, up to approximately 24 hours

,
Interventionparticipants (Number)
NIDTP (n=1, 40)MIDTP (n=0, 25)Surgical procedures (n=0, 12)
Dose Level 1000
Dose Level 22172

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Number of Subjects Who Had Success in Sedation

"Success in sedation was defined by a combined endpoint which was the combination of the following:~Subject had adequate level of sedation (University of Michigan Sedation Scale [UMSS] score between 1 to 3 [minimally sedated to deeply sedated] or Neonatal Pain, Agitation and Sedation Scale [N-PASS] score between -5 to -2 [Light sedation]) at least 80% of the time the subject was given the study drug.~Subject had successfully completed the procedure without a need for rescue sedation (Midazolam).~Subject had undergone the procedure without artificial ventilation or intervention to restore baseline or normal hemodynamic status" (NCT01519167)
Timeframe: From baseline to end of post-treatment period (approximately 24 hours)

,
Interventionparticipants (Number)
NIDTP (n=1, 40)MIDTP (n=0, 25)Surgical procedures (n=0, 12)
Dose Level 1000
Dose Level 2200

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Frequency of Midazolam Required for Sedation

Frequency of rescue sedation (midazolam) required to maintain a subject within the target sedation range (UMSS score greater than 1 or N-PASS score less than -2). (NCT01519167)
Timeframe: During the treatment period, up to approximately 24 hours

InterventionOccurrence (Median)
NIDTP (n=0, 28)MIDTP (n=0, 20)Surgical procedures (n=0, 11)
Dose Level 2211

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Number of Subjects Who Have Undergone Procedures Without Artificial Ventilation or Intervention

(NCT01519167)
Timeframe: During the treatment period, up to approximately 24 hours

,
Interventionparticipants (Number)
NIDTP (n=1, 40)MIDTP (n=0, 25)Surgical procedures (n=0, 12)
Dose Level 1100
Dose Level 2371912

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Frequency of Fentanyl Use for Analgesia

Frequency of rescue analgesia (fentanyl) required from the start of IV sedation to completion of the procedure. (NCT01519167)
Timeframe: During the treatment period, up to approximately 24 hours

InterventionOccurrence (Median)
NIDTP (n=0, 6)MIDTP (n=0, 22)Surgical procedures (n=0, 12)
Dose Level 2112.50

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Number of Subjects Not Receiving Rescue Midazolam

Number of subjects who did not receive any rescue midazolam for sedation during the study drug infusion. (NCT01519167)
Timeframe: During the treatment period, up to approximately 24 hours

,
Interventionparticipants (Number)
NIDTP (n=1, 40)MIDTP (n=0, 25)Surgical procedures (n=0, 12)
Dose Level 1100
Dose Level 21251

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Time to First Dose of Rescue Midazolam From Start of Dexmedetomidine Infusion

Kaplan-Meier estimates of time in minutes to first dose of rescue midazolam from onset of study drug infusion (NCT01519167)
Timeframe: During the treatment period, up to approximately 24 hours

,
InterventionHours (Median)
NIDTP (n=1, 40)MIDTP (n=0, 25)Surgical procedures (n=0, 12)
Dose Level 1NANANA
Dose Level 223.520.0020.00

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Total Amount of Rescue Analgesia (Fentanyl)

Total amount of rescue analgesia (fentanyl) required from the start of IV sedation to completion of the procedure (NCT01519167)
Timeframe: During the treatment period, up to approximately 24 hours

Interventionmicrogram (Mean)
NIDTP (n=0, 6)MIDTP (n=0, 22)Surgical procedures (n=0, 12)
Dose Level 210.8361.86104.83

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Total Amount of Rescue Sedation (Midazolam)

Total amount of rescue sedation (midazolam) required from the start of IV sedation to completion of the procedure (NCT01519167)
Timeframe: During the treatment period, up to approximately 24 hours

Interventionmilligram (Mean)
NIDTP (n=0, 28)MIDTP (n=0, 20)Surgical procedures (n=0, 11)
Dose Level 22.621.702.45

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Number of Subjects Converted to Alternative Sedation or Anesthetic Therapy Due to Failure of Treatment of Study Drug and Rescue Medication

(NCT01519167)
Timeframe: During the treatment period, up to approximately 24 hours

,
InterventionParticipants (Number)
NIDTP (n=1, 40)MIDTP (n=0, 25)Surgical procedures (n=0, 12)
Dose Level 1000
Dose Level 2002

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Cmax of Midazolam

Maximum concentration of an analyte in plasma (NCT01525628)
Timeframe: 5 min before and 1 hour (h), 2h, 3h, 4h, 5h, 6h, 8h, 10h, 11:55h, 15h, 23:55h, 26h, 28h, 29:55h, 32h after first drug administration on day 1 also 5 min before, 1h, 2h, 3h, 4h, 5h, 5:55h, 8h, 10h, 11:55h, 15h, 23:55h after drug on days 9, 17 and 66.

,
Interventionnmol/L (Geometric Mean)
Day 1 (N=16, 19)Day 9 (N=15, 17)Day 17 (N=14, 19)Day 66 (N=13, 15)
Group A21.129.931.921.3
Group B23.829.828.823.2

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Cmax of Tolbutamide

Maximum concentration of an analyte in plasma (NCT01525628)
Timeframe: 5 min before and 1 hour (h), 2h, 3h, 4h, 5h, 6h, 8h, 10h, 11:55h, 15h, 23:55h, 26h, 28h, 29:55h, 32h after first drug administration on day 1 also 5 min before, 1h, 2h, 3h, 4h, 5h, 5:55h, 8h, 10h, 11:55h, 15h, 23:55h after drug on days 9, 17 and 66.

,
Interventionnmol/L (Geometric Mean)
Day 1 (N=16, 19)Day 9 (N=15, 17)Day 17 (N=14, 19)Day 66 (N=13, 15)
Group A152000146000130000110000
Group B170000158000126000127000

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AUC 0-6hr of Deleobuvir Reduction Metabolite CD 6168

Area under the concentration-time curve of the analyte in plasma over the time interval from 0 to 6 hours (NCT01525628)
Timeframe: PK plasma samples were taken at: 5 minutes before drug administration and 1 hour (h), 2h, 3h, 4h, 5h, 5:55h, 8h, 10h, 11:55h, 15h, 23:55h after first drug administration on days 9, 17 and 66.

,
Interventionnmol*h/L (Geometric Mean)
Day 9 (N=0, 17)Day 17 (N=14, 19)Day 66 (N=13, 15)
Group ANA4170019300
Group B133006220039100

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AUC 0-6hr of Deleobuvir Metabolite Acyl-glucuronide (BI 208333)

Area under the concentration-time curve of the analyte in plasma over the time interval from 0 to 6 hours (NCT01525628)
Timeframe: PK plasma samples were taken at: 5 minutes before drug administration and 1 hour (h), 2h, 3h, 4h, 5h, 5:55h, 8h, 10h, 11:55h, 15h, 23:55h after first drug administration on days 9, 17 and 66.

,
Interventionnmol*h/L (Geometric Mean)
Day 9 (N=0, 17)Day 17 (N=14, 19)Day 66 (N=13, 15)
Group ANA6180015000
Group B243009880027600

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AUC 0-6hr of Deleobuvir (BI 207127)

Area under the concentration-time curve of the analyte in plasma over the time interval from 0 to 6 hours (NCT01525628)
Timeframe: PK plasma samples were taken at: 5 minutes before drug administration and 1 hour (h), 2h, 3h, 4h, 5h, 5:55h, 8h, 10h, 11:55h, 15h, 23:55h after first drug administration on days 9, 17 and 66.

,
Interventionnmol*h/L (Geometric Mean)
Day 9 (N=0, 17)Day 17 (N=14, 19)Day 66 (N=13, 15)
Group ANA11900036200
Group B4110013500059200

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Area Under the Concentration-time Curve (AUC) of Faldaprevir (BI 201335) From 0 to 24 Hours

Area under the concentration-time curve of the analyte in plasma over the time interval from 0 to 24 hours (NCT01525628)
Timeframe: PK plasma samples were taken at: 5 minutes before drug administration and 1 hour (h), 2h, 3h, 4h, 5h, 5:55h, 8h, 10h, 11:55h, 15h, 23:55h after first drug administration on days 9, 17 and 66.

,
Interventionng*h/mL (Geometric Mean)
Day 9 (N=15,0)Day 17 (N=14,19)Day 66 (N=13,15)
Group A4560013800056200
Group BNA17300097300

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Number of Participants With Sustained Virological Response (SVR12)

Sustained virologic response (SVR12): Plasma Hepatitis C virus Ribonucleic acid (HCV RNA) level <25 IU/mL(international units per millilitre) undetectable at 12 weeks after the end of treatment. SVR12 was analyzed in a descriptive manner using frequency of participants who achieved SVR12. (NCT01525628)
Timeframe: 12 weeks post treatment

InterventionParticipants (Number)
Group A13
Group B13
Group C11
Group D10
Group E3

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AUC 0-6hr of Deleobuvir Metabolite CD 6168 ag (Acylglucuronide)

Area under the concentration-time curve of the analyte in plasma over the time interval from 0 to 6 hours (NCT01525628)
Timeframe: PK plasma samples were taken at: 5 minutes before drug administration and 1 hour (h), 2h, 3h, 4h, 5h, 5:55h, 8h, 10h, 11:55h, 15h, 23:55h after first drug administration on days 9, 17 and 66.

,
Interventionnmol*h/L (Geometric Mean)
Day 9 (N=0, 17)Day 17 (N=14, 19)Day 66 (N=13, 15)
Group ANA29801620
Group B89357003510

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Cmax of Deleobuvir Reduction Metabolite CD 6168

Maximum concentration of an analyte in plasma (NCT01525628)
Timeframe: PK plasma samples were taken at: 5 minutes before drug administration and 1 hour (h), 2h, 3h, 4h, 5h, 5:55h, 8h, 10h, 11:55h, 15h, 23:55h after first drug administration on days 9, 17 and 66.

,
Interventionnmol/L (Geometric Mean)
Day 9 (N=0, 17)Day 17 (N=14, 19)Day 66 (N=13, 15)
Group ANA85204510
Group B3040124008880

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AUC 0-infinity of 1-OH-Midazolam (1-hydroxy-midazolam)

Area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity. (NCT01525628)
Timeframe: 5 min before and 1 hour (h), 2h, 3h, 4h, 5h, 6h, 8h, 10h, 11:55h, 15h, 23:55h, 26h, 28h, 29:55h, 32h after first drug administration on day 1 also 5 min before, 1h, 2h, 3h, 4h, 5h, 5:55h, 8h, 10h, 11:55h, 15h, 23:55h after drug on days 9, 17 and 66.

,
Interventionnmol*h/L (Geometric Mean)
Day 1 (N=16, 19)Day 9 (N=15, 17)Day 17 (N=14, 19)Day 66 (N=13, 13)
Group A23.624.223.518.3
Group B26.028.522.820.8

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AUC 0-infinity of Caffeine

Area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity. (NCT01525628)
Timeframe: 5 min before and 1 hour (h), 2h, 3h, 4h, 5h, 6h, 8h, 10h, 11:55h, 15h, 23:55h, 26h, 28h, 29:55h, 32h after first drug administration on day 1 also 5 min before, 1h, 2h, 3h, 4h, 5h, 5:55h, 8h, 10h, 11:55h, 15h, 23:55h after drug on days 9, 17 and 66.

,
Interventionng*h/mL (Geometric Mean)
Day 1 (N=16, 19)Day 9 (N=15, 15)Day 17 (N=14, 19)Day 66 (N=13, 15)
Group A549004210071900120000
Group B77500142000170000159000

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AUC 0-infinity of Midazolam

Area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity. (NCT01525628)
Timeframe: 5 min before and 1 hour (h), 2h, 3h, 4h, 5h, 6h, 8h, 10h, 11:55h, 15h, 23:55h, 26h, 28h, 29:55h, 32h after first drug administration on day 1 also 5 min before, 1h, 2h, 3h, 4h, 5h, 5:55h, 8h, 10h, 11:55h, 15h, 23:55h after drug on days 9, 17 and 66.

,
Interventionnmol*h/L (Geometric Mean)
Day 1 (N=16, 19)Day 9 (N=15, 17)Day 17 (N=14, 19)Day 66 (N=13, 15)
Group A79.711712775.5
Group B10713014095.6

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AUC 0-infinity of Tolbutamide

Area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity. (NCT01525628)
Timeframe: 5 min before and 1 hour (h), 2h, 3h, 4h, 5h, 6h, 8h, 10h, 11:55h, 15h, 23:55h, 26h, 28h, 29:55h, 32h after first drug administration on day 1 also 5 min before, 1h, 2h, 3h, 4h, 5h, 5:55h, 8h, 10h, 11:55h, 15h, 23:55h after drug on days 9, 17 and 66.

,
Interventionnmol*h/L (Geometric Mean)
Day 1 (N=16, 19)Day 9 (N=13, 17)Day 17 (N=14, 18)Day 66 (N=12, 15)
Group A1940000180000015200001330000
Group B2220000194000014100001390000

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Cmax of Faldaprevir (BI 201335)

Maximum concentration of an analyte in plasma (NCT01525628)
Timeframe: PK plasma samples were taken at: 5 minutes before drug administration and 1 hour (h), 2h, 3h, 4h, 5h, 5:55h, 8h, 10h, 11:55h, 15h, 23:55h after first drug administration on days 9, 17 and 66.

,
Interventionng/mL (Geometric Mean)
Day 9 (N=15,0)Day 17 (N=14,14)Day 66 (N=13,15)
Group A352087804410
Group BNA99506690

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C24hr of Faldaprevir (BI 201335)

Concentration of an analyte in plasma at 24 hours (NCT01525628)
Timeframe: PK plasma samples were taken at: 5 minutes before drug administration and 1 hour (h), 2h, 3h, 4h, 5h, 5:55h, 8h, 10h, 11:55h, 15h, 23:55h after first drug administration on days 9, 17 and 66.

,
Interventionng/mL (Geometric Mean)
Day 9 (N=15,0)Day 17 (N=14,19)Day 66 (N=13,14)
Group A98336701140
Group BNA54102580

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C6hr of Deleobuvir (BI 207127)

Concentration of an analyte in plasma at 6 hours (NCT01525628)
Timeframe: PK plasma samples were taken at: 5 minutes before drug administration and 1 hour (h), 2h, 3h, 4h, 5h, 5:55h, 8h, 10h, 11:55h, 15h, 23:55h after first drug administration on days 9, 17 and 66.

,
Interventionnmol/L (Geometric Mean)
Day 9 (N=0, 17)Day 17 (N=14, 19)Day 66 (N=13, 14)
Group ANA179005080
Group B58002080010100

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C6hr of Deleobuvir Metabolite Acyl-glucuronide (BI 208333)

Concentration of an analyte in plasma at 6 hours (NCT01525628)
Timeframe: PK plasma samples were taken at: 5 minutes before drug administration and 1 hour (h), 2h, 3h, 4h, 5h, 5:55h, 8h, 10h, 11:55h, 15h, 23:55h after first drug administration on days 9, 17 and 66.

,
Interventionnmol/L (Geometric Mean)
Day 9 (N=0, 17)Day 17 (N=14, 19)Day 66 (N=13, 14)
Group ANA112002740
Group B4330175005780

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C6hr of Deleobuvir Metabolite CD 6168 ag (Acylglucuronide)

Concentration of an analyte in plasma at 6 hours (NCT01525628)
Timeframe: PK plasma samples were taken at: 5 minutes before drug administration and 1 hour (h), 2h, 3h, 4h, 5h, 5:55h, 8h, 10h, 11:55h, 15h, 23:55h after first drug administration on days 9, 17 and 66.

,
Interventionnmol/L (Geometric Mean)
Day 9 (N=0, 17)Day 17 (N=14, 19)Day 66 (N=13, 14)
Group ANA508295
Group B159962712

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C6hr of Deleobuvir Reduction Metabolite CD 6168

Concentration of an analyte in plasma at 6 hours (NCT01525628)
Timeframe: PK plasma samples were taken at: 5 minutes before drug administration and 1 hour (h), 2h, 3h, 4h, 5h, 5:55h, 8h, 10h, 11:55h, 15h, 23:55h after first drug administration on days 9, 17 and 66.

,
Interventionnmol/L (Geometric Mean)
Day 9 (N=0, 17)Day 17 (N=14, 19)Day 66 (N=13, 14)
Group ANA69803360
Group B2250102007460

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Cmax of 1-OH-Midazolam (1-hydroxy-midazolam)

Maximum concentration of an analyte in plasma (NCT01525628)
Timeframe: 5 min before and 1 hour (h), 2h, 3h, 4h, 5h, 6h, 8h, 10h, 11:55h, 15h, 23:55h, 26h, 28h, 29:55h, 32h after first drug administration on day 1 also 5 min before, 1h, 2h, 3h, 4h, 5h, 5:55h, 8h, 10h, 11:55h, 15h, 23:55h after drug on days 9, 17 and 66.

,
Interventionnmol/L (Geometric Mean)
Day 1 (N=16, 19)Day 9 (N=15, 17)Day 17 (N=14, 19)Day 66 (N=13, 15)
Group A5.576.506.465.05
Group B6.686.525.024.67

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Cmax of Caffeine

Maximum concentration of an analyte in plasma (NCT01525628)
Timeframe: 5 min before and 1 hour (h), 2h, 3h, 4h, 5h, 6h, 8h, 10h, 11:55h, 15h, 23:55h, 26h, 28h, 29:55h, 32h after first drug administration on day 1 also 5 min before, 1h, 2h, 3h, 4h, 5h, 5:55h, 8h, 10h, 11:55h, 15h, 23:55h after drug on days 9, 17 and 66.

,
Interventionng/mL (Geometric Mean)
Day 1 (N=16, 19)Day 9 (N=15, 17)Day 17 (N=14, 19)Day 66 (N=13, 15)
Group A5170489048305590
Group B5340722065306450

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Cmax of Deleobuvir (BI 207127)

Maximum concentration of an analyte in plasma (NCT01525628)
Timeframe: PK plasma samples were taken at: 5 minutes before drug administration and 1 hour (h), 2h, 3h, 4h, 5h, 5:55h, 8h, 10h, 11:55h, 15h, 23:55h after first drug administration on days 9, 17 and 66.

,
Interventionnmol/L (Geometric Mean)
Day 9 (N=0, 17)Day 17 (N=14, 19)Day 66 (N=13, 15)
Group ANA2700010100
Group B109003140016000

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Cmax of Deleobuvir Metabolite Acyl-glucuronide (BI 208333)

Maximum concentration of an analyte in plasma (NCT01525628)
Timeframe: PK plasma samples were taken at: 5 minutes before drug administration and 1 hour (h), 2h, 3h, 4h, 5h, 5:55h, 8h, 10h, 11:55h, 15h, 23:55h after first drug administration on days 9, 17 and 66.

,
Interventionnmol/L (Geometric Mean)
Day 9 (N=0, 17)Day 17 (N=14, 19)Day 66 (N=13, 15)
Group ANA127003790
Group B5620202006550

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Cmax of Deleobuvir Metabolite CD 6168 ag (Acylglucuronide)

Maximum concentration of an analyte in plasma (NCT01525628)
Timeframe: PK plasma samples were taken at: 5 minutes before drug administration and 1 hour (h), 2h, 3h, 4h, 5h, 5:55h, 8h, 10h, 11:55h, 15h, 23:55h after first drug administration on days 9, 17 and 66.

,
Interventionnmol/L (Geometric Mean)
Day 9 (N=0, 17)Day 17 (N=14, 19)Day 66 (N=13, 15)
Group ANA596386
Group B2031130806

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Number of Participants With Cocaine Use/Drop Out

Number of participants who use cocaine and drop from study. During phase 2, patients will be assessed twice weekly by TLFB and urine toxicology for cocaine use. The day of first use will determine the length of time that transpired from discharge to the first lapse onto cocaine. (NCT01535937)
Timeframe: Over the four week period following discharge from the inpatient unit at Day 5

InterventionParticipants (Count of Participants)
Ketamine16
Midazolam26

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Abstinence

Abstinence is defined as 2 or greater weeks of no cocaine use, as ascertained by the TLFB and urine toxicology. (NCT01535937)
Timeframe: Abstinence will be assessed over 4 weeks starting at the last day of week 1 and continuing through the end of study at the last day of week 5

InterventionParticipants (Count of Participants)
Ketamine13
Midazolam3

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Percent Intra-op Blood Glucose Level of 140mg/dL or Less

blood glucose level will be tested perioperatively at 30 minute intervals following induction. All glucose levels will be recorded .midazolam group will maintain a blood glucose level perioperatively of 140mg/dL or less (NCT01641653)
Timeframe: perioperatively

Interventionpercentage of glucose levels<140 (Number)
Placebo100
Midazolam86.6

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Glucose Level Percent Change From Pre-op to Maximum Glucose Level

blood glucose level measured preoperatively, through surgical period and in PACU at 30 min and 60 min (NCT01641653)
Timeframe: Preoperatively, intraoperatively 30 min for duration of surgery

Interventionpercentage of increase in glucose level (Median)
Placebo24.9
Midazolam14.9

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Maximum Perioperative Blood Glucose Level of 30 Minute Interval Measurements

Non diabetic subjects undergoing hernia repair were randomized into 2 groups. Midazolam vs. placebo. Blood glucose level was monitored preoperatively and following induction of anesthesia at 30 minute intervals perioperatively, and after in the PACU at 30 minutes and 60 minutes following arrival. All readings were performed using the Abbott Freestyle Glucose Monitor. (NCT01641653)
Timeframe: every 30 min for duration of surgery

Interventionmg/dL (Median)
Placebo114.0
Midazolam108.0

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Success Rate Without Supplementation

"After injection of local anesthetic a waiting period of 30-60 minutes was defined before completing a failed block.~success without supplementation = no additional analgetics or rescue blocks required (success rate without supplementation, outcome measure 1)~success with supplementation = analgetics or selective rescue blocks distal of the sciatic division required (success rate without supplementation and additionally all supplemented blocks, outcome measure 3)~failed block = change of anesthetic procedure (general, spinal) or rescue blocks proximal of the sciatic division" (NCT01643616)
Timeframe: within 30-60 minutes after injection of the local anesthetic

Interventionparticipants (Number)
Group US112
Group NS73

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Success Rate With Supplementation

"After injection of local anesthetic a waiting period of 30-60 minutes was defined before completing a failed block.~success without supplementation = no additional analgetics or rescue blocks required (success rate without supplementation, outcome measure 1)~success with supplementation = analgetics or selective rescue blocks distal of the sciatic division required (success rate without supplementation and additionally all supplemented blocks, outcome measure 3)~failed block = change of anesthetic procedure (general, spinal) or rescue blocks proximal of the sciatic divisionSucces rate with supplementation" (NCT01643616)
Timeframe: later than 30-60 minutes after injection of the local anesthetic

Interventionparticipants (Number)
Group US116
Group NS85

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Time Until Readiness for Surgery (Minutes)

(NCT01643616)
Timeframe: within 60 minutes after injection of the local anesthetic

Interventionminutes (Mean)
Group US15.1
Group NS28

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FLACC Pain Score Greater Than or Equal to 4

The Face, Legs, Activity, Cry, Consolability scale or FLACC scale is a measurement used to assess pain for children between the ages of 2 months and 7 years or individuals that are unable to communicate their pain. The scale is scored in a range of 0-10 with 0 representing no pain. 5 pain measurements were performed at 0, 5, 15, 30, and 60 minutes after PACU arrival. This is the number of participants who reached a FLACC score >/= 4 at one or more time points. (NCT01691690)
Timeframe: 0-60 mins post-operatively

InterventionParticipants (Count of Participants)
IV Acetaminophen58
Saline Placebo69

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Time of First Opioid Analgesia in PACU

Mean time to first drug administration among patients requiring opioid analgesia in the PACU. (NCT01691690)
Timeframe: 0-90 minutes post-operatively

Interventionminutes (Mean)
IV Acetaminophen56.80
Saline Placebo Infused Intraoperatively60.46

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Analgesics Administered After Arrival to Inpatient Ward and Number of Participants Requiring Each

Analgesics administered after arrival to the inpatient ward included hydrocodone/acetaminophen, oxycodone, NSAIDS, acetaminophen, and morphine. (NCT01691690)
Timeframe: 8-12 hours post-operatively

,
InterventionParticipants (Count of Participants)
hydrocodone/acetaminophenoxycodoneNSAIDSacetaminophenmorphine
IV Acetaminophen68311531
Saline Placebo Infused Intraoperatively57392220

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The Recovery Time

"Time from completing the colonoscopy to achieving Aldrete score 10 in the recovery unit~Aldrete score~Respiration: Able to take deep breath and cough = 2, Dyspnea/shallow breathing = 1, Apnea = 0~O2 saturation: Maintains > 92% on room air =2, Needs O2 inhalation to maintain O2 saturation > 90% =1 , O2 saturation < 90% even with supplemental oxygen =0~Consciousness: Fully awake= 2, Arousable on calling = 1, Not responding = 0~Circulation: BP +/- 20 mm Hg preop =2, BP +/- 20-50 mm Hg preop =1, BP +/- 50 mm Hg preop =0~Activity: Able to move 4 extremities = 2, Able to move 2 extremities = 1, Able to move 0 extremities = 0~To estimate the required sample size, we conducted a pilot study to measure the recovery of 10 patients in each of groups-MM and -R before the present study. The means and standard deviations were 22.5 ± 9.5 and 7.5 ± 9.2 min respectively. We wished to be able to distinguish a difference of 7.5 min, thus half of the observed difference." (NCT01693185)
Timeframe: every 5 minutes after completing colonoscopy up to 30 min

Interventionminute (Median)
Remifentanil0
Midazolam and Meperidine30

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Patient's Distress Score

patients' distress in visual analogue scale 100 mm minimal distress=0, maximal distress=100 (NCT01693185)
Timeframe: 5 min after the end of colonoscopy

Interventionunits on a scale (Median)
Remifentanil37
Midazolam and Meperidine30

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Participants Assumed to Feel Frequent Pain

"patients sound Ah at feeling pain during colonosocpy: if a patients sounds Ah > 6 times, the patient was assumed to feel frequent pain." (NCT01693185)
Timeframe: during and after colonoscopy

Interventionparticipants (Number)
Remifentanil4
Midazolam and Meperidine7

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Indigence of Patient's Recall

The numbers of patients who recalled instructions and explanations given during colonoscopy (NCT01693185)
Timeframe: after colonoscopy

Interventionparticipants (Number)
Remifentanil27
Midazolam and Meperidine13

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Endoscopist Satisfaction

endoscopist's satisfaction after colonoscopy in visual analogue scale 100 mm (NCT01693185)
Timeframe: 5 min after the colonoscopy

Interventionunits on a scale (Median)
Remifentanil5
Midazolam and Meperidine20

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Bispectra Lindex Score

Bispectral index (BIS) score 0-100 maximal sedation=0, maximal sedation=100 (NCT01693185)
Timeframe: every 5 min during and after colonoscopy

Interventionunits on a scale (Median)
Remifentanil92
Midazolam and Meperidine84

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Change in Scale for Suicidal Ideation

Change in suicidal ideation in depressed patients with moderate to severe suicidal thoughts from the pre-infusion baseline to 24 hours after the infusion with ketamine or midazolam, a sedative not known to reduce suicidal ideation, measured with Beck Scale for Suicidal Ideation - clinician rated version. This scale has 19 items scaled 0 (least severe) to 2 (most severe) and a potential score ranging from 0 to 38, with higher score indicating greater severity. (NCT01700829)
Timeframe: Day 1 (24 hours) post-treatment

Interventionunits on a scale (Mean)
Midazolam-3.66
Ketamine-8.62

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Neuropsychological Effects

The average Z-scores reported below are the average of the Z-scores for all tests administered. The Z-scores for each test were based on published normative data and normative data available in our laboratory. The population mean for a Z-score is zero, with a SD of 1, thus scores below zero would indicate performance below the population norm; a score close to zero indicates performance close to the population norm (or a normalizing of performance). (NCT01700829)
Timeframe: Baseline and Day 1

,
Interventionscore on a scale (Mean)
Pre-infusion overall neuropsych performanceDay1 post-infusion overall neuropsych performance
Ketamine-0.306-0.01
Midazolam-0.252-0.146

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Saliva Cortisol Awakening Response (CAR).

"On the mornings of an infusion day and on post-treatment day1, participants used salivettes (Sarstedt AG & Co.) to provide saliva samples upon awakening (Cort1) and 30 minutes later (Cort2) to measure cortisol awakening response (CAR) = (Cort2 - Cort1).~Differences between the midazolam and ketamine groups were tested using an analysis of covariance (ANCOVA) model of the change in CAR from baseline to day1, with treatment group and baseline measurement of the outcome variable as predictors.~Range from 0.1 to 12.5 ng/ml and lower means less stress response, higher means greater stress response." (NCT01700829)
Timeframe: Cort2 - Cort1 = (Day 1 30-mins post-awakening cortisol) - (Day 1 awakening cortisol)

,
Interventionlog(ng/mL) (Mean)
Baseline awakeningBaseline 30 mins post-awakeningDay1 awakeningDay1 30 minutes post-awakening
Ketamine0.470.880.741.06
Midazolam0.941.290.771.19

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Cardiovascular Adverse Events.

(1) desaturation(oxygen saturation < 90 % at least 10 second ) (2) hypotension ( systolic blood pressure < 90 mmHg or dropped more than 25 % of baseline ) (3)bradycardia (heart rate < 50 beats/min) and (4) apnea ( cessation of respiratory activity for over 10 seconds ). When patients developed oxygen saturation < 90 %, then nasal oxygen was administered, If patients not able to recover from oxygen therapy and tactile stimulations thus the procedure was terminated. The procedure was terminated if patients developed serious adverse event as heart rate below 5 beats/min and or apnea. (NCT01709422)
Timeframe: participants will be followed for the duration of procedure, an expected average of 2.0 hours

,
InterventionParticipants (Number)
Participants with desatuartionParticipants with hypotensionParticipants with bradycardia
Midazolam and Meperidine40140
Propofol,Midazolam and Meperidine26121

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Time of Maximum Observed Plasma Concentration (Tmax) of the Inje Cocktail Components (Midazolam, Losartan, Omeprazole, Dextromethorphan, and Caffeine) With and Without Coadministration of Belatacept - PK Evaluable Population

Samples for assessment of plasma concentrations of Inje cocktail components (midazolam, losartan, omeprazole, dextromethorphan and caffeine) were collected at time = 0 (predose), 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, and 24 hours relative to the dosing of belatacept on Day 4 and Inje cocktail dosing on Days 1, 4, 7, and 11, respectively. The poor metabolizer of CYP2D6 was excluded from summary of dextromethorphan parameters. Inje cocktail components were each measured using HPLC with MS/MS detection. Tmax was measured in hours (h). (NCT01766050)
Timeframe: Pre-dose to 24 hours after dose of the Inje Cocktail on Days 1, 4, 7 and 11

,,,
Interventionh (Median)
Midazolam (N=22,21,21,20)Losartan (N= 22, 21, 21, 20)Omeprazole (N=22,21,21,20)Dextromethorphan (N=21, 19, 19, 19)Caffeine (N= 22,21,21,18)
Day 1 Inje Cocktail0.501.522.003.001.00
Day 11 Inje Cocktail1.01.503.003.001.50
Day 4 Inje Cocktail Plus Belatacept0.502.003.003.001.00
Day 7 Inje Cocktail0.501.503.003.001.50

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T-HALF of Inje Cocktail Component Metabolites (1'-Hydroxy-Midazolam, E-3174, 5-Hydroxyomeprazole, Dextrorphan, and Paraxanthine) With and Without the Coadministration of Belatacept - PK Evaluable Population

Plasma half-life (T-HALF) was measured in hours (h). Samples for assessment of plasma concentrations of Inje cocktail components metabolites (1'-hydroxy-midazolam, E-3174, 5-hydroxyomeprazole, dextrorphan, and paraxanthine) were collected at time = 0 (predose), 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, and 24 hours relative to the dosing of belatacept on Day 4 and Inje cocktail dosing on Days 1, 4, 7, and 11, respectively. The poor metabolizer of CYP2D6 was excluded from summary of Dextrorphan parameters. Inje cocktail components were each measured using HPLC with MS/MS detection. (NCT01766050)
Timeframe: Pre-dose to 24 hours after dose of the Inje Cocktail on Days 1, 4, 7 and 11

,,,
Interventionh (Mean)
1'-Hydroxy-Midazolam (N=22,21,20,20)E-3174 (N=22, 20, 21, 20)5-Hydroxyomeprazole (N=22,20,21,17)Dextrorphan (N=21,20,20,19)Paraxanthine (N=7,8,6,6)
Day 1 Inje Cocktail5.294.861.434.267.33
Day 11 Inje Cocktail5.314.881.544.087.44
Day 4 Inje Cocktail Plus Belatacept6.354.571.554.366.86
Day 7 Inje Cocktail5.614.751.524.237.33

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Ratio of Paraxanthine AUC(0-T) to Caffeine AUC(0-T) and Paraxanthine AUC (INF) to Caffeine AUC (INF), Corrected for Molecular Weight [MR_AUC(0-T) and MR_AUC (INF)] With and Without Coadministration of Belatacept - PK Evaluable Population

Metabolite (paraxanthine) to parent (caffeine) ratio was corrected for molecular weight. AUC (0-T) and AUC (INF) measured in ng*h/mL. Samples for assessment of plasma concentrations of Inje cocktail components and the metabolites of those components were collected at time = 0 (predose), 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, and 24 hours relative to the dosing of belatacept on Day 4 and Inje cocktail dosing on Days 1, 4, 7, and 11, respectively. Inje cocktail components were each measured using HPLC with MS/MS detection. (NCT01766050)
Timeframe: Pre-dose to 24 hours after dose of the Inje Cocktail on Days 1, 4, 7 and 11

,,,
Interventionratio (Geometric Mean)
MR_AUC(0-T) ratio; N=17,19,18,18MR_AUC(INF) ratio; N=7, 8, 6, 6
Day 1 Inje Cocktail0.6270.827
Day 11 Inje Cocktail0.6030.781
Day 4 Inje Cocktail Plus Belatacept0.6770.827
Day 7 Inje Cocktail0.6350.799

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Ratio of E-3174 AUC(0-T) to Losartan AUC(0-T) and E3174 AUC (INF) to Losartan AUC (INF) Corrected for Molecular Weight [MR_AUC(0-T), MR_AUC(INF)] With and Without Coadministration of Belatacept - PK Evaluable Population

Metabolite (E-3174) to parent (losartan) ratio was corrected for molecular weight. AUC (0-T) and AUC (INF) measured in ng*h/mL. Samples for assessment of plasma concentrations of Inje cocktail components and the metabolites of those components were collected at time = 0 (predose), 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, and 24 hours relative to the dosing of belatacept on Day 4 and Inje cocktail dosing on Days 1, 4, 7, and 11, respectively. Inje cocktail components were each measured using HPLC with MS/MS detection. (NCT01766050)
Timeframe: Pre-dose to 24 hours after dose of the Inje Cocktail on Days 1, 4, 7 and 11

,,,
Interventionratio (Geometric Mean)
MR_AUC (0-T) ratio; N=22,21,21,20MR_AUC (INF) ratio; N=22,20,21,20
Day 1 Inje Cocktail5.816.02
Day 11 Inje Cocktail6.176.37
Day 4 Inje Cocktail Plus Belatacept5.755.99
Day 7 Inje Cocktail5.996.16

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Ratio of 5-Hydroxyomeprazole AUC(0-T) to Omeprazole AUC(0-T) and 5-Hydroxyomeprazole AUC(INF) to Omeprazole AUC(INF) , Corrected for Molecular Weight [MR_AUC(0-T), MR_AUC(INF)] With and Without Coadministration of Belatacept - PK Evaluable Population

Metabolite (5-Hydroxyomeprazole) to parent (omeprazole) ratio was corrected for molecular weight. AUC (0-T) and AUC (INF) measured in ng*h/mL. Samples for assessment of plasma concentrations of Inje cocktail components and the metabolites of those components were collected at time = 0 (predose), 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, and 24 hours relative to the dosing of belatacept on Day 4 and Inje cocktail dosing on Days 1, 4, 7, and 11, respectively. Inje cocktail components were each measured using HPLC with MS/MS detection. (NCT01766050)
Timeframe: Pre-dose to 24 hours after dose of the Inje Cocktail on Days 1, 4, 7 and 11

,,,
Interventionratio (Geometric Mean)
MR_AUC (0-T) ratio; N=22,21,21,20MR_AUC (INF) ratio; N=22,19,21,17
Day 1 Inje Cocktail0.7000.705
Day 11 Inje Cocktail0.6100.679
Day 4 Inje Cocktail Plus Belatacept0.6090.558
Day 7 Inje Cocktail0.5510.553

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Ratio of 5-Dextrorphan AUC(0-T) to Dextromethorphan AUC(0-T) and 5-Dextrorphan AUC(INF) to Dextromethorphan AUC(INF), Corrected for Molecular Weight [MR_AUC(0-T), MR_AUC (INF)] With and Without Coadministration of Belatacept - PK Evaluable Population

Metabolite (5-dextrorphan ) to parent (dextromethorphan) ratio was corrected for molecular weight. AUC (0-T) and AUC (INF) measured in ng*h/mL. Samples for assessment of plasma concentrations of Inje cocktail components and the metabolites of those components were collected at time = 0 (predose), 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, and 24 hours relative to the dosing of belatacept on Day 4 and Inje cocktail dosing on Days 1, 4, 7, and 11, respectively. The poor metabolizer of CYP2D6 was excluded from summary of Dextrorphan parameters. Inje cocktail components were each measured using HPLC with MS/MS detection. (NCT01766050)
Timeframe: Pre-dose to 24 hours after dose of the Inje Cocktail on Days 1, 4, 7 and 11

,,,
Interventionratio (Geometric Mean)
MR_AUC (0-T) ratio; N=21,20,20,19MR_AUC (INF) ratio; N=18,17,18,15
Day 1 Inje Cocktail201173
Day 11 Inje Cocktail193173
Day 4 Inje Cocktail Plus Belatacept200177
Day 7 Inje Cocktail177170

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Plasma Half-Life (T-HALF) of the Inje Cocktail Components (Midazolam, Losartan, Omeprazole, Dextromethorphan, and Caffeine) With and Without Coadministration of Belatacept - PK Evaluable Population

Samples for assessment of plasma concentrations of Inje cocktail components (midazolam, losartan, omeprazole, dextromethorphan and caffeine) were collected at time = 0 (predose), 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, and 24 hours relative to the dosing of belatacept on Day 4 and Inje cocktail dosing on Days 1, 4, 7, and 11, respectively. The poor metabolizer of CYP2D6 was excluded from summary of dextromethorphan parameters. Inje cocktail components were each measured using HPLC with MS/MS detection. T-HALF was measured in hours (h). (NCT01766050)
Timeframe: Pre-dose to 24 hours after dose of the Inje Cocktail on Days 1, 4, 7 and 11

,,,
Interventionh (Mean)
Midazolam (N=22, 21, 21, 20)Losartan (N=22, 21, 21, 20)Omeprazole (N= 22, 19, 21, 18)Dextromethorphan (N=18, 17, 18, 15)Caffeine (N=22, 21, 21, 18)
Day 1 Inje Cocktail4.012.961.196.765.61
Day 11 Inje Cocktail4.052.871.366.706.03
Day 4 Inje Cocktail Plus Belatacept4.432.561.396.985.71
Day 7 Inje Cocktail4.273.301.286.336.17

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Number of Participants With Marked Serum Chemistry Laboratory Abnormalities - All Treated Participants

Samples for laboratory tests were obtained at Screening visit, Day -1 or prior to dosing on Day 1, Days 3, 6, 10, 46, and at early termination, after 10 hours fasting. Upper limits of normal (ULN); Lower limits of normal (LLN); Pre-therapy (Rx); micromoles per liter (µmol/L); millimoles per liter (mmol/L); grams per liter (g/L); Units per liter (U/L); Aspartate Aminotransferase (AST); Blood Urea Nitrogen (BUN) Total Bilirubin: >1.1*ULN if Pre-Rx<= ULN or Pre-Rx is missing, or >1.2*Pre-Rx if Pre-Rx >ULN. AST: >1.25*Pre-Rx if Pre-Rx >ULN or 1.25*ULN if Pre-Rx <= ULN or Pre-Rx is missing. BUN: >1.1*ULN if Pre-Rx<= ULN or Pre-Rx is missing, or >1.2*Pre-Rx if Pre-Rx >ULN. Phosphorus: <0.85*LLN if Pre-RX >= LLN or is missing or if Pre-Rx < LLN. total Protein: <0.9*LLN if Pre-Rx>= LLN or is missing or Pre-Rx > LLN. Creatine Kinase: >1.5*Pre-Rx if Pre-Rx > ULN or is missing or Pre-Rx is <= ULN. Lactate Dehydrogenase: >1.25*ULN if Pre-Rx <= ULN or missing, >1.5*Pre-Rx if Pre-Rx > ULN. (NCT01766050)
Timeframe: Day -1 to Day 46 ±2 days or at early termination

Interventionparticipants (Number)
Total bilirubin >1.1*ULN µmol/L (N=22)AST >1.25*Pre-Rx U/L (N=22)BUN >1.1*ULN mmol/L (N=22)Inorganic Phosphorus <0.85*LLN mmol/L (N=22)Total Protein <0.9*LLN g/L (N=22)Creatine Kinase > 1.5* Pre-Rx U/L (N=22)Lactate Dehydrogenase >1.25*ULN U/L (N=22)
Inje Cocktail Alone and Inje Cocktail Plus Belatacept1111121

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Number of Participants With Marked Hematology and Urinalysis Laboratory Abnormalities - All Treated Participants

Samples for laboratory tests were obtained at Screening visit, Day -1 or prior to dosing on Day 1, Days 3, 6, 10, 46 ±2, and at early termination, after 10 hours fasting. Leukocytes: *10^9 cells per liter (c/L) < 0.85*Pre-Rx if Pre-Rx < LLN or <0.9*LLN if LLN <= Pre-Rx or Pre-Rx is missing. Neutrophils (absolute): *10^12 c/L < 0.85* Pre-Rx if Pre-Rx < 1.5, <1.5 if Pre-Rx >= 1.5, < 1.5 if Pre-Rx missing. Urine blood from dipstick: >=2 if Pre-Rx <1 or was missing or if Pre-Rx >=1. Urinary microscopic white blood cells (WBC) and red blood cells (RBC) >= 2 if Pre-Rx <2 or if Pre-Rx was missing or >=4 if Pre-Rx >=2. (NCT01766050)
Timeframe: Day -1 to Day 46 ±2 days or at early termination

Interventionparticipants (Number)
Leukocytes <0.85*Pre-Rx *10^9 c/L (N=22)Neutrophils <0.85*Pre-Rx *10^12 c/L (N=22)Urine Blood >= 2 (N=22)Urinary RBC microscopic >= 2 (N=8)Urinary WBC microscopic >= 2 (N=8)
Inje Cocktail Alone and Inje Cocktail Plus Belatacept14211

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Number of Participants With Adverse Events (AEs), Serious AEs (SAEs), Deaths, and AEs Leading to Discontinuation - All Treated Participants

Adverse events were coded according to the Medical Dictionary for Regulatory Activities (MedDRA), version 15.1. AE=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. SAE=a medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization. Events captured from Day 1 (pre-dose) to last day prior to discharge (Day 46 ±2). In the total group, a participant with an AE is only counted once (ie, data reflected in Days 1, 4, 7, and 11 below could be the same participant with an AE on multiple days of the study). (NCT01766050)
Timeframe: Day 1 to Day of discharge (Day 46±2)

,,,,
Interventionparticipants (Number)
Adverse EventsSAEsDeathsAEs leading to discontinuation
All Participants5001
Day 1 Inje Cocktail4000
Day 11 Inje Cocktail1000
Day 4 Inje Cocktail Plus Belatacept2000
Day 7 Inje Cocktail1001

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Apparent Total Body Clearance (CLT/F) of the Inje Cocktail Components (Midazolam, Losartan, Omeprazole, Dextromethorphan and Caffeine) With and Without Coadministration of Belatacept - PK Evaluable Population

Samples for assessment of plasma concentrations of Inje cocktail components (midazolam, losartan, omeprazole, dextromethorphan and caffeine) were collected at time = 0 (predose), 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, and 24 hours relative to the dosing of belatacept on Day 4 and Inje cocktail dosing on Days 1, 4, 7, and 11, respectively. The poor metabolizer of CYP2D6 was excluded from summary of dextromethorphan parameters. Inje cocktail components were each measured using HPLC with MS/MS detection. CLT/F was measured as liters/hour (L/h) (NCT01766050)
Timeframe: Pre-dose to 24 hours after dose of the Inje Cocktail on Days 1, 4, 7 and 11

,,,
InterventionL/h (Geometric Mean)
Midazolam (N=22, 21, 21, 20)Losartan (N=22, 21, 21, 20)Omeprazole (N=22, 19, 21, 18)Dextromethorphan (N=18,17,18,18)Caffeine (N=22, 21, 21, 18)
Day 1 Inje Cocktail73.814829.239164.99
Day 11 Inje Cocktail71.415125.339684.83
Day 4 Inje Cocktail Plus Belatacept71.314623.742475.30
Day 7 Inje Cocktail77.314624.742644.97

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Adjusted Geometric Mean AUC (0-T) and AUC (INF) of Omeprazole With and Without the Coadministration of Belatacept - Pharmacokinetic (PK) Evaluable Population

AUC(0-T): Area under the plasma concentration-time curve from time zero zero to the time of the last quantifiable concentration and AUC (INF): AUC extrapolated to infinity were measured in ng*h/mL. Samples for assessment of plasma concentrations of Inje cocktail components (midazolam, losartan, omeprazole, dextromethorphan and caffeine) and their metabolites (1'-hydroxy-midazolam, E-3174, 5-hydroxyomeprazole, dextrorphan, and paraxanthine) were collected at time = 0 (predose), 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, and 24 hours relative to the dosing of belatacept on Day 4 and Inje cocktail dosing on Days 1, 4, 7, and 11, respectively. Adjusted geometric mean for omeprazole with and without belatacept, along with adjusted geometric mean ratios for Days 4, 7, and 11 versus Day 1, respectively, are presented. Inje cocktail components (omeprazole) measured using HPLC with MS/MS Detection. (NCT01766050)
Timeframe: Pre-dose to 24 hours after dose of the Inje Cocktail on Days 1, 4, 7 and 11

,,,
Interventionng*h/mL (Geometric Mean)
AUC (0-T); (N= 22, 21, 21, 20)AUC (INF); (N= 22, 19, 21, 18)
Day 1 Inje Cocktail1361.0241368.593
Day 11 Inje Cocktail1653.4911779.717
Day 4 Inje Cocktail Plus Belatacept1577.0171632.455
Day 7 Inje Cocktail1671.1731679.693

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Adjusted Geometric Mean AUC (0-T) and AUC (INF) of Losartan With and Without the Coadministration of Belatacept - Pharmacokinetic (PK) Evaluable Population

AUC (0-T): area under the concentration curve from time 0 to the time of the last quantifiable concentration and AUC (INF) extrapolated to infinity were measured in ng*h/mL. Samples for assessment of plasma concentrations of Inje cocktail components (midazolam, losartan, omeprazole, dextromethorphan and caffeine) and their metabolites (1'-hydroxy-midazolam, E-3174, 5-hydroxyomeprazole, dextrorphan, and paraxanthine) were collected at time = 0 (predose), 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, and 24 hours relative to the dosing of belatacept on Day 4 and Inje cocktail dosing on Days 1, 4, 7, and 11, respectively. Adjusted geometric mean for losartan with and without belatacept, along with adjusted geometric mean ratios for Days 4, 7, and 11 versus Day 1, respectively, are presented. Inje cocktail components (losartan) measured using HPLC with MS/MS Detection. (NCT01766050)
Timeframe: Pre-dose to 24 hours after dose of the Inje Cocktail on Days 1, 4, 7 and 11

,,,
Interventionng*h/mL (Geometric Mean)
AUC (0-T) N=22, 21, 21, 20)AUC (INF) N=22, 21, 21, 20)
Day 1 Inje Cocktail332.191338.033
Day 11 Inje Cocktail332.400338.646
Day 4 Inje Cocktail Plus Belatacept336.531341.644
Day 7 Inje Cocktail337.487343.508

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Mean Change From Baseline in Heart Rate at Study Discharge (Day 46±2 Days)

Heart Rate was taken after the participant had been sitting quietly for at least 5 minutes and was measured in beats per minute (bpm). Hear rate was taken on Day 46 (day of discharge) during the follow up period. Baseline was defined as last non-missing result with a collection date-time less than the date-time of the first active dose of study drug. (NCT01766050)
Timeframe: Baseline and Day 46 ±2 days

Interventionbpm (Mean)
Post Treatment1.0

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Ratio of 5-Dextrorphan (Cmax) to Dextromethorphan (Cmax), Corrected for Molecular Weight (MR_Cmax) With and Without Coadministration of Belatacept - PK Evaluable Population

Metabolite (5-dextrorphan) to parent (dextromethorphan) ratio was corrected for molecular weight. Cmax measured in ng/mL. Samples for assessment of plasma concentrations of Inje cocktail components and the metabolites of those components were collected at time = 0 (predose), 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, and 24 hours relative to the dosing of belatacept on Day 4 and Inje cocktail dosing on Days 1, 4, 7, and 11, respectively. The poor metabolizer of CYP2D6 was excluded from summary of Dextrorphan parameters. Inje cocktail components were each measured using HPLC with MS/MS detection. (NCT01766050)
Timeframe: Pre-dose to 24 hours after dose of the Inje Cocktail on Days 1, 4, 7 and 11

Interventionratio (Geometric Mean)
Day 1 Inje Cocktail280
Day 4 Inje Cocktail Plus Belatacept303
Day 7 Inje Cocktail275
Day 11 Inje Cocktail303

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Ratio of 5-Hydroxyomeprazole (Cmax) to Omeprazole (Cmax), Corrected for Molecular Weight (MR_Cmax) With and Without Coadministration of Belatacept - PK Evaluable Population

Metabolite (5-hydroxyomeprazole) to parent (omeprazole) ratio was corrected for molecular weight. Cmax measured in ng/mL. Samples for assessment of plasma concentrations of Inje cocktail components and the metabolites of those components were collected at time = 0 (predose), 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, and 24 hours relative to the dosing of belatacept on Day 4 and Inje cocktail dosing on Days 1, 4, 7, and 11, respectively. Inje cocktail components were each measured using HPLC with MS/MS detection. (NCT01766050)
Timeframe: Pre-dose to 24 hours after dose of the Inje Cocktail on Days 1, 4, 7 and 11

Interventionratio (Geometric Mean)
Day 1 Inje Cocktail0.548
Day 4 Inje Cocktail Plus Belatacept0.471
Day 7 Inje Cocktail0.424
Day 11 Inje Cocktail0.478

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Ratio of E-3174 (Cmax) to Losartan (Cmax), Corrected for Molecular Weight (MR_Cmax) With and Without Coadministration of Belatacept - PK Evaluable Population

Metabolite (E-3174) to parent (losartan) ratio was corrected for molecular weight. Cmax measured in ng/mL. Samples for assessment of plasma concentrations of Inje cocktail components and the metabolites of those components were collected at time = 0 (predose), 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, and 24 hours relative to the dosing of belatacept on Day 4 and Inje cocktail dosing on Days 1, 4, 7, and 11, respectively. Inje cocktail components were each measured using HPLC with MS/MS detection. (NCT01766050)
Timeframe: Pre-dose to 24 hours after dose of the Inje Cocktail on Days 1, 4, 7 and 11

Interventionratio (Geometric Mean)
Day 1 Inje Cocktail2.31
Day 4 Inje Cocktail Plus Belatacept2.24
Day 7 Inje Cocktail2.26
Day 11 Inje Cocktail2.26

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Ratio of Paraxanthine (Cmax) to Caffeine (Cmax), Corrected for Molecular Weight (MR_Cmax) With and Without Coadministration of Belatacept - PK Evaluable Population

Metabolite (paraxanthine) to parent (caffeine) ratio was corrected for molecular weight. Cmax measured in ng/mL. Samples for assessment of plasma concentrations of Inje cocktail components and their metabolites were collected at time = 0 (predose), 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, and 24 hours relative to the dosing of belatacept on Day 4 and Inje cocktail dosing on Days 1, 4, 7, and 11, respectively. Inje cocktail components were each measured using HPLC with MS/MS detection. (NCT01766050)
Timeframe: Pre-dose to 24 hours after dose of the Inje Cocktail on Days 1, 4, 7 and 11

Interventionratio (Geometric Mean)
Day 1 Inje Cocktail0.303
Day 4 Inje Cocktail Plus Belatacept0.337
Day 7 Inje Cocktail0.333
Day 11 Inje Cocktail0.323

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Adjusted Geometric Mean Cmax of Caffeine With and Without the Coadministration of Belatacept - PK Evaluable Population

Samples for assessment of plasma concentrations of Inje cocktail components (midazolam, losartan, omeprazole, dextromethorphan and caffeine) were collected at time = 0 (predose), 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, and 24 hours relative to the dosing of belatacept on Day 4 and Inje cocktail dosing on Days 1, 4, 7, and 11, respectively. Inje cocktail components were each measured using HPLC with MS/MS detection. Cmax was measured in ng/mL. (NCT01766050)
Timeframe: Pre-dose to 24 hours after dose of the Inje Cocktail on Days 1, 4, 7 and 11

Interventionng/mL (Geometric Mean)
Day 1 Inje Cocktail4696.505
Day 4 Inje Cocktail Plus Belatacept4450.019
Day 7 Inje Cocktail4332.326
Day 11 Inje Cocktail4479.687

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Adjusted Geometric Mean AUC (0-T) and AUC (INF) of Dextromethorphan With and Without the Coadministration of Belatacept - PK Evaluable Population

AUC(0-T): area under the plasma concentration-time curve from time zero to the time of the last quantifiable concentration and AUC (INF): AUC extrapolated to infinity, were measured as ng*h/mL. Samples for assessment of plasma concentrations of Inje cocktail components (midazolam, losartan, omeprazole, dextromethorphan and caffeine) and their metabolites (1'-hydroxy-midazolam, E-3174, 5-hydroxyomeprazole, dextrorphan, and paraxanthine) were collected at time = 0 (predose), 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, and 24 hours relative to the dosing of belatacept on Day 4 and Inje cocktail dosing on Days 1, 4, 7, and 11, respectively. Adjusted geometric mean for dextromethorphan with and without belatacept, along with adjusted geometric mean ratios for Days 4, 7, and 11 versus Day 1, respectively, are presented. The poor metabolizer of CYP2D6 was excluded from the statistical analysis. Inje cocktail components (dextromethorphan) measured using HPLC with MS/MS Detection. (NCT01766050)
Timeframe: Pre-dose to 24 hours after dose of the Inje Cocktail on Days 1, 4, 7 and 11

,,,
Interventionng*h/mL (Geometric Mean)
AUC (0-T); N= 21, 19, 19, 19AUC (INF); N= 18, 17, 18, 15
Day 1 Inje Cocktail6.1766.220
Day 11 Inje Cocktail5.9496.359
Day 4 Inje Cocktail Plus Belatacept5.6515.455
Day 7 Inje Cocktail6.1956.412

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Adjusted Geometric Mean Cmax of Dextromethorphan With and Without the Coadministration of Belatacept - PK Evaluable Population

Cmax was measured in ng/mL. Samples for assessment of plasma concentrations of Inje cocktail components (midazolam, losartan, omeprazole, dextromethorphan and caffeine) and their metabolites (1'-hydroxy-midazolam, E-3174, 5-hydroxyomeprazole, dextrorphan, and paraxanthine) were collected at time = 0 (predose), 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, and 24 hours relative to the dosing of belatacept on Day 4 and Inje cocktail dosing on Days 1, 4, 7, and 11, respectively. Adjusted geometric mean for dextromethorphan with and without belatacept, along with adjusted geometric mean ratios for Days 4, 7, and 11 versus Day 1, respectively, are presented. The poor metabolizer of CYP2D6 was excluded from the statistical analysis. Inje cocktail components (dextromethorphan) measured using HPLC with MS/MS Detection. (NCT01766050)
Timeframe: Pre-dose to 24 hours after dose of the Inje Cocktail on Days 1, 4, 7 and 11

Interventionng/mL (Geometric Mean)
Day 1 Inje Cocktail0.927
Day 4 Inje Cocktail Plus Belatacept0.800
Day 7 Inje Cocktail0.855
Day 11 Inje Cocktail0.794

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Adjusted Geometric Mean Cmax of Losartan With and Without the Coadministration of Belatacept - PK Evaluable Population

Cmax measured in ng/mL. Samples for assessment of plasma concentrations of Inje cocktail components (midazolam, losartan, omeprazole, dextromethorphan and caffeine) and their metabolites (1'-hydroxy-midazolam, E-3174, 5-hydroxyomeprazole, dextrorphan, and paraxanthine) were collected at time = 0 (predose), 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, and 24 hours relative to the dosing of belatacept on Day 4 and Inje cocktail dosing on Days 1, 4, 7, and 11, respectively. Adjusted geometric mean for losartan with and without belatacept, along with adjusted geometric mean ratios for Days 4, 7, and 11 versus Day 1, respectively, are presented. Inje cocktail components (losartan) measured using HPLC with MS/MS Detection. (NCT01766050)
Timeframe: Pre-dose to 24 hours after dose of the Inje Cocktail on Days 1, 4, 7 and 11

Interventionng/mL (Geometric Mean)
Day 1 Inje Cocktail119.789
Day 4 Inje Cocktail Plus Belatacept118.663
Day 7 Inje Cocktail127.184
Day 11 Inje Cocktail126.461

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AUC(0-T) of Inje Cocktail Component Metabolites (1'-Hydroxy-Midazolam, E-3174, 5-Hydroxyomeprazole, Dextrorphan, and Paraxanthine) With and Without Coadministration of Belatacept - PK Evaluable Population

Area under the plasma concentration-time curve from zero to the last time of the last quantifiable concentration [AUC(0-T)] was measured in ng*h/mL. Samples for assessment of plasma concentrations of Inje cocktail components metabolites (1'-hydroxy-midazolam, E-3174, 5-hydroxyomeprazole, dextrorphan, and paraxanthine) were collected at time = 0 (predose), 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, and 24 hours relative to the dosing of belatacept on Day 4 and Inje cocktail dosing on Days 1, 4, 7, and 11, respectively. The poor metabolizer of CYP2D6 was excluded from summary of Dextrorphan parameters. Inje cocktail components were each measured using HPLC with MS/MS detection. (NCT01766050)
Timeframe: Pre-dose to 24 hours after dose of the Inje Cocktail on Days 1, 4, 7 and 11

,,,
Interventionng*h/mL (Geometric Mean)
1'-hydroxy-midazolam (N=22, 21, 21, 20)E-3174 (N= 22,21,21,20)5-hydroxyomeprazole (N=22,21,21,20)dextrorphan (N=21,20,20,19)paraxanthine (N=17,19,18,18)
Day 1 Inje Cocktail28.91995997163620592
Day 11 Inje Cocktail33.62072995164421353
Day 4 Inje Cocktail Plus Belatacept31.81999967157021077
Day 7 Inje Cocktail32.52089929151920680

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Adjusted Geometric Mean Maximum Drug Concentration (Cmax) of Midazolam With and Without the Coadministration of Belatacept - Pharmacokinetic (PK) Evaluable Population

Samples for the assessment of plasma concentrations of Inje cocktail components (midazolam, losartan, omeprazole, dextromethorphan and caffeine) and their metabolites (1'-hydroxy-midazolam, E-3174, 5-hydroxyomeprazole, dextrorphan, and paraxanthine) were collected at time = 0 (predose), 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, and 24 hours relative to the dosing of belatacept on Day 4 and Inje cocktail dosing on Days 1, 4, 7, and 11, respectively. Adjusted geometric mean for midazolam with and without belatacept, along with adjusted geometric mean ratios for Days 4, 7, and 11 versus Day 1, respectively, are presented. Cmax measured in nanograms per milliliter (ng/mL). Inje cocktail components (Midazolam) measured using High Performance Liquid Chromatography (HPLC) with Tandem Mass Spectrometry (MS/MS) Detection. (NCT01766050)
Timeframe: Pre-dose to 24 hours after dose of the Inje Cocktail on Days 1, 4, 7 and 11

Interventionng/mL (Geometric Mean)
Day 1 Inje Cocktail24.376
Day 4 Inje Cocktail Plus Belatacept24.152
Day 7 Inje Cocktail22.211
Day 11 Inje Cocktail24.220

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Tmax of Inje Cocktail Component Metabolites (1'-Hydroxy-Midazolam, E-3174, 5-Hydroxyomeprazole, Dextrorphan, and Paraxanthine) With and Without the Coadministration of Belatacept - PK Evaluable Population

Samples for assessment of plasma concentrations of Inje cocktail components metabolites (1'-hydroxy-midazolam, E-3174, 5-hydroxyomeprazole, dextrorphan, and paraxanthine) were collected at time = 0 (predose), 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, and 24 hours relative to the dosing of belatacept on Day 4 and Inje cocktail dosing on Days 1, 4, 7, and 11, respectively. The poor metabolizer of CYP2D6 was excluded from summary of Dextrorphan parameters. Inje cocktail components were each measured using HPLC with MS/MS detection. Time of maximum observed plasma concentration (Tmax) was measured in hours (h). (NCT01766050)
Timeframe: Pre-dose to 24 hours after dose of the Inje Cocktail on Days 1, 4, 7 and 11

,,,
Interventionh (Median)
1'-Hydroxy-Midazolam (N=22,21,21,20)E-3174 (N=22, 21, 21, 20)5-Hydroxyomeprazole (N=22,21,21,20)Dextrorphan (N=21,20,20,19)Paraxanthine (N=17, 19, 18, 18)
Day 1 Inje Cocktail1.004.002.002.008.00
Day 11 Inje Cocktail1.004.002.532.008.00
Day 4 Inje Cocktail Plus Belatacept1.004.003.002.008.00
Day 7 Inje Cocktail1.004.003.002.008.00

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Ratio of 1'-Hydroxy-Midazolam AUC(0-T) to Midazolam AUC(0-T) and 1'-Hydroxy-Midazolam AUC(INF) to Midazolam AUC(INF), Corrected for Molecular Weight [MR_AUC(0-T), MR_AUC (INF)] With and Without Coadministration of Belatacept - PK Evaluable Population

Metabolite (1'-hydroxy-midazolam) to parent (midazolam) ratio was corrected for molecular weight. AUC (0-T) and AUC (INF) measured in ng*h/mL. Samples for assessment of plasma concentrations of Inje cocktail components and the metabolites of those components were collected at time = 0 (predose), 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, and 24 hours relative to the dosing of belatacept on Day 4 and Inje cocktail dosing on Days 1, 4, 7, and 11, respectively. Inje cocktail components were each measured using HPLC with MS/MS detection. (NCT01766050)
Timeframe: Pre-dose to 24 hours after dose of the Inje Cocktail on Days 1, 4, 7 and 11

,,,
Interventionratio (Geometric Mean)
MR_AUC (0-T) ratio; N=22, 21, 21, 20MR_(INF) ratio; N=22, 21, 20, 20
Day 1 Inje Cocktail0.4210.428
Day 11 Inje Cocktail0.4720.478
Day 4 Inje Cocktail Plus Belatacept0.4470.460
Day 7 Inje Cocktail0.4950.479

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AUC(INF) of Inje Cocktail Component Metabolites (1'-Hydroxy-Midazolam, E-3174, 5-Hydroxyomeprazole, Dextrorphan, and Paraxanthine) With and Without Coadministration of Belatacept - PK Evaluable Population

Area under the plasma concentration-time curve from time zero extrapolated to infinite time [AUC(INF)] was measured in ng*h/mL. Samples for assessment of plasma concentrations of Inje cocktail components metabolites (1'-hydroxy-midazolam, E-3174, 5-hydroxyomeprazole, dextrorphan, and paraxanthine) were collected at time = 0 (predose), 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, and 24 hours relative to the dosing of belatacept on Day 4 and Inje cocktail dosing on Days 1, 4, 7, and 11, respectively. The poor metabolizer of CYP2D6 was excluded from summary of Dextrorphan parameters. Inje cocktail components were each measured using HPLC with MS/MS detection. (NCT01766050)
Timeframe: Pre-dose to 24 hours after dose of the Inje Cocktail on Days 1, 4, 7 and 11

,,,
Interventionng*h/mL (Geometric Mean)
1'-hydroxy-midazolam (N=22,21,20,20)E-3174 (N=22,20,21,20)5-hydroxyomeprazole (N=22,20,21,17dextrorphan (N=21,20,20,19)paraxanthine (N=7,8,6,6)
Day 1 Inje Cocktail30.521031010167922401
Day 11 Inje Cocktail35.121821063168221874
Day 4 Inje Cocktail Plus Belatacept33.82060990161022905
Day 7 Inje Cocktail32.92187938156222063

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Mean Change From Baseline in Systolic and Diastolic Blood Pressure at Study Discharge (Day 46±2 Days)

Systolic and Diastolic blood pressures were taken after the participant had been sitting quietly for at least 5 minutes and the pressures were measured in millimeters of mercury (mm Hg). Systolic and Diastolic blood pressures were taken on Day 46 (day of discharge from the study). Baseline was defined as last non-missing result with a collection date-time less than the date-time of the first active dose of study drug. (NCT01766050)
Timeframe: Baseline and Day 46 ±2 days

Interventionmm Hg (Mean)
Systolic (N=18)Diastolic (N=18)
Post Treatment-5.9-5.7

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Number of Participants With Out-of-Range Electrocardiogram Intervals - All Treated Participants

Participants had 12-Lead electrocardiograms (ECGs) performed at Screening Visit, Day 1 prior to dosing, Day 46 ±2, and at early termination. Definition of out-of-range: PR Interval >210 milliseconds (msec); QRS > 120 msec, QT > 500 msec or > 30 msec change from baseline (Day 1); QT with Fridericia correction (QTcF) > 450 msec or change from baseline of > 30 msec to <= 60 msec or change from baseline > 60 msec. (NCT01766050)
Timeframe: Day 1 to Day 46 ±2 days or at early termination

Interventionparticipants (Number)
Day 46 (N=18)Early Termination (N=2)
Inje Cocktail Alone and Inje Cocktail Plus Belatacept00

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Adjusted Geometric Mean Area Under the Concentration Time Curve (AUC) From Zero to Last Concentration (0-T) and AUC Extrapolated to Infinity (INF) of Midazolam With and Without the Coadministration of Belatacept - Pharmacokinetic (PK) Evaluable Population

AUC(0-T): area under the plasma concentration-time curve from zero to the last time of the last quantifiable concentration and AUC (INF): AUC from time zero extrapolated to infinite time were measured in ng*h/mL. Samples for the assessment of plasma concentrations of Inje cocktail components (midazolam, losartan, omeprazole, dextromethorphan and caffeine) and their metabolites (1'-hydroxy-midazolam, E-3174, 5-hydroxyomeprazole, dextrorphan, and paraxanthine) were collected at time = 0 (predose), 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, and 24 hours relative to the dosing of belatacept on Day 4 and Inje cocktail dosing on Days 1, 4, 7, and 11, respectively. Adjusted geometric mean for midazolam with and without belatacept, along with adjusted geometric mean ratios for Days 4, 7, and 11 versus Day 1, respectively, are presented. Midazolam measured using HPLC with MS/MS Detection. (NCT01766050)
Timeframe: Pre-dose to 24 hours after dose of the Inje Cocktail on Days 1, 4, 7and 11

,,,
Interventionng*h/mL (Geometric Mean)
AUC (0-T);N=22, 21, 21, 20)AUC (INF);N=22, 21, 21, 20)
Day 1 Inje Cocktail65.54867.743
Day 11 Inje Cocktail67.71769.841
Day 4 Inje Cocktail Plus Belatacept68.83371.039
Day 7 Inje Cocktail63.30365.555

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Cmax of Inje Cocktail Metabolites (1'-Hydroxy-Midazolam, E-3174, 5-Hydroxyomeprazole, Dextrorphan, and Paraxanthine) With and Without Coadministration of Belatacept - PK Evaluable Population

Samples for assessment of plasma concentrations of Inje cocktail component metabolites (1'-hydroxy-midazolam, E-3174, 5-hydroxyomeprazole, dextrorphan, and paraxanthine) were collected at time = 0 (predose), 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, and 24 hours relative to the dosing of belatacept on Day 4 and Inje cocktail dosing on Days 1, 4, 7, and 11, respectively. The poor metabolizer of CYP2D6 was excluded from summary of Dextrorphan parameters. Inje cocktail component metabolites were each measured using HPLC with MS/MS detection. Cmax was measured in ng/mL. (NCT01766050)
Timeframe: Pre-dose to 24 hours after dose of the Inje Cocktail on Days 1, 4, 7 and 11

,,,
Interventionng/mL (Geometric Mean)
1'-Hydroxy-Midazolam (N=22, 21, 21, 20)E-3174 (N=22, 21, 21, 20)5-Hydroxyomeprazole (N=22, 21, 21, 20)Dextrorphan (N=21,20,20,19)Paraxanthine (N=17,19,18,18)
Day 1 Inje Cocktail11.12623353421291
Day 11 Inje Cocktail12.32913373311358
Day 4 Inje Cocktail Plus Belatacept11.92763603241367
Day 7 Inje Cocktail11.43003323121320

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Mean Change From Baseline in Sitting Heart Rate - All Treated Participants

Heart Rate was taken after the participant had been sitting quietly for at least 5 minutes and the heart rate was measured in beats per minute (bpm). Heart Rates were obtained at screening visit, Day -1, and at 0 hour (pre-dose), 0.5 hour (post dose), and 2 hours (post dose) on Days 1, 4, 7, 11. Baseline was defined as last non-missing result with a collection date-time less than the date-time of the first active dose of study drug. (NCT01766050)
Timeframe: Baseline and 0.5 and 2.0 hours Post Dose on Days 1, 4, 7, and 11

,,,
Interventionbpm (Mean)
Heart Rate 0.5 hour post dose (N=22, 21, 21, 20)Heart Rate 2.0 hour post dose (N=22, 21, 21, 20)
Day 1 Inje Cocktail-3.3-3.5
Day 11 Inje Cocktail-1.63.1
Day 4 Inje Cocktail Plus Belatacept-4.20.2
Day 7 Inje Cocktail-1.80.5

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Ratio of 1'-Hydroxy-Midazolam (Cmax) to Midazolam (Cmax), Corrected for Molecular Weight (MR_Cmax) With and Without Coadministration of Belatacept - PK Evaluable Population

Metabolite (1'-hydroxy-midazolam) to parent (midazolam) ratio was corrected for molecular weight. Cmax measured in ng/mL. Samples for assessment of plasma concentrations of Inje cocktail components and the metabolites of those components were collected at time = 0 (predose), 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, and 24 hours relative to the dosing of belatacept on Day 4 and Inje cocktail dosing on Days 1, 4, 7, and 11, respectively. Inje cocktail components were each measured using HPLC with MS/MS detection. (NCT01766050)
Timeframe: Pre-dose to 24 hours after dose of the Inje Cocktail on Days 1, 4, 7 and 11

Interventionratio (Geometric Mean)
Day 1 Inje Cocktail0.432
Day 4 Inje Cocktail Plus Belatacept0.476
Day 7 Inje Cocktail0.497
Day 11 Inje Cocktail0.490

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Adjusted Geometric Mean AUC (0-T) and AUC (INF) of Caffeine With and Without the Coadministration of Belatacept - PK Evaluable Population

Samples for assessment of plasma concentrations of Inje cocktail components (midazolam, losartan, omeprazole, dextromethorphan and caffeine) were collected at time = 0 (predose), 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, and 24 hours relative to the dosing of belatacept on Day 4 and Inje cocktail dosing on Days 1, 4, 7, and 11, respectively. Inje cocktail components were each measured using HPLC with MS/MS detection. AUC (0-T) and AUC (INF) were measured as ng*h/mL. (NCT01766050)
Timeframe: Pre-dose to 24 hours after dose of the Inje Cocktail on Days 1, 4, 7 and 11

,,,
Interventionng*h/mL (Geometric Mean)
AUC (0-T); N= 22, 21, 21, 18AUC (INF); N= 22, 21, 21, 18
Day 1 Inje Cocktail37394.540084.1
Day 11 Inje Cocktail38407.041537.6
Day 4 Inje Cocktail Plus Belatacept35200.337647.8
Day 7 Inje Cocktail36853.440149.9

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Mean Change From Baseline in Sitting Systolic and Diastolic Blood Pressure - All Treated Participants

Systolic and Diastolic blood pressures were taken after the participant had been sitting quietly for at least 5 minutes and the pressures were measured in millimeters of mercury (mm Hg). Pressures were obtained at screening visit, Day -1, and at 0 hour (pre-dose), 0.5 hour (post dose), and 2 hours (post dose) on Days 1, 4, 7, 11. Baseline was defined as last non-missing result with a collection date-time less than the date-time of the first active dose of study drug. (NCT01766050)
Timeframe: Baseline and 0.5 and 2.0 hours Post Dose on Days 1, 4, 7, and 11

,,,
Interventionmm Hg (Mean)
Systolic 0.5 hour post dose (N=22,21,21,20)Systolic 2.0 hour post dose (N=22,21,21,20)Diastolic 0.5 hour post dose (N=22,21,21,20)Diastolic 2.0 hour post dose (N=22,21,21,20)
Day 1 Inje Cocktail-0.60.2-1.70.9
Day 11 Inje Cocktail-4.7-2.9-2.2-1.0
Day 4 Inje Cocktail Plus Belatacept0.12.0-0.2-2.0
Day 7 Inje Cocktail-4.9-2.7-2.2-3.4

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Adjusted Geometric Mean Cmax of Omeprazole With and Without the Coadministration of Belatacept - Pharmacokinetic (PK) Evaluable Population

Cmax: Maximum observed plasma concentration was measured in ng/mL. Samples for assessment of plasma concentrations of Inje cocktail components (midazolam, losartan, omeprazole, dextromethorphan and caffeine) and their metabolites (1'-hydroxy-midazolam, E-3174, 5-hydroxyomeprazole, dextrorphan, and paraxanthine) were collected at time = 0 (predose), 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, and 24 hours relative to the dosing of belatacept on Day 4 and Inje cocktail dosing on Days 1, 4, 7, and 11, respectively. Adjusted geometric mean for omeprazole with and without belatacept, along with adjusted geometric mean ratios for Days 4, 7, and 11 versus Day 1, respectively, are presented. Inje cocktail components (omeprazole) measured using HPLC with MS/MS Detection. (NCT01766050)
Timeframe: Pre-dose to 24 hours after dose of the Inje Cocktail on Days 1, 4, 7 and 11

Interventionng/mL (Geometric Mean)
Day 1 Inje Cocktail583.047
Day 4 Inje Cocktail Plus Belatacept734.776
Day 7 Inje Cocktail753.126
Day 11 Inje Cocktail686.929

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Number of Patients Who Achieve Adequate Sedation to Allow Colonoscopy (Defined as MOAA/S ≤3)

Modified Observer's Assessment of Alertness/Sedation (MOAA/S) scale. This scale ranges from 0 to 5, where 0 denotes general anesthesia, in which the patient has no response to painful stimuli, and 5 denotes a level of minimal sedation in which the patient is fully awake. (NCT01769586)
Timeframe: Approximately 10 minutes or less

Interventionparticipants (Number)
Diphenhydramine27
Midazolam65

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Subject Perception of Pain and Anxiety Post Procedure

Subjects will be asked to rate anxiety and pain 30 minutes post-operatively by marking along a mm Visual Analog Scale, with 0mm being No Pain/Anxiety and 100mm being Worst Imaginable Pain/Anxiety (NCT01830881)
Timeframe: 30 minutes post operatively

,
Interventionmm (Mean)
Anxiety Post ProcedurePain Post Procedure
Midazolam and Ibuprofen14.437.1
Placebo-cherry Syrup and Ibuprofen20.934.7

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Subject Perception of Pain and Anxiety Upon Entering Procedure Room

Subjects will be asked to rate anxiety and pain upon entering procedure room by marking along a mm Visual Analog Scale, with 0mm being No Pain/Anxiety and 100mm being Worst Imaginable Pain/Anxiety (NCT01830881)
Timeframe: upon entering procedure room (30-60 minutes after premedication)

,
Interventionmm (Mean)
Anxiety at Room EntryPain at Room Entry
Midazolam and Ibuprofen34.510.1
Placebo-cherry Syrup and Ibuprofen51.417.5

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Subject Satisfaction With Pain and Anxiety 1-3 Days Post Procedure

To assess whether oral midazolam is associated with differences in overall patient satisfaction with pain and anxiety control and abortion experience at 1-3 days postoperatively as measured by a mm VAS with 0mm being Not At All Satisfied and 100mm being Very Satisfied (NCT01830881)
Timeframe: 1-3 days post-operatively

,
Interventionmm on a 100 mm Visual Analog Scale (Mean)
Satisfaction with anxiety control (100-mm VAS)Satisfaction with pain control (100-mm VAS)
Midazolam and Ibuprofen64.748.2
Placebo-cherry Syrup and Ibuprofen50.236.6

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Subject's Correct Identification of Receiving Midazolam or Placebo

Number of patient's who could correctly determine if they received study drug or placebo when asked (NCT01830881)
Timeframe: 30 minutes postoperatively

InterventionParticipants (Count of Participants)
Placebo-cherry Syrup and Ibuprofen43
Midazolam and Ibuprofen48

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Number of Participants With Need for Additional Postoperative Pain Medication

Subjects will be assessed 30 minutes postoperatively for need of additional pain medications. (NCT01830881)
Timeframe: 30 minutes postoperatively

,
InterventionParticipants (Count of Participants)
OndansetronHydrocodone/acetaminophen
Midazolam and Ibuprofen32
Placebo-cherry Syrup and Ibuprofen21

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Patient Satisfaction With Pain and Anxiety 30 Minutes Postoperatively

To assess whether oral midazolam is associated with differences in overall patient satisfaction with pain and anxiety control and abortion experience at 30 min postoperatively as measured by a mm Visual Analog Scale with 0mm being Not At All Satisfied and 100mm being Very Satisfied (NCT01830881)
Timeframe: 30 minutes post-operatively

,
Interventionmm on a 100 mm Visual Analog Scale (Mean)
Satisfaction with anxiety control (100-mm VAS)Satisfaction with pain control (100-mm VAS)
Midazolam and Ibuprofen68.950.0
Placebo-cherry Syrup and Ibuprofen56.143.2

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Subject Vital Signs (Heart Rate) 30 Minutes Postprocedure

Subject vital signs (heart rate) will be assessed 30 minutes postoperatively (NCT01830881)
Timeframe: 30 minutes postoperatively

Interventionbpm (Mean)
Placebo-cherry Syrup and Ibuprofen70.1
Midazolam and Ibuprofen72

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State-Trait Anxiety Inventory for Anxiety at Baseline

"To measure the mean State-Trait Anxiety Inventory (STAI) Form Y-1 for anxiety. State anxiety items include: I am tense; I am worried and I feel calm; I feel secure. Trait anxiety items include: I worry too much over something that really doesn't matter and I am content; I am a steady person. Each type of anxiety has its own 4-point scale of 20 different questions that are scored. The 4-point scale for S-anxiety is as follows: 1.) not at all, 2.) somewhat, 3.) moderately so, 4.) very much so. The 4-point scale for T-anxiety is as follows: 1.) almost never, 2.) sometimes, 3.) often, 4.) almost always. Scores range from 20 to 80, with higher scores indicate greater anxiety. State anxiety items and Trait anxiety items were each summed in assessment to provide two total scores for each participant, a State anxiety score and a Trait anxiety score. Mean and standard deviation of total scores for each group are reported." (NCT01830881)
Timeframe: Baseline (upon entry into study)

,
Interventionunits on a scale (Mean)
State anxiety levelTrait anxiety level
Midazolam and Ibuprofen51.338.6
Placebo-cherry Syrup and Ibuprofen50.840.1

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Subject Perception of Pain and Anxiety During Uterine Aspiration

Subjects will be asked to rate anxiety and pain at the time of uterine aspiration by marking along a 100 mm Visual Analog Scale, with 0mm being No Pain/Anxiety and 100mm being Worst Imaginable Pain/Anxiety (NCT01830881)
Timeframe: at time of uterine aspiration (30-60 minutes after premedication)

,
Interventionmm (Mean)
Pain with AspirationAnxiety with Aspiration
Midazolam and Ibuprofen70.160.9
Placebo-cherry Syrup and Ibuprofen74.368.2

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Subject Sleepiness 30 Minutes Postprocedure

Subject sleepiness will be assessed 30 minutes postoperatively using a 100mm Visual Analog Scale with 0mm being None and 100mm being Worst Imaginable (NCT01830881)
Timeframe: 30 minutes postoperatively

Interventionunits on a scale (Mean)
Placebo-cherry Syrup and Ibuprofen40.1
Midazolam and Ibuprofen56.6

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Subject Perception of Pain During Cervical Dilation

Subjects will be asked to rate pain at the time of cervical dilation by marking along a mm Visual Analog Scale, with 0mm being No Pain and 100mm being Worst Imaginable Pain (NCT01830881)
Timeframe: with cervical dilation (30-60 minutes after premedication)

Interventionmm (Mean)
Placebo-cherry Syrup and Ibuprofen73.0
Midazolam and Ibuprofen69.3

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Subject Nausea 30 Minutes Postprocedure

Subject nausea will be assessed 30 minutes postoperatively using a 100mm Visual Analog Scale with 0mm being None and 100mm being Worst Imaginable (NCT01830881)
Timeframe: 30 minutes postoperatively

Intervention100-mm visual analog sclae for nausea (Mean)
Placebo-cherry Syrup and Ibuprofen9.5
Midazolam and Ibuprofen3.5

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Subject Extent of Amnesia

To assess the extent of amnesia 1-3 days postoperatively as measured by 100mm Visual Analog Scale with 0mm being Remember Nothing and 100mm being Remember Everything. (NCT01830881)
Timeframe: 1-3 days postoperatively

Interventionmm (Mean)
Placebo-cherry Syrup and Ibuprofen91.5
Midazolam and Ibuprofen61.3

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Subject Anticipated Perception of Pain and Anxiety During Uterine Aspiration at Baseline

Subjects will be asked to rate their anticipated anxiety and pain at the time of uterine aspiration by marking along a mm Visual Analog Scale, with 0mm being No Pain/Anxiety and 100mm being Worst Imaginable Pain/Anxiety (NCT01830881)
Timeframe: Baseline (upon entry into study)

,
Interventionmm (Mean)
Expected AnxietyExpected Pain
Midazolam and Ibuprofen74.269.2
Placebo-cherry Syrup and Ibuprofen77.567.2

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Subject Vital Signs (Heart Rate)

Subject heart rate will be assessed for the duration of the procedure (NCT01830881)
Timeframe: intraoperatively (30-60 minutes after premedication)

Interventionbmp (Mean)
Placebo-cherry Syrup and Ibuprofen80
Midazolam and Ibuprofen78.5

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Subject Vital Signs (Oxygenation Saturation)

Subject oxygenation status will be assessed for the duration of the procedure (NCT01830881)
Timeframe: intraoperatively (30-60 minutes after premedication)

Interventionpercent saturation (Mean)
Placebo-cherry Syrup and Ibuprofen98.3
Midazolam and Ibuprofen98.1

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Subject Extent of Amnesia Using Amnesia Score

To assess the extent of amnesia 30 min postoperatively as measured by ability to recall procedure using 4-point scale (0 = unable to recall any proportion of the procedure, 1 = able to recall and describe some portions of the procedure, but overall has minimal recall of the procedure, 2 = able to recall and describe most of the procedure, but admits to inability to recall some portion of the procedure, 3 = able to recall and describe the entire procedure). (NCT01830881)
Timeframe: 30 minutes postoperatively

,
InterventionParticipants (Count of Participants)
Partial to complete amnesia (score 0,1,2)No Amnesia (score 3)
Midazolam and Ibuprofen3130
Placebo-cherry Syrup and Ibuprofen1645

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Subject Extent of Sedation

Subject extent of sedation 30-60 minutes after premedication, just prior to procedure as measured by the 6-point Ramsay Scale (1 = patient anxious agitated, or restless; 2 = patient cooperative, oriented, and tranquil; 3 = patient asleep, responds to commands only; 4 = patient asleep, responds to gentle shaking, light glabellar tap, or loud auditory stimulus; 5 = patient asleep, responds to noxious stimuli such as firm nail bed pressure; 6 = patient asleep, has no response to firm nail bed pressure or other noxious stimuli) (NCT01830881)
Timeframe: 30-60 minutes after premedication

,
InterventionParticipants (Count of Participants)
1234 or greater
Midazolam and Ibuprofen105110
Placebo-cherry Syrup and Ibuprofen115000

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Subject Vital Signs (Oxygenation Saturation) 30 Minutes Postprocedure

Subject vital signs (oxygenation saturation) will be assessed 30 minutes postoperatively (NCT01830881)
Timeframe: 30 minutes postoperatively

Interventionpercent saturation (Mean)
Placebo-cherry Syrup and Ibuprofen98.3
Midazolam and Ibuprofen98.1

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Subject Perception of Anxiety With Patient Positioning Procedure

Subjects will be asked to rate anxiety prior to starting pelvic exam by marking along a mm Visual Analog Scale, with 0mm being No Anxiety and 100mm being Worst Imaginable Anxiety (NCT01830881)
Timeframe: prior to starting pelvic exam (30-60 minutes after premedication)

Interventionmm (Mean)
Placebo-cherry Syrup and Ibuprofen56.6
Midazolam and Ibuprofen45.4

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Maintenance of Optimal Sedation Target in Both Groups.

Both arms will be assessed by the patient assessor with RASS score measurement at baseline and every 20 minutes thereafter for the length of the procedure (up to 8 hours) and then averaged together to get one over all score . In the Dexmedetomidine arm the drug will be titrated by 0.1mcg/Kg/hour by the treating physician clinical judgment, in order to achieve and maintain RASS of 0 - 1. In the control arm the drug adjustment will not be based on the RASS score, but by physician discretion only. It is a 10-point scale to determine sedation, with a score from +4 (very combative, violent, dangerous to staff) to -5 (unarousable, no response to voice or physical stimulation). (NCT01845441)
Timeframe: Up to 8 hours

Interventionscore on a scale (Median)
Dexmedetomidine Arm-1
Control Arm0

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Preserved Neurological Examination.

Neurological status using modified NIHSS (National Institutes of Health Stroke Scale) is a 15-item neurologic examination stroke scale, between 0 and 4, with 0 being normal functioning and 4 being completely impaired. (NCT01845441)
Timeframe: Up to 8 hours

Interventionscore on a scale (Median)
Dexmedetomidine Arm19
Control Arm18.5

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Numbers of Patient Movements (Events) That Delay or Adversely Affect the Procedure Performance and Safety.

Patient will be continuously monitored for movements that delays or adversely affect the performance of the procedure by the patient assessor in a safe and timely manner (an event). One minute interval between patient event assessments will be given to prevent subjective bias. After every one minute, it will be determined if an event has occurred. Over the length of the procedure, the total number of one-minute intervals with an event occurrence will be summed and then divided by the total of minutes in the procedure to obtain a standardized value as the primary outcome. This will allow for direct comparison of values across the procedures of varying length. This approach will be more systematic and more easily replicable than counting events directly, which requires interpretation as to when a movement event begins and ends, which can be difficult and more subjective. (NCT01845441)
Timeframe: Primary outcome will be assessed during the procedure, up to 4 hours.

InterventionEvents (Median)
Dexmedetomidine Arm30
Control Arm36

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Clinical Global Impressions-Improvement (CGI-I) Scale

"The CGI-I is a clinician rated single-item scale: Compared to the patient's condition at admission, how much has the patient changed?, rated on a 7-point response scale: 1 = Very much improved, 2 = Much improved, 3 = Minimally improved, 4 = No change, 5 = Minimally worse, 6 = Much worse, and 7 = Very much worse. In this case, admission referred to the CGI-S screening assessments performed between Day -28 an -7, one conducted during the screening visit, and a second rating conducted by a remote, independent rater." (NCT01920555)
Timeframe: A baseline assessment was made on Day 0, preceding infusion (i.e., treatment). Outcome assessments were made on days 1, 3, 5, 7, 14, and 30. The primary endpoint for this study was Day 3. Thus, the outcome measure table provides data on Days 0, 1 and 3

,,,,
Interventionunits on a scale (Mean)
Day 0Day 1Day 3
Ketamine 0.1mg3.88888893.06250002.9333333
Ketamine 0.2mg4.05000003.36842112.8421053
Ketamine 0.5mg4.13636362.63636362.5714286
Ketamine 1.0mg4.00000003.05000002.5500000
Midazolam 0.045mg4.15789473.61111113.1666667

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Clinical Global Impressions-Severity (CGI-S)

"The CGI-S is a clinician rated single-item scale: How depressed is the patient at this time?, rated on a 7-point response scale: 1 = Normal, not at all depressed, 2 = Borderline depressed, 3 = Mildly depressed, 4 = Moderately depressed. 5 = Markedly depressed, 6 = severely depressed, 7 = Among the most severely depressed patients. When rating patients, clinicians were asked to consider the past 24 hours." (NCT01920555)
Timeframe: A baseline assessment was made on Day 0, preceding infusion (i.e., treatment). Outcome assessments were made on days 1, 3, 5, 7, 14, and 30. The primary endpoint for this study was Day 3. Thus, the outcome measure table provides data on Days 0, 1 and 3

,,,,
Interventionunits on a scale (Mean)
Day 0Day 1Day 3
Ketamine 0.1mg5.00000003.56250003.4000000
Ketamine 0.2mg5.20000004.26315793.7368421
Ketamine 0.5mg4.86363643.27272733.1428571
Ketamine 1.0mg5.20000003.50000003.3000000
Midazolam 0.045mg5.0000004.5555564.1666667

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Clinical Positive Affect Scale (CPAS)

"The CPAS is a 16-item self-report scale to assess the level to which participants experience persistent distress due to feeling that they have not returned to their normal or premorbid state. Items (e.g., I look forward to things) are rated on a 5-point scale (0=not at all, 1=very much less than normal, 2=much less than normal, 3=slightly less than normal, 4=same as best or normal self). The possible scale range is 0 to 64, with higher scores indicating greater recovery from depression. Patients were asked to rate their experience of the past 24 hours." (NCT01920555)
Timeframe: A baseline assessment was made on Day 0, preceding infusion (i.e., treatment). Outcome assessments were made on days 1, 3, 5, 7, 14, and 30. The primary endpoint for this study was Day 3. Thus, the outcome measure table provides data on Days 0, 1 and 3

,,,,
Interventionunits on a scale (Mean)
Day 0Day 1Day 3
Ketamine 0.1mg19.333333335.250000038.8666667
Ketamine 0.2mg20.500000027.052631628.3888889
Ketamine 0.5mg20.636363640.869696439.7619048
Ketamine 1.0mg21.250000033.000000037.4500000
Midazolam 0.045mg21.263157924.444444433.3750000

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Clinician-Administered Dissociative States Scale (CADSS) Scores During Infusion

"The CADSS is a 23-item self-report scale for the assessment of dissociative states. It is a reliable, valid self-report instrument. The severity of each dissociative symptom ranges from 0 (not present) to 4 (extreme). The total score is calculated by summing across items, with a total possible range of 0-92. The CADSS was administered right before infusion, and 40, 80 minute and 120 minutes after the start of infusion. The timeframe is at this moment." (NCT01920555)
Timeframe: Day 0/baseline at 0, 40, 80, and 120 minutes

,,,,
Interventionunits on a scale (Mean)
Minute 0Minute 40Minute 80Minute 120
Ketamine 0.1mg0.11111113.00000000.44444440.0555556
Ketamine 0.2mg0.10000004.05000000.10000000
Ketamine 0.5mg014.27272730.77272730.1363636
Ketamine 1.0mg0.100000024.68421051.80000000.6500000
Midazolam 0.045mg0.42105262.68421051.15789470.5789474

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Hamilton Rating Scale for Depression - 6 Items

The HAMD6 is a 6-item clinician-rated scale, where clinicians rate the presence of depression symptoms (i.e., depressed mood, guilt, work and interests, psychomotor retardation, psychic anxiety, somatic symptoms) on a 5-point scale, where 0 = not present, and 1-4 represent increasingly severe symptoms. One item (i.e., somatic symptoms) is rated on only a 3-point scale, ranging from 0-2. The possible scale range is 0-22, where higher values represent more severe depression. This instrument is completed with a structured interview guide by the clinician based on his/her assessment of the patient's symptoms. This structured interview has been validated for use with time frames shorter than one week. In this study, the HAMD6 was used to assess symptoms occurring in the past 24 hours. (NCT01920555)
Timeframe: A baseline assessment was made on Day 0, preceding infusion (i.e., treatment). Outcome assessments were made on days 1, 3, 5, 7, 14, and 30. The primary endpoint for this study was Day 3. Thus, the outcome measure table provides data on Days 0, 1, & 3

,,,,
Interventionunits on a scale (Mean)
Day 0Day 1Day 3
Ketamine 0.1mg12.55555567.50000006.8000000
Ketamine 0.2mg12.75000009.26315798.4736842
Ketamine 0.5mg12.59090915.86363645.9047619
Ketamine 1.0mg12.63157896.90000007.2000000
Midazolam 0.045mg13.052631610.66666679.0555556

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Montgomery-Asberg Depression Rating Scale (MADRS)

"The MADRS is a 10-item clinician-rated scale measuring depression severity. Symptoms are rated on a 7-point scale, where 0 = not present, and 1-6 represent increasing severity. Values 2, 4, and 6 have specific anchoring text (e.g., 2=Difficulties in starting activities. 4=Difficulties in starting simple routine activities which are carried out with effort, 6=Complete lassitude. Unable to do anything without help.) Values 1, 3, and 5 do not have specific text. The possible scale range is 0-60, where higher values represent higher severity. In this study, the MADRS was used to rate symptoms occurring in the past 3 days." (NCT01920555)
Timeframe: A baseline assessment was made on Day 0, preceding infusion (i.e., treatment). Outcome assessments were made on days 3, 5, 7, 14, and 30. The primary endpoint for this study was Day 3. Thus, the outcome measure table provides data on Days 0 and 3.

,,,,
Interventionunits on a scale (Mean)
Day 0Day 3
Ketamine 0.1mg33.833333319.6666667
Ketamine 0.2mg34.450000022.6315789
Ketamine 0.5mg31.590909114.7619048
Ketamine 1.0mg32.650000017.1000000
Midazolam 0.045mg33.631578924.8333333

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Number of Participants Reporting Suicidal Ideation/Behavior on the Columbia Suicide Severity Rating Scale (C-SSRS)

The Columbia Suicide Severity Rating Scale (C-SSRS): The C-SSRS is a low-burden measure of the spectrum of suicidal ideation and behavior that was developed in the National Institute of Mental Health Treatment of Adolescent Suicide Attempters Study to assess severity and track suicidal events through any treatment. It is a clinical interview providing a summary of both ideation and behavior that can be administered during any evaluation or risk assessment to identify the level and type of suicidality present. The C-SSRS can also be used during treatment to monitor for clinical worsening or improvement. It contains 5 rating scale questions (yes/no) for suicidal ideation increasing severity and 5 rating scale questions (yes/no) for suicidal behavior of increasing severity. The time frame is for both lifetime and the past six months for the Baseline/Screening scale and since the last visit for the Since Last Visit scale. (NCT01920555)
Timeframe: Screening Visit and Days 0, 1, 3, 5, 7, 14 and 30 combined

,,,,
InterventionParticipants (Count of Participants)
Screening: # with suicidal ideation/behaviorFollow-Up: # with suicidal ideation/behavior
Ketamine 0.1mg1715
Ketamine 0.2mg159
Ketamine 0.5mg1710
Ketamine 1.0mg146
Midazolam 0.045mg1713

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Number of Participants With Abnormal and Clinically Significant CBC and Chemistry Labs by Treatment

"CBC~Chemistry (Total bilirubin, AST, ALT, GGT, ALK Phosphatase, Creatinine, BUN/Urea, Glucose, Uric Acid)~Testing was performed by study site laboratories and used institutional normal lab value ranges." (NCT01920555)
Timeframe: Day 3 and Early Termination Visit (approximately 3 weeks following intervention)

,,,,
InterventionParticipants (Count of Participants)
Chemistry ALT(SGPT)Chemistry AST(SGOT)Chemistry Total BilirubinChemistry Remaining TestsCBC
Ketamine 0.1mg00000
Ketamine 0.2mg11100
Ketamine 0.5mg00000
Ketamine 1.0mg00000
Midazolam 0.045mg00000

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Snaith-Hamilton Pleasure-Scale (SHAPS)

"The SHAPS is a 14-item self-report scale to measure hedonic tone. Items (e.g., I would enjoy reading a book, magazine, or newspaper.) are rated on a 4-point scale (1=strongly disagree, 2=disagree, 3=agree, 4=strongly agree). Either of the 'disagree' responses scores 1 point, and either of the 'agree' responses scores 0 points, for a total scale range of 0-14. Higher scores indicate greater inability to experience pleasure. Patients were asked to rate their experience of the past 24 hours." (NCT01920555)
Timeframe: A baseline assessment was made on Day 0, preceding infusion (i.e., treatment). Outcome assessments were made on days 1, 3, 5, 7, 14, and 30. The primary endpoint for this study was Day 3. Thus, the outcome measure table provides data on Days 0, 1 and 3

,,,,
Interventionunits on a scale (Mean)
Day 0Day 1Day 3
Ketamine 0.1mg7.22222223.93750003.5333333
Ketamine 0.2mg7.55000005.73684216.3888889
Ketamine 0.5mg6.59090912.227272733.0000000
Ketamine 1.0mg7.35000004.30000003.6500000
Midazolam 0.045mg6.47368425.00000004.2500000

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Symptoms of Depression Questionnaire (SDQ)

"The SDQ is a 44-item self-report scale, which aims to measure depression more comprehensively by including the assessment of symptoms in the anxiety-depression spectrum, including symptoms of irritability, anger attacks, and anxiety. Items are rated on an 6-point Likert scale, where participants are asked to rate if a specific symptom (e.g. How has your mood been over the past 24 hours?) is normal for him or her (score = 2), what is better than normal (score = 1), and what is worse than normal (scores = 3-6). The total scale score is calculated by averaging across the items, resulting in a possible range from 1 to 6. Higher scores indicate greater depression severity. When rating, patients were asked to consider their symptoms during the past 24 hours." (NCT01920555)
Timeframe: A baseline assessment was made on Day 0, preceding infusion (i.e., treatment). Outcome assessments were made on days 1, 3, 5, 7, 14, and 30. The primary endpoint for this study was Day 3. Thus, the outcome measure table provides data on Days 0, 1 and 3

,,,,
Interventionunits on a scale (Mean)
Day 0Day 1Day 3
Ketamine 0.1mg3.51641412.57528432.5106061
Ketamine 0.2mg3.46363642.90961952.7828283
Ketamine 0.5mg3.53925622.31095042.5573593
Ketamine 1.0mg3.41136362.61136362.5909091
Midazolam 0.045mg3.42645072.92005732.8751353

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Change in Systolic Blood Pressure

Blood pressure is measured in millimeters of mercury. (NCT01944293)
Timeframe: During study infusion

Interventionmm Hg (Mean)
Ketamine23
Midazolam3

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Change in Suicidal Ideation Measured With the Beck Scale for Suicidal Ideation

Change in suicidal ideation in Bipolar Disorder during a Major Depressive Episode (MDE), with moderate to severe suicidal thoughts, from the pre-infusion baseline to 24 hours after the infusion of Ketamine (study drug) or Midazolam (active control). (NCT01944293)
Timeframe: At 24 hours post-Infusion

Interventionunits on a scale (Mean)
Ketamine-12.4
Midazolam-6.7

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Observational Scale of Behavioral Distress - Revised

The Observational Scale of Behavioral Distress - revised (OSBD-r) is an eight-factor, weighted observational scale used to measure distress associated with medical procedures in children 1 to 20 years of age. The total OSBD-r score is the sum of the OSBD-r scores for predetermined clinically relevant phases of the procedure, with each phase assigned a score from 0 to 23.5 (0=no distress, 23.5=maximum distress), based on the frequency and types of behaviors observed during a pre-determined number of 15-second intervals during each phase. (NCT01948908)
Timeframe: 60 minutes

Interventionunits (Mean)
200 mcL VOA6.06
500 mcL VOA7.90
1000 mcL VOA8.56

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Number of Patients With Physicians Who Were Satisfied or Very Satisfied With Ease of Medication Administration

This outcome is designed to examine MD satisfaction with ease of administration of intranasal medication - physicians who expressed that they were satisfied or very satisfied with ease of medication administration will be counted. (NCT01948908)
Timeframe: 60 minutes

Interventionparticipants (Number)
200 mcL VOA13
500 mcL VOA30
1000 mcL VOA30

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Median Time (Minutes) After Administration of Intranasal Midazolam Until Patient Achieves Minimal Sedation

This outcome is designed to examine time to onset of minimal sedation, defined as a University of Michigan Sedation Score (UMSS) of 1. (NCT01948908)
Timeframe: 20 minutes

Interventionminutes (Median)
200 mcL VOA4.7
500 mcL VOA4.3
1000 mcL VOA5.2

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Produces Amnesia(Memory Recall)

"Ability to recall (memory of):~•recall of 2 pictures" (NCT01976845)
Timeframe: one day

Interventionparticipants (Number)
Propofol30
Midazolam12
Saline38

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Scores on the Verbal Rating Scale For Anxiety

Using the verbal rating scale (VRS) for anxiety (0= none to 10 = extremely nervous) (NCT01976845)
Timeframe: one day

InterventionScores on a Scale (0-10) (Mean)
Propofol1.8
Midazolam2.3
Saline2.8

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Scores on the Verbal Rating Scale For Sleepiness (Sedation)

Using the verbal rating scale (VRS) for anxiety (0= none to 10 = extremely sleepiness) (NCT01976845)
Timeframe: one day

InterventionScores on a Scale (0-10) (Mean)
Propofol4.6
Midazolam5.2
Saline2.5

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Area Under the Concentration-time Curve From Time Zero to the Time of the Last Measureable Concentration (AUClast) of Midazolam

AUClast is the area under the concentration versus time curve from the time of dosing to the last measurable concentration. AUC can be used as a measure of drug exposure. It is derived from drug concentration and time so it gives a measure how much and how long a drug stays in a body. (NCT01989169)
Timeframe: Study Periods 1 & 2: Within 60 minutes pre-dose, and Post-dose 0.167, 0.33, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 24, 48, 72 hours.

Interventionng*h/ml (Mean)
Midazolam100.935
SSP-004184SS + Midazolam116.902

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Area Under the Plasma Concentration-time Curve (AUC) From Time Zero to Infinity (AUCinf) of Midazolam

AUCinf is the area under the plasma concentration versus time curve extrapolated from time 0 to infinity, calculated using the observed value of the last non-zero concentration. AUC can be used as a measure of drug exposure. It is derived from drug concentration and time so it gives a measure how much and how long a drug stays in a body. (NCT01989169)
Timeframe: Study Periods 1 & 2: Within 60 minutes pre-dose, and Post-dose 0.167, 0.33, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 24, 48, 72 hours.

Interventionng*hr/mL (Mean)
Midazolam103.348
SSP-004184SS + Midazolam120.1

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Maximum Plasma Concentration (Cmax) of Midazolam

Cmax is a term that refers to the maximum (or peak) concentration that a drug achieves in the body after the drug has been administrated. (NCT01989169)
Timeframe: Study Periods 1 & 2: Within 60 minutes pre-dose, and Post-dose 0.167, 0.33, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 24, 48, 72 hours.

Interventionng/mL (Mean)
Midazolam35.124
SSP-004184SS + Midazolam48.29

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Duration of CR (DCR)

DCR was defined as the time from the date of first CR until the date of documented relapse for participants who achieved CR. Participants who died without report of relapse were considered non-events and censored at their last relapse-free disease assessment date. Other participants who did not relapse on study were considered non-events and censored at the last relapse-free disease assessment date. DCR was calculated using Kaplan-Meier method and therefore data are estimated. (NCT02014558)
Timeframe: From date of remission until end of study (median treatment duration was 69.5 days, minimum of 3 days and maximum of 1320 days)

Interventiondays (Median)
FLT3 Mutation NegativeAll Participants
Gilteritinib 20 mgNANA

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Duration of CR (DCR)

DCR was defined as the time from the date of first CR until the date of documented relapse for participants who achieved CR. Participants who died without report of relapse were considered non-events and censored at their last relapse-free disease assessment date. Other participants who did not relapse on study were considered non-events and censored at the last relapse-free disease assessment date. DCR was calculated using Kaplan-Meier method and therefore data are estimated. (NCT02014558)
Timeframe: From date of remission until end of study (median treatment duration was 69.5 days, minimum of 3 days and maximum of 1320 days)

,,,
Interventiondays (Median)
FLT3 Mutation PositiveAll Participants
Gilteritinib 120 mgNANA
Gilteritinib 200 mg419.0419.0
Gilteritinib 300 mgNANA
Gilteritinib 80 mgNANA

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Duration of CRc (DCRc)

DCRc was defined as the time from the date of first CRc until the date of documented relapse for participants who achieved CRc. Participants who died without report of relapse and participants who did not relapse were considered non-events and censored at the last relapse-free disease assessment date. DCRc was calculated using Kaplan-Meier method and therefore data are estimated. (NCT02014558)
Timeframe: From date of remission until end of study (median treatment duration was 69.5 days, minimum of 3 days and maximum of 1320 days)

Interventiondays (Median)
FLT3 Mutation PositiveAll Participants
Gilteritinib 300 mgNANA

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Duration of CRc (DCRc)

DCRc was defined as the time from the date of first CRc until the date of documented relapse for participants who achieved CRc. Participants who died without report of relapse and participants who did not relapse were considered non-events and censored at the last relapse-free disease assessment date. DCRc was calculated using Kaplan-Meier method and therefore data are estimated. (NCT02014558)
Timeframe: From date of remission until end of study (median treatment duration was 69.5 days, minimum of 3 days and maximum of 1320 days)

,,,
Interventiondays (Median)
FLT3 Mutation PositiveFLT3 Mutation NegativeAll Participants
Gilteritinib 120 mg98.099.099.0
Gilteritinib 20 mgNANANA
Gilteritinib 200 mg191.0NA191.0
Gilteritinib 80 mgNA41.079.0

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Duration of CRi (DCRi)

DCRi was defined as the time from the date of first CRi until the date of documented relapse for participants who achieved CRi. Participants who died without report of relapse and participants who did not relapse were considered non-events and censored at the last relapse-free disease assessment date. DCRi was calculated using Kaplan-Meier method and therefore data are estimated. (NCT02014558)
Timeframe: From date of remission until end of study (median treatment duration was 69.5 days, minimum of 3 days and maximum of 1320 days)

,,
Interventiondays (Median)
FLT3 Mutation PositiveAll Participants
Gilteritinib 20 mgNANA
Gilteritinib 200 mg191.0191.0
Gilteritinib 300 mgNANA

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Duration of CRi (DCRi)

DCRi was defined as the time from the date of first CRi until the date of documented relapse for participants who achieved CRi. Participants who died without report of relapse and participants who did not relapse were considered non-events and censored at the last relapse-free disease assessment date. DCRi was calculated using Kaplan-Meier method and therefore data are estimated. (NCT02014558)
Timeframe: From date of remission until end of study (median treatment duration was 69.5 days, minimum of 3 days and maximum of 1320 days)

,
Interventiondays (Median)
FLT3 Mutation PositiveFLT3 Mutation NegativeAll Participants
Gilteritinib 120 mg120.099.0120.0
Gilteritinib 80 mgNA41.079.0

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Duration of CRp (DCRp)

DCRp was defined as the time from the date of first CRp until the date of documented relapse for participants who achieved CRp. Participants who died without report of relapse were considered non-events and censored at their last relapse-free disease assessment date. Other participants who did not relapse on study were considered non-events and censored at the last relapse-free disease assessment date. DCRp was calculated using Kaplan-Meier method and therefore data are estimated. (NCT02014558)
Timeframe: From date of remission until end of study (median treatment duration was 69.5 days, minimum of 3 days and maximum of 1320 days)

,,,
Interventiondays (Median)
FLT3 Mutation PositiveAll Participants
Gilteritinib 120 mgNANA
Gilteritinib 200 mg450.0450.0
Gilteritinib 300 mgNANA
Gilteritinib 80 mgNANA

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Duration of Response

Duration of response was defined as the time from the date of either first CRc or PR until the date of documented relapse of any type for participants who achieved CRc or PR. Participants who died without report of relapse were considered non-events and censored at their last relapse-free disease assessment date. Other participants who did not relapse on study are considered non-events and censored at the last relapse-free assessment date. Duration of response was calculated using Kaplan-Meier method and therefore data are estimated. (NCT02014558)
Timeframe: From date of remission until end of study (median treatment duration was 69.5 days, minimum of 3 days and maximum of 1320 days)

,,
Interventiondays (Median)
FLT3 Mutation PositiveAll Participants
Gilteritinib 300 mg59.059.0
Gilteritinib 40 mgNANA
Gilteritinib 450 mgNANA

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Duration of Response

Duration of response was defined as the time from the date of either first CRc or PR until the date of documented relapse of any type for participants who achieved CRc or PR. Participants who died without report of relapse were considered non-events and censored at their last relapse-free disease assessment date. Other participants who did not relapse on study are considered non-events and censored at the last relapse-free assessment date. Duration of response was calculated using Kaplan-Meier method and therefore data are estimated. (NCT02014558)
Timeframe: From date of remission until end of study (median treatment duration was 69.5 days, minimum of 3 days and maximum of 1320 days)

,,,
Interventiondays (Median)
FLT3 Mutation PositiveFLT3 Mutation NegativeAll Participants
Gilteritinib 120 mg141.0109.5126.0
Gilteritinib 20 mgNANANA
Gilteritinib 200 mg220.085.0220.0
Gilteritinib 80 mg88.041.079.0

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Event Free Survival (EFS)

"EFS was defined as the time from the date of first dose of study drug until the date of documented relapse, treatment failure or death from any cause, whichever occurred first. For a participant with none of these events, EFS was censored at the date of last relapse-free disease assessment. A participant without post-treatment disease assessment was censored at randomization date. Treatment failure included those participants who discontinued the treatment due to progressive disease or lack of efficacy without a previous response of CR, CRp, CRi or PR. Treatment failure date referred to the start of new anti-leukemia therapy or the last treatment evaluation date when new anti-leukemia therapy date was not available. For participants who were censored, last relapse-free disease assessment date referred to the participant's last disease assessment date. EFS was calculated using Kaplan-Meier method and therefore data are estimated." (NCT02014558)
Timeframe: From first dose of study drug up to end of study (median time on study was 157.0 days, minimum of 5 days and maximum of 1320 days)

,,,,,,
Interventiondays (Median)
FLT3 Mutation PositiveFLT3 Mutation NegativeAll Participants
Gilteritinib 120 mg112.085.5108.0
Gilteritinib 20 mg52.058.058.0
Gilteritinib 200 mg121.045.0118.0
Gilteritinib 300 mg85.043.065.0
Gilteritinib 40 mg109.039.055.5
Gilteritinib 450 mg86.071.071.0
Gilteritinib 80 mg93.574.076.0

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Fraction of Drug Excreted Into Urine in Percentage (%Ae) of Cephalexin Administered With and Without Gilteritinib

Urine samples were used for pharmacokinetic assessments. (NCT02014558)
Timeframe: Day -1 and cycle 1 day 15: 0-3 hours, 3-6 hours, 6-24 hours postdose (cephalexin)

Interventionpercentage (Mean)
Cephalexin Alone (Day -1)Cephalexin + Gilteritinib (Cycle 1 Day 15)
Gilteritinib 200 mg in Expansion Phase109.889.75

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Leukemia Free Survival (LFS)

LFS was defined as the time from the date of first CRc until the date of documented relapse or death for participants who achieved CRc. For a participant who was not known to have relapsed or died, LFS was censored on the date of last relapse-free disease assessment date. LFS was calculated using Kaplan-Meier method and therefore data are estimated. (NCT02014558)
Timeframe: From first dose of study drug up to end of study (median time on study was 157.0 days, minimum of 5 days and maximum of 1320 days)

Interventiondays (Median)
FLT3 Mutation PositiveAll Participants
Gilteritinib 300 mg296.0296.0

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Leukemia Free Survival (LFS)

LFS was defined as the time from the date of first CRc until the date of documented relapse or death for participants who achieved CRc. For a participant who was not known to have relapsed or died, LFS was censored on the date of last relapse-free disease assessment date. LFS was calculated using Kaplan-Meier method and therefore data are estimated. (NCT02014558)
Timeframe: From first dose of study drug up to end of study (median time on study was 157.0 days, minimum of 5 days and maximum of 1320 days)

,,,
Interventiondays (Median)
FLT3 Mutation PositiveFLT3 Mutation NegativeAll Participants
Gilteritinib 120 mg98.099.098.0
Gilteritinib 20 mg242.0NA242.0
Gilteritinib 200 mg146.038.0146.0
Gilteritinib 80 mg98.041.079.0

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Maximum Concentration (Cmax) After Single and Multiple Doses of Gilteritinib

Plasma samples were used for pharmacokinetic assessments. (NCT02014558)
Timeframe: Day -2 and cycle 1 day 15: predose, 0.5, 1, 2, 4, 6, 24 hours postdose

,,,,,,
Interventionng/mL (Mean)
Day -2Cycle 1 day 15
Gilteritinib 120 mg in Escalation Phase136.7374.2
Gilteritinib 20 mg in Escalation Phase28.1364.64
Gilteritinib 200 mg in Escalation Phase168.21462
Gilteritinib 300 mg in Escalation Phase204.31525
Gilteritinib 40 mg in Escalation Phase24.98107.6
Gilteritinib 450 mg in Escalation Phase207.61528
Gilteritinib 80 mg in Escalation Phase75.29376.4

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Number of Participants With Adverse Events (AEs)

Safety was assessed by AEs, which included abnormalities identified during a medical test (e.g. laboratory tests, vital signs, electrocardiogram, etc.) if the abnormality induced clinical signs or symptoms, needed active intervention, interruption or discontinuation of study medication or was clinically significant. A treatment-emergent AE (TEAE) was defined as an AE observed after starting administration of the study drug up to 30 days after last dose of study drug (for participants who underwent hematopoietic stem cell transplantation [HSCT]: defined as AEs observed after starting study drug until the last dose before on study HSCT plus 30 days, and AEs that began after resumption of gilteritinib and within 30 days after the last dose of gilteritinib). AEs were graded using the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.03 (1-Mild, 2-Moderate, 3-Severe, 4-LifeThreatening, 5-Death). (NCT02014558)
Timeframe: From first dose of study drug up to 30 days after last dose of study drug (median treatment duration was 69.5 days, minimum of 3 days and maximum of 1320 days)

,,,,,,,,,,,,
InterventionParticipants (Count of Participants)
AEsDrug-Related AEsDeathsSerious AEsDrug-Related Serious AEsAEs Leading to Discontinuation of Study DrugDrug-Related AEs Leading to Discont. of Study DrugGrade 3 or Higher TEAEsAEs During On-Study HSCT PeriodSerious AEs During On-Study HSCT
Gilteritinib 120 mg in Escalation Phase3311100100
Gilteritinib 120 mg in Expansion Phase64522352191255930
Gilteritinib 20 mg in Escalation Phase5322020300
Gilteritinib 20 mg in Expansion Phase12738221900
Gilteritinib 200 mg in Escalation Phase3312110200
Gilteritinib 200 mg in Expansion Phase1007749923646109973
Gilteritinib 300 mg in Escalation Phase3212000200
Gilteritinib 300 mg in Expansion Phase17137144631400
Gilteritinib 40 mg in Escalation Phase3222000200
Gilteritinib 40 mg in Expansion Phase1364121511300
Gilteritinib 450 mg in Escalation Phase3312210300
Gilteritinib 80 mg in Escalation Phase3102010200
Gilteritinib 80 mg in Expansion Phase20171119101142000

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Number of Participants With Dose Limiting Toxicities (DLTs)

To determine the maximum tolerated dose, safety was assessed by DLTs, defined as any grade ≥ 3 non-hematologic or extramedullary toxicity that occurred within 30 days starting with the first dose taken on day -2, and included the first treatment cycle in the dose escalation phase and in the first treatment cycle (28 days) in the dose expansion phase, that was considered to be possibly or probably related to study drug. Exceptions to this were the following: (1) Alopecia, anorexia or fatigue, (2) Grade 3 nausea and/or vomiting if not required tube feeding or total parenteral nutrition, or diarrhea if not required or prolonged hospitalization that was managed to grade ≤ 2 with standard antiemetic or antidiarrheal medications used at prescribed dose within 7 days of onset, (3) Grade 3 fever with neutropenia, with or without infection, (4) Grade 3 infection. (NCT02014558)
Timeframe: From first dose up to end of cycle 1 (30 days)

,,,,,,,,,,,,
InterventionParticipants (Count of Participants)
Any DLTBlood and lymphatic system disordersCardiac disordersEye disordersGastrointestinal disordersGeneral disorders & administration site conditionsHepatobiliary disordersInfections and infestationsInvestigationsMetabolism and nutrition disordersMusculoskeletal and connective tissue disordersNervous system disordersRenal and urinary disordersReproductive system and breast disordersRespiratory, thoracic and mediastinal disordersVascular disorders
Gilteritinib 120 mg in Escalation Phase0000000000000000
Gilteritinib 120 mg in Expansion Phase7010101020001010
Gilteritinib 20 mg in Escalation Phase0000000000000000
Gilteritinib 20 mg in Expansion Phase1000000000010000
Gilteritinib 200 mg in Escalation Phase0000000000000000
Gilteritinib 200 mg in Expansion Phase15000410062130122
Gilteritinib 300 mg in Escalation Phase0000000000000000
Gilteritinib 300 mg in Expansion Phase3100100020100011
Gilteritinib 40 mg in Escalation Phase0000000000000000
Gilteritinib 40 mg in Expansion Phase1000000100000000
Gilteritinib 450 mg in Escalation Phase2000100010000000
Gilteritinib 80 mg in Escalation Phase0000000000000000
Gilteritinib 80 mg in Expansion Phase2001000100000000

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Overall Survival (OS)

The time from the date of first dose of study drug until the date of death from any cause. For a participant who was not known to have died by the end of study follow-up, OS was censored at the date of last contact. OS was calculated using Kaplan-Meier method and therefore data are estimated. (NCT02014558)
Timeframe: From first dose of study drug up to end of study (median time on study was 157.0 days, minimum of 5 days and maximum of 1320 days)

,,,,,,
Interventiondays (Median)
FLT3 Mutation PositiveFLT3 Mutation NegativeAll Participants
Gilteritinib 120 mg246.0144.0216.0
Gilteritinib 20 mg123.0NA149.5
Gilteritinib 200 mg214.067.0176.0
Gilteritinib 300 mg157.068.0128.5
Gilteritinib 40 mg199.571.595.0
Gilteritinib 450 mg204.089.089.0
Gilteritinib 80 mg197.5136.0154.0

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Percentage of Participants Who Achieved Transfusion Conversion

Participants who achieved transfusion conversion were defined as the number of participants who were transfusion dependent at baseline period but became transfusion independent at post-baseline period divided by the total number of participants who were transfusion dependent at baseline period. Participants were considered baseline transfusion dependent if there were RBC or platelet transfusions within the baseline period. Participants were considered post-baseline transfusion independent if they were on treatment >=84 days, and if there was one consecutive 56 days without any RBC or platelet transfusion within post-baseline period. If participants were on treatment >28 days but <84 days, and there was no RBC or platelet transfusion within post-baseline period, or on treatment <=28 days, post-baseline transfusion status was not evaluable. Exact 95% confidence interval was estimated using the binomial distribution. (NCT02014558)
Timeframe: Baseline (28 days prior to first dose until 28 days after the first dose) and postbaseline (from 29 days after first dose date until last dose date); median treatment duration was 69.5 days, minimum of 3 days and maximum of 1320 days

,,,,,,
Interventionpercentage of participants (Number)
FLT3 Mutation PositiveFLT3 Mutation NegativeAll Participants
Gilteritinib 120 mg27.522.226.5
Gilteritinib 20 mg0NANA
Gilteritinib 200 mg40.433.339.7
Gilteritinib 300 mgNANANA
Gilteritinib 40 mg0NANA
Gilteritinib 450 mgNANANA
Gilteritinib 80 mg37.512.525.0

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Percentage of Participants Who Achieved Transfusion Maintenance

Participants who achieved transfusion maintenance were defined as the number of participants who were transfusion independent at baseline period and still maintained transfusion independent at post-baseline period divided by the total number of participants who were transfusion independent at baseline period. (NCT02014558)
Timeframe: Baseline (28 days prior to first dose until 28 days after the first dose) and postbaseline (from 29 days after first dose date until last dose date); median treatment duration was 69.5 days, minimum of 3 days and maximum of 1320 days

,,
Interventionpercentage of participants (Number)
FLT3 Mutation PositiveAll Participants
Gilteritinib 200 mg80.080.0
Gilteritinib 450 mg100.0100.0
Gilteritinib 80 mg100.0100.0

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Percentage of Participants Who Achieved Transfusion Maintenance

Participants who achieved transfusion maintenance were defined as the number of participants who were transfusion independent at baseline period and still maintained transfusion independent at post-baseline period divided by the total number of participants who were transfusion independent at baseline period. (NCT02014558)
Timeframe: Baseline (28 days prior to first dose until 28 days after the first dose) and postbaseline (from 29 days after first dose date until last dose date); median treatment duration was 69.5 days, minimum of 3 days and maximum of 1320 days

Interventionpercentage of participants (Number)
FLT3 Mutation PositiveFLT3 Mutation NegativeAll Participants
Gilteritinib 120 mg75.033.357.1

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Percentage of Participants With Best Response

Best response was defined according to modified Cheson criteria (2003), using centrally evaluated myeloblast counts from bone marrow aspirate/biopsy assessments and centrally evaluated hematology results; if neither central bone marrow aspirate nor biopsy was available, myeloblast was imputed with locally evaluated bone marrow aspirate/biopsy assessments (derived response). BR was defined as the best measured response for all visits (in the order of CR, CRp, CRi, and PR) post-treatment. Participants who achieved the best response of CR, CRp, CRi or PR were classified as responders. Participants who did not achieve at least PR were considered as non-responders. Exact 95% confidence interval was estimated using the binomial distribution. (NCT02014558)
Timeframe: Up to end of treatment (median treatment duration was 69.5 days, minimum of 3 days and maximum of 1320 days)

,,,,,,
Interventionpercentage of participants (Number)
FLT3 Mutation PositiveFLT3 Mutation NegativeAll Participants
Gilteritinib 120 mg53.614.345.7
Gilteritinib 20 mg14.350.018.8
Gilteritinib 200 mg48.318.245.0
Gilteritinib 300 mg60.0030.0
Gilteritinib 40 mg37.5018.8
Gilteritinib 450 mg50.0033.3
Gilteritinib 80 mg66.716.741.7

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Percentage of Participants With Complete Remission (CR) During the First 2 Cycles

CR was defined according to modified Cheson criteria (2003), using centrally evaluated myeloblast counts from bone marrow aspirate/biopsy assessments and centrally evaluated hematology results; if neither central bone marrow aspirate nor biopsy was available, myeloblast was imputed with locally evaluated bone marrow aspirate/biopsy assessments (derived response). Participants were classified as being in CR when they had bone marrow regenerating normal hematopoietic cells, achieved a morphologic leukemia-free state, had an absolute neutrophil count (ANC) > 1 x 10^9/L, platelet count ≥ 100 x 10^9/L, normal marrow differential with < 5% blasts, had been red blood cell (RBC) and platelet transfusion independent (defined as 1 week without RBC transfusion and 1 week without platelet transfusion), had no presence of Auer rods and no evidence of extramedullary leukemia, and blast counts in peripheral blood had been ≤ 2%. Exact 95% confidence interval was estimated using binomial distribution. (NCT02014558)
Timeframe: During the first 2 cycles (56 days)

,,,,,,
Interventionpercentage of participants (Number)
FLT3 Mutation PositiveFLT3 Mutation NegativeAll Participants
Gilteritinib 120 mg3.602.9
Gilteritinib 20 mg050.06.3
Gilteritinib 200 mg3.403.0
Gilteritinib 300 mg1005.0
Gilteritinib 40 mg000
Gilteritinib 450 mg000
Gilteritinib 80 mg8.304.2

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Percentage of Participants With Composite CR (CRc)

CRc was defined according to modified Cheson criteria (2003), using centrally evaluated myeloblast counts from bone marrow aspirate/biopsy assessments and centrally evaluated hematology results; if neither central bone marrow aspirate nor biopsy was available, myeloblast was imputed with locally evaluated bone marrow aspirate/biopsy assessments (derived response). Participants were classified as being in CRc when they had achieved either CR, complete remission with incomplete platelet recovery (CRp, defined as had achieved CR except for incomplete platelet recovery (< 100 x 10^9/L) or complete remission with incomplete hematologic recovery (CRi, defined as had fulfilled all the criteria for CR except for incomplete hematological recovery with residual neutropenia < 1 x 10^9/L with or without complete platelet recovery; RBC platelet transfusion independence not required). Exact 95% confidence interval was estimated using the binomial distribution. (NCT02014558)
Timeframe: Up to end of treatment (median treatment duration was 69.5 days, minimum of 3 days and maximum of 1320 days)

,,,,,,
Interventionpercentage of participants (Number)
FLT3 Mutation PositiveFLT3 Mutation NegativeAll Participants
Gilteritinib 120 mg46.47.138.6
Gilteritinib 20 mg7.150.012.5
Gilteritinib 200 mg40.49.137.0
Gilteritinib 300 mg30.0015.0
Gilteritinib 40 mg000
Gilteritinib 450 mg000
Gilteritinib 80 mg41.716.729.2

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Percentage of Participants With CR During Treatment

CR was defined according to modified Cheson criteria (2003), using centrally evaluated myeloblast counts from bone marrow aspirate/biopsy assessments and centrally evaluated hematology results; if neither central bone marrow aspirate nor biopsy was available, myeloblast was imputed with locally evaluated bone marrow aspirate/biopsy assessments (derived response). Participants were classified as being in CR when they had bone marrow regenerating normal hematopoietic cells, achieved a morphologic leukemia-free state, had an absolute neutrophil count (ANC) > 1 x 10^9/L, platelet count ≥ 100 x 10^9/L, normal marrow differential with < 5% blasts, had been red blood cell (RBC) and platelet transfusion independent (defined as 1 week without RBC transfusion and 1 week without platelet transfusion), had no presence of Auer rods and no evidence of extramedullary leukemia, and blast counts in peripheral blood had been ≤ 2%. Exact 95% confidence interval was estimated using binomial distribution. (NCT02014558)
Timeframe: Up to end of treatment (median treatment duration was 69.5 days, minimum of 3 days and maximum of 1320 days)

,,,,,,
Interventionpercentage of participants (Number)
FLT3 Mutation PositiveFLT3 Mutation NegativeAll Participants
Gilteritinib 120 mg12.5010.0
Gilteritinib 20 mg050.06.3
Gilteritinib 200 mg11.2010.0
Gilteritinib 300 mg10.005.0
Gilteritinib 40 mg000
Gilteritinib 450 mg000
Gilteritinib 80 mg16.708.3

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Percentage of Participants With CR With Incomplete Hematological Recovery (CRi)

CRi was defined according to modified Cheson criteria (2003), using centrally evaluated myeloblast counts from bone marrow aspirate/biopsy assessments and centrally evaluated hematology results; if neither central bone marrow aspirate nor biopsy was available, myeloblast was imputed with locally evaluated bone marrow aspirate/biopsy assessments (derived response). Participants were classified as being in CRi when they fulfilled all the criteria for CR except for incomplete hematological recovery with residual neutropenia < 1 x 10^9/L with or without complete platelet recovery. RBC and platelet transfusion independence were not required. Exact 95% confidence interval was estimated using the binomial distribution. (NCT02014558)
Timeframe: Up to end of treatment (median treatment duration was 69.5 days, minimum of 3 days and maximum of 1320 days)

,,,,,,
Interventionpercentage of participants (Number)
FLT3 Mutation PositiveFLT3 Mutation NegativeAll Participants
Gilteritinib 120 mg30.47.125.7
Gilteritinib 20 mg7.106.3
Gilteritinib 200 mg20.29.119.0
Gilteritinib 300 mg10.005.0
Gilteritinib 40 mg000
Gilteritinib 450 mg000
Gilteritinib 80 mg25.016.720.8

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Percentage of Participants With CR With Incomplete Platelet Recovery (CRp)

CRp was defined according to modified Cheson criteria (2003), using centrally evaluated myeloblast counts from bone marrow aspirate/biopsy assessments and centrally evaluated hematology results; if neither central bone marrow aspirate nor biopsy was available, myeloblast was imputed with locally evaluated bone marrow aspirate/biopsy assessments (derived response). Participants were classified as being in CRp when they achieved CR except for incomplete platelet recovery (< 100 x 10^9/L). Exact 95% confidence interval was estimated using the binomial distribution. (NCT02014558)
Timeframe: Up to end of treatment (median treatment duration was 69.5 days, minimum of 3 days and maximum of 1320 days)

,,,,,,
Interventionpercentage of participants (Number)
FLT3 Mutation PositiveFLT3 Mutation NegativeAll Participants
Gilteritinib 120 mg3.602.9
Gilteritinib 20 mg000
Gilteritinib 200 mg9.008.0
Gilteritinib 300 mg10.005.0
Gilteritinib 40 mg000
Gilteritinib 450 mg000
Gilteritinib 80 mg000

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Percentage of Participants With Partial Remission (PR)

PR was defined according to modified Cheson criteria (2003), using centrally evaluated myeloblast counts from bone marrow aspirate/biopsy assessments and centrally evaluated hematology results; if neither central bone marrow aspirate nor biopsy was available, myeloblast was imputed with locally evaluated bone marrow aspirate/biopsy assessments (derived response). Participants were classified as being in PR when they had bone marrow regenerating normal hematopoietic cells with evidence of peripheral recovery with no (or only a few regenerating) circulating blasts and with a decrease of at least 50% in the percentage of blasts in the bone marrow aspirate with the total marrow blasts between 5% and 25%. A value of less or equal than 5% blasts was also considered a PR if Auer rods were present. There should be no evidence of extramedullary leukemia. Exact 95% confidence interval was estimated using the binomial distribution. (NCT02014558)
Timeframe: Up to end of treatment (median treatment duration was 69.5 days, minimum of 3 days and maximum of 1320 days)

,,,,,,
Interventionpercentage of participants (Number)
FLT3 Mutation PositiveFLT3 Mutation NegativeAll Participants
Gilteritinib 120 mg7.17.17.1
Gilteritinib 20 mg7.106.3
Gilteritinib 200 mg7.99.18.0
Gilteritinib 300 mg30.0015.0
Gilteritinib 40 mg37.5018.8
Gilteritinib 450 mg50.0033.3
Gilteritinib 80 mg25.0012.5

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Renal Clearance (CLr) of Cephalexin in Administered With and Without Gilteritinib

Urine samples were used for pharmacokinetic assessments. (NCT02014558)
Timeframe: Day -1 and cycle 1 day 15: 0-3 hours, 3-6 hours, 6-24 hours postdose (cephalexin)

InterventionL/h (Mean)
Cephalexin Alone (Day -1)Cephalexin + Gilteritinib (Cycle 1 Day 15)
Gilteritinib 200 mg in Expansion Phase8.78411.04

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T1/2 of Cephalexin Administered With and Without Gilteritinib

Plasma samples were used for pharmacokinetic assessments. (NCT02014558)
Timeframe: Day -1 and cycle 1 day 15: predose, 0.5, 1, 1.5, 2, 3, 4, 6, 24 hours postdose (cephalexin)

Interventionhours (Mean)
Cephalexin Alone (Day -1)Cephalexin + Gilteritinib (Cycle 1 Day 15)
Gilteritinib 200 mg in Expansion Phase1.8221.827

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Time to Best Response (TTBR)

TTBR was defined as the time from the first dose of study drug until the first disease assessment date when participant achieved best response. TTBR was evaluated in participants who achieved best response of CR, CRp, CRi, or PR. (NCT02014558)
Timeframe: From first dose of study drug up to end of treatment (median treatment duration was 69.5 days, minimum of 3 days and maximum of 1320 days)

,,
Interventiondays (Median)
FLT3 Mutation PositiveAll Participants
Gilteritinib 300 mg29.029.0
Gilteritinib 40 mg57.057.0
Gilteritinib 450 mg31.031.0

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Time to Best Response (TTBR)

TTBR was defined as the time from the first dose of study drug until the first disease assessment date when participant achieved best response. TTBR was evaluated in participants who achieved best response of CR, CRp, CRi, or PR. (NCT02014558)
Timeframe: From first dose of study drug up to end of treatment (median treatment duration was 69.5 days, minimum of 3 days and maximum of 1320 days)

,,,
Interventiondays (Median)
FLT3 Mutation PositiveFLT3 Mutation NegativeAll Participants
Gilteritinib 120 mg43.529.530.0
Gilteritinib 20 mg75.530.057.0
Gilteritinib 200 mg57.029.556.0
Gilteritinib 80 mg44.071.558.0

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Time to CR (TTCR)

TTCR was defined as the time from the first dose of study drug until the date of first CR. (NCT02014558)
Timeframe: From first dose of study drug up to end of treatment (median treatment duration was 69.5 days, minimum of 3 days and maximum of 1320 days)

Interventiondays (Median)
FLT3 Mutation NegativeAll Participants
Gilteritinib 20 mg30.030.0

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Time to CR (TTCR)

TTCR was defined as the time from the first dose of study drug until the date of first CR. (NCT02014558)
Timeframe: From first dose of study drug up to end of treatment (median treatment duration was 69.5 days, minimum of 3 days and maximum of 1320 days)

,,,
Interventiondays (Median)
FLT3 Mutation PositiveAll Participants
Gilteritinib 120 mg141.0141.0
Gilteritinib 200 mg93.093.0
Gilteritinib 300 mg56.056.0
Gilteritinib 80 mg171.5171.5

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Time to CRc (TTCRc)

TTCRc was defined as the time from the first dose of study drug until the date of first CRc. TTCRc was evaluated for participants who achieved CRc. (NCT02014558)
Timeframe: From first dose of study drug up to end of treatment (median treatment duration was 69.5 days, minimum of 3 days and maximum of 1320 days)

Interventiondays (Median)
FLT3 Mutation PositiveAll Participants
Gilteritinib 300 mg28.028.0

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Time to CRc (TTCRc)

TTCRc was defined as the time from the first dose of study drug until the date of first CRc. TTCRc was evaluated for participants who achieved CRc. (NCT02014558)
Timeframe: From first dose of study drug up to end of treatment (median treatment duration was 69.5 days, minimum of 3 days and maximum of 1320 days)

,,,
Interventiondays (Median)
FLT3 Mutation PositiveFLT3 Mutation NegativeAll Participants
Gilteritinib 120 mg30.030.030.0
Gilteritinib 20 mg57.030.043.5
Gilteritinib 200 mg31.530.031.0
Gilteritinib 80 mg56.071.557.0

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Time to CRi (TTCRi)

TTCRi was defined as the time from the first dose of study drug until the date of first CRi. TTCRi was evaluated for participants who achieved CRi. (NCT02014558)
Timeframe: From first dose of study drug up to end of treatment (median treatment duration was 69.5 days, minimum of 3 days and maximum of 1320 days)

,
Interventiondays (Median)
FLT3 Mutation PositiveAll Participants
Gilteritinib 20 mg57.057.0
Gilteritinib 300 mg28.028.0

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Time to CRi (TTCRi)

TTCRi was defined as the time from the first dose of study drug until the date of first CRi. TTCRi was evaluated for participants who achieved CRi. (NCT02014558)
Timeframe: From first dose of study drug up to end of treatment (median treatment duration was 69.5 days, minimum of 3 days and maximum of 1320 days)

,,
Interventiondays (Median)
FLT3 Mutation PositiveFLT3 Mutation NegativeAll Participants
Gilteritinib 120 mg57.030.043.5
Gilteritinib 200 mg39.530.035.0
Gilteritinib 80 mg57.071.564.0

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Time to CRp (TTCRp)

TTCRp was defined as the time from the first dose of study drug until the date of first CRp. TTCRp was evaluated for participants who achieved CRp. (NCT02014558)
Timeframe: From first dose of study drug up to end of treatment (median treatment duration was 69.5 days, minimum of 3 days and maximum of 1320 days)

,,,
Interventiondays (Median)
FLT3 Mutation PositiveAll Participants
Gilteritinib 120 mg195.0195.0
Gilteritinib 200 mg84.584.5
Gilteritinib 300 mg29.029.0
Gilteritinib 80 mg140.0140.0

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Time to Observed Cmax (Tmax) After Single and Multiple Doses of Gilteritinib

Plasma samples were used for pharmacokinetic assessments. (NCT02014558)
Timeframe: Day -2 and cycle 1 day 15: predose, 0.5, 1, 2, 4, 6, 24 hours postdose

,,,,,,
Interventionhours (Median)
Day -2Cycle 1 day 15
Gilteritinib 120 mg in Escalation Phase2.0832.167
Gilteritinib 20 mg in Escalation Phase2.004.008
Gilteritinib 200 mg in Escalation Phase5.2336.033
Gilteritinib 300 mg in Escalation Phase6.0676.050
Gilteritinib 40 mg in Escalation Phase5.9833.867
Gilteritinib 450 mg in Escalation Phase5.7835.933
Gilteritinib 80 mg in Escalation Phase4.0004.333

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Time to Response (TTR)

TTR was defined as the time from the first dose of study drug until the date of either first CRc or PR. TTR was evaluated for participants who achieved CRc or PR. (NCT02014558)
Timeframe: From first dose of study drug up to end of treatment (median treatment duration was 69.5 days, minimum of 3 days and maximum of 1320 days)

,,
Interventiondays (Median)
FLT3 Mutation PositiveAll Participants
Gilteritinib 300 mg28.028.0
Gilteritinib 40 mg57.057.0
Gilteritinib 450 mg31.031.0

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Time to Response (TTR)

TTR was defined as the time from the first dose of study drug until the date of either first CRc or PR. TTR was evaluated for participants who achieved CRc or PR. (NCT02014558)
Timeframe: From first dose of study drug up to end of treatment (median treatment duration was 69.5 days, minimum of 3 days and maximum of 1320 days)

,,,
Interventiondays (Median)
FLT3 Mutation PositiveFLT3 Mutation NegativeAll Participants
Gilteritinib 120 mg29.029.529.0
Gilteritinib 20 mg61.530.030.0
Gilteritinib 200 mg29.029.529.0
Gilteritinib 80 mg31.071.543.5

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Tmax of 1-Hydroxymidazolam After Administration of Midazolam With and Without Gilteritinib

Plasma samples were used for pharmacokinetic assessments. (NCT02014558)
Timeframe: Day -1 and cycle 1 day 15: predose, 0.5, 1, 2, 4, 6, 24 hours postdose (midazolam)

Interventionhours (Median)
Midazolam Alone (Day -1)Midazolam + Gilteritinib (Cycle 1 Day 15)
Gilteritinib 300 mg in Expansion Phase0.55831.00

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Tmax of Cephalexin Administered With and Without Gilteritinib

Plasma samples were used for pharmacokinetic assessments. (NCT02014558)
Timeframe: Day -1 and cycle 1 day 15: predose, 0.5, 1, 1.5, 2, 3, 4, 6, 24 hours postdose (cephalexin)

Interventionhours (Median)
Cephalexin Alone (Day -1)Cephalexin + Gilteritinib (Cycle 1 Day 15)
Gilteritinib 200 mg in Expansion Phase1.5001.483

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Tmax of Midazolam Administered With and Without Gilteritinib

Plasma samples were used for pharmacokinetic assessments. (NCT02014558)
Timeframe: Day -1 and cycle 1 day 15: predose, 0.5, 1, 2, 4, 6, 24 hours postdose (midazolam)

Interventionhours (Median)
Midazolam Alone (Day -1)Midazolam + Gilteritinib (Cycle 1 Day 15)
Gilteritinib 300 mg in Expansion Phase0.50001.00

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Cmax of Midazolam Administered With and Without Gilteritinib

Plasma samples were used for pharmacokinetic assessments. (NCT02014558)
Timeframe: Day -1 and cycle 1 day 15: predose, 0.5, 1, 2, 4, 6, 24 hours postdose (midazolam)

Interventionng/mL (Mean)
Midazolam Alone (Day -1)Midazolam + Gilteritinib (Cycle 1 Day 15)
Gilteritinib 300 mg in Expansion Phase14.6818.45

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Accumulation Ratio After Multiple Doses of Gilteritinib

Plasma samples were used for pharmacokinetic assessments. (NCT02014558)
Timeframe: Cycle 1 day 15: predose, 0.5, 1, 2, 4, 6, 24 hours postdose

Interventionratio (Mean)
Gilteritinib 20 mg in Escalation Phase4.259
Gilteritinib 40 mg in Escalation Phase9.640
Gilteritinib 80 mg in Escalation Phase5.693
Gilteritinib 120 mg in Escalation Phase3.290
Gilteritinib 200 mg in Escalation Phase9.041
Gilteritinib 300 mg in Escalation Phase9.057

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AUC24 of Gilteritinib in Co-administration With Voriconazole

Plasma samples were used for pharmacokinetic assessments. (NCT02014558)
Timeframe: Cycle 1 Day 15 and Cycle 2 Day 1: predose, 0.5, 1, 2, 4, 6, 24 hours postdose (gilteritinib)

Interventionng*h/mL (Mean)
Gilteritinib 20 mg in Expansion Phase919.3

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AUClast of Gilteritinib in Co-administration With Voriconazole

Plasma samples were used for pharmacokinetic assessments. (NCT02014558)
Timeframe: Cycle 1 Day 15 and Cycle 2 Day 1: predose, 0.5, 1, 2, 4, 6, 24 hours postdose (gilteritinib)

Interventionng*h/mL (Mean)
Gilteritinib 20 mg in Expansion Phase919.3

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Cmax of Gilteritinib in Co-administration With Voriconazole

Plasma samples were used for pharmacokinetic assessments. (NCT02014558)
Timeframe: Cycle 1 Day 15 and Cycle 2 Day 1: predose, 0.5, 1, 2, 4, 6, 24 hours postdose (gilteritinib)

Interventionng/mL (Mean)
Gilteritinib 20 mg in Expansion Phase63.79

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Duration of CR/CRh (DCRCRh)

DCRCRh was defined as the time from the date of first DCRCRh until the date of documented relapse for participants who achieved CR or CRh. For participants who achieved both CR and CRh, the first CR date or CRh date, whichever occurred first, was used. Participants who died without report of relapse and participants who did not relapse were considered non-events and censored at the last relapse-free disease assessment date. DCRCRh was calculated using Kaplan-Meier method and therefore data are estimated. DCRCRh was calculated only for participants who were FLT3 mutation positive. (NCT02014558)
Timeframe: From date of remission until end of study (median treatment duration was 69.5 days, minimum of 3 days and maximum of 1320 days)

Interventiondays (Median)
Gilteritinib 20 mgNA
Gilteritinib 80 mgNA
Gilteritinib 120 mg307.0
Gilteritinib 200 mg308.0
Gilteritinib 300 mgNA

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Duration of CRh (DCRh)

DCRh was defined as the time from the date of first CRh until the date of documented relapse for participants who achieved CRh but did not have a best response of CR. Participants who died without report of relapse and participants who did not relapse were considered non-events and censored at the last relapse-free disease assessment date. DCRh was calculated using Kaplan-Meier method and therefore data are estimated. DCRh was calculated only for participants who were FLT3 mutation positive. (NCT02014558)
Timeframe: From date of remission until end of study (median treatment duration was 69.5 days, minimum of 3 days and maximum of 1320 days)

Interventiondays (Median)
Gilteritinib 20 mgNA
Gilteritinib 80 mgNA
Gilteritinib 120 mg64.0
Gilteritinib 200 mg101.0
Gilteritinib 300 mgNA

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Percentage of Participants With Complete Remission and Complete Remission With Partial Hematologic Recovery (CR/CRh)

Participants with CR/CRh were defined as participants who achieved either CR or CRh. Participants with CR had bone marrow regenerating normal hematopoietic cells, achieved a morphologic leukemia-free state, had an ANC > 1 x 10^9/L, platelet count ≥ 100 x 10^9/L, and normal marrow differential with < 5% blasts, had been RBC and platelet transfusion independent (defined as 1 week without RBC transfusion and 1 week without platelet transfusion). Also, there had been no presence of Auer rods, no evidence of extramedullary leukemia, and blast counts in peripheral blood had been ≤ 2%. Participants with CRh could not be classified as being in CR and had bone marrow blasts < 5%, partial hematologic recovery ANC >= 0.5 x 10^9/L and platelets >= 50 x 10^9/L. There should not be evidence of extramedullary leukemia. Exact 95% confidence interval was estimated using the binomial distribution. CR/CRh was calculated only for participants who were FLT3 mutation positive. (NCT02014558)
Timeframe: Up to end of treatment (median treatment duration was 69.5 days, minimum of 3 days and maximum of 1320 days)

Interventionpercentage of participants (Number)
Gilteritinib 20 mg7.1
Gilteritinib 40 mg0
Gilteritinib 80 mg25.0
Gilteritinib 120 mg23.2
Gilteritinib 200 mg19.1
Gilteritinib 300 mg30.0
Gilteritinib 450 mg0

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Percentage of Participants With Complete Remission With Partial Hematologic Recovery (CRh)

CRh was defined according to modified Cheson criteria (2003), using centrally evaluated myeloblast counts from bone marrow aspirate/biopsy assessments and centrally evaluated hematology results; if neither central bone marrow aspirate nor biopsy was available, myeloblast was imputed with locally evaluated bone marrow aspirate/biopsy assessments (derived response). Participants were classified as being in CRh when they could not be classified as being in CR and had bone marrow blasts < 5% and partial hematologic recovery ANC >= 0.5 x 10^9/L and platelets >= 50 x 10^9/L. There should not be evidence of extramedullary leukemia. Exact 95% confidence interval was estimated using the binomial distribution. CRh was calculated only for participants who were FLT3 mutation positive. (NCT02014558)
Timeframe: Up to end of treatment (median treatment duration was 69.5 days, minimum of 3 days and maximum of 1320 days)

Interventionpercentage of participants (Number)
Gilteritinib 20 mg7.1
Gilteritinib 40 mg0
Gilteritinib 80 mg8.3
Gilteritinib 120 mg10.7
Gilteritinib 200 mg7.9
Gilteritinib 300 mg20.0
Gilteritinib 450 mg0

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Terminal Elimination Half-life (t1/2) After Multiple Doses of Gilteritinib

Plasma samples were used for pharmacokinetic assessments. (NCT02014558)
Timeframe: Cycle 1 day 15: predose, 0.5, 1, 2, 4, 6, 24 hours postdose

Interventionhours (Mean)
Gilteritinib 20 mg in Escalation Phase62.14
Gilteritinib 40 mg in Escalation Phase151.8
Gilteritinib 80 mg in Escalation Phase86.11
Gilteritinib 120 mg in Escalation Phase45.85
Gilteritinib 200 mg in Escalation Phase141.9
Gilteritinib 300 mg in Escalation Phase142.2

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Time to Best CR/CRh (TTBCRCRh)

TTBCRCRh was defined as the time from the first dose of study drug until the first date that the best response of CR or CRh was achieved. TTBCRCRh was evaluated for participants who achieved CR or CRh. For participants who achieve both CR and CRh, the first CR date was used. TTBCRCRh was calculated only for participants who were FLT3 mutation positive. (NCT02014558)
Timeframe: From first dose of study drug up to end of treatment (median treatment duration was 69.5 days, minimum of 3 days and maximum of 1320 days)

Interventiondays (Median)
Gilteritinib 20 mg57.0
Gilteritinib 80 mg57.0
Gilteritinib 120 mg63.0
Gilteritinib 200 mg88.0
Gilteritinib 300 mg30.0

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Time to First CR/CRh (TTFCRCRh)

TTFCRCRh was defined as the time from the first dose of study drug until the date of first either CR or CRh. TTFCRCRh was evaluated for participants who achieved CR or CRh. For participants who achieve both CR and CRh, the first CR date or CRh date, whichever occurs first was used. TTFCRCRh was calculated only for participants who were FLT3 mutation positive. (NCT02014558)
Timeframe: From first dose of study drug up to end of treatment (median treatment duration was 69.5 days, minimum of 3 days and maximum of 1320 days)

Interventiondays (Median)
Gilteritinib 20 mg57.0
Gilteritinib 80 mg57.0
Gilteritinib 120 mg59.0
Gilteritinib 200 mg57.0
Gilteritinib 300 mg28.0

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Tmax of Gilteritinib in Co-administration With Voriconazole

Plasma samples were used for pharmacokinetic assessments. (NCT02014558)
Timeframe: Cycle 1 Day 15 and Cycle 2 Day 1: predose, 0.5, 1, 2, 4, 6, 24 hours postdose (gilteritinib)

Interventionhours (Median)
Gilteritinib 20 mg in Expansion Phase2.08

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Amount of Drug Excreted in Urine (Aelast) of Cephalexin Administered With and Without Gilteritinib

Urine samples were used for pharmacokinetic assessments. (NCT02014558)
Timeframe: Day -1 and cycle 1 day 15: 0-3 hours, 3-6 hours, 6-24 hours postdose (cephalexin)

Interventionmg (Mean)
Cephalexin Alone (Day -1)Cephalexin + Gilteritinib (Cycle 1 Day 15)
Gilteritinib 200 mg in Expansion Phase548.9448.8

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Apparent Total Systemic Clearance After Single or Multiple Extravascular Dosing (CL/F) of Cephalexin Administered With and Without Gilteritinib

Plasma samples were used for pharmacokinetic assessments. (NCT02014558)
Timeframe: Day -1 and cycle 1 day 15: predose, 0.5, 1, 1.5, 2, 3, 4, 6, 24 hours postdose (cephalexin)

InterventionL/h (Mean)
Cephalexin Alone (Day -1)Cephalexin + Gilteritinib (Cycle 1 Day 15)
Gilteritinib 200 mg in Expansion Phase9.71310.58

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Apparent Volume of Distribution During the Terminal Elimination Phase After Single Extravascular Dosing (Vz/F) of Cephalexin Administered With and Without Gilteritinib

Plasma samples were used for pharmacokinetic assessments. (NCT02014558)
Timeframe: Day -1 and cycle 1 day 15: predose, 0.5, 1, 1.5, 2, 3, 4, 6, 24 hours postdose (cephalexin)

Interventionliters (Mean)
Cephalexin Alone (Day -1)Cephalexin + Gilteritinib (Cycle 1 Day 15)
Gilteritinib 200 mg in Expansion Phase24.0725.86

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Area Under the Concentration-time Curve From the Time of Dosing Extrapolated to Time Infinity (AUCinf) of Cephalexin Administered With and Without Gilteritinib

Plasma samples were used for pharmacokinetic assessments. (NCT02014558)
Timeframe: Day -1 and cycle 1 day 15: predose, 0.5, 1, 1.5, 2, 3, 4, 6, 24 hours postdose (cephalexin)

Interventionng*h/mL (Mean)
Cephalexin Alone (Day -1)Cephalexin + Gilteritinib (Cycle 1 Day 15)
Gilteritinib 200 mg in Expansion Phase5765051873

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Area Under the Concentration-time Curve From the Time of Dosing to the Last Measurable Concentration (AUClast) After Single and Multiple Doses of Gilteritinib

Plasma samples were used for pharmacokinetic assessments. (NCT02014558)
Timeframe: Day -2 and cycle 1 day 15: predose, 0.5, 1, 2, 4, 6, 24 hours postdose

,,,,,,
Interventionng*h/mL (Mean)
Day -2Cycle 1 day -15
Gilteritinib 120 mg in Escalation Phase24806943
Gilteritinib 20 mg in Escalation Phase303.01030
Gilteritinib 200 mg in Escalation Phase302432248
Gilteritinib 300 mg in Escalation Phase418131749
Gilteritinib 40 mg in Escalation Phase360.41990
Gilteritinib 450 mg in Escalation Phase254435506
Gilteritinib 80 mg in Escalation Phase12167111

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Area Under the Concentration-time Curve Over the 24-Hour Dosing Interval (AUC24) After Single and Multiple Doses of Gilteritinib

Plasma samples were used for pharmacokinetic assessments. (NCT02014558)
Timeframe: Day -2 and cycle 1 day 15: predose, 0.5, 1, 2, 4, 6, 24 hours postdose

,,,,,,
Interventionng*h/mL (Mean)
Day -2Cycle 1 Day 15
Gilteritinib 120 mg in Escalation Phase24806943
Gilteritinib 20 mg in Escalation Phase302.11299
Gilteritinib 200 mg in Escalation Phase302231428
Gilteritinib 300 mg in Escalation Phase416331005
Gilteritinib 40 mg in Escalation Phase360.02482
Gilteritinib 450 mg in Escalation Phase332434768
Gilteritinib 80 mg in Escalation Phase12166958

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AUC24 of Metabolite 1-Hydroxymidazolam After Administration of Midazolam With and Without Gilteritinib

Plasma samples were used for pharmacokinetic assessments. (NCT02014558)
Timeframe: Day -1 and cycle 1 day 15: predose, 0.5, 1, 2, 4, 6, 24 hours postdose (midazolam)

Interventionng*h/mL (Mean)
Midazolam Alone (Day -1)Midazolam + Gilteritinib (Cycle 1 Day 15)
Gilteritinib 300 mg in Expansion Phase20.4423.10

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AUC24 of Midazolam Administered With and Without Gilteritinib

Plasma samples were used for pharmacokinetic assessments. (NCT02014558)
Timeframe: Day -1 and cycle 1 day 15: predose, 0.5, 1, 2, 4, 6, 24 hours postdose (midazolam)

Interventionng*h/mL (Mean)
Midazolam Alone (Day -1)Midazolam + Gilteritinib (Cycle 1 Day 15)
Gilteritinib 300 mg in Expansion Phase66.5581.56

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AUClast of 1-Hydroxymidazolam After Administration of Midazolam With and Without Gilteritinib

Plasma samples were used for pharmacokinetic assessments. (NCT02014558)
Timeframe: Day -1 and cycle 1 day 15: predose, 0.5, 1, 2, 4, 6, 24 hours postdose (midazolam)

Interventionng*h/mL (Mean)
Midazolam Alone (Day -1)Midazolam + Gilteritinib (Cycle 1 Day 15)
Gilteritinib 300 mg in Expansion Phase17.0523.58

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AUClast of Cephalexin Administered With and Without Gilteritinib

Plasma samples were used for pharmacokinetic assessments. (NCT02014558)
Timeframe: Day -1 and cycle 1 day 15: predose, 0.5, 1, 1.5, 2, 3, 4, 6, 24 hours postdose (cephalexin)

Interventionng*h/mL (Mean)
Cephalexin Alone (Day -1)Cephalexin + Gilteritinib (Cycle 1 Day 15)
Gilteritinib 200 mg in Expansion Phase5318354963

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AUClast of Midazolam Administered With and Without Gilteritinib

Plasma samples were used for pharmacokinetic assessments. (NCT02014558)
Timeframe: Day -1 and cycle 1 day 15: predose, 0.5, 1, 2, 4, 6, 24 hours postdose (midazolam)

Interventionng*h/mL (Mean)
Midazolam Alone (Day -1)Midazolam + Gilteritinib (Cycle 1 Day 15)
Gilteritinib 300 mg in Expansion Phase59.4882.44

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Cmax of 1-Hydroxymidazolam After Administration of Midazolam With and Without Gilteritinib

Plasma samples were used for pharmacokinetic assessments. (NCT02014558)
Timeframe: Day -1 and cycle 1 day 15: predose, 0.5, 1, 2, 4, 6, 24 hours postdose (midazolam)

Interventionng/mL (Mean)
Midazolam Alone (Day -1)Midazolam + Gilteritinib (Cycle 1 Day 15)
Gilteritinib 300 mg in Expansion Phase4.5625.053

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Cmax of Cephalexin Administered With and Without Gilteritinib

Plasma samples were used for pharmacokinetic assessments. (NCT02014558)
Timeframe: Day -1 and cycle 1 day 15: predose, 0.5, 1, 1.5, 2, 3, 4, 6, 24 hours postdose (cephalexin)

Interventionng/mL (Mean)
Cephalexin Alone (Day -1)Cephalexin + Gilteritinib (Cycle 1 day 15)
Gilteritinib 200 mg in Expansion Phase1768816075

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Number of Intervention

The frequency of intervention which was defined as any restraint of the patient's head, arms, or legs if they became agitated, or if patient movement was not controlled with verbal instruction from the endoscopist during the whole intraoperative phases. (NCT02027311)
Timeframe: Throughout the whole ERCP procedure

InterventionNumber of intervention (Mean)
Etomidate1.9
Midazolam7.5

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Event of Hypoxia

Hypoxia defined as peripheral blood oxygen saturation measured by pulse oxymeter < 90% (NCT02027311)
Timeframe: Every 5min in Preoperative, intraoperative phase and 15 min in Recovery phase

InterventionHypoxia events (Number)
Midazolam19
Etomidate27

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Patient's Satisfaction (Visual Analog Scale) About Sedation Before Discharge

When completely awake, patients will be asked to rate the degree of pain/discomfort and the degree of satisfaction about quality of sedation from 0 to100 (0=dissatisfaction - 100=complete satisfaction) (NCT02062177)
Timeframe: before discharge

,
Interventionunits on a scale (Mean)
Upper endoscopyColonoscopy
Midazolam Group; n=35, 357685
Propofol Group; n=35, 359495

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Endoscopist's Satisfaction (Visual Analog Scale) About Sedation

Visual Analog Scale from 0 to100 (0=dissatisfaction - 100=complete satisfaction) will be used to assess the technical difficulty of examination and the satisfaction with sedation of patient experienced by endoscopist (NCT02062177)
Timeframe: at the end of the exam

,
Interventionunits on a scale (Mean)
upper endoscopycolonoscopy
Midazolam Group; n=35, 358387
Propofol Group; n=35, 359398

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Patient's Satisfaction (Visual Analog Scale) About Sedation 24-72 Hours After Procedure

Patients will be contacted by telephone 24-72 hours after discharge and asked about their satisfaction about the quality of sedation, rated on a verbal rating scale, from 0 to 100 (0=dissatisfaction; 100=complete satisfaction) (NCT02062177)
Timeframe: at 24-72 hours after procedure

,
Interventionunits on a scale (Mean)
Upper endoscopyColonoscopy
Midazolam Group; n=35, 357788
Propofol Group; n=35, 359397

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Modified Yale Preoperative Anxiety Scale (mYPAS) Score at Separation (mYPAS2) Based on Baseline (mYPAS1) Score.

"Midazolam group participants will be separated into two groups; non-anxious (mYPAS1 ≤ 30) at baseline and anxious (mYPAS1 > 30) at baseline. The mYAPS2 scores of these two groups will be compared to the mYPAS2 scores of the Zolpidem group participants.~The modified Yale Preoperative Anxiety scale (m-YPAS) is a structured observational measure of preoperative anxiety in children that takes less than a minute to preform. It consists of assessment of 27 items in 5 domains of behavior indicating anxiety in young children; activity, emotional expressivity, state of arousal, vocalization, and use of parents. Each item is weighted in calculation of the total score that ranges from 22.5 -100. A cut off 30 on the m-YPAS scale was found to balance the high specificity and sensitivity while maintaining high positive predictive value. Children with a score above 30 are considered anxious while those with the score of 30 or less were considered not anxious." (NCT02096900)
Timeframe: Up to 24 hours including pre-operative, peri-operative and post-operative periods.

,
Interventionunits on a scale (Median)
mYPAS2 - non-anxious baselinemYPAS2 - anxious baseline
Midazolam23.3229.97
Zolpidem28.3060.75

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Patient Anxiety at the Time of Separation

"The primary outcome measure of patient anxiety will be measured using the validated Modified Yale Preoperative Anxiety Score (mYPAS). The mYPAS is the current standard for evaluation of anxiety in children receiving anesthesia for surgical procedures.~The modified Yale Preoperative Anxiety scale (m-YPAS) is a structured observational measure of preoperative anxiety in children. It was developed by the study group lead by Kain Z. It consists of assessment of 27 items in 5 domains of behavior indicating anxiety in young children; activity, emotional expressivity, state of arousal, vocalization, and use of parents. Each item is weighted in calculation of the total score that ranges from 22.5 -100. Children with a score above 30 are considered anxious while those with the score of 30 or less were considered not anxious." (NCT02096900)
Timeframe: Up to 24 hours including preoperative, preoperative, and postoperative periods.

Interventionunits on a scale (Median)
Midazolam26.69
Zolpidem30.00

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Parental/Caregiver Anxiety Assessed Using the Validated State-Trait Anxiety Inventory for Adults (STAI)

"Parental/caregiver anxiety, was assessed using the validated State-Trait Anxiety Inventory for Adults (STAI), a validated self-evaluation questionnaire.~The STAI is compromised of separate self-report scales for measuring state and trait anxiety. The S-Anxiety scale (STAI Form Y-1) consists of twenty statements that evaluate how respondents feel right now, at this moment. The T-Anxiety scale (STAI Form Y-2) consists of twenty statements that assess how respondents generally feel. The score ranges from 20 (most relaxed) to 80 (highest stress).~The baseline STAI inventory was completed by e parent/caregiver after obtaining the informed consent in the preoperative holding area and before the subject was separated from the caregiver. Baseline STAI inventory consisted of form STAIY-1 (State Anxiety) and form STAIY-2 (Trait Anxiety) anxiety.~After caregiver/patient separation,form STAIY-1(State Anxiety) was completed again by the caregiver." (NCT02096900)
Timeframe: Preoperative holding area from the time of informed consent until caregiver/patient separation.

,
Interventionunits on a scale (Mean)
STAIY-1 (at informed consent)STAIY-2 (at informed consent)STAIY-1 (at separation)
Midazolam41.7431.8144.33
Zolpidem41.1234.1243.85

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Percent Change in Blood Pressure From Baseline

Change in blood pressure from baseline. (NCT02129426)
Timeframe: during sedation and recovery (generally 2-3 hours)

Interventionpercent change from baseline (Mean)
Dexmedetomidine and Ketamine-18.7
Dexmedetomidine and Midazolam-14.9

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Percent Change in Heart Rate From Baseline

Change in heart rate from baseline. (NCT02129426)
Timeframe: during sedation and recovery (generally 2-3 hours)

Interventionpercent change from baseline (Mean)
Dexmedetomidine and Ketamine-29.9
Dexmedetomidine and Midazolam-29.6

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The Number of Participants With Hypotension and/or Bradycardia During Sedation and Recovery (Generally 2-3 Hours)

number of participants developing hypotension and or bradycardia (NCT02129426)
Timeframe: a total of 2-3 hours during sedation and recovery.

,
InterventionParticipants (Count of Participants)
HypotensionBradycardia
Dexmedetomidine and Ketamine00
Dexmedetomidine and Midazolam00

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Number of Participants With Death, Serious Adverse Events, Treatment Emergent Adverse Events (TEAEs) Leading to Discontinuation

Number of Participants with Death, Serious Adverse Events, Treatment emergent adverse events (TEAEs) leading to subject discontinuation from study (NCT02161185)
Timeframe: Duration of individual subject participation was open-ended. Study ended early. Longest subject participation approximately 6 months.

InterventionParticipants (Count of Participants)
USL2610

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Time to First Ingestion of Solid Food

(NCT02164929)
Timeframe: Participants will be followed for the duration of hospital stay, an estimated 1 week

InterventionDays (Mean)
Paravertebral Block1
TAP Block2
Epidural0.75
No Block (PCA Alone)1.5

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Time to First Bowel Movement

(NCT02164929)
Timeframe: Participants will be followed for the duration of hospital stay, an estimated 1 week

Interventiondays (Mean)
Paravertebral Block1
TAP Block2
Epidural1
No Block (PCA Alone)2

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Quality of Recovery

Quality of Recovery Score (QoR-15) is measured on a scale of 0-150 (0=poor, 150 = excellent). Scores were collected daily for 72 hours and then averaged. (NCT02164929)
Timeframe: 72 hours

InterventionUnits on a scale (Mean)
Paravertebral Block89.5
TAP Block117
Epidural115.5
No Block (PCA Alone)99

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Postoperative Opioid Consumption

If opioid other than fentanyl is used, the dose will be converted to morphine equivalent. (NCT02164929)
Timeframe: 24 hours after surgery

Interventionmcg (Mean)
Paravertebral Block734
TAP Block666
Epidural125
No Block (PCA Alone)1017.5

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Pain Scores

"Pain scores at rest and with activity using a verbal rating scales (VRS) of 0-10, where 0 represents no pain and 10 represents worst pain ever, at 30, 60, 90, 120 min and every 6 hours for 24 hours and every 12 hours for 48 hours and once a day thereafter until discharge. Data were collected at the indicated time points and an average pain score was calculated." (NCT02164929)
Timeframe: Participants will be followed for the duration of hospital stay, an estimated 1 week

InterventionUnits on a scale (Mean)
Paravertebral Block4.66
TAP Block2.66
Epidural1.75
No Block (PCA Alone)6

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Length of Stay

(NCT02164929)
Timeframe: Participants will be followed for the duration of hospital stay, an estimated 1 week

InterventionDays (Mean)
Paravertebral Block2.66
TAP Block4.33
Epidural4
No Block (PCA Alone)3.5

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VAS for Anxiety as Completed by Caregiver and Observer

"VAS, Visual Analog Scale for anxiety. Scale from 0-10 written on a 10 cm horizontal line with the extremes labeled as no anxiety to very anxious.~Vertical line is drawn on the scale at the level of anxiety. The distance was measured.~Higher numbers equal higher anxiety." (NCT02168439)
Timeframe: Day 1

,
Interventionunits on a scale (Mean)
VAS BaselineVAS PositionVAS Recovery
Dexmedetomidine3.81.7.7
Midazolam3.51.61.2

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mYPAS Scores at Other Time Points

mYPAS stands for modified Yale Preoperative anxiety scale. The scale is from minimum 23.3- maximum 100. Higher scores indicate higher anxiety. By prior characterization, scores less than or equal to 30 are classified as not anxious. (NCT02168439)
Timeframe: Day 1

,
Interventionunits on a scale (Median)
Baseline AnxietyAnxiety at Wound WashoutAnxiety at First Stitch Placement
Dexmedetomidine48.842.523.3
Midazolam47.147.135.4

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Anxiolysis Satisfaction

"Likert scale parent, child life and proceduralist survey~5 point likert scale asking how satisfied the parent or proceduralist is with the anxiolysis from the medication.~1 being not satisfied at all, 3 neutral, 5 very satisfied." (NCT02168439)
Timeframe: Day 1

,
Interventionunits on a scale (Median)
Parent SatisfactionProceduralist Satisfaction
Dexmedetomidine54.5
Midazolam55

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Procedure Completion

note of whether the procedure was able to be completed (NCT02168439)
Timeframe: Day 1

Interventionpercentage of participants (Number)
Dexmedetomidine100
Midazolam100

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Need for Procedural Sedation

Whether the patient required procedural sedation for completion of the procedure (NCT02168439)
Timeframe: Day 1

Interventionpercentage of participants (Number)
Dexmedetomidine0
Midazolam0

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mYPAS Score as Completed by Researchers to Assess Anxiety

"Primary outcome was the mYPAS scores at the time of positioning for procedure.~mYPAS stands for modified Yale Preoperative anxiety scale. The scale is from minimum 23.3- maximum 100. Higher scores indicate higher anxiety. By prior characterization, scores less than or equal to 30 are classified as not anxious." (NCT02168439)
Timeframe: Day 1

Interventionunits on a scale (Median)
Dexmedetomidine23.3
Midazolam36.3

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Number of Patients Who Met and Exceeded Response Criteria of Yale-Brown Obsessive-Compulsive Scale.

Patients given YBOCS (Yale Brown Obsessive-Compulsive Scale), a gold standard measure of obsessions and compulsions. For the YBOCS the minimum units are 0 and Maximum units on the total scale are 40. The higher the number on the YBOCS, the more severe the symptoms. Response was defined as at least a 35% reduction on the YBOCS. (NCT02206776)
Timeframe: Baseline and 1 Week

InterventionParticipants (Count of Participants)
Midazolam0
Ketamine0

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University of Michigan Sedation Scale

"Level of sedation at separation from parents and at the time of mask induction will be measured on a scale of 0 to 4 (University of Michigan Sedation Scale)~University of Michigan Sedation Scale:~0 -Awake/Alert~1 -Minimally Sedated: Tired/sleepy, appropriate response to verbal conversation and/or sounds.~2- Moderately Sedated: Somnolent/sleeping, easily aroused with light tactile stimulation.~3 - Deeply Sedated: Deep sleep, arousable only with significant physical stimulation.~4 - Unarousable~Moderately and Deeply sedated: Satisfactory Awake, minimally sedate, unarousable: Unsatisfactory" (NCT02250703)
Timeframe: Day 0:Just before the patient will be brought to the operating room

,
InterventionParticipants (Count of Participants)
Satisfactory sedation on separation from parentsUnsatisfactory sedation on separation from parentsSatisfactory sedation on transfer to OR tableUnsatisfactory sedation on transfer to OR table
Dexmedetomidine25112214
Midazolam15221225

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Emergence Agitation

The primary endpoint is the incidence of postoperative emergence agitation that was defined as an Aono's four-point scale(AFPS) score of 3 or higher. (NCT02256358)
Timeframe: During 30 minutes after extubation at post-anesthetic care unit, every 5 minutes

Interventionparticipants (Number)
Midazolam6
Ketamine0

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Time to Fully Alert

The time to fully alert (time to first of three consecutive Modified Observer's Assessment of Alertness/Sedation [MOAA/S] scores of 5) after the end of colonoscopy procedure [colonoscope out], and after the last dose of study drug or rescue sedative medication (NCT02290873)
Timeframe: From the end of colonoscopy (colonoscope out) until the patient has recovered to fully alert and from the last injection of the study drug or rescue sedative medication until the patient has recovered to fully alert

,,
Interventionminutes (Median)
After the end of colonoscopyAfter last dose of study drug or rescue sedative
Midazolam1324
Placebo1528
Remimazolam614

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Time to Start of Procedure

The time to the start of the procedure after administration of the first dose of randomized study drug (NCT02290873)
Timeframe: From first dose of study drug until insertion of the colonoscope

Interventionminutes (Median)
Remimazolam4
Placebo19.5
Midazolam19

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Success Rates of the Procedure

Success of the Procedure is measured by completion of colonoscopy, no requirement for an alternative sedative and no requirement for more than 5 top-ups of study medication within any 15 minute period in the blinded arms (remimazolam/placebo) or no requirement for more than 3 doses within any 12 minute window in the midazolam arm. (NCT02290873)
Timeframe: From administration of the first dose of the study drug to the end of colonoscopy

InterventionParticipants (Count of Participants)
Remimazolam272
Placebo1
Midazolam26

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Time to Ready for Discharge

The time after the end of colonoscopy procedure (colonoscope out) and after the last injection of study drug or rescue sedative medication, until discharge (defined as ability to walk unassisted). (NCT02290873)
Timeframe: From the end of the colonoscopy until discharge (expected to be the same day). After the last dose of study drug or rescue sedative, until discharge (expected to be the same day).

,,
Interventionminutes (Median)
After the end of colonoscopy procedureAfter last dose of study drug or rescue sedative
Midazolam4857
Placebo4960.5
Remimazolam4451

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Patient Outcome Questionnaire (painOUT) Most Pain for 0-24 Hours Postoperatively

Painout most pain experienced 0-24 hours postoperatively, measured from 0-10. 0 being no pain to 10 being the worst pain imaginable (NCT02292082)
Timeframe: 0-24 hours postoperatively

Interventionscore on a scale (Mean)
Peri-Articular Injections Only6.7
Peri-Articular Injections and Adductor Canal Block5.3

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Patient Outcome Questionnaire (painOUT) Least Pain for 24-48 Hours Postoperatively

Least pain experienced from 24-48 hours postoperative on a scale from 0-10. 0 being no pain at all to 10 being the worst pain imaginable (NCT02292082)
Timeframe: 24-48 hours postoperative

Interventionscore on a scale (Mean)
Peri-Articular Injections Only1.7
Peri-Articular Injections and Adductor Canal Block1.8

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Patient Outcome Questionnaire (painOUT) Least Pain for 0-24 Hours Postoperatively

Measures: least pain in the last 24 hours. Scores are measured from 0-10. 0 being no pain to 10 being the worst pain imaginable. (NCT02292082)
Timeframe: Participants will be followed for the duration of 2 days post operatively in the hospital

Interventionscore on a scale (Mean)
Peri-Articular Injections Only1.5
Peri-Articular Injections and Adductor Canal Block0.8

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Opioid Consumption Postoperative Day (POD) 1

Opioid consumption for patients from 0-24 hours postoperative, measured in mg OME (oral morphine equivalents) (NCT02292082)
Timeframe: 0-24 hours postoperatively

Interventionmg OME (Mean)
Peri-Articular Injections Only58.4
Peri-Articular Injections and Adductor Canal Block47.5

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Opioid Consumption POD2

Opioid consumption over hours 24-48 postoperatively. Measured in mg OME (oral morphine equivalents). Higher equates to more opioids consumed. (NCT02292082)
Timeframe: 24-48 hours postoperative

Interventionmg OME (Mean)
Peri-Articular Injections Only67.9
Peri-Articular Injections and Adductor Canal Block60.1

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Time to Meet Physical Therapy Discharge Criteria

Time to reach physical therapy (PT) goals (NCT02292082)
Timeframe: First 3 days post-operatively

InterventionMinutes (Mean)
Peri-Articular Injections Only2109.3
Peri-Articular Injections and Adductor Canal Block1883.1

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NRS Pain Score With Movement POD2

NRS pain with movement as reported by the patient. Rated from 0-10. 0 being no pain, 10 being the worst pain imaginable. (NCT02292082)
Timeframe: 48 hours after surgery

Interventionscore on a scale (Mean)
Peri-Articular Injections Only4.7
Peri-Articular Injections and Adductor Canal Block5.2

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Knee Society Score (KSS) at 6 Weeks Postoperatively

KSS (Knee Society Score) score measured at 6 weeks postoperatively. The scale is from 0-100. Scores below 60 indicate poor function, 60-69 indicate fair, 70-79 indicate good, and 80-100 indicate excellent functional scores. KSS measures knee pain, flexion contracture,extension lag, alignment, stability, and total range of flexion and generates an associated score correlating to knee function. Higher is better. There is no sub score - only the cumulative Knee Society Score. (NCT02292082)
Timeframe: Post operatively at approximately 6 weeks after surgery

Interventionscore on a scale (Mean)
Peri-Articular Injections Only85.2
Peri-Articular Injections and Adductor Canal Block75.2

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Hospital Length of Stay

Measured in minutes. (NCT02292082)
Timeframe: Average of 3 days

InterventionMinutes (Mean)
Peri-Articular Injections Only3491
Peri-Articular Injections and Adductor Canal Block3394.4

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Patient Outcome Questionnaire (painOUT) Most Pain for 24-48 Hours Postoperatively

Painout most pain experienced 24-48 hours postoperatively measured on a scale from 0-10. Higher scores indicate higher pain levels. (NCT02292082)
Timeframe: 24-48 hours postoperative

Interventionscore on a scale (Mean)
Peri-Articular Injections Only6.9
Peri-Articular Injections and Adductor Canal Block6.6

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Numerical Rating Scale (NRS) Pain Scores With Ambulation Postoperative Day 1

Patient reported pain scores on postoperative day 1 from 0-10. 0 being no pain, 10 being the worst pain imaginable. (NCT02292082)
Timeframe: 24 hours after operating room discharge

Interventionscore on a scale (Mean)
Peri-Articular Injections Only4.3
Peri-Articular Injections and Adductor Canal Block3.9

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Number of Participants With a Successful Procedure

Success of Procedure measured by completion of bronchoscopy, no requirement for an alternative rescue sedative medication and no requirement for more than 5 doses of study medication within any 15 minute period in the blinded arms (remimazolam/placebo) or no requirement for more than 3 doses within any 12 minute window in the open-label midazolam arm. (NCT02296892)
Timeframe: From first dose of study drug to removal of bronchoscope (average time not known)

InterventionParticipants (Count of Participants)
Remimazolam250
Placebo3
Midazolam24

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Time to Start of Procedure

The time from the first dose of study drug until bronchoscope insertion on Day 1 (NCT02296892)
Timeframe: From first dose of study drug until insertion of the bronchoscope

Interventionminutes (Median)
Remimazolam4.1
Placebo17.0
Midazolam15.5

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Time to Fully Alert

"The time to fully alert defined as time to first of 3 consecutive Modified Observer's Assessment of Alertness and Sedation (MOAA/S) scores after the end of the bronchoscopy procedure (bronchoscope out).~MOAA/S scores: 5 = Responds readily to name spoken in normal tone [alert], 4 =Lethargic response to name spoken in normal tone, 3 = Responds only after name is called loudly and/or repeatedly, 2 = Responds only after mild prodding or shaking, 1 = Responds only after painful trapezius squeeze, 0 = Does not respond to painful trapezius squeeze.~MOAA/S scores were assessed by the investigators." (NCT02296892)
Timeframe: From the last dose of study drug or rescue sedative AND from end of bronchoscopy until the patient has recovered to fully alert

,,
Interventionminutes (Median)
After last dose of study drug or rescue sedativeAfter bronchoscope out
Midazolam18.012.0
Placebo20.013.6
Remimazolam11.66.0

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Time to Ready for Discharge

Time from the last dose of study drug or rescue sedative and from the end of bronchoscopy until discharge (defined as the ability to walk unassisted) (NCT02296892)
Timeframe: After the last dose of study drug AND after the end of the bronchoscopy, until discharge

,,
Interventionminutes (Median)
after last dose of study drug or rescue sedativeAfter bronchoscope out
Midazolam70.066.0
Placebo93.081.0
Remimazolam64.860.0

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Parental Observed Behavioral Distress Score

Measured by the accompanying parent using a Visual Analog Scale. The scale ranges from a minimum score of 0 (no distress at all) to a maximum of 10 (most distress possible). (NCT02314546)
Timeframe: 1 minute post-administration

Interventionunits on a scale (Mean)
Saline Placebo0.08
Nasal Midazolam Only3.10
Midazolam Plus Xylocaine1.96

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Time From Administration to Discharge

(NCT02314546)
Timeframe: Minutes from administration to discharge

Interventionminutes (Mean)
Saline Placebo87.0
Nasal Midazolam Only74.2
Midazolam Plus Xylocaine97.0

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Sedation Scale Score

Measured by the administering RN. Measured as: agitated, alert, calm, drowsy, asleep. (NCT02314546)
Timeframe: 10 minutes post-sedation

,,
Interventionparticipants (Number)
AgitatedAlertCalmDrowsyAsleep
Midazolam Plus Xylocaine02300
Nasal Midazolam Only02200
Saline Placebo01300

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Sedation Scale Score

Measured by the administering RN. Measured as: agitated, alert, calm, drowsy, asleep. (NCT02314546)
Timeframe: 15 minutes post-sedation

,,
Interventionparticipants (Number)
AgitatedAlertCalmDrowsyAsleep
Midazolam Plus Xylocaine01200
Nasal Midazolam Only01200
Saline Placebo01300

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Verbal Complaint

Recorded by the administering RN at the time of administration. (NCT02314546)
Timeframe: At time of administration

,,
Interventionparticipants (Number)
No ComplaintComplaint Reported
Midazolam Plus Xylocaine23
Nasal Midazolam Only14
Saline Placebo32

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Verbal Complaints

Recorded by the administering RN at one minute post-administration (NCT02314546)
Timeframe: 1 minute post-administration

,,
Interventionparticipants (Number)
No ComplaintComplaint Reported
Midazolam Plus Xylocaine41
Nasal Midazolam Only32
Saline Placebo50

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RN Observed Behavioral Distress Score

Measured by the administering RN using a Visual Analog Scale. The scale ranges from a minimum score of 0 (no distress at all) to a maximum of 10 (most distress possible). (NCT02314546)
Timeframe: 1 minute post-administration

Interventionunits on a scale (Mean)
Saline Placebo0.1
Nasal Midazolam Only2.4
Midazolam Plus Xylocaine1.9

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Time to Discharge

The time (in minutes) from release from the operating room to discharge home (NCT02356705)
Timeframe: approximately 3 hours

Interventionminutes (Median)
Saline Placebo35
Nasal Midazolam Only39.5
Midazolam Plus Xylocaine35.5

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Observational Distress Score at 1 Minute (Blinded Study Nurse Assessment)

Visual analog scale measured from 0cm (no distress) to 10cm (high level of distress). Recorded by the blinded study nurse. (NCT02356705)
Timeframe: 1 minute

Interventioncm VAS (Median)
Saline Placebo0.02
Nasal Midazolam Only0.3
Midazolam Plus Xylocaine0.4

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Number of Participants With Nosebleeds From Time of Drug Administration to Discharge Home

Number of participants with nosebleeds recorded in the pre-operative, intra-operative and post-operative record after study drug administration. (NCT02356705)
Timeframe: approximately 3 hours

InterventionParticipants (Count of Participants)
Saline Placebo0
Nasal Midazolam Only0
Midazolam Plus Xylocaine0

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Observational Distress Score 5 Min (Blinded Study Nurse Assessmnet)

Visual analog scale measured from 0cm (no distress) to 10cm (high level of distress) as measured by the blinded study nurse. (NCT02356705)
Timeframe: 5minutes

Interventioncm VAS (Median)
Saline Placebo0
Nasal Midazolam Only0.02
Midazolam Plus Xylocaine0

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Time From Post-infusion Response to Occurrence of Relapse Defined as <50% of Baseline MADRS Score

The length of time from post-infusion response until relapse (defined as >50% of MADRS baseline score) assessed for up to 6 months. (NCT02360280)
Timeframe: 6 months

Interventionweeks (Median)
Six Ketamine Infusions6.00
Single Ketamine Infusion Preceded by 5 Midazolam Infusions2.00

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Remission Defined as MADRS Score Equal or Less Than 9

Comparing the number of subjects that achieve remission between groups as defined above (NCT02360280)
Timeframe: 13 days

InterventionParticipants (Count of Participants)
Six Ketamine Infusions12
Single Ketamine Infusion Preceded by 5 Midazolam Infusions11

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Change From Baseline in Montgomery-Asberg Depression Rating Scale (MADRS) Score After 12 Days of Treatment

Average difference in the Montgomery-Asberg Depression Rating Scale (MADRS) score change between groups. The MADRS has 10-items which are based on mood symptoms over the past 7 days. Each items is scored 0 (normal) to 6 (severe depression) with overall score ranges from 0 (normal) to 60 (severe depression). (NCT02360280)
Timeframe: 13 days

Interventionunits on a scale (Mean)
Six Ketamine Infusions21.0
Single Ketamine Infusion Preceded by 5 Midazolam Infusions17.2

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Antidepressant Response Defined as >50% Decrease in MADRS Baseline Score

Comparing the number of subjects that achieve response between groups as defined above. (NCT02360280)
Timeframe: 13 days

InterventionParticipants (Count of Participants)
Six Ketamine Infusions19
Single Ketamine Infusion Preceded by 5 Midazolam Infusions20

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Main Study: Progression-free Survival (PFS)

Progression-free survival is defined as the duration from the date of the first dose of study drug until the date of first documented evidence of progressive disease (or relapse for participants who experience CR during the study) or death due to any cause, whichever occurs first, regardless of the use of subsequent anticancer therapy. As per RECIST version 1.1, CR was defined as the disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must had reduction in the short axis to less than (<) 10 millimeters (mm). PR was defined as at least a 30 percent (%) decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. (NCT02365597)
Timeframe: From screening up to 6 years 2 months

Interventionmonths (Median)
Main Study: Regimen 1: Erdafitinib 10 Milligrams (mg)/ 12 mg4.80
Main Study: Regimen 2: Erdafitinib 6 mg/ 8 mg5.26
Main Study: Regimen 3: Erdafitinib 8 mg/ 9 mg5.52

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Main Study: Plasma Concentration of Erdafitinib at 2 Hours (C2h)

C2h is the plasma concentration of erdafitinib at 2 hours. (NCT02365597)
Timeframe: Cycle 1 Days 1 and 21: Pre-dose up to 2 hours post-dose (each cycle length=28 days)

,,
Interventionng/mL (Mean)
Cycle 1 Day 1Cycle 1 Day 21
Main Study: Regimen 1: Erdafitinib 10 Milligrams (mg)/ 12 mg529.51686.5
Main Study: Regimen 2: Erdafitinib 6 mg/ 8 mg311.01255.1
Main Study: Regimen 3: Erdafitinib 8 mg/ 9 mg373.01371.4

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Main Study: Plasma Concentration of Erdafitinib at 4 Hours (C4h)

C4h is the plasma concentration of erdafitinib at 4 hours. (NCT02365597)
Timeframe: Cycle 1 Days 1 and 21: Pre-dose up to 4 hours post-dose (each cycle length=28 days)

,,
Interventionng/mL (Mean)
Cycle 1 Day 1Cycle 1 Day 21
Main Study: Regimen 1: Erdafitinib 10 Milligrams (mg)/ 12 mg504.01753.4
Main Study: Regimen 2: Erdafitinib 6 mg/ 8 mg290.01257.4
Main Study: Regimen 3: Erdafitinib 8 mg/ 9 mg365.31329.9

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Drug-Drug Interaction (DDI) Substudy: Area Under the Plasma Concentration Versus Time Curve From Time 0 to the Infinite Time (AUC[0-Infinity]) of Midazolam Alone or in Combination With Erdafitinib

AUC(0-Infinity) is the area under the plasma concentration versus time curve from time 0 to the infinite time of midazolam alone or in combination with erdafitinib. (NCT02365597)
Timeframe: Cycle 1 Day -2 (predose) up to Day 13 post dose (each cycle length=28 days)

Interventionng*h/mL (Mean)
DDI Study: Midazolam 2.5 mg Alone69.8
DDI Study: Midazolam 2.5 mg + Erdafitinib 8 mg55.9

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Drug-Drug Interaction (DDI) Substudy: Area Under the Plasma Concentration Versus Time Curve From Time 0 to the Infinite Time (AUC[0-Infinity]) of 1-OH-Midazolam (Midazolam Metabolite) Alone or in Combination With Erdafitinib

AUC(0-Infinity) is the area under the plasma concentration versus time curve from time 0 to the infinite time of 1-OH-Midazolam alone or in combination with erdafitinib. (NCT02365597)
Timeframe: Cycle 1 Day -2 (predose) up to Day 13 post dose (each cycle length=28 days)

Interventionng*h/mL (Mean)
DDI Study: 1-OH-Midazolam 2.5 mg Alone18.1
DDI Study: 1-OH-Midazolam 2.5 mg + Erdafitinib 8 mg18.4

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Drug-Drug Interaction (DDI) Substudy: Area Under the Plasma Concentration Versus Time Curve From Time 0 to the Infinite Time (AUC[0-Infinity]) of Metformin Alone or in Combination With Erdafitinib

AUC(0-Infinity) is the area under the plasma concentration versus time curve from time 0 to the infinite time of metformin alone or in combination with erdafitinib (NCT02365597)
Timeframe: Cycle 1 Day -1 (predose) up to Day 14 post dose (each cycle length=28 days)

Interventionng*h/mL (Mean)
DDI Study: Metformin 1000 mg Alone22917
DDI Study: Metformin 1000 mg + Erdafitinib 8 mg28853

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Drug-Drug Interaction (DDI) Substudy: Area Under the Plasma Concentration Versus Time Curve From Time 0 to the Time of the Last Measurable Concentration (AUC[0-last]) of 1-OH-Midazolam (Midazolam Metabolite) Alone or in Combination With Erdafitinib

AUC(0-last) is the area under the plasma concentration versus time curve from time 0 to the time of the last measurable concentration of 1-OH-Midazolam alone or in combination with erdafitinib. (NCT02365597)
Timeframe: Cycle 1 Day -2 (predose) up to Day 13 post dose (each cycle length=28 days)

Interventionng*h/mL (Mean)
DDI Study: 1-OH-Midazolam 2.5 mg Alone15.8
DDI Study: 1-OH-Midazolam 2.5 mg + Erdafitinib 8 mg15.1

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Drug-Drug Interaction (DDI) Substudy: Area Under the Plasma Concentration Versus Time Curve From Time 0 to the Time of the Last Measurable Concentration (AUC[0-last]) of Metformin Alone or in Combination With Erdafitinib

AUC(0-last) is the area under the plasma concentration versus time curve from time 0 to the time of the last measurable concentration of metformin alone or in combination with erdafitinib. (NCT02365597)
Timeframe: Cycle 1 Day -1 (predose) up to Day 14 post dose (each cycle length=28 days)

Interventionng*h/mL (Mean)
DDI Study: Metformin 1000 mg Alone22015
DDI Study: Metformin 1000 mg + Erdafitinib 8 mg26917

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Drug-Drug Interaction (DDI) Substudy: Area Under the Plasma Concentration Versus Time Curve From Time 0 to the Time of the Last Measurable Concentration (AUC[0-last]) of Midazolam Alone or in Combination With Erdafitinib

AUC(0-last) is the area under the plasma concentration versus time curve from time 0 to the time of the last measurable concentration of midazolam alone or in combination with erdafitinib. (NCT02365597)
Timeframe: Cycle 1 Day -2 (predose) up to Day 13 post dose (each cycle length=28 days)

InterventionNanograms hours per milliliter (ng*h/mL) (Mean)
DDI Study: Midazolam 2.5 mg Alone64.4
DDI Study: Midazolam 2.5 mg + Erdafitinib 8 mg57.1

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Drug-Drug Interaction (DDI) Substudy: Maximum Observed Plasma Concentration (Cmax) of 1-OH-Midazolam (Midazolam Metabolite) Alone or in Combination With Erdafitinib

Cmax is the maximum observed plasma concentration of 1-OH-Midazolam (midazolam metabolite) alone or in combination with erdafitinib. (NCT02365597)
Timeframe: Cycle 1 Day -2 (predose) up to Day 13 post dose (each cycle length=28 days)

Interventionng/mL (Mean)
DDI Study: 1-OH-Midazolam 2.5 mg Alone5.39
DDI Study: 1-OH-Midazolam 2.5 mg + Erdafitinib 8 mg4.82

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Drug-Drug Interaction (DDI) Substudy: Maximum Observed Plasma Concentration (Cmax) of Metformin Alone or in Combination With Erdafitinib

Cmax is the maximum observed plasma concentration of metformin alone or in combination with erdafitinib (NCT02365597)
Timeframe: Cycle 1 Day -1 (predose) up to Day 14 post dose (each cycle length=28 days)

Interventionng/mL (Mean)
DDI Study: Metformin 1000 mg Alone2465
DDI Study: Metformin 1000 mg + Erdafitinib 8 mg2687

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Drug-Drug Interaction (DDI) Substudy: Maximum Observed Plasma Concentration (Cmax) of Midazolam Alone or in Combination With Erdafitinib

Cmax is the maximum observed plasma concentration of midazolam alone or in combination with erdafitinib. (NCT02365597)
Timeframe: Cycle 1 Day -2 (predose) up to Day 13 post dose

Interventionnanograms per milliliter (ng/mL) (Mean)
DDI Study: Midazolam 2.5 mg Alone18.4
DDI Study: Midazolam 2.5 mg + Erdafitinib 8 mg15.4

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Drug-Drug Interaction (DDI) Substudy: Time to Reach the Maximum Observed Plasma Concentration (Tmax) of 1-OH-Midazolam (Midazolam Metabolite) Alone or in Combination With Erdafitinib

Tmax is the time to reach the maximum observed plasma concentration of 1-OH-Midazolam alone or in combination with erdafitinib. (NCT02365597)
Timeframe: Cycle 1 Day -2 (predose) up to Day 13 post dose (each cycle length=28 days)

InterventionHours (Median)
DDI Study: 1-OH-Midazolam 2.5 mg Alone0.58
DDI Study: 1-OH-Midazolam 2.5 mg + Erdafitinib 8 mg0.58

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Drug-Drug Interaction (DDI) Substudy: Time to Reach the Maximum Observed Plasma Concentration (Tmax) of Metformin Alone or in Combination With Erdafitinib

Tmax is the time to reach maximum observed plasma concentration of metformin alone or in combination with erdafitinib (NCT02365597)
Timeframe: Cycle 1 Day -1 (predose) up to Day 14 post dose (each cycle length=28 days)

InterventionHours (Median)
DDI Study: Metformin 1000 mg Alone2.04
DDI Study: Metformin 1000 mg + Erdafitinib 8 mg3.00

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Drug-Drug Interaction (DDI) Substudy: Time to Reach the Maximum Observed Plasma Concentration (Tmax) of Midazolam Alone or in Combination With Erdafitinib

Tmax is the time to reach the maximum observed plasma concentration of midazolam alone or in combination with erdafitinib. (NCT02365597)
Timeframe: Cycle 1 Day -2 (predose) up to Day 13 post dose (each cycle length=28 days)

InterventionHours (Median)
DDI Study: Midazolam 2.5 mg Alone0.50
DDI Study: Midazolam 2.5 mg + Erdafitinib 8 mg0.58

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Main Study: Duration of Response (DoR)

DOR is defined as the time (in months) from the date of first observation of response (PR or CR) to the date of the first observation of progression or date of death, whatever the cause based on the RECIST version 1.1. CR: disappearance of all target and non-target lesions. All pathological (whether target or non-target) must have a reduction in their short axis <10 mm. PR: at least a 30% decrease in the SOD of target lesions, taking as reference the baseline sum diameters. PD was defined as at least 20% increase (including an absolute increase of at least 5 mm) in the SOD of target lesions, taking as reference the smallest sum and/or unequivocal progression of existing non-target lesions and/or appearance of 1 or more new lesions. (NCT02365597)
Timeframe: From screening up to 6 years 2 months

Interventionmonths (Median)
Main Study: Regimen 1: Erdafitinib 10 Milligrams (mg)/ 12 mg13.37
Main Study: Regimen 2: Erdafitinib 6 mg/ 8 mg4.90
Main Study: Regimen 3: Erdafitinib 8 mg/ 9 mg5.98

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Main Study: Overall Survival

Overall survival is defined as the time from the date of first dose of study drug to the date of the participant's death from any cause. (NCT02365597)
Timeframe: From screening up to 6 years 2 months

Interventionmonths (Median)
Main Study: Regimen 1: Erdafitinib 10 Milligrams (mg)/ 12 mg7.46
Main Study: Regimen 2: Erdafitinib 6 mg/ 8 mg8.64
Main Study: Regimen 3: Erdafitinib 8 mg/ 9 mg11.30

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Main Study: Percentage of Participants With Best (Overall) Objective Response

Percentage of participants with best (overall) objective response were reported. Best objective response is defined as the best (overall) objective response a participants achieved during the study in the order of complete response (CR), partial response (PR), stable disease (SD), progressive disease (PD), where CR and PR were confirmed as per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. As per RECIST version 1.1, CR was defined as the disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must had reduction in the short axis to less than (<) 10 millimeters (mm). PR was defined as at least a 30 percent (%) decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Responders are participants with BOR of CR or PR. (NCT02365597)
Timeframe: From Cycle 1 Day 1 up to 6 years 2 months

InterventionPercentage of Participants (Number)
Main Study: Regimen 1: Erdafitinib 10 Milligrams (mg)/ 12 mg21.2
Main Study: Regimen 2: Erdafitinib 6 mg/ 8 mg34.6
Main Study: Regimen 3: Erdafitinib 8 mg/ 9 mg39.6

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Main Study: Percentage of Participants With Treatment-emergent Adverse Event (TEAEs)

Percentage of participants with TEAEs were reported. An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/biological agent under study. TEAEs are those events that occurred from first dose date through 30 days after last dose date, or day before subsequent anticancer therapy, whichever occurs first. (NCT02365597)
Timeframe: From Day 1 up to 6 years 2 months

InterventionPercentage of Participants (Number)
Main Study: Regimen 1: Erdafitinib 10 Milligrams (mg)/ 12 mg100
Main Study: Regimen 2: Erdafitinib 6 mg/ 8 mg100
Main Study: Regimen 3: Erdafitinib 8 mg/ 9 mg100

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Number of Participants With Clinically Significant Change From Baseline in Continuous Pulse Oximetry (SpO2) in Cohort 2

(NCT02370615)
Timeframe: Cohort 2: Baseline up to Day 15

Interventionparticipants (Number)
Cohort 2: Midazolam + Digoxin + TAK-2720

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Cmax: Maximum Observed Plasma Concentration for Midazolam and 1'Hydroxymidazolam in Cohort 2

(NCT02370615)
Timeframe: Day 1 and Day 7: pre-dose and at multiple time-points (upto 24 hours) postdose; Day 1 for Cohort 2: Midazolam and Day 7 for Cohort 2: Midazolam + TAK-272

,
Interventionng/mL (Geometric Mean)
Midazolam1'hydroxymidazolam
Cohort 2: Midazolam10.024.813
Cohort 2: Midazolam + TAK-27212.374.270

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Cmax: Maximum Observed Plasma Concentration for Digoxin in Cohort 2

(NCT02370615)
Timeframe: Day 1 and Day 7: pre-dose and at multiple time-points (upto 48 hours) postdose; Day 1 for Cohort 2: Digoxin and Day 7 for Cohort 2: Digoxin + TAK-272

Interventionng/mL (Geometric Mean)
Cohort 2: Digoxin1.212
Cohort 2: Digoxin + TAK-2721.635

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Cmax: Maximum Observed Plasma Concentration for TAK 272F and TAK 272-Metabolite (M-I) in Cohort 1

(NCT02370615)
Timeframe: Day 1 and Day 10: pre-dose and at multiple time-points (upto 72 hours) postdose; Day 1 for Cohort 1: TAK-272 and Day 10 for Cohort 1: TAK-272 + Itraconazole

,
Interventionnanogram per milliliter (ng/mL) (Geometric Mean)
TAK 272TAK 272-M-I
Cohort 1: TAK-272387.810.02
Cohort 1: TAK-272 + Itraconazole780.30.9550

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Urinary Excretion Ratio of Digoxin From 0 to 48 Hours Postdose in Cohort 2

(NCT02370615)
Timeframe: Day 1 and Day 7: pre-dose and at multiple time-points (upto 48 hours) postdose; Day 1 for Cohort 2: Digoxin and Day 7 for Cohort 2: Digoxin + TAK-272

Interventionpercentage of dose (Mean)
Cohort 2: Digoxin31.391
Cohort 2: Digoxin + TAK-27235.983

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AUC(0-inf): Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for Midazolam and 1'Hydroxymidazolam in Cohort 2

(NCT02370615)
Timeframe: Day 1 and Day 7: pre-dose and at multiple time-points (upto 24 hours) postdose; Day 1 for Cohort 2: Midazolam and Day 7 for Cohort 2: Midazolam + TAK-272

,
Interventionng*hr/mL (Geometric Mean)
Midazolam1'hydroxymidazolam
Cohort 2: Midazolam27.1113.00
Cohort 2: Midazolam + TAK-27238.5514.06

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AUC(0-inf): Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK 272F and TAK 272-M-I in Cohort 1

(NCT02370615)
Timeframe: Day 1 and Day 10: pre-dose and at multiple time-points (upto 72 hours) postdose; Day 1 for Cohort 1: TAK-272 and Day 10 for Cohort 1: TAK-272 + Itraconazole

,
Interventionnanogram hours per milliliter (ng*hr/mL) (Geometric Mean)
TAK 272TAK 272-M-I
Cohort 1: TAK-272186146.53
Cohort 1: TAK-272 + Itraconazole90989.373

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Number of Participants Who Had Clinically Significant Changes From Baseline in 12-lead Electrocardiograms

"Number of participants who had ECG findings changed from within normal limit or abnormal, clinically significant to abnormal and clinically significant after study drug administration." (NCT02370615)
Timeframe: Cohort 1: Baseline up to Day 19; Cohort 2: Baseline up to Day 15

Interventionparticipants (Number)
Cohort 1: TAK-272 + Itraconazole0
Cohort 2: Midazolam + Digoxin + TAK-2720

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AUC(0-tlqc): Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration for Midazolam and 1'Hydroxymidazolam in Cohort 2

(NCT02370615)
Timeframe: Day 1 and Day 7: pre-dose and at multiple time-points (upto 24 hours) postdose; Day 1 for Cohort 2: Midazolam and Day 7 for Cohort 2: Midazolam + TAK-272

,
Interventionng*hr/mL (Geometric Mean)
Midazolam1'hydroxymidazolam
Cohort 2: Midazolam26.7712.49
Cohort 2: Midazolam + TAK-27238.1613.25

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AUC(0-tlqc): Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK 272F and TAK 272-M-I in Cohort 1

(NCT02370615)
Timeframe: Day 1 and Day 10: pre-dose and at multiple time-points (upto 72 hours) postdose; Day 1 for Cohort 1: TAK-272 and Day 10 for Cohort 1: TAK-272 + Itraconazole

,
Interventionng*hr/mL (Geometric Mean)
TAK 272TAK 272-M-I
Cohort 1: TAK-272184238.34
Cohort 1: TAK-272 + Itraconazole86590.9092

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Cumulative Urinary Excretion Ratio of TAK 272F and TAK 272-M-I From 0 to 72 Hours Postdose in Cohort 1

(NCT02370615)
Timeframe: Day 1 and Day 10: pre-dose and at multiple time-points (upto 72 hours) postdose; Day 1 for Cohort 1: TAK-272 and Day 10 for Cohort 1: TAK-272 + Itraconazole

,
Interventionpercentage of dose (Mean)
TAK 272TAK 272-M-I
Cohort 1: TAK-27211.5230.556
Cohort 1: TAK-272 + Itraconazole37.8030.071

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AUC(0-tlqc): Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration for Digoxin in Cohort 2

(NCT02370615)
Timeframe: Day 1 and Day 7: pre-dose and at multiple time-points (upto 48 hours) postdose; Day 1 for Cohort 2: Digoxin and Day 7 for Cohort 2: Digoxin + TAK-272

Interventionng*hr/mL (Geometric Mean)
Cohort 2: Digoxin9.191
Cohort 2: Digoxin + TAK-27210.61

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AUC(0-inf): Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for Digoxin in Cohort 2

(NCT02370615)
Timeframe: Day 1 and Day 7: pre-dose and at multiple time-points (upto 48 hours) postdose; Day 1 for Cohort 2: Digoxin and Day 7 for Cohort 2: Digoxin + TAK-272

Interventionng*hr/mL (Geometric Mean)
Cohort 2: Digoxin15.49
Cohort 2: Digoxin + TAK-27215.79

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Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs)

(NCT02370615)
Timeframe: Cohort 1: Baseline up to Day 19; Cohort 2: Baseline up to Day 15

Interventionparticipants (Number)
Cohort 1: TAK-272 + Itraconazole10
Cohort 2: Midazolam + Digoxin + TAK-2727

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Discomfort With Intranasal Midazolam Administration

"subject self-reports pain with intranasal midazolam utilizing the Wong-Baker FACES Pain Scale. This scale is a well-established ordinal pain scale for pediatric patients. It is one score (no subscales), with a minimum score of 0 (signifying No Hurt) and a maximum score of 10 (Hurts Worst). Values between include 2 (Hurts Little Bit), 4 (Hurts Little More), 6 (Hurts Even More), and 8 (Hurts Whole Lot.). Children indicate one value/answer. Thus, a higher score indicates a worse outcome (more pain)." (NCT02396537)
Timeframe: immediately after administration of intranasal midazolam

Interventionunits on a scale (Median)
Intranasal Lidocaine3
Intranasal 0.9% Saline8

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The Impact of Event Scale - Revised (IES-R)

full range score from 0-88, with higher scores indicating greater PTSD symptoms (NCT02397889)
Timeframe: 24 hours after the first drug infusion

Interventionscore on a scale (Mean)
Experimental Ketamine Group19.7
Active Control Midazolam Group24.8

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Clinician-Administered PTSD Scale for DSM-5 (CAPS-5)

full range score from 0-80, with higher scores indicating greater PTSD symptoms (NCT02397889)
Timeframe: 2 weeks after the first infusion

Interventionscore on a scale (Mean)
Experimental Ketamine Group22.5
Active Control Midazolam Group33.2

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Montgomery Asberg Depression Rating Scale (MADRS)

full range score from 0-60, with higher scores indicating greater depressive symptoms (NCT02397889)
Timeframe: 2 weeks after the first drug infusion

Interventionscore on a scale (Mean)
Experimental Ketamine Group14.7
Active Control Midazolam Group21.9

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Montgomery Asberg Depression Rating Scale (MADRS)

full range score from 0-60, with higher scores indicating greater depressive symptoms (NCT02397889)
Timeframe: 24 hours after the first drug infusion

Interventionscore on a scale (Mean)
Experimental Ketamine Group16.5
Active Control Midazolam Group17.1

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Number of Participants With Patient-Rated Inventory of Side Effects (PRISE)

All side effects listed in Adverse Event section. (NCT02397889)
Timeframe: up to 21 weeks

InterventionParticipants (Count of Participants)
Experimental Ketamine Group15
Active Control Midazolam Group15

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Quick Inventory of Depression Symptomatology - Self-Report (QIDS-SR)

full range score from 0-27, with higher scores indicating greater depressive symptoms (NCT02397889)
Timeframe: 2 weeks after the first drug infusion

Interventionscore on a scale (Mean)
Experimental Ketamine Group6.6
Active Control Midazolam Group6.7

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Number of Participants With Serious and Non-Serious Adverse Events

Refer to the result of adverse event. (NCT02403635)
Timeframe: Up to 32 days after the last dose

Interventionparticipants (Number)
Non-serious adverse eventserious adverse event
All Subjects180

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Area Under Concentration-Time Curve up to Last Non-zero Value (AUC0-tn) of Midazolam

(NCT02403635)
Timeframe: prior to initial dose of Day 1 and 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16 and 24 h after dosing on Day 1, Days 12, 19 and 26

Interventionh*ng/mL (Geometric Mean)
Day 1111
Day 1256.7
Day 19121.9
Day 26118.9

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Peak Plasma Concentration (Cmax) of Midazolam

(NCT02403635)
Timeframe: prior to initial dose of Day 1 and 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16 and 24 h after dosing on Day 1, Days 12, 19 and 26

Interventionng/mL (Geometric Mean)
Day 134.5
Day 1223.4
Day 1938.8
Day 2636.8

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Peak Plasma Concentration (Cmax) of ASP2151

(NCT02403635)
Timeframe: pre-dose and at 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16 and 24 h after dosing on Day 12

Interventionng/mL (Geometric Mean)
Day 121761.4

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Peak Plasma Concentration (Cmax) of 1-hydroxymidazolam

(NCT02403635)
Timeframe: prior to initial dose of Day 1 and 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16 and 24 h after dosing on Day 1, Days 12, 19 and 26

Interventionng/mL (Geometric Mean)
Day 115.7
Day 1215.9
Day 1914.9
Day 2614.2

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Area Under Concentration-Time Curve up to Last Non-zero Value (AUC0-tn) of 1-hydroxymidazolam

(NCT02403635)
Timeframe: prior to initial dose of Day 1 and 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16 and 24 h after dosing on Day 1, Days 12, 19 and 26

Interventionh*ng/mL (Geometric Mean)
Day 144
Day 1239
Day 1942.2
Day 2640.4

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Half-life (t1/2) of Midazolam

(NCT02403635)
Timeframe: prior to initial dose of Day 1 and 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16 and 24 h after dosing on Day 1, Days 12, 19 and 26

Interventionh (Geometric Mean)
Day 14.2
Day 123.3
Day 194.3
Day 264.1

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Area Under Concentration-Time Curve Extrapolated to Infinite Time (AUC0-∞) of Midazolam

(NCT02403635)
Timeframe: prior to initial dose of Day 1 and 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16 and 24 h after dosing on Day 1, Days 12, 19 and 26

Interventionh*ng/mL (Geometric Mean)
Day 1113.1
Day 1258
Day 19124.4
Day 26122.1

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Half-life (t1/2) of ASP2151

(NCT02403635)
Timeframe: pre-dose and at 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16 and 24 h after dosing on Day 12

Interventionh (Geometric Mean)
Day 127.3

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Area Under Concentration-Time Curve Extrapolated to Infinite Time (AUC0-∞) of ASP2151

(NCT02403635)
Timeframe: pre-dose and at 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16 and 24 h after dosing on Day 12

Interventionh*ng/mL (Geometric Mean)
Day 1219334.2

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Apparent Total Body Clearance (CL/F) of Midazolam

(NCT02403635)
Timeframe: prior to initial dose of Day 1 and 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16 and 24 h after dosing on Day 1, Days 12, 19 and 26

InterventionL/h (Mean)
Day 1444
Day 12679.1
Day 19401.3
Day 26394

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Area Under Concentration-Time Curve Over the Dosing Interval (AUC0-tau) of ASP2151

(NCT02403635)
Timeframe: pre-dose and at 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16 and 24 h after dosing on Day 12

Interventionh*ng/mL (Geometric Mean)
Day 1217167

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Time of Peak Concentration (Tmax) of Midazolam

(NCT02403635)
Timeframe: prior to initial dose of Day 1 and 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16 and 24 h after dosing on Day 1, Days 12, 19 and 26

Interventionh (Median)
Day 10.5
Day 120.5
Day 190.5
Day 260.5

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Apparent Total Body Clearance (CL/F) of ASP2151

(NCT02403635)
Timeframe: pre-dose and at 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16 and 24 h after dosing on Day 12

InterventionL/h (Mean)
Day 1221.61

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Trough Plasma Concentration (Ctrough) of ASP2151

(NCT02403635)
Timeframe: Days 5 to 12

Interventionng/mL (Mean)
Day 5277.6
Day 6265.7
Day 7238.9
Day 8240.7
Day 9223.9
Day 10228.5
Day 11209.7
Day 12214.2

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Apparent Volume of Distribution (Vd/F) of ASP2151

(NCT02403635)
Timeframe: pre-dose and at 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16 and 24 h after dosing on Day 12

InterventionL (Mean)
Day 12225.9

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Time of Peak Concentration (Tmax) of ASP2151

(NCT02403635)
Timeframe: pre-dose and at 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16 and 24 h after dosing on Day 12

Interventionh (Median)
Day 123

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Half-life (t1/2) of 1-hydroxymidazolam

(NCT02403635)
Timeframe: prior to initial dose of Day 1 and 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16 and 24 h after dosing on Day 1, Days 12, 19 and 26

Interventionh (Geometric Mean)
Day 13.8
Day 123.1
Day 193.5
Day 263.3

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Apparent Volume of Distribution (Vd/F) of Midazolam

(NCT02403635)
Timeframe: prior to initial dose of Day 1 and 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16 and 24 h after dosing on Day 1, Days 12, 19 and 26

InterventionL (Mean)
Day 1406.5
Day 12622
Day 19370.8
Day 26366.6

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Time of Peak Concentration (Tmax) of 1-hydroxymidazolam

(NCT02403635)
Timeframe: prior to initial dose of Day 1 and 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16 and 24 h after dosing on Day 1, Days 12, 19 and 26

Interventionh (Median)
Day 10.5
Day 120.5
Day 190.5
Day 260.5

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PK Profile for Midazolam: AUC(0-∞) Oral and IV Dose

(NCT02406261)
Timeframe: Day 1, 3, 17, 35, and 37: Predose, 0.25, 0.5, 1, 2, 3, 5, 8, and 12 hours (Cohort A)

Interventionng*h/mL (Geometric Mean)
AUC(0-∞) Oral Day 1AUC(0-∞) Oral Day 17AUC(0-∞) Oral Day 35AUC(0-∞) IV Day 3AUC(0-∞) IV Day 37
Cohort A6.536.245.5911.411.6

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PK Profile for Donepezil: AUC(0-∞)

(NCT02406261)
Timeframe: Day 1 and 28: predose 0.5,1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96,120, 216, 288, and 360 hours (Cohort B)

Interventionng*h/mL (Geometric Mean)
Day 1Day 28
Cohort B271285

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PK Profile for Simvastatin: AUC(0-∞)

(NCT02406261)
Timeframe: Day 2 and 36: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24 hours (Cohort A)

Interventionng*h/mL (Geometric Mean)
AUC(0-∞) Simvastatin Day 2AUC(0-∞) Simvastatin Day 36
Cohort A15.121.2

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Pharmacokinetic (PK): Area Under the Curve Zero to Infinity (AUC[0-∞]) for LY3314814

(NCT02406261)
Timeframe: Day 4: Predose, 0.5, 1, 2, 3, 4, 8, 12, 24, 48, 72, 96, and 120 hours (Cohort A)

InterventionNanogram * hour per milliliter (ng*h/mL) (Geometric Mean)
Cohort A3200

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Number of Participants Experiencing Suicidal Ideation or Suicidal Behavior Based on Columbia-Suicide Severity Rating Scale (C-SSRS)

"C-SSRS captures occurrence, severity, and frequency of suicide-related thoughts and behaviors. Suicidal behavior is defined as a yes answer to any of 5 suicidal behavior questions: preparatory acts or behavior, aborted attempt, interrupted attempt, actual attempt, and completed suicide. Suicidal ideation is defined as a yes answer to any one of 5 suicidal ideation questions: wish to be dead, and 4 different categories of active suicidal ideation." (NCT02406261)
Timeframe: Cohort A: Baseline to Study Completion (Up to Day 50); Cohort B: Baseline to Study Completion (Up to Day 70)

,
InterventionParticipants (Count of Participants)
Suicidal IdeationSuicidal Behavior
Cohort A00
Cohort B00

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Completion Rate for Randomised Treatment

Process outcomes are primary in this pilot trial. These include recruitment methods and rate of completion and will be assessed following the completion of the trial (NCT02414932)
Timeframe: 30 months

InterventionParticipants (Count of Participants)
Ketamine0
Midazolam0

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Depression Relapse Rate

Clinical outcomes are secondary in this pilot trial. The 24-item Hamilton Rating Scale for Depression (HRSD-24) will be used to assess for the main clinical outcome, the relapse rate over six months. Criteria for relapse are ≥10 point increase in HRSD-24 compared to baseline Phase 2 score plus HRSD ≥16; in addition, increase in the HRSD should be maintained one week later (if indicated, additional follow-ups will be arranged). Hospital admission, further ECT, and deliberate self-harm/suicide also constitute relapse. (NCT02414932)
Timeframe: 6 months

InterventionParticipants (Count of Participants)
Ketamine1
Midazolam1

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Number of Participants Who Had Inducible Ventricular Tachycardia Under General Anesthesia.

Patients before induction of GA undergo noninvasive programmed stimulation (NIPS) using the patient's ICD. Subjects receive minimal versed/fentanyl during the NIPS. The anesthesiologist will decide whether to use propofol prior to the second induction, depending on the patient's cardiac function and hemodynamic status. After induction of GA with IV propofol, programmed stimulation will be performed from the RV catheter. Mapping under volatile agent will commence any time after twice the redistribution half-life of either agent has elapsed (propofol 4-16 mins) or have passed. Once the drug is out of the central compartment it is unlikely to affect myocardial electrolytes or ion channels. GA will be maintained with an inhalation agent, sevoflurane. A repeat programmed stimulation test will be performed. Endpoint for programmed stimulation will be induction of sustained monomorphic VT (SMVT). (NCT02419547)
Timeframe: While under General Anesthesia, an average of 6 hours

Interventionparticipants (Number)
Phase 1 Concious SedationPhase 2 PropofolPhase 3 Sevoflurane
Ventriuclar Tachycardia Induction755

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Task Completing Time Change Between Sedation and Baseline Measured by 9-hole Peg Test

this is a focal neurologic deficits induced by sedatives, the outcome is the performing time changes after sedation as : sedation-baseline. (NCT02439164)
Timeframe: after sedation

,
Interventionseconds (Mean)
baseline for contralesional handafter sedation for contralesional handbaseline for ipsilesional handafter sedation for ipsilesional hand
Glioma Group27.854.321.835.5
Non-neurosurgical Group19.121.419.121.4

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Mean Arterial Blood Pressure (MAP) as a Measure of Physiological Change

The MAP was measured at three time points: baseline, sedation and sedation reversal. (NCT02439164)
Timeframe: 1 hour

,
InterventionmmHg (Mean)
baseline MAPsedation MAPsedation reversal MAP
Glioma Group96.596.295.4
Non-neurosurgical Group95.791.288.2

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Heart Rate as a Measure of Physiological Change

The HR was measured at three time points: baseline, sedation and sedation reversal. (NCT02439164)
Timeframe: 1 hour

,
Interventionbpm (Mean)
baselinesedationsedation reversal
Glioma Group78.184.381.5
Non-neurosurgical Group79.079.071.5

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Number of Participants With OAA/S=4 After Sedation

OAA/S is Observer Assessment of Sedation with 5 levels (5 = alert, 4 = lethargic, 3 = aroused by voice, 2 = aroused by shaking, 1 = deep sleep), all participants have to achieve OAA/S=4 after sedation. (NCT02439164)
Timeframe: withing 1 hour

InterventionParticipants (Count of Participants)
Glioma Group15
Non-neurosurgical Group17

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AUClast: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-915

(NCT02461160)
Timeframe: SRD and ESSD Cohorts: Day 1 pre-dose and at multiple timepoints (up to 96 hours) post dose; MRD cohorts: Days 1, 8 and 14 pre-dose and at multiple timepoints (up to 96 hours) post dose

,,,,,,,
Interventionng*hr/mL (Mean)
Day 1Day 8Day 14
ESSD Cohort 12: TAK-915 50 mg11552.2NANA
MRD Cohort 5: TAK-915 30 mg5380.92301.712653.2
MRD Cohort 6: TAK-915 100 mg15640.08334.627924.7
MRD Cohort 7: TAK-915 200 mg30251.612549.367706.4
SRD Cohort 1 TAK-915 30 mg5187.3NANA
SRD Cohort 2: TAK-915 100 mg18229.5NANA
SRD Cohort 3: TAK-915 200 mg10812.4NANA
SRD Cohort 4: TAK-915 200 mg24204.7NANA

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AUClast: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-915 and TAK-915 Metabolite M-I in BA/FE Cohort

(NCT02461160)
Timeframe: Day 1 of Periods 1, 2 and 3 predose and at multiple time points (up to 96 hours) post-dose

,,
Interventionng*hr/mL (Mean)
TAK-915Metabolite M-I
BA/FE Cohort Regimen A8412.33785.3
BA/FE Cohort Regimen B7310.02992.1
BA/FE Cohort Regimen C5740.22208.7

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CL/F: Apparent Clearance for TAK-915

(NCT02461160)
Timeframe: SRD and ESSD Cohorts: Day 1 pre-dose and at multiple timepoints (up to 96 hours) post dose; MRD cohorts: Days 1 and 14 pre-dose and at multiple timepoints (up to 96 hours) post dose

,,,,,,,
InterventionL/hr (Mean)
Day 1Day 14
ESSD Cohort 12: TAK-915 50 mg5.651NA
MRD Cohort 5: TAK-915 30 mg5.4376.289
MRD Cohort 6: TAK-915 100 mg5.9936.791
MRD Cohort 7: TAK-915 200 mg5.3136.625
SRD Cohort 1 TAK-915 30 mg4.966NA
SRD Cohort 2: TAK-915 100 mg5.565NA
SRD Cohort 3: TAK-915 200 mg16.566NA
SRD Cohort 4: TAK-915 200 mg6.928NA

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Cmax: Maximum Observed Plasma Concentration for Midazolam Alone (Day 1) and in the Presence of TAK-915 (Day 16) in DDI Cohort

(NCT02461160)
Timeframe: Days 1 and 16 pre-dose and at multiple timepoints (up to 24 hours) post dose

Interventionng/mL (Mean)
Day 1Day 16
DDI Cohort 7: TAK-915 + Midazolam 2 mg9.68.3

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Cmax: Maximum Observed Plasma Concentration for TAK-915

(NCT02461160)
Timeframe: SRD and ESSD Cohorts: Day 1 pre-dose and at multiple timepoints (up to 96 hours) post dose; MRD cohorts: Days 1, 8 and 14 pre-dose and at multiple timepoints (up to 96 hours) post dose

,,,,,,,
Interventionng/mL (Mean)
Day 1Day 8Day 14
ESSD Cohort 12: TAK-915 50 mg414.0NANA
MRD Cohort 5: TAK-915 30 mg209.5196.0397.5
MRD Cohort 6: TAK-915 100 mg651.8651.01081.0
MRD Cohort 7: TAK-915 200 mg743.8836.71865.0
SRD Cohort 1 TAK-915 30 mg203.7NANA
SRD Cohort 2: TAK-915 100 mg654.8NANA
SRD Cohort 3: TAK-915 200 mg417.3NANA
SRD Cohort 4: TAK-915 200 mg675.8NANA

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Cmax: Maximum Observed Plasma Concentration for TAK-915 and TAK-915 Metabolite M-I in BA/FE Cohort

(NCT02461160)
Timeframe: Day 1 of Periods 1, 2 and 3 predose and at multiple time points (up to 96 hours) post-dose

,,
Interventionng/mL (Mean)
TAK-915Metabolite M-I
BA/FE Cohort Regimen A337.079.2
BA/FE Cohort Regimen B208.048.9
BA/FE Cohort Regimen C143.434.6

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Fraction of Drug Excreted in Urine (Fe) for TAK-915

(NCT02461160)
Timeframe: SRD Cohorts: Day 1 pre-dose and at multiple timepoints (up to 96 hours) post dose; MRD cohorts: Days 1 and 14 pre-dose and at multiple timepoints (up to 96 hours) post dose

,,,,,,
Interventionfraction excreted (Mean)
Day 1Day 14
MRD Cohort 5: TAK-915 30 mg0.0390.079
MRD Cohort 6: TAK-915 100 mg0.0760.108
MRD Cohort 7: TAK-915 200 mg0.0420.099
SRD Cohort 1 TAK-915 30 mg0.036NA
SRD Cohort 2: TAK-915 100 mg0.056NA
SRD Cohort 3: TAK-915 200 mg0.020NA
SRD Cohort 4: TAK-915 200 mg0.035NA

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Percentage of Participants With Markedly Abnormal Values of 12-Lead Electrocardiogram (ECG) Parameters

The percentage of participants who meet markedly abnormal criteria for ECG parameters as specified by the protocol and statistical analysis plan during the treatment period. ECG parameters were considered abnormal if they were beyond the values defined in categories. (NCT02461160)
Timeframe: Day 1 up to follow-up (SRD Cohorts: up to Day 13, MRD Cohorts: up to Day 26, DDI Cohort: up to Day 28, BA/FE Cohorts: up to Day 13, ESSD Cohort: up to Day 28)

,,,,,,,,,,,,,,
Interventionpercentage of participants (Number)
Heart Rate, <50 beats/minHeart Rate, >120 beats/minPR Interval, <=80 msec (ms)PR Interval, >=200 msQRS Interval, <=80 msQRS Interval, >=180 msQT Interval, <=300 msQT Interval, >=460 msQTcB Interval, <=300 msQTcB Interval,≥500ms OR ≥450ms and ≥30ms CFBQTcF Interval, <= 300 msQTcF Interval, ≥500 msec OR ≥ 450 msec and ≥30 CFB
BA/FE Cohort Regimen A8.3002516.70000000
BA/FE Cohort Regimen B0002516.700008.300
BA/FE Cohort Regimen C0008.38.30000000
DDI Cohort 8: Midazolam 2 mg0008.38.30000000
DDI Cohort 8: TAK-915 + Midazolam 2 mg00016.725.00000000
DDI Cohort 8: TAK-915 100 mg0008.325.00000000
ESSD Cohort 12: TAK-915 50 mg00012.5250012.50000
MRD Cohort 5: TAK-915 30 mg500016.700000000
MRD Cohort 6: TAK-915 100 mg50016.716.700000000
MRD Cohort 7: TAK-915 200 mg00033.333.3000016.700
MRD Cohorts Pooled Placebo66.70033.300016.70000
SRD Cohort 1 TAK-915 30 mg00016.716.70000000
SRD Cohort 2: TAK-915 100 mg16.700016.70000000
SRD Cohort 3: TAK-915 200 mg25008.38.30000000
SRD Cohorts Pooled Placebo37.50012.512.50000000

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Percentage of Participants With Markedly Abnormal Vital Sign Measurements

The percentage of participants who meet markedly abnormal criteria for vital signs after dosing, including oral body temperature (temp.), respiration rate, pulse rate (PR) Systolic blood pressure (SBP) and Diastolic blood pressure (DBP) for assessment in positions of supine or standing. Vital signs were considered abnormal if they were beyond the values defined in categories. (NCT02461160)
Timeframe: Day 1 up to follow-up (SRD Cohorts: up to Day 13, MRD Cohorts: up to Day 26, DDI Cohort: up to Day 28, BA/FE Cohorts: up to Day 13, ESSD Cohort: up to Day 28)

,,,,,,,,,,,,,,
Interventionpercentage of participants (Number)
Standing, after 1 minute SBP, <85 mmHgStanding, after 1 minutes SBP, >180 mmHgStanding, after 3 minutes SBP(mmHg), <85 mmHgStanding, after 3 minutes SBP, >180 mmHgSupine, after 5 minutes SBP, <85 mmHgSupine, after 5 minutes SBP, >180 mmHgStanding, after 1 minute DBP, <50 mmHgStanding, after 1 minute DBP, >110 mmHgStanding, after 3 minutes DBP, <50 mmHgStanding, after 3 minutes DBP, >110 mmHgSupine, after 5 minutes DBP, <50 mmHgSupine, after 5 minutes DBP, >110 mmHgStanding, after 1 min PR, <50 beats/minStanding, after 1 min PR, >120 beats/minStanding, after 3 mins PR, <50 beats/minStanding, after 3 mins PR, >120 beats/minSupine, after 5 mins PR, <50 beats/minSupine, after 5 mins PR, >120 beats/minStanding, after 1 min Temperature, <35.6 °CStanding, after 1 min Temperature, >37.7 °CStanding, after 3 mins Temperature, <35.6 °CStanding, after 3 mins Temperature, >37.7 °CSupine, after 5 mins Temperature, <35.6 °CSupine, after 5 mins Temperature, >37.7 °C
BA/FE Cohort Regimen A000016.7000008.300008.300000000
BA/FE Cohort Regimen B00008.30000000000000000000
BA/FE Cohort Regimen C00008.3000000008.3000000008.30
DDI Cohort 8: Midazolam 2 mg00000000008.30000000000000
DDI Cohort 8: TAK-915 + Midazolam 2 mg8.3000008.30008.30008.38.300000000
DDI Cohort 8: TAK-915 100 mg16.7016.7016.70008.300008.308.30000008.30
ESSD Cohort 12: TAK-915 50 mg000000000012.5000000012.5012.5012.50
MRD Cohort 5: TAK-915 30 mg000000000000016.7016.7500000033.30
MRD Cohort 6: TAK-915 100 mg16.7016.7033.300016.7033.3016.7016.716.7500000000
MRD Cohort 7: TAK-915 200 mg16.70016.700000000033.3016.700000016.70
MRD Cohorts Pooled Placebo00000000000033.3000500000016.70
SRD Cohort 1 TAK-915 30 mg00000000000000016.70016.7016.7016.70
SRD Cohort 2: TAK-915 100 mg000016.70000016.70000016.70000000
SRD Cohort 3: TAK-915 200 mg008.300000008.30000016.7016.7016.7016.70
SRD Cohorts Pooled Placebo000000000012.500000250000000

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Ratio of TAK-915 Metabolite Cmax to TAK-915 Cmax in SRD and MRD Cohorts

(NCT02461160)
Timeframe: Day 1 predose and at multiple time points (up to 96 hours) post-dose

,,,,,,,
Interventionratio (Mean)
Day 1Day 14
ESSD Cohort 12: TAK-915 50 mg0.207NA
MRD Cohort 5: TAK-915 30 mg0.2120.356
MRD Cohort 6: TAK-915 100 mg0.2670.480
MRD Cohort 7: TAK-915 200 mg0.2770.0764
SRD Cohort 1 TAK-915 30 mg0.230NA
SRD Cohort 2: TAK-915 100 mg0.248NA
SRD Cohort 3: TAK-915 200 mg0.254NA
SRD Cohort 4: TAK-915 200 mg0.273NA

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Renal Clearance (CLr) for TAK-915

(NCT02461160)
Timeframe: SRD Cohorts: Day 1 pre-dose and at multiple timepoints (up to 96 hours) post dose; MRD cohorts: Days 1 and 14 pre-dose and at multiple timepoints (up to 96 hours) post dose

,,,,,,
InterventionmL/hr (Mean)
Day 1Day 14
MRD Cohort 5: TAK-915 30 mg2.2652.208
MRD Cohort 6: TAK-915 100 mg5.0474.696
MRD Cohort 7: TAK-915 200 mg2.9343.246
SRD Cohort 1 TAK-915 30 mg2.140NA
SRD Cohort 2: TAK-915 100 mg3.191NA
SRD Cohort 3: TAK-915 200 mg3.612NA
SRD Cohort 4: TAK-915 200 mg2.915NA

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Terminal Elimination Half-life (t1/2) for TAK-915

(NCT02461160)
Timeframe: SRD and ESSD Cohorts: Day 1 pre-dose and at multiple timepoints (up to 96 hours) post dose; MRD cohorts: Days 1 and 14 pre-dose and at multiple timepoints (up to 96 hours) post dose

,,,,,,,
Interventionhr (Median)
Day 1Day 14
ESSD Cohort 12: TAK-915 50 mg61.244NA
MRD Cohort 5: TAK-915 30 mg37.16632.770
MRD Cohort 6: TAK-915 100 mg23.32623.517
MRD Cohort 7: TAK-915 200 mg46.40835.503
SRD Cohort 1 TAK-915 30 mg35.246NA
SRD Cohort 2: TAK-915 100 mg34.008NA
SRD Cohort 3: TAK-915 200 mg32.621NA
SRD Cohort 4: TAK-915 200 mg37.826NA

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Terminal Elimination Half-life (t1/2) for TAK-915 and TAK-915 Metabolite M-I in BA/FE Cohort

(NCT02461160)
Timeframe: Day 1 of Periods 1, 2 and 3 predose and at multiple time points (up to 96 hours) post-dose

,,
Interventionhr (Median)
TAK-915Metabolite M-I
BA/FE Cohort Regimen A34.97339.937
BA/FE Cohort Regimen B45.35950.010
BA/FE Cohort Regimen C40.10148.406

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Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-915

(NCT02461160)
Timeframe: SRD and ESSD Cohorts: Day 1 pre-dose and at multiple timepoints (up to 96 hours) post dose; MRD cohorts: Days 1, 8 and 14 pre-dose and at multiple timepoints (up to 96 hours) post dose

,,,,,,,
Interventionhr (Median)
Day 1Day 8Day 14
ESSD Cohort 12: TAK-915 50 mg1.500NANA
MRD Cohort 5: TAK-915 30 mg1.5001.5001.500
MRD Cohort 6: TAK-915 100 mg1.5002.0002.500
MRD Cohort 7: TAK-915 200 mg3.0582.003.000
SRD Cohort 1 TAK-915 30 mg1.750NANA
SRD Cohort 2: TAK-915 100 mg2.000NANA
SRD Cohort 3: TAK-915 200 mg2.000NANA
SRD Cohort 4: TAK-915 200 mg2.508NANA

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Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-915 and TAK-915 Metabolite M-I in BA/FE Cohort

(NCT02461160)
Timeframe: Day 1 of Periods 1, 2 and 3 predose and at multiple time points (up to 96 hours) post-dose

,,
Interventionhr (Median)
TAK-915Metabolite M-I
BA/FE Cohort Regimen A1.5002.250
BA/FE Cohort Regimen B3.00010.000
BA/FE Cohort Regimen C7.00024.000

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Total Amount of Drug Excreted in Urine (Ae) for TAK-915

(NCT02461160)
Timeframe: SRD Cohorts: Day 1 pre-dose and at multiple timepoints (up to 96 hours) post dose; MRD cohorts: Days 1 and 14 pre-dose and at multiple timepoints (up to 96 hours) post dose

,,,,,,
Interventionng (Mean)
Day 1Day 14
MRD Cohort 5: TAK-915 30 mg11637.53823712.223
MRD Cohort 6: TAK-915 100 mg75873.405107635.360
MRD Cohort 7: TAK-915 200 mg84953.950173279.223
SRD Cohort 1 TAK-915 30 mg10716.238NA
SRD Cohort 2: TAK-915 100 mg56307.372NA
SRD Cohort 3: TAK-915 200 mg39016.323NA
SRD Cohort 4: TAK-915 200 mg70789.157NA

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λz: Terminal Elimination Rate Constant for TAK-915 and TAK-915 Metabolite M-I in BA/FE Cohort

(NCT02461160)
Timeframe: Day 1 of Periods 1, 2 and 3 predose and at multiple time points (up to 96 hours) post-dose

,,
Intervention1/hr (Mean)
TAK-915Metabolite M-I
BA/FE Cohort Regimen A0.02020.0180
BA/FE Cohort Regimen B0.01870.0155
BA/FE Cohort Regimen C0.02020.0162

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AUC(0-24): Area Under the Plasma Concentration-Time Curve From Time 0 to 24 Hours Postdose for TAK-915 on Day 1 in DDI Cohort

(NCT02461160)
Timeframe: Days 1 at multiple time points (up to 96 hours) post dose

Interventionng*hr/mL (Mean)
DDI Cohort 7: TAK-915 + Midazolam 2 mg7324.5

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AUC(0-24) for Midazolam After Single Dose (Day 1)/AUC(0-24) for Midazolam After 7 Daily Doses of TAK-915 (Day 16) in DDI Cohort

(NCT02461160)
Timeframe: Days 1 and 16 pre-dose and at multiple timepoints (up to 24 hours) post dose

InterventionRatio (Mean)
DDI Cohort 7: TAK-915 + Midazolam 2 mg0.735

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Time Dependency Assessment From AUC(0-24) After Last Dose for TAK-915 on Day 14 in MRD Cohorts Compared to AUC(0-inf) After a Single Dose on Day 1

(NCT02461160)
Timeframe: Days 1 and 14 pre-dose and at multiple time points (up to 96 hours) post dose

Interventionratio (Mean)
MRD Cohort 5: TAK-915 30 mg0.873
MRD Cohort 6: TAK-915 100 mg0.883
MRD Cohort 7: TAK-915 200 mg0.846

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Apparent Volume of Distribution (Vz/F) for TAK-915

(NCT02461160)
Timeframe: SRD and ESSD Cohorts: Day 1 pre-dose and at multiple timepoints (up to 96 hours) post dose; MRD cohorts: Days 1 and 14 pre-dose and at multiple timepoints (up to 96 hours) post dose

,,,,,,,
InterventionL (Mean)
Day 1Day 14
ESSD Cohort 12: TAK-915 50 mg251.206NA
MRD Cohort 5: TAK-915 30 mg253.191290.034
MRD Cohort 6: TAK-915 100 mg219.807231.463
MRD Cohort 7: TAK-915 200 mg289.052373.816
SRD Cohort 1 TAK-915 30 mg271.621NA
SRD Cohort 2: TAK-915 100 mg253.274NA
SRD Cohort 3: TAK-915 200 mg739.900NA
SRD Cohort 4: TAK-915 200 mg384.373NA

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AUC(0-tau): Area Under the Plasma Concentration-Time Curve From Time 0 to Time Tau Over a Dosing Interval Where Tau is the Length of the Dosing Interval for TAK-915 in DDI Cohort

(NCT02461160)
Timeframe: Days 16 at multiple time points (up to 96 hours) post dose

Interventionng*hr/mL (Mean)
DDI Cohort 7: TAK-915 + Midazolam 2 mg17093.9

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AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-915

(NCT02461160)
Timeframe: Day 1 pre-dose and at multiple time points (up to 96 hours) post dose

Interventionng*hr/mL (Mean)
SRD Cohort 1 TAK-915 30 mg6197.1
SRD Cohort 2: TAK-915 100 mg19345.6
SRD Cohort 3: TAK-915 200 mg12198.3
SRD Cohort 4: TAK-915 200 mg30243.3
MRD Cohort 5: TAK-915 30 mg6565.6
MRD Cohort 6: TAK-915 100 mg17507.2
MRD Cohort 7: TAK-915 200 mg40326.7
ESSD Cohort 12: TAK-915 50 mg16991.5

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AUC(0-24): Area Under the Plasma Concentration-Time Curve From Time 0 to 24 Hours Postdose for Midazolam Alone (Day 1) and in the Presence of TAK-915 (Day 16) in DDI Cohort

(NCT02461160)
Timeframe: Days 1 and 16 pre-dose and at multiple timepoints (up to 24 hours) post dose

Interventionng*hr/mL (Mean)
Day 1Day 16
DDI Cohort 7: TAK-915 + Midazolam 2 mg25.017.4

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AUC(0-24): Area Under the Plasma Concentration-Time Curve From Time 0 to 24 Hours Postdose for TAK-915

(NCT02461160)
Timeframe: SRD and ESSD Cohorts: Day 1 pre-dose and at multiple timepoints (up to 96 hours) post dose; MRD cohorts: Days 1, 8 and 14 pre-dose and at multiple timepoints (up to 96 hours) post dose

,,,,,,,
Interventionng*hr/mL (Mean)
Day 1Day 8Day 14
ESSD Cohort 12: TAK-915 50 mg4693.0NANA
MRD Cohort 5: TAK-915 30 mg2610.02301.75688.9
MRD Cohort 6: TAK-915 100 mg7984.68333.915068.7
MRD Cohort 7: TAK-915 200 mg11640.512549.331656.0
SRD Cohort 1 TAK-915 30 mg2560.0NANA
SRD Cohort 2: TAK-915 100 mg8293.3NANA
SRD Cohort 3: TAK-915 200 mg5478.1NANA
SRD Cohort 4: TAK-915 200 mg10285.1NANA

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AUC(0-inf): Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-915 and TAK-915 Metabolite M-I in BA/FE Cohort

(NCT02461160)
Timeframe: Day 1 of Periods 1, 2 and 3 predose and at multiple time points (up to 96 hours) post-dose

,,
Interventionng*hr/mL (Mean)
TAK-915Metabolite M-I
BA/FE Cohort Regimen A10155.24727.2
BA/FE Cohort Regimen B9414.54145.2
BA/FE Cohort Regimen C7151.53011.6

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Cmax: Maximum Observed Plasma Concentration for TAK-915 on Day 1 in DDI Cohort

(NCT02461160)
Timeframe: Days 1 at multiple time points (up to 96 hours) post dose

Interventionng/mL (Mean)
DDI Cohort 7: TAK-915 + Midazolam 2 mg519.7

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Percentage of Participants Who Experience at Least One Treatment Emergent Adverse Event (TEAE)

An Adverse Event (AE) is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavourable and unintended sign (eg, a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, whether or not it is considered related to the drug. A TEAE is defined as an adverse event with an onset that occurs after receiving study drug. (NCT02461160)
Timeframe: Day 1 up to follow-up (SRD Cohorts: up to Day 13, MRD Cohorts: up to Day 26, DDI Cohort: up to Day 28, BA/FE Cohorts: up to Day 13, ESSD Cohort: up to Day 28)

Interventionpercentage of participants (Number)
SRD Cohorts Pooled Placebo0
SRD Cohort 1 TAK-915 30 mg16.7
SRD Cohort 2: TAK-915 100 mg33.3
SRD Cohort 3: TAK-915 200 mg16.7
MRD Cohorts Pooled Placebo16.7
MRD Cohort 5: TAK-915 30 mg33.3
MRD Cohort 6: TAK-915 100 mg16.7
MRD Cohort 7: TAK-915 200 mg33.3
DDI Cohort 8: Midazolam 2 mg0
DDI Cohort 8: TAK-915 100 mg41.7
DDI Cohort 8: TAK-915 + Midazolam 2 mg8.3
BA/FE Cohort Regimen A16.7
BA/FE Cohort Regimen B0
BA/FE Cohort Regimen C25
ESSD Cohort 12: TAK-915 50 mg25

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Percentage of Participants With Markedly Abnormal Safety Laboratory Tests

The percentage of participants with any markedly abnormal standard safety laboratory values, including haematology, serum chemistries, or urinalysis, during the treatment period. (NCT02461160)
Timeframe: Day 1 up to follow-up (SRD Cohorts: up to Day 13, MRD Cohorts: up to Day 26, DDI Cohort: up to Day 28, BA/FE Cohorts: up to Day 13, ESSD Cohort: up to Day 28)

Interventionpercentage of participants (Number)
SRD Cohorts Pooled Placebo0
SRD Cohort 1 TAK-915 30 mg0
SRD Cohort 2: TAK-915 100 mg0
SRD Cohort 3: TAK-915 200 mg0
MRD Cohorts Pooled Placebo0
MRD Cohort 5: TAK-915 30 mg0
MRD Cohort 6: TAK-915 100 mg0
MRD Cohort 7: TAK-915 200 mg0
DDI Cohort 8: Midazolam 2 mg0
DDI Cohort 8: TAK-915 100 mg0
DDI Cohort 8: TAK-915 + Midazolam 2 mg0
BA/FE Cohort Regimen A0
BA/FE Cohort Regimen B0
BA/FE Cohort Regimen C0
ESSD Cohort 12: TAK-915 50 mg0

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Rac(AUC): Accumulation Ratios Between Day 14 AUC(0-24) and Day 1 AUC(0-24) for TAK-915

(NCT02461160)
Timeframe: Days 1 and 14 pre-dose and at multiple time points (up to 96 hours) post dose

InterventionRatio (Mean)
MRD Cohort 5: TAK-915 30 mg2.100
MRD Cohort 6: TAK-915 100 mg1.973
MRD Cohort 7: TAK-915 200 mg2.761

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Rac(Cmax): Accumulation Ratios Between Day 14 Cmax and Day 1 Cmax for TAK-915

(NCT02461160)
Timeframe: Days 1 and 14 pre-dose and at multiple time points (up to 96 hours) post dose

InterventionRatio (Mean)
MRD Cohort 5: TAK-915 30 mg1.884
MRD Cohort 6: TAK-915 100 mg1.859
MRD Cohort 7: TAK-915 200 mg2.556

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Ratio of TAK-915 Metabolite Area Under the Plasma Concentration-Time Curve From Time 0 to Time Tau Over a Dosing Interval [AUC(0-tau)] Where Tau is the Length of the Dosing Interval to TAK-915 AUC(0-tau) in MRD Cohorts

(NCT02461160)
Timeframe: Day 14 predose and at multiple time points (up to 96 hours) post-dose

Interventionratio (Mean)
MRD Cohort 5: TAK-915 30 mg0.496
MRD Cohort 6: TAK-915 100 mg0.640
MRD Cohort 7: TAK-915 200 mg0.505

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Ratio of TAK-915 Metabolite AUC(0-inf) to TAK-915 AUC(0-inf) in SRD Cohorts

(NCT02461160)
Timeframe: Day 1 predose and at multiple time points (up to 96 hours) post-dose

Interventionratio (Mean)
SRD Cohort 1 TAK-915 30 mg0.492
SRD Cohort 2: TAK-915 100 mg0.475
SRD Cohort 3: TAK-915 200 mg0.483
SRD Cohort 4: TAK-915 200 mg0.576
ESSD Cohort 12: TAK-915 50 mg0.451

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Mean Arterial Pressure

mean arterial blood pressure as measured in mmHg (NCT02486328)
Timeframe: Baseline and 1,2,3,5,10,15 and 20 minutes

,
InterventionmmHg (Mean)
baseline1 minute in procedure2 minute in procedure3 minute in procedure5 minute in procedure10 minute in procedure15 minute in procedure20 minute in procedure
Group MM105.7103104.5105.8101.5103.8102.499.3
Group RP113.110492.989.387.110091.694.3

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Heart Rate

Heart rate as measured in beats per minute (NCT02486328)
Timeframe: Baseline and 1,2,3,5,10,15 and 20 minutes

,
Interventionbeats per minute (Mean)
baseline1 minute in procedure2 minute in procedure3 minute in procedure5 minute in procedure10 minute in procedure15 minute in procedure20 minute in procedure
Group MM90.289.68887.687.785.385.485
Group RP82.681.37669.970.37071.673.1

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Change in Visual Analogue Scale Scores From the Baseline

Pain as measured by Visual Analogue Scale. Range 1-10. No cut-off value, Higher results represent worse outcomes (NCT02486328)
Timeframe: Baseline and 5, 15, 30 minutes after the procedure

,
Interventionunits on a scale (Mean)
5 minutes after the procedure15 minutes after the procedure30 minutes after the procedure
Group MM0.90.50.1
Group RP0.40.40.1

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Peripheral Oxygen Saturation

peripheral oxygen saturation as measured by pulse oximeter. Units are percentages, Scale range 0-100. (NCT02486328)
Timeframe: Baseline and 1,2,3,5,10,15 and 20 minutes

,
InterventionPercent of oxygenated hemoglobin (Mean)
baseline1 minute in procedure2 minute in procedure3 minute in procedure5 minute in procedure10 minute in procedure15 minute in procedure20 minute in procedure
Group MM97.297.297.597.697.497.297.297.4
Group RP98.69898.598.497.198.198.398.2

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Change in Cognitive Function

As measured by Digit Symbol Substitution Test. Scale range 0-9. No cut-off value. Higher results represent better outcomes (NCT02486328)
Timeframe: Baseline and 5, 15, 30 minutes after the procedure

,
Interventionunits on a scale (Mean)
5th minute15th minute30th minute
Group MM1.62.12.4
Group RP22.83.5

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Change in Cognitive Function

As measured by Trieger Dot Test. The test does not have an upper limit; the time taken to complete the test is added to the number of dots missed by the patient and a result is obtained. The lowest score possible is 0. Higher values represent worse outcomes. (NCT02486328)
Timeframe: Baseline and 5, 15, 30 minutes after the procedure

,
Interventionunits on a scale (Mean)
5th minute15th minute30th minute
Group MM47.544.742
Group RP40.437.835.4

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Clinical Pregnancy Rate

presence of intrauterine sac in ultrasound after a positive pregnancy test (NCT02494180)
Timeframe: will be assessed within ten weeks of oocyte retrieval

Interventionpercentage of participants (Number)
A: Intravenous Fentanyl, Midazolam14.1
B: Intravenous Pethidine, Diazepam23.5

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Ongoing Pregnancy Rate

positive fetal heart pulsation seen in ultrasound at eight weeks of gestation (NCT02494180)
Timeframe: will be assessed within ten weeks of oocyte retrieval

Interventionpercentage of participants (Number)
A: Intravenous Fentanyl, Midazolam12.9
B: Intravenous Pethidine, Diazepam21.2

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Patient's Satisfaction on Pain Relief

satisfaction on pain relief will be scored at 0-10 (10 being most satisfied) (NCT02494180)
Timeframe: within 4 hours after retrieval

Interventionscore on a scale (Median)
A: Intravenous Fentanyl, Midazolam8
B: Intravenous Pethidine, Diazepam7

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Pain Level After Oocyte Retrieval

The pain level will be scored using visual analogue scale 0-10, 0 = no pain, 10 =most painful (NCT02494180)
Timeframe: will be assessed within 4 hours of oocyte retrieval

,
Interventionscore on a scale (Median)
vaginal painabdominal pain
A: Intravenous Fentanyl, Midazolam02.3
B: Intravenous Pethidine, Diazepam02

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Pain Level During Oocyte Retrieval

The pain level will be scored using visual analogue scale 0-10, 0 = no pain, 10 =most painful (NCT02494180)
Timeframe: will be assessed within 4 hours of oocyte retrieval

,
Interventionscore on a scale (Median)
vaginal painabdominal pain
A: Intravenous Fentanyl, Midazolam02.5
B: Intravenous Pethidine, Diazepam45

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Patient's Satisfaction on Oocyte Retrieval

satisfaction will be scored from 0-3 (0=excellent, 1=satisfactory, 2=fair, 3=unsatisfactory) (NCT02494180)
Timeframe: will be assessed within 4 hours of oocyte retrieval

,
Interventionpercentage of participants (Number)
excellentsatisfactoryfairunsatisfactory
A: Intravenous Fentanyl, Midazolam47.738.811.84.7
B: Intravenous Pethidine, Diazepam15.355.322.47.1

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Percentage of Participants With Side Effects by Type

side effects will be scored by yes or no (NCT02494180)
Timeframe: will be assessed within 4 hours of oocyte retrieval

,
Interventionpercentage of participants (Number)
nauseavomitingdizzinessdrowsinessshortness of breath
A: Intravenous Fentanyl, Midazolam2.4016.58.20
B: Intravenous Pethidine, Diazepam7.11.24.73.51.2

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Request of Sedation/Termination of AVA

Request of Sedation/Termination of AVA (After consent has been obtained until spinal resolution in the recovery room, average of 6 hours) (NCT02506673)
Timeframe: From consent until spinal resolution (avg 6 hs)

InterventionParticipants (Count of Participants)
Number of Participants (AVA Randomization)Request of Sedation/Termination of AVA
Sedation & Audiovisual Aids With Skin Conductance Monitor1313

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Number of Providers That Were Satisfied With Their Experience With the Audio-visual Aids

Anesthesia providers were asked to provide feedback on their experience with the audio-visual aids when the randomization was for the use of the device. This was collected upon surgery end. (NCT02506673)
Timeframe: Sent to providers at end of surgery.

InterventionParticipants (Count of Participants)
Sedation & Audiovisual Aids With Skin Conductance Monitor07

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Skin Conductance Response

Primary outcome will be number of skin conductance responses per second (SCR/sec) and amplitude of skin conductance responses averaged over time in 5 minute intervals and at key time points such before, during and after insertion of an IV, discussion with surgeon, anesthesiologist, immediately before leaving the holding area, immediately after entering the OR, during application of monitors, before and after administration of sedatives, before, during and after spinal insertion, incision, immediately prior to leaving the OR, after arrival at PACU and monitors are placed, before discharge from the PACU. (NCT02506673)
Timeframe: Measured in 5 minute intervals, from holding area until PACU discharge.

Interventionskin conductance responses per second (Mean)
Sedation Only With Skin Conductance MonitorNA
Sedation & Audiovisual Aids With Skin Conductance MonitorNA

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Beats Per Minute (BPM)

The change in heart rate from holding area until PACU discharge. (NCT02506673)
Timeframe: Measured from preop to postop

,
InterventionBeats Per Minute (Mean)
BPM BaselineBPM change IntraopBPM change Postop
Sedation & Audiovisual Aids With Skin Conductance Monitor66.817-6
Sedation Only With Skin Conductance Monitor71.7172

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Narcotic Consumption

"Narcotic consumption intraop, postop and POD1" (NCT02506673)
Timeframe: Preop until 24 hours after surgery (holding area until POD 1)

,
Interventionoral morphine equivalents mg (Mean)
OME mg IntraopOME mg Inpatient postopOME mg POD1
Sedation & Audiovisual Aids With Skin Conductance Monitor3.510.811.5
Sedation Only With Skin Conductance Monitor2.39.811.0

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Number of Participants With Complications

The percentage of patients who experienced complications (headache, transient neurologic symptoms, nausea and vomiting, ...) (NCT02506673)
Timeframe: Intraoperatively and in the recovery room, average of 3 hours

,
InterventionParticipants (Count of Participants)
Incidence of Complication IntraopIncidence of Complication PACU
Sedation & Audiovisual Aids With Skin Conductance Monitor00
Sedation Only With Skin Conductance Monitor00

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Pain Numerical Rating Scale (NRS) Levels

Pain scores at rest will be collected from patients using the numerical rating scale (NRS), which asks patients to report their level of pain on a scale from 0 to 10, where 0 represents no pain and 10 represents the worst possible pain. NRS levels in holding area, PACU until discharge from the PACU and one day after surgery, postop day 1. (NCT02506673)
Timeframe: Holding area, Postop (PACU, 30 minutes after arrival to PACU and POD1)

,
Interventionunits on a scale (Mean)
Holding areaPACU arrival30 minutes after arrival to PACUPOD1
Sedation & Audiovisual Aids With Skin Conductance Monitor2.2002.1
Sedation Only With Skin Conductance Monitor1.900.62.5

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Number of Patients Who Requested Additional Sedation

Number of patients who requested additional sedative medication in the operating room. (NCT02506673)
Timeframe: In the operating room

InterventionParticipants (Count of Participants)
Sedation Only With Skin Conductance Monitor5
Sedation & Audiovisual Aids With Skin Conductance Monitor3

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Respiratory Rate

The maxmimum change in postoperative respiratory rate from holding area until PACU discharge. (NCT02506673)
Timeframe: Measured from preop to postop

,
Interventionbreaths/minute (Mean)
RR BaselineRR change intraopRR change postop
Sedation & Audiovisual Aids With Skin Conductance Monitor16.941
Sedation Only With Skin Conductance Monitor17.25-1

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State-Trait Anxiety Inventory Questionnaire (STAI)

Questionnaire to measure state anixety levels based on a 4-point likert scale and consists of 40 questions. The questionnaire measures two types of anxiety: state anxiety and trait anxiety. State anxiety relates to anxiety about an event, while trait anxiety in anxiety level as a personal characteristic. Scores can range from 20 to 80 and higher scores correlate with more anxiety. (NCT02506673)
Timeframe: holding area and PACU

,
Interventionscore on a scale (Mean)
STAI-State in holding areaSTAI-Trait in holding areaSTAI-State in PACUSTAI-Trait in PACU
Sedation & Audiovisual Aids With Skin Conductance Monitor32.331.827.132.8
Sedation Only With Skin Conductance Monitor33.533.426.132.3

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Systolic and Diastolic Blood Pressure

The maximum change in postoperative systolic and diastolic blood pressure from holding area until PACU discharge. (NCT02506673)
Timeframe: Measured from preop to postop

,
InterventionmmHg (Mean)
DBP BaselineDBP change intraopDBP change postopSBP BaselineSBP change intraopSBP change postop
Sedation & Audiovisual Aids With Skin Conductance Monitor79.62-4129.27-2
Sedation Only With Skin Conductance Monitor82.83-2135.37-8

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Client Satisfaction Questionnaire (CSQ-8)

The client satisfaction questionnaire (CSQ-8) is a standardized satisfaction measure and was used to collect patient feedback on the audio visual devices. Response options differ, but all are on a 4-point scale. Scores range from 8 to 32, with higher values indicating higher satisfaction. Patient feedback (CSQ8) in PACU upon spinal resolution provider feedback (form sent to providers at end of surgery day) (NCT02506673)
Timeframe: PACU upon spinal resolution

Interventionscores on a scale (Median)
Sedation & Audiovisual Aids With Skin Conductance Monitor31.5

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Heidelberg Peri-anaesthetic Questionnaire

The questionnaire consists of 38 questions assessing perioperative satisfaction about five identified themes: trust and atmosphere; fear; discomfort; treatment by personnel; and information and waiting. The questions are rated on a 4-point Likert scale ranging from 0 (unimportant to me) to 3 (very important to me). Higher scores indicate higher levels of satisfaction. Patient satisfaction (Heidelberg Peri-Anaesthetic Questionnaire) in PACU upon spinal resolution. (NCT02506673)
Timeframe: At PACU upon spinal resolution.

Interventionscore on a scale (Mean)
Sedation Only With Skin Conductance Monitor97.2
Sedation & Audiovisual Aids With Skin Conductance Monitor98.9

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Memory Testing

Subjects completed the Remember, Know, New (RKN) task during next day testing. Their d' memory score was calculated based on their ability to discriminate between previously heard words and new words. A higher d' score indicates stronger recollection. D' scores were compared across the control condition (saline) and the drug conditions dexmedetomidine, midazolam, and ketamine. Performance was also calculated according to words associated with Pain and No Pain conditions. (NCT02515890)
Timeframe: At memory testing 1 day later

,,,
Interventiond' score (Mean)
All ConditionsNo Pain ConditionPain Condition
Dexmedetomidine1.201.121.28
Ketamine.82.85.78
Midazolam.56.55.57
Saline1.181.181.10

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Montreal Cognitive Assessment (MOCA) at Last Infusion

MoCA scores range between 0 and 30. Higher scores reflect higher cognition. (NCT02522377)
Timeframe: visit 17

Interventionscore on a scale (Mean)
Ketamine Infusions24.81
Midazolam25.79

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Montgomery Asberg Depression Rating Scale (MADRS) at Last Infusion

Higher MADRS score indicates more severe depression, and each item yields a score of 0 to 6. The overall score ranges from 0 to 60 (NCT02522377)
Timeframe: visit 17

Interventionscore on a scale (Mean)
Ketamine Infusions22.29
Midazolam24.27

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Hopkins Verbal Learning Test - Revised (HVLT-R) at Last Infusion

The number of words remembered are recorded. Scores range from 0 to 12 with higher scores reflecting better acquisition. (NCT02522377)
Timeframe: visit 17

Interventionscore on a scale (Mean)
Ketamine Infusions9.42
Midazolam11.20

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Hamilton Depression Rating Scale (HAMD-17) at Last Infusion

Change in HAMD-17 at Infusion 6. Scores range from 0 to 50, with higher scores representing more depression. (NCT02522377)
Timeframe: visit 17

Interventionscore on a scale (Mean)
Ketamine Infusions13.74
Midazolam14.97

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Controlled Oral Word Association Test (COWAT) at Last Infusion

This is a verbal fluency measure. Outcome is the count of words that meet criteria within 1 minute, so the minimum is 0 and no fixed maximum exists. Higher scores reflect a better outcome. (NCT02522377)
Timeframe: visit 17

Interventionnumber of words (Mean)
Ketamine Infusions33.45
Midazolam37.17

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Time to Fully Alert

Time to first of 3 Modified Observer's Assessment of Alertness/Sedation (MOAA/S) scores of 5 after the end of colonoscopy procedure (colonoscope out) and after the last injection of study drug (NCT02532647)
Timeframe: From the last injection of the study drug AND from end of colonoscopy until the patient has recovered to fully alert

,,
Interventionminutes (Median)
After last dose of trial or rescue sedativeAfter the end of colonoscopy
Midazolam18.87.0
Placebo18.05.3
Remimazolam11.03.0

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Time to Start of Procedure

The time from the first administration of the study drug to the beginning of the colonoscopy (NCT02532647)
Timeframe: From the first administration of the study drug to the beginning of the colonoscopy

Interventionminutes (Median)
Remimazolam5.0
Placebo18.3
Midazolam19.0

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Success Rates of the Procedure

The success of the procedure, as measured by completion of the colonoscopy procedure, AND no requirement for a rescue sedative medication, AND no requirement of more than 5 doses of study medication within any 15 minute window. (For midazolam: 3 doses within any 12 minute window) (NCT02532647)
Timeframe: From first dose of study drug until the end of colonoscopy

InterventionParticipants (Count of Participants)
Remimazolam27
Placebo0
Midazolam4

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Change in Systolic Blood Pressure (Millimeters of Mercury, mm Hg)

Change in systolic blood pressure from pre-infusion baseline to 30 minutes after start of infusion (NCT02556606)
Timeframe: Baseline to 30 minutes after start of infusion

,,,
Interventionmm Hg (Mean)
Pre-infusion baseline30 minutes after start of infusion
Ketamine 0.10 mg/kg154.25152.75
Ketamine 0.25 mg/kg142.2148.2
Ketamine 0.50 mg/kg132.91160.36
Midazolam 0.03 mg/kg125.54116.62

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Change in Resting-state Quantitative Electroencephalography (EEG) Frontal Gamma Band Power (Log of Microvolt Squared)

Change in EEG frontal gamma power from pre-infusion baseline to 30 minutes after start of infusion to assess engagement of the study drug with the N-methyl-D-aspartate receptor. (NCT02556606)
Timeframe: Baseline to 30 minutes after start of infusion

,,,
InterventionuV^2 (Mean)
Pre-infusion baseline30 minutes after start of infusion
Ketamine 0.10 mg/kg0.00190.0035
Ketamine 0.25 mg/kg0.0550.0057
Ketamine 0.50 mg/kg0.00420.0098
Midazolam 0.03 mg/kg0.00610.004

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Change in Diastolic Blood Pressure (Millimeters of Mercury, mm Hg)

Change in systolic blood pressure from pre-infusion baseline to 30 minutes after start of infusion (NCT02556606)
Timeframe: Baseline to 30 minutes after start of infusion

,,,
Interventionmm Hg (Mean)
Pre-infusion baseline30 minutes after start of infusion
Ketamine 0.10 mg/kg80.591.25
Ketamine 0.25 mg/kg74.682.6
Ketamine 0.50 mg/kg82.6495.45
Midazolam 0.03 mg/kg72.2373.54

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Change in Clinician-Administered Dissociative States Scale (CADSS)

Change from pre-infusion baseline to end of infusion at 40 minutes after start of infusion on the Clinician-Administered Dissociative States Scale (CADSS; scale form 0 [no psychosis-like symptoms] to 90 [severe psychosis-like symptoms]) to assess psychosis-like side effect on day of infusion. (NCT02556606)
Timeframe: Baseline to 40 minutes after start of infusion

,,,
InterventionScore on CADSS scale (Mean)
Pre-infusion baselineEnd of infusion at 40 minutes
Ketamine 0.10 mg/kg1.414.79
Ketamine 0.25 mg/kg014.98
Ketamine 0.50 mg/kg0.0921.36
Midazolam 0.03 mg/kg0.234.38

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Percentage of Patients With Continuation From Day 7 to Day 28 Post-infusion of at Least a 50% Improvement in MADRS

Patients with a day 7 treatment response (at least a 50% improvement from baseline in Montgomery-Asberg Depression Rating Scale [MADRS]) are followed until day 28 post-infusion; day 7 non-responders are not followed. Outcome measure is the percentage of patients who continue to be responder at day 28, and is interpreted as a measure of durability of efficacy. (NCT02556606)
Timeframe: 28 days post-infusion follow-up

InterventionParticipants (Count of Participants)
Ketamine 0.10 mg/kg0
Ketamine 0.25 mg/kg1
Ketamine 0.50 mg/kg7
Midazolam 0.03 mg/kg4

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Percentage of Participants Demonstrating at Least a 50% Reduction on Montgomery-Asberg Depression Rating Scale Scores

To determine the best performing intervention among three sub-anesthetic doses of a single ketamine (0.1 mg/kg, 0.25 mg/kg, and 0.50 mg/kg) and midazolam (0.03 mg/kg) in Veterans with LL-TRD as measured by the percentage of participants demonstrating at least a 50% reduction from pre-treatment baseline on Montgomery-Asberg Depression Rating Scale (MADRS; score range 0 - 60, higher scores meaning more severe depression) scores at 7 days post-infusion. (NCT02556606)
Timeframe: Day 7 post-infusion

InterventionParticipants (Count of Participants)
Ketamine 0.10 mg/kg0
Ketamine 0.25 mg/kg2
Ketamine 0.50 mg/kg8
Midazolam 0.03 mg/kg6

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Montgomery-Asberg Depression Rating Scale Score 1 Day After Infusion

"Depressive symptoms (measured by Montgomery-Asberg Depression Rating Scale, revised (MADRS) score) on 1 day after infusion, for the cohort of subjects enrolled in the MDD arm of this trial.~Higher MADRS score indicates more severe depression, and each item yields a score of 0 to 6. The overall score ranges from 0 to 60.~Usual cutoff points are:~0 to 6 - normal /symptom absent. 7 to 19 - mild depression. 20 to 34 - moderate depression. >34 - severe depression." (NCT02579928)
Timeframe: 1 day after the infusion

Interventionunits on a scale (Mean)
Ketamine15.44
Midazolam24.13

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Guardian/Parent's Prediction is Respect to Intervention Drug

This is a measure how how many times the parent/guardian was correct in predicting whether the patient received intranasal saline or intranasal midazolam as the intervention drug. (NCT02618772)
Timeframe: Day 1: parent asked immediately after procedure complete

,
InterventionTimes correct (Number)
Intention to Treat (ITT): (Total n = 35, 38)Per-Protocol (PP): (Total n = 32, 35)
Intranasal Midazolam3128
Intranasal Saline2522

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Length of Procedure (Mins)

This is a measure of the length of the procedure (suturing) in minutes. (NCT02618772)
Timeframe: Day 1

,
Interventionminutes (Mean)
Intention to Treat (ITT): (n = 36, 39)Per-Protocol (PP): (n = 33, 37)
Intranasal Midazolam23.1823.19
Intranasal Saline14.7215.00

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Per-Protocol: Modified Yale Preoperative Anxiety Score (mYPAS)

"Measurement of patient anxiety used to test effect of anxiolytic pre-medication.The mYPAS consists of 5 items (activity, vocalizations, emotional expressivity, state of apparent arousal, and use of parents). Each item has Likert scale whereby participant's behavior is rated from 1 to 4 (Note: Vocalizations is the only item rated from 1 to 6), with higher numbers indicating the highest severity within that item. Each participant was given a mYPAS score for the suturing by two independent raters. These raters watched a digital recording of the participant undergoing suturing and from this digital recording used the mYPAS scale to assign a measurement of the participant's anxiety.~The mYPAS scale is rated as follows: Final scores = (Activity/4 + Vocal/6 + Emotional/4 + Arousal/4 + Parents/4) X 20. Scores range from 23 to 100 where a lower score is indicative of a lower level of anxiety and a higher is indicative of a higher level of anxiety." (NCT02618772)
Timeframe: Day 1: Baseline, Intervention & Lidocaine

,
Interventionunits on a scale (Mean)
Baseline (n = 33, 36)Intervention (n = 30, 36)Lidocaine (n = 34, 35)Suturing Minus Baseline (n = 32, 36)
Intranasal Midazolam32.973657.991760.959612.4897
Intranasal Saline30.031843.063868.827529.1328

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Per-Protocol: State Trait Anxiety Inventory (STAI)

"Validated measurement of anxiety, to be used to test parental/guardian anxiety at two time points. These time points are before intervention and immediately after suturing (prior to patient discharge from the ER, i.e. same day). The STAI contains 10 items for assessing trait anxiety and 10 for state anxiety. All items are rated on a standard scale (Not at all, Somewhat, Moderately so, Very much so) with a range of 20 to 80 where higher scores indicate greater anxiety and lower scores indicate lower levels of anxiety." (NCT02618772)
Timeframe: Before intervention and immediately after suturing (prior to patient discharge from the ER, i.e. same day)

,
Interventionunits on a scale (Mean)
STAI Pre (n = 32, 34)STAI Post (n = 34, 37)STAI Post Minus Pre (n = 32, 34)
Intranasal Midazolam41.735333.7568-7.6471
Intranasal Saline39.343838.4118-0.8750

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Physician's Prediction is Respect to Intervention Drug

This is a measure how how many times the physician was correct in predicting whether the patient received intranasal saline or intranasal midazolam as the intervention drug. (NCT02618772)
Timeframe: Day 1: physician asked immediately after procedure finished

,
InterventionTimes correct (Number)
Intention to Treat (ITT): (Total n = 37, 36)Per-Protocol (PP): (Total n = 34, 33)
Intranasal Midazolam3128
Intranasal Saline3028

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Time That the Participant Remained in Hospital After Procedure (Mins)

Length of stay in the emergency department, measured from the end of the procedure to the time of discharge. (NCT02618772)
Timeframe: Day 1: at discharge from emergency department (i.e. same day)

,
Interventionminutes (Mean)
Intentiont to Treat (ITT): (n = 36, 39)Per-Protocol (PP): (n = 33, 37)
Intranasal Midazolam25.4125.08
Intranasal Saline10.8911.24

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Intention to Treat (ITT): State Trait Anxiety Inventory (STAI)

"Validated measurement of anxiety, to be used to test parental/guardian anxiety at two time points. These time points are before intervention and immediately after suturing (prior to patient discharge from the ER, i.e. same day). The STAI contains 10 items for assessing trait anxiety and 10 for state anxiety. All items are rated on a standard scale (Not at all, Somewhat, Moderately so, Very much so) with a range of 20 to 80 where higher scores indicate greater anxiety and lower scores indicate lower levels of anxiety." (NCT02618772)
Timeframe: Day 1: Before intervention and immediately after suturing (prior to patient discharge from the ER, i.e. same day)

,
Interventionunits on a scale (Mean)
STAI Pre (n = 36, 37)STAI Post (n = 37, 40)STAI Post Minus Pre (n = 35, 37)
Intranasal Midazolam43.135134.5500-8.2162
Intranasal Saline39.333338.3784-0.5143

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Intention to Treat (ITT): Dartmouth Operative Conditions Scale

A tool to measure the effectiveness and safety of pediatric sedation, regardless of technique used for decreasing anxiety or pain during a procedure. The scale asks the physician to rate patient states (pain/stress, movement, consciousness & sedation side effects) based on observed behaviors (each observed behavior is given a score). The scores are then added together to give a score where -3 to 5 where the lower number is indicative of less anxiety/pain. (NCT02618772)
Timeframe: Day 1: Immediately after suturing (prior to patient discharge from the ER, i.e. same day)

Interventionunits on a scale (Mean)
Intranasal Saline1.92
Intranasal Midazolam1.15

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Intention to Treat (ITT): Modified Yale Preoperative Anxiety Score (mYPAS)

"Measurement of patient anxiety used to test effect of anxiolytic pre-medication.The mYPAS consists of 5 items (activity, vocalizations, emotional expressivity, state of apparent arousal, and use of parents). Each item has Likert scale whereby participant's behavior is rated from 1 to 4 (Note: Vocalizations is the only item rated from 1 to 6), with higher numbers indicating the highest severity within that item. Each participant was given a mYPAS score for the suturing by two independent raters. These raters watched a digital recording of the participant undergoing suturing and from this digital recording used the mYPAS scale to assign a measurement of the participant's anxiety.~The mYPAS scale is rated as follows: Final scores = (Activity/4 + Vocal/6 + Emotional/4 + Arousal/4 + Parents/4) X 20. Scores range from 23 to 100 where a lower score is indicative of a lower level of anxiety and a higher is indicative of a higher level of anxiety." (NCT02618772)
Timeframe: Day 1: During suturing

Interventionunits on a scale (Mean)
Intranasal Saline59.9201
Intranasal Midazolam46.2871

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Per-Protocol: Dartmouth Operative Conditions Scale

A tool to measure the effectiveness and safety of pediatric sedation, regardless of technique used for decreasing anxiety or pain during a procedure. The scale asks the physician to rate patient states (pain/stress, movement, consciousness & sedation side effects) based on observed behaviors (each observed behavior is given a score). The scores are then added together to give a score where -3 to 5 where the lower number is indicative of less anxiety/pain. (NCT02618772)
Timeframe: Day 1: Immediately after suturing (prior to patient discharge from the ER, i.e. same day)

Interventionunits on a scale (Mean)
Intranasal Saline1.88
Intranasal Midazolam1.08

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Per-Protocol: Faces Pain Scale-Revised/ FLACC Scale

"Faces Pain Scale: Validated self-report tool of pain for participants less than 5 years old. It is a scale that allows one to score the sensation of pain from zero to ten. The scale shows a visuals (faces) for each levels 0, 2, 4, 6, 8 and 10 of the scale. For example, 0 is represented by a face visual that expresses no hurt.~FLACC Scale: Tool to assess pain in children unable to use Faces Pain Scale-revised. The Face, Legs, Activity, Cry, Consolability scale or FLACC scale is a measurement used to assess individuals that are unable to communicate their pain. The scale is scored in a range of 0-10 (0 represents no pain)." (NCT02618772)
Timeframe: Day 1: immediately after intervention

Interventionunits on a scale (Mean)
Intranasal Saline2.47
Intranasal Midazolam5.19

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Intention to Treat (ITT): Faces Pain Scale-Revised/ FLACC Scale

"Faces Pain Scale: Validated self-report tool of pain for participants less than 5 years old. It is a scale that allows one to score the sensation of pain from zero to ten. The scale shows a visuals (faces) for each levels 0, 2, 4, 6, 8 and 10 of the scale. For example, 0 is represented by a face visual that expresses no hurt.~FLACC Scale: Tool to assess pain in children unable to use Faces Pain Scale-revised. The Face, Legs, Activity, Cry, Consolability scale or FLACC scale is a measurement used to assess individuals that are unable to communicate their pain. The scale is scored in a range of 0-10 (0 represents no pain)." (NCT02618772)
Timeframe: Day 1: immediately after intervention

Interventionunits on a scale (Mean)
Intranasal Saline2.61
Intranasal Midazolam5.25

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Per-Protocol: Modified Yale Preoperative Anxiety Score (mYPAS)

"Measurement of patient anxiety used to test effect of anxiolytic pre-medication.The mYPAS consists of 5 items (activity, vocalizations, emotional expressivity, state of apparent arousal, and use of parents). Each item has Likert scale whereby participant's behavior is rated from 1 to 4 (Note: Vocalizations is the only item rated from 1 to 6), with higher numbers indicating the highest severity within that item. Each participant was given a mYPAS score for the suturing by two independent raters. These raters watched a digital recording of the participant undergoing suturing and from this digital recording used the mYPAS scale to assign a measurement of the participant's anxiety.~The mYPAS scale is rated as follows: Final scores = (Activity/4 + Vocal/6 + Emotional/4 + Arousal/4 + Parents/4) X 20. Scores range from 23 to 100 where a lower score is indicative of a lower level of anxiety and a higher is indicative of a higher level of anxiety." (NCT02618772)
Timeframe: Day 1: During suturing

Interventionunits on a scale (Mean)
Intranasal Saline58.7056
Intranasal Midazolam45.4633

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Intention to Treat (ITT): Modified Yale Preoperative Anxiety Score (mYPAS)

"Measurement of patient anxiety used to test effect of anxiolytic pre-medication.The mYPAS consists of 5 items (activity, vocalizations, emotional expressivity, state of apparent arousal, and use of parents). Each item has Likert scale whereby participant's behavior is rated from 1 to 4 (Note: Vocalizations is the only item rated from 1 to 6), with higher numbers indicating the highest severity within that item. Each participant was given a mYPAS score for the suturing by two independent raters. These raters watched a digital recording of the participant undergoing suturing and from this digital recording used the mYPAS scale to assign a measurement of the participant's anxiety.~The mYPAS scale is rated as follows: Final scores = (Activity/4 + Vocal/6 + Emotional/4 + Arousal/4 + Parents/4) X 20. Scores range from 23 to 100 where a lower score is indicative of a lower level of anxiety and a higher is indicative of a higher level of anxiety." (NCT02618772)
Timeframe: Day 1: During Baseline, Intervention & Lidocaine

,
Interventionunits on a scale (Mean)
Baseline (n = 35, 38)Intervention (n = 32, 38)Lidocaine (n = 34, 36)Suturing Minus Baseline (n = 33, 38))
Intranasal Midazolam32.946158.580361.187113.2166
Intranasal Saline29.925745.137368.827530.3485

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Onset of Motor Blockade

assessed with modified bromage scale. (NCT02619799)
Timeframe: every 5 minute intervals for initial 30 min , then every 30 minute intervals for first 6-8 hrs after completion of surgery.

Interventiontime in minutes (Mean)
GROUP A(MAGNESIUM GROUP)12.5
GROUP B(MIDAZOLAM GROUP)7.68

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Onset of Sensory Blockade

the onset time of sensory blockade was assessed with pinprick . (NCT02619799)
Timeframe: every 2- 3 minutes for initial 20 minutes ,then every 30 min intervals for first 6 -8 hrs after completion of surgery..

Interventiontime in minutes (Mean)
GROUP A(MAGNESIUM GROUP)9.86
GROUP B(MIDAZOLAM GROUP)7.93

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Perioperative Side Effects

through out the intraoperative period and initial 12 hours postoperatively parturients were assessed for PONV,sedation,respiratory depression hypotension ,bradycardia and shivering. (NCT02619799)
Timeframe: through out the intraoperative period and first 12 postoperative hours.

,
Interventionparticipants (Number)
Nausea and vomitingshivering
GROUP A(MAGNESIUM GROUP)21
GROUP B(MIDAZOLAM GROUP)33

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Duration of Motor Blockade

assessed with modified bromage scale. (NCT02619799)
Timeframe: every 5 minute intervals for initial 30 min , then every 30 minute intervals for first 6-8 hrs after completion of surgery.

Interventiontime in minutes (Mean)
GROUP A(MAGNESIUM GROUP)265
GROUP B(MIDAZOLAM GROUP)223

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Duration of Postoperative Analgesia

pain is assessed using visual analogue scale every hour after completion of surgery until first 12 postoperative hours. (NCT02619799)
Timeframe: first 12 hours after completion of surgery.

Interventiontime in minutes (Mean)
GROUP A(MAGNESIUM GROUP)334
GROUP B(MIDAZOLAM GROUP)280

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Duration of Sensory Blockade

the duration of sensory blockade was assessed with pinprick . (NCT02619799)
Timeframe: every 2- 3 minutes for initial 20 minutes ,then every 30 min intervals for first 6 -8 hrs after completion of surgery..

Interventiontime in minutes (Mean)
GROUP A(MAGNESIUM GROUP)295
GROUP B(MIDAZOLAM GROUP)245

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Completion Rate for Randomised Treatment Phase

The outcomes for this pilot trial are process outcomes, primarily rates of recruitment and retention. Thus, the completion rate for the randomised treatment phase is the primary outcome. The study is not designed to assess efficacy. (NCT02661061)
Timeframe: 2 years

InterventionParticipants (Count of Participants)
Ketamine3
Midazolam2

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Depression Relapse Rate During Treatment and Follow-up Phase

Clinical outcomes are secondary in this pilot trial. The 24-item Hamilton Rating Scale for Depression (HRSD-24) was used to assess for the main clinical outcome, the relapse rate over six months. Criteria for relapse are ≥10 point increase in HRSD-24 compared to baseline score plus HRSD ≥16; in addition, increase in the HRSD should be maintained one week later (if indicated, additional follow-ups will be arranged). Hospital admission, and deliberate self-harm/suicide also constitute relapse. Relapse may also occur during the eight-week treatment phase and is captured here. (NCT02661061)
Timeframe: 8 months

InterventionParticipants (Count of Participants)
Ketamine2
Midazolam3

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Behavior During Dental Treatment

"the effect of oral or nasal midazolam on behaviour will be assessed by blind observer using Houpt scale. Houpt scale measures behavior by rating overall behavior. the scale is 1 to 6, higher score mean a better behavior.~= Aborted, no treatment rendered.~= Poor, treatment interrupted, only partial treatment was completed 3= Fair, treatment interrupted but eventually completed 4= Good, difficult but all treatment was performed 5= Very good, some limited crying or movement 6= Excellent, no crying or movement" (NCT02679781)
Timeframe: the effect of oral or nasal midazolam on behaviour will be assessed during dental treatment.The length of each treatment is estimated as 30-45 minutes.

Interventionscore on a scale (Mean)
Oral Sedation5.17
Nasal Sedation4.80

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Single Time-point Platelet Reactivity Using Verify Now

Blood test of Platelet Cell Reactivity using Verify Now (P2Y12 Reactivity Units) (NCT02683707)
Timeframe: Measured at 2 hours

InterventionPRUs (Mean)
PCI Without IV Opiate78
PCI With IV Opiate112

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Patient Self-reported Pain

"Patient self report of pain using a visual analog scale (VAS). Scale ranges from 0 to 10 with 0 being No pain and 10 being Most severe pain." (NCT02683707)
Timeframe: 2 hours

Interventionunits on a scale (Mean)
PCI Without IV Opiate2.3
PCI With IV Opiate1.5

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Platelet Reactivity Using Light Transmission Aggregometry

Blood test of Platelet Cell Reactivity using Light Transmission Aggregometry (reported as percent of baseline aggregation in response to adenosine diphosphate stimulation) (NCT02683707)
Timeframe: Measured at 2 hours

Interventionpercentage of baseline aggregation (Mean)
PCI Without IV Opiate27.5
PCI With IV Opiate39.3

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Ticagrelor Pharmacokinetics

Area under the curve for Ticagrelor Absorption (NCT02683707)
Timeframe: Measured over 24 hours (at 0, 0.5, 1, 2, 4, and 24 hours)

Interventionng*hr/mL (Mean)
PCI Without IV Opiate3301
PCI With IV Opiate2107

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Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)

(NCT02686164)
Timeframe: First dose of study drug (Baseline) up to 28 days after last dose of study drug or until resolution, whichever came first (up to approximately 2.5 years)

Interventionparticipants (Number)
TEAEsSAEs
Midazolam + Lenvatinib3010

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AUC(0-24): Area Under the Concentration-time Curve From Time Zero to 24 Hours Postdose for Midazolam and 1'-Hydroxymidazolam

(NCT02686164)
Timeframe: Cycle 1 Day-3: 0-24 hours; Cycle 1 Day 1: 0-24 hours; Cycle 1 Day 14: 0-24 hours (Duration of each cycle=28 days)

,,
Interventionhour*nanograms per milliliter (h*ng/mL) (Mean)
Midazolam1'-hydroxymidazolam
Cycle 1 Day -3: Midazolam92.538.5
Cycle 1 Day 1: Lenvatinib + Midazolam89.748.6
Cycle 1 Day 14: Lenvatinib + Midazolam11741.3

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Cmax: Maximum Observed Plasma Concentration for Midazolam and 1'-Hydroxymidazolam

(NCT02686164)
Timeframe: Cycle 1 Day-3: 0-24 hours; Cycle 1 Day 1: 0-24 hours; Cycle 1 Day 14: 0-24 hours (Duration of each cycle=28 days)

,,
Interventionnanogram per milliliter (ng/mL) (Mean)
Midazolam1'-hydroxy midazolam
Cycle 1 Day -3: Midazolam26.511.0
Cycle 1 Day 1: Lenvatinib + Midazolam24.812.7
Cycle 1 Day 14: Lenvatinib + Midazolam28.310.7

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Pharmacokinetics: Maximum Concentration (Cmax) of Caffeine

Maximum concentration of caffeine after single dose of drug cocktail on Day 1 in Period 1 and in combination with Abemaciclib on Day 8 in Period 2. (NCT02688088)
Timeframe: Days 1 and 8: Predose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, and 48 hours (hr) Postdose

Interventionnanograms per milliliter (ng/mL) (Geometric Mean)
100 mg Caffeine2890
Abemaciclib + 100 mg Caffeine2950

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Pharmacokinetics: Maximum Concentration (Cmax) of Dextromethorphan

Maximum concentration of dextromethorphan after single dose of drug cocktail on Day 1 of Period 1 and in combination with Abemaciclib on Day 8 in Period 2. (NCT02688088)
Timeframe: Days 1 and 8: Predose, 1, 2, 4, 6, 8, 10, 24, 48, 72 hr postdose

Interventionng/mL (Geometric Mean)
30 mg Dextromethorphan3.18
200 Abemaciclib + 30 mg Dextromethorphan3.30

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Pharmacokinetics: Maximum Concentration (Cmax) of Midazolam

Maximum concentration of midazolam after single dose of drug cocktail on Day 1 of Period 1 and in combination with Abemaciclib on Day 8 in Period 2. (NCT02688088)
Timeframe: Days 1 and 8: Predose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24 hr Postdose

Interventionng/mL (Geometric Mean)
0.2 mg Midazolam (Drug Cocktail)2.12
200 mg Abemaciclib + 0.2 mg Midazolam1.75

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Pharmacokinetics: Maximum Concentration (Cmax) S-Warfarin

Maximum concentration of S-warfarin after single dose of drug cocktail on Day 1 in Period 1and in combination with Abemaciclib on Day 8 in Period 2. (NCT02688088)
Timeframe: Days 1 and 8: Predose, 0.5 1, 2, 3, 4, 6, 8, 12, 48, 72, 96 hr Postdose

Interventionng/mL (Geometric Mean)
10 mg Warfarin561
200 mg Abemaciclib + 10 mg Warfarin526

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Mean Change From Baseline at 24 Hours in Systolic and Diastolic Blood Pressure in Period 1

Mean change from predose in systolic and diastolic blood pressure (BP) over 24 hours (h) postdose following single dose drug cocktail in Period 1. (NCT02688088)
Timeframe: Day 8: Baseline, 24 h postdose

Interventionmillimeter of mercury (mmHg) (Mean)
Systolic BPDiastolic BP
Drug Cocktail Period 1-2.5-0.7

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Mean Change From Baseline at 24 Hours in Systolic and Diastolic Blood Pressure in Period 2

Mean change from baseline in systolic and diastolic blood pressure (BP) at 24 h postdose following 200 mg abemaciclib and drug cocktail. (NCT02688088)
Timeframe: Day 8: Baseline, 24 h postdose

InterventionmmHg (Mean)
Systolic BPDiastolic BP
200 mg Abemaciclib + Drug Cocktail-11.6-6.1

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Mean Change From Baseline at 24 Hours in Systolic and Diastolic Blood Pressure in Period 2

Mean change from baseline in systolic and diastolic blood pressure (BP) over 24 hours (h) postdose following single dose of abemaciclib in Period 2, Day 1. (NCT02688088)
Timeframe: Day 1: Baseline, 24 h postdose

InterventionmmHg (Mean)
Systolic BPDiastolic BP
200 mg Abemaciclib-7.8-1.8

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Pharmacokinetics: Area Under the Concentration Versus Time Curve [AUC(0-infinity)] of S-Warfarin

AUC (zero to infinity) of S-warfarin after single dose of drug cocktail on Day 1 in Period 1 and in combination with Abemaciclib on Day 8 in Period 2. (NCT02688088)
Timeframe: Days 1 and 8: Predose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96 hr Postdose

Interventionng*h/mL (Geometric Mean)
10 mg Warfarin21400
200 mg Abemaciclib + 10 mg Warfarin20600

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Mean Change From Baseline at 24 Hours in Pulse Rate in Period 1

Mean change from baseline in pulse rate over 24 hours (h) postdose following single dose drug cocktail in Period 1. (NCT02688088)
Timeframe: Day 8: Baseline, 24 h postdose

InterventionBeats per minute (bpm) (Mean)
Drug Cocktail Period 1-1.3

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Mean Change From Baseline at 24 Hours in Pulse Rate in Period 2

Mean change from baseline in pulse rate at 24 h postdose following 200 mg abemaciclib and drug cocktail. (NCT02688088)
Timeframe: Day 8: Baseline, 24 h postdose

Interventionbpm (Mean)
200 mg Abemaciclib + Drug Cocktail4.1

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Mean Change From Baseline at 24 Hours in Pulse Rate in Period 2

Mean change from baseline in pulse rate over 24 hours (h) postdose following single dose drug cocktail in Period 2, Day 1. (NCT02688088)
Timeframe: Day 1: Baseline, 24 h postdose

Interventionbpm (Mean)
200 mg Abemaciclib-0.2

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Pharmacokinetics: Area Under the Concentration Versus Time Curve [AUC(0-infinity)] of Caffeine

PK: AUC zero to infinity of caffeine after single dose of drug cocktail on Day 1 in Period 1 and in combination with Abemaciclib on Day 8 in Period 2. (NCT02688088)
Timeframe: Days 1 and 8: Predose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48 hr Postdose

Interventionnanograms*hour per milliliter (ng*h/mL) (Geometric Least Squares Mean)
100 mg Caffeine32500
200 mg Abemaciclib + 100 mg Caffeine47100

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Pharmacokinetics: Area Under the Concentration Versus Time Curve [AUC(0-infinity)] of Dextromethorphan

PK: AUC (zero to infinity) of dextromethorphan after single dose of drug cocktail on Day 1 in Period 1 and in combination with Abemaciclib on Day 8 in Period 2. (NCT02688088)
Timeframe: Days 1 and 8: 1, 2, 4, 6, 8, 10, 24, 48, 72 hr Postdose

Interventionng*h/mL (Geometric Mean)
30 mg Dextromethorphan32.6
200 mg Abemaciclib + 30 mg Dextromethorphan32.1

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Pharmacokinetics: Area Under the Concentration Versus Time Curve [AUC(0-infinity)] of Midazolam

PK: AUC (zero to infinity) of midazolam after single dose of drug cocktail on Day 1 in Period 1 and in combination with Abemaciclib on Day 8 in Period 2. (NCT02688088)
Timeframe: Days 1 and 8: Predose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24 hr Postdose

Interventionng*h/mL (Geometric Mean)
0.2 mg Midazolam7.34
200 mg Abemaciclib + 0.2 mg Midazolam6.03

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Change in Beck Depression Inventory (BDI-II)

The self-report BDI-II will be used to assess severity of depressive symptoms. A higher score is associated with higher severity of depression. The score is interpreted as follows: 0-13 indicates minimal depression, 14-19 indicates mild depression, 20-28 indicates moderate depression and 29-63 indicates severe depression (NCT02727998)
Timeframe: Baseline, 7 days, 30 days and 90 days

,
Interventionscore on a scale (Mean)
BaselineEnd of Treatment (7 Days)30 Days Follow Up90 Days Follow Up
Midazolam With Prolonged Exposure47.639.936.536.8
Single Infusion of Ketamine With Prolonged Exposure48.538.943.042.8

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Change in PTSD Symptoms

"PTSD symptoms severity will be evaluated overtime using the PTSD Checklist for DSM-5 (PCL-5), a 20 items self-report measure. Items are scored 0-4 (0=not at all to 4=Extremely), thus total PCL-5 score ranges from 0 to 80. Higher scores reflect greater severity of PTSD.~Total PCL-5 scores are reported. PCL score>33 indicates probable PTSD diagnosis. Evidence for the PCL suggested 5 points reduction as a minimum threshold for determining whether an individual has responded to treatment and 10 points reduction in the PCL-5 as a minimum threshold for determining whether the improvement is clinically meaningful." (NCT02727998)
Timeframe: Baseline, 7 days, 30 days and 90 days

,
Interventionscore on a scale (Mean)
BaselineEnd of Treatment (7 days)30 Days Follow Up90 Days Follow Up
Midazolam With Prolonged Exposure44.435.128.528.7
Single Infusion of Ketamine With Prolonged Exposure48.829.532.734.2

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Length of Hospital Stay

Length of hospital stay (NCT02856698)
Timeframe: Up to 30 days

Interventiondays (Median)
Midazolam7
Morphine6

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Number of Participants That Required Invasive Mechanical Ventilation

(NCT02856698)
Timeframe: Up to 1 week

Interventionparticipants (Number)
Midazolam3
Morphine1

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In-hospital Mortality

In hospital mortality (NCT02856698)
Timeframe: 28 days after of the hospitalization

InterventionParticipants (Count of Participants)
Midazolam7
Morphine10

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Number of Participants With Bradycardia

Patients will be monitored for bradycardia which may be associated with sedation drug. Average heart rate before, during and after use of drug will be recorded for each patient. (NCT02903407)
Timeframe: One month or hospital discharge, whichever time point comes first

InterventionParticipants (Count of Participants)
Midazolam0
Propofol or Dexmedetomidine0

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In Hospital Mortality

All-cause mortality during the hospitalization (NCT02903407)
Timeframe: One month or hospital discharge, whichever time point comes first

Interventionparticipants (Number)
Midazolam1
Propofol or Dexmedetomidine1

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Intensive Care Unit Length of Stay

Number of days of admission to the CICU during the index hospitalization (NCT02903407)
Timeframe: One month or hospital discharge, whichever time point comes first

InterventionDays (Median)
Midazolam4.1
Propofol or Dexmedetomidine10.0

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Number of Days Alive During Admission and Free From Delirium or Coma

The number of days alive and free from delirium or coma during admission will be evaluated among patients with CAM-ICU documented (NCT02903407)
Timeframe: One month or hospital discharge, whichever time point comes first

InterventionDays (Median)
Midazolam14.0

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Number of Days From Decision to Extubate to True Extubation

The time (in days) from when the clinical care team documents a decision to pursue extubation until the time the patient was extubated (NCT02903407)
Timeframe: One month or hospital discharge, whichever time point comes first

InterventionDays (Median)
Midazolam0
Propofol or Dexmedetomidine0

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Number of Participants Requiring Reintubation

Following ICU discharge, patient charts will be reviewed to evaluate whether they required reintubation. If so, will determine whether necessity of reintubation was related to delirium. (NCT02903407)
Timeframe: One month or hospital discharge, whichever time point comes first

InterventionParticipants (Count of Participants)
Midazolam0
Propofol or Dexmedetomidine1

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Number of Participants With Increased Vasopressor Requirement

Patients will be monitored for increased pressor requirement during the CICU stay (NCT02903407)
Timeframe: One month or hospital discharge, whichever time point comes first

InterventionParticipants (Count of Participants)
Midazolam2
Propofol or Dexmedetomidine2

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Number of Ventilator Days

Days requiring mechanical ventilation during the initial episode of intubation during the hospitalization (NCT02903407)
Timeframe: One month or hospital discharge, whichever time point comes first

InterventionDays (Median)
Midazolam2.5
Propofol or Dexmedetomidine6.8

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Pain Management

Will use the CPOT (Critical-Care Pain Observation Tool) score to assess pain level as per standard of care by nurses in the CICU. The CPOT has a range of 0 to 8. A CPOT score of ≤ 2 = minimal to no pain present and >2 = unacceptable level of pain. Data that is recorded will be evaluated following discharge. (NCT02903407)
Timeframe: One month or hospital discharge, whichever time point comes first

Interventionscore on a scale (Median)
Midazolam0.0
Propofol or Dexmedetomidine0.0

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Number of Participants With Delirium

Will use the Confusion Assessment Method for the ICU (CAM-ICU) to assess presence of delirium as per standard of care by nurses in the CICU. Patients with CAM-ICU data recorded will be included. (NCT02903407)
Timeframe: One month or hospital discharge, whichever time point comes first

InterventionParticipants (Count of Participants)
Midazolam1

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Percentage of Time at Goal Sedation

Will use RASS (Richmond Agitation and Sedation Scale) to assess level of sedation as per standard of care by nurses in the CICU. Data that is recorded will be evaluated following discharge. The RASS ranges from -5 (unrousable) to +4 (combative) and 0 (zero) = alert and calm and goal sedation is considered a RASS level of 0 to -2. (NCT02903407)
Timeframe: One month or hospital discharge, whichever time point comes first

Interventionpercentage of time (Median)
Midazolam63.3
Propofol or Dexmedetomidine63.2

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Time From Withdrawal of Sedation to ICU Discharge

The duration, in days, from withdrawal of sedation for mechanical ventilation until the time of discharge from the ICU (NCT02903407)
Timeframe: One month or hospital discharge, whichever time point comes first

InterventionDays (Median)
Midazolam1.6
Propofol or Dexmedetomidine5.6

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Hospital Length of Stay

Index hospitalization length of stay in days (NCT02903407)
Timeframe: One month or hospital discharge, whichever time point comes first

InterventionDays (Median)
Midazolam19.5
Propofol or Dexmedetomidine30.0

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Pharmacokinetics (PK): Maximum Observed Drug Concentration (Cmax) of CYP450 Substrate-Omeprazole and Its Metabolite 5-Hydroxyomeprazole

Pharmacokinetics (PK): Maximum Observed Drug Concentration (Cmax) of CYP450 Substrate (Omeprazole and its metabolite 5-Hydroxyomeprazole) (NCT02993471)
Timeframe: Predose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, and 48 hours postdose

,,
Interventionng/mL (Geometric Mean)
Omeprazole5-Hydroxyomeprazole
160 mg Ixekizumab + 20 mg Omeprazole340143
20 mg Omeprazole333148
80 mg Ixekizumab Q2W + 20 mg Omeprazole368137

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Pharmacokinetics (PK): Maximum Observed Drug Concentration (Cmax) of CYP450 Substrate-Caffeine

Pharmacokinetics (PK): Maximum Observed Drug Concentration (Cmax) of CYP450 Substrate (Caffeine) (NCT02993471)
Timeframe: Predose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, and 48 hours postdose

Interventionng/mL (Geometric Mean)
100 mg Caffeine2230
160 mg Ixekizumab + 100 mg Caffeine2220
80 mg Ixekizumab Q2W + 100 mg Caffeine2240

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Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Zero to 48 Hours (AUC[0-48h]) of CYP450 Substrate-Caffeine

Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve from Zero to 48 hours (AUC[0-48h]) of CYP450 Substrate (Caffeine) (NCT02993471)
Timeframe: Predose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, and 48 hours postdose

Interventionng*h/mL (Geometric Mean)
100 mg Caffeine25000
160 mg Ixekizumab + 100 mg Caffeine22400
80 mg Ixekizumab Q2W + 100 mg Caffeine22400

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Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Zero to Infinity (AUC[0-∞]) of CYP450 Substrate-Dextromethorphan

Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve from Zero to Infinity (AUC[0-∞]) of CYP450 Substrate (Dextromethorphan) (NCT02993471)
Timeframe: Predose, 1, 2, 4, 6, 8, 10, 24, 48, and 72 hours postdose

Interventionng*h/mL (Geometric Mean)
30 mg Dextromethorphan11.7
160 mg Ixekizumab + 30 mg Dextromethorphan12.6
80 mg Ixekizumab Q2W + 30 mg Dextromethorphan8.53

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Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Zero to Infinity (AUC[0-∞]) of CYP450 Substrate-Midazolam

Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve from Zero to Infinity (AUC[0-∞]) of CYP450 Substrate (Midazolam) (NCT02993471)
Timeframe: Predose, 0.5, 1, 2, 3, 4, 6, 8, 12, and 24 hours postdose

Interventionnanogram*hour per milliliter (ng*h/mL) (Geometric Mean)
1 mg Midazolam16.6
160 mg Ixekizumab + 1 mg Midazolam15.9
80 mg Ixekizumab Q2W + 1 mg Midazolam15.4

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Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Zero to Infinity (AUC[0-∞]) of CYP450 Substrate-Warfarin

Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve from Zero to Infinity (AUC[0-∞]) of CYP450 Substrate (Warfarin) (NCT02993471)
Timeframe: Predose, 1, 2, 4, 6, 8, 10, 24, 48, 72, and 96 hours postdose

Interventionng*h/mL (Geometric Mean)
10 mg Warfarin17600
160 mg Ixekizumab + 10 mg Warfarin17700
80 mg Ixekizumab Q2W + 10 mg Warfarin16200

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Pharmacokinetics (PK): Maximum Observed Drug Concentration (Cmax) of CYP450 Substrate-Dextromethorphan

Pharmacokinetics (PK): Maximum Observed Drug Concentration (Cmax) of CYP450 Substrate (Dextromethorphan) (NCT02993471)
Timeframe: Predose, 1, 2, 4, 6, 8, 10, 24, 48, and 72 hours postdose

Interventionng/mL (Geometric Mean)
30 mg Dextromethorphan0.691
160 mg Ixekizumab + 30 mg Dextromethorphan0.878
80 mg Ixekizumab Q2W + 30 mg Dextromethorphan0.658

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Pharmacokinetics (PK): Maximum Observed Drug Concentration (Cmax) of CYP450 Substrate-Warfarin

Pharmacokinetics (PK): Maximum Observed Drug Concentration (Cmax) of CYP450 Substrate (Warfarin) (NCT02993471)
Timeframe: Predose, 1, 2, 4, 6, 8, 10, 24, 48, 72, and 96 hours postdose

Interventionng/mL (Geometric Mean)
10 mg Warfarin510
160 mg Ixekizumab + 10 mg Warfarin525
80 mg Ixekizumab Q2W + 10 mg Warfarin510

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Pharmacokinetics (PK): Maximum Observed Drug Concentration (Cmax) of Cytochrome P450 (CYP450) Substrate-Midazolam

Pharmacokinetics (PK): Maximum Observed Drug Concentration (Cmax) of Cytochrome P450 (CYP450) Substrate (Midazolam) (NCT02993471)
Timeframe: Predose, 0.5, 1, 2, 3, 4, 6, 8, 12, and 24 hours postdose

Interventionnanogram per milliliter (ng/mL) (Geometric Mean)
1 mg Midazolam4.56
160 mg Ixekizumab + 1 mg Midazolam4.92
80 mg Ixekizumab Q2W (Once Every Two Weeks) + 1 mg Midazolam4.83

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Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Zero to Infinity (AUC[0-∞]) of CYP450 Substrate-Omeprazole and Its Metabolite 5-Hydroxyomeprazole

Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve from Zero to Infinity (AUC[0-∞]) of CYP450 Substrate (Omeprazole and its metabolite 5-Hydroxyomeprazole) (NCT02993471)
Timeframe: Predose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, and 48 hours postdose

,,
Interventionng*h/mL (Geometric Mean)
Omeprazole5-Hydroxyomeprazole
160 mg Ixekizumab + 20 mg Omeprazole829475
20 mg Omeprazole1060519
80 mg Ixekizumab Q2W + 20 mg Omeprazole913455

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Postoperative Discomfort and Needs (Post-op Pain, Sore Throat, Back Pain, Nausea, Cold, Hunger, Thirst)

Leiden Perioperative Care Patient Satisfaction questionnaire (LPPSq) score. Performed at 1 hour postoperatively. To what degree did patients have the following symptoms. Rated 1-5, 1 being not at all. 5 being extremely. (NCT02996591)
Timeframe: 1 hour after surgery

,
Interventionscore on a scale (Mean)
PainA Sore ThroatBack PainVomitingColdHungerThirst
General Anesthesia With Popliteal and Adductor Canal Blocks.1.61.61.211.31.72.5
Spinal Anesthesia With Popliteal and Adductor Canal Blocks.1.11.21.211.41.92.7

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Cognitive Recovery on POD1

Postoperative Quality Recovery Scale Cognitive Domain questionnaire. Asked on postoperative day 1. Either yes (return to pre-operative cognitive function levels) or no (not yet returned to pre-operative function levels) (NCT02996591)
Timeframe: Postoperative day 1

,
InterventionParticipants (Count of Participants)
NoYes
General Anesthesia With Popliteal and Adductor Canal Blocks.215
Spinal Anesthesia With Popliteal and Adductor Canal Blocks.314

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Cognitive Recovery at 2 Hours Post-operative

Postoperative Quality Recovery Scale Cognitive Domain questionnaire. Asked at 2 hour post-operatively. Either yes (return to pre-operative cognitive function levels) or no (not yet returned to pre-operative function levels) (NCT02996591)
Timeframe: 2 hours after PACU admission

,
InterventionParticipants (Count of Participants)
NoYes
General Anesthesia With Popliteal and Adductor Canal Blocks.413
Spinal Anesthesia With Popliteal and Adductor Canal Blocks.116

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Incidence of Transient Neurologic Symptoms

(NCT02996591)
Timeframe: Postoperative day 1 and if present, monitored until resolution

,
InterventionParticipants (Count of Participants)
NormalTransient Neurological Symptoms
General Anesthesia With Popliteal and Adductor Canal Blocks.180
Spinal Anesthesia With Popliteal and Adductor Canal Blocks.180

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Back Pain on POD1

Back pain (yes/no) on POD1 (NCT02996591)
Timeframe: Postoperative day 1

,
InterventionParticipants (Count of Participants)
NoYes
General Anesthesia With Popliteal and Adductor Canal Blocks.143
Spinal Anesthesia With Popliteal and Adductor Canal Blocks.162

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Time Until Patient is Ready for Discharge From Post-Anesthesia Care Unit (PACU) to Home.

Modified Aldrete Scoring System and Marshall and Chung Postanesthesia Discharge Scoring System, measured in time until discharge criteria is met (in minutes) (NCT02996591)
Timeframe: Duration of stay in recovery room after surgery

InterventionMinutes (Mean)
Spinal Anesthesia With Popliteal and Adductor Canal Blocks.81
General Anesthesia With Popliteal and Adductor Canal Blocks.43.5

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Numerical Rating Scale Pain Scores at 2 Hours Postop

Numerical rating scale pain score as reported by the patient at 2 hours post-operatively. Rated on a scale of 0 (no pain) to 10 (worst pain imaginable). (NCT02996591)
Timeframe: 2 hours after PACU admission

Interventionunits on a scale (Mean)
Spinal Anesthesia With Popliteal and Adductor Canal Blocks..4
General Anesthesia With Popliteal and Adductor Canal Blocks..9

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Postoperative Discomfort and Needs (Post-op Pain, Sore Throat, Back Pain, Nausea, Cold, Hunger, Thirst)

Leiden Perioperative Care Patient Satisfaction questionnaire (LPPSq). From 1-5. 1 being not at all. 5 being extremely. (NCT02996591)
Timeframe: Postoperative day 1

,
Interventionscore on a scale (Mean)
PainSore ThroatBack PainVomitingColdHungerThirst
General Anesthesia With Popliteal and Adductor Canal Blocks.1.51.51.2111.72.2
Spinal Anesthesia With Popliteal and Adductor Canal Blocks.1.41.21.111.31.42.3

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Postoperative Discomfort and Needs (Post-op Pain, Sore Throat, Back Pain, Nausea, Cold, Hunger, Thirst)

Rating the Nausea/Vomiting of patients post-operatively. (NCT02996591)
Timeframe: 2 hours after surgery

,
Interventionscore on a scale (Mean)
PainSore ThroatBack PainVomitingColdHungerThirst
General Anesthesia With Popliteal and Adductor Canal Blocks.1.41.61.211.11.21.8
Spinal Anesthesia With Popliteal and Adductor Canal Blocks.1.21.21.111.11.42.1

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Opioid Consumption Through First Postoperative Day. Measured in mg OME

(NCT02996591)
Timeframe: Postoperative day 1

Interventionmg OME (Mean)
Spinal Anesthesia With Popliteal and Adductor Canal Blocks.8.3
General Anesthesia With Popliteal and Adductor Canal Blocks.11

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Opioid Consumption

Opioid consumption (mg OME) during inpatient stay (NCT02996591)
Timeframe: Duration of stay in recovery room after surgery (average 2 hours)

Interventionmg OME (Mean)
Spinal Anesthesia With Popliteal and Adductor Canal Blocks.2.2
General Anesthesia With Popliteal and Adductor Canal Blocks.5

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Numerical Rating Scale Pain Scores on Postoperative Day (POD) 1

Numerical Rating Scale Pain from 0-10. 0 being no pain at all. 10 being the worst pain imaginable. (NCT02996591)
Timeframe: 24 hours after surgery

Interventionscore on a scale (Mean)
Spinal Anesthesia With Popliteal and Adductor Canal Blocks.1
General Anesthesia With Popliteal and Adductor Canal Blocks.1

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Assessment of Patient Blinding to Group Assignment

Patients will be asked whether they believe they were in the general anesthesia or spinal anesthesia group. These responses are then validated using the Bang Blinding Index, which either confirms or refutes the validity of the blinding. The scale runs from -1 to 1, with a score of 0 indicating complete blinding, -1 indicating opposite guessing of groups, and 1 indicating a complete lack of blinding. (NCT02996591)
Timeframe: Postoperative day 1

InterventionBang blinding index (Number)
Spinal Anesthesia With Popliteal and Adductor Canal Blocks..588
General Anesthesia With Popliteal and Adductor Canal Blocks..722

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Nausea Intensity

Nausea intensity ranked on NRS score following PACU admission to 2 hours after discharge. Scored from 0-10. 0 Being no nausea, 10 being worst nausea imaginable. (NCT02996591)
Timeframe: 2 hours after PACU admission

Interventionscore on a scale (Mean)
Spinal Anesthesia With Popliteal and Adductor Canal Blocks.0
General Anesthesia With Popliteal and Adductor Canal Blocks.0

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Numerical Rating Scale (NRS) Pain Scores at 1 Hour Postop

NRS Pain scores at 1 hour after surgery. Rated on a scale of 0 (no pain) to 10 (worst pain imaginable). (NCT02996591)
Timeframe: 1 hour after PACU admission

Interventionunits on a scale (Mean)
Spinal Anesthesia With Popliteal and Adductor Canal Blocks.0
General Anesthesia With Popliteal and Adductor Canal Blocks.1.8

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PACU Length of Stay

This is obtained from the records as time spent in the PACU (Recovery Room) after surgery. (NCT03054103)
Timeframe: This will occur one time only, in a range of 20 to 30 minutes after the surgery is completed.

InterventionMinutes (Mean)
Midazolam Alone19.2
Midazolam + Ketamine 5 mg19.0
Midazolam + Ketamine 10 mg20.1

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Nausea

Self-reported incidence of nausea. This will be assessed by asking the subjects once (just prior to discharge from the PACU) whether they experienced any nausea while they were in the PACU (Recovery Room) and will be a measurement of the count of participants that experienced nausea during this period (NCT03054103)
Timeframe: This will occur from time of entry into PACU to time of departure after their surgery. (One time only, in a range of 20 to 30 minutes after surgery.

InterventionParticipants (Count of Participants)
Midazolam Alone0
Midazolam + Ketamine 5 mg0
Midazolam + Ketamine 10 mg0

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Parental Satisfaction

If my child needed medications to stay calm for a procedure, I would like to use these same medications again. (NCT03054844)
Timeframe: 1 minute

InterventionParticipants (Count of Participants)
PREMED10
PREMIX12

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Procedural Distress, Cry Duration

Cry duration was measured in seconds and defined as the time from onset of crying following administration of an IN medication until the cessation of crying sounds and/or tears. If a patient did not cry, the cry duration was zero (NCT03054844)
Timeframe: 10 minutes

Interventionseconds (Mean)
PREMED84
PREMIX73

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Procedural Distress, FLACC

The Faces, Legs, Activity, Cry, Consolability (FLACC) scale is comprised of five criteria (face, legs, activity, cry, consolability), with a possible score of 0 to 2 units on a scale for each criteria and a possible total score of 0 to 10 units on a scale (0 meaning no pain, 10 meaning most pain). (NCT03054844)
Timeframe: 10 minutes

InterventionUnits on a scale (Mean)
PREMED6.7
PREMIX7

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Procedural Distress, OSBD-R

The Observational Scale of Behavioral Distress-Revised (OSBD-R) is an observational measure of pain and distress shown to have strong validity in children. The scale is an 8-factor, weighted observational scale used to measure distress associated with medical procedures, which has been validated in children and adults aged 1 to 20 years. The total Observational Scale of Behavioral Distress-Revised score is the sum of the scale scores for each phase, with each phase assigned a score from 0 to 23.5 units on a scale (0=no distress, 23.5=maximum distress), based on the frequency and types of behaviors observed during a predetermined number of 15-second intervals during each phase. There were four phases so the range of scores for the total OSBD-R was 0 to 94 units on a scale, with a higher score indicated a greater degree of distress. (NCT03054844)
Timeframe: 10 minutes

InterventionUnits on a scale (Mean)
PREMED6.4
PREMIX7

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Provider Satisfaction

I would like to use this method of administering intranasal midazolam and lidocaine again in the future (NCT03054844)
Timeframe: 1 minute

InterventionParticipants (Count of Participants)
PREMED8
PREMIX24

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Procedural Pain

The Children's Hospital of Eastern Ontario Pain Scale (CHEOPS) utilizes six observational factors (cry, facial, verbal, torso, touch, and legs) to evaluate pain in young children and can be used to monitor the effectiveness of interventions for reducing the pain and discomfort of an intervention. This scale rates each behavior numerically, with a score of 4-6 units on a scale representing no pain, and a maximum score of 13 units on a scale representing (most pain perceived). (NCT03054844)
Timeframe: 10 minutes

InterventionUnits on a scale (Mean)
PREMED10.6
PREMIX10.5

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Evaluation of Difficulties in Communication From Provider to Patient and Patient to Provider

"surveyed on a 5-point Likert scale~Scale ranges from 1 to 5; the higher the number, the more difficult it is to communicate." (NCT03069677)
Timeframe: immediately after nerve block placement (less than 1 minute after)

,
Interventionscore on a scale (Median)
Patient Perspective on CommunicationPhysician Perspective on Communication
Midazolam Group11
Music Group11

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Block Times

differences amongst music and midaz group (NCT03069677)
Timeframe: immediately after nerve block placement (less than 1 minute after)

Interventionminutes (Mean)
Music Group6.7
Midazolam Group7

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Change in STAI-6 Scores From Post to Pre.

"Spielberger State-Trait Anxiety Inventory 6~Scale range is from 20 to 80. Higher the score, the higher the anxiety level is." (NCT03069677)
Timeframe: 1-2 minutes before conducting golden moment for nerve block placement and immediately after nerve block placement (less than 1 minute after)

Interventionscore on a scale (Mean)
Music Group-1.6
Midazolam Group-4.2

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Patient Satisfaction Scores of the Experience During Procedure

"survey which assess satisfaction on a 10-point numeric rating scale~Scale ranges from 0 to 10. A higher number indicates a higher satisfaction" (NCT03069677)
Timeframe: immediately after nerve block placement (less than 1 minute after)

Interventionunits on a scale (Median)
Music Group8
Midazolam Group9

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Provider Satisfaction Scores of the Experience During Procedure

"survey which assess satisfaction on a 10-point numeric rating scale~Scale ranges from 0 to 10. A higher number indicates a higher satisfaction" (NCT03069677)
Timeframe: immediately after nerve block placement (less than 1 minute after)

Interventionunits on a scale (Median)
Music Group9
Midazolam Group10

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Anxiety Levels

"Spielberger State-Trait Anxiety Inventory 6~Scale range is from 20 to 80. Higher the score, the higher the anxiety level is." (NCT03069677)
Timeframe: 1-2 minutes before conducting golden moment for nerve block placement and immediately after nerve block placement (less than 1 minute after)

,
Interventionscore on a scale (Median)
Pre-STAI-6 ScoresPost-STAI-6 Scores
Midazolam Group3023.3
Music Group33.330

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The C-reactive Protein (CRP) Quantitative Titer Daily as Part of the Routine Clinical Care as a Prognostic Factor for Delirium (mg/L)

(NCT03078946)
Timeframe: The maximum serum CRP level during the ICU stay was designated as max-CRP on day 7 post-surgery

Interventionmg/L (Mean)
Dexmedetomidine Group (N=30)127.1
Morphine With Midazolam (N=30)101

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The Incidence of Delirium (Number of Patients (in Digits))

(NCT03078946)
Timeframe: Delirium was reported on day 7 post-surgery

Interventionparticipants (Number)
Dexmedetomidine Group (N=30)1
Morphine With Midazolam (N=30)2

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Change in Quality of Life as Measured by the Veterans RAND12 Questionnaire Mental Health Summary Measure

"The 12 items in the questionnaire correspond to eight principal physical and mental health domains including general health perceptions; physical functioning; role limitations due to physical and emotional problems; bodily pain; energy-fatigue, social functioning and mental health. The 12 items are summarized into two scores, a Physical Health Summary Measure (PCS) and a Mental Health Summary Measure (MCS).~The higher the score the better quality of life.~Scores are standardized to a mean of 50 with a range of -1.465-77.09." (NCT03084536)
Timeframe: At baseline and 1 year post-surgery

Interventionscore on a scale (Median)
Preoperative PECS Blocks0
Placebo PECS Blocks1.9

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Change in Quality of Life as Measured by the Veterans RAND12 Questionnaire Physical Health Summary Measure

"The 12 items in the questionnaire correspond to eight principal physical and mental health domains including general health perceptions; physical functioning; role limitations due to physical and emotional problems; bodily pain; energy-fatigue, social functioning and mental health. The 12 items are summarized into two scores, a Physical Health Summary Measure (PCS) and a Mental Health Summary Measure (MCS).~The higher the score the better quality of life.~Scores are standardized to a mean of 50 with a range of -0.809-70.71." (NCT03084536)
Timeframe: At baseline and 1 year post-surgery

Interventionscore on a scale (Median)
Preoperative PECS Blocks-3.1
Placebo PECS Blocks-0.8

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Interference as Measured by the Brief Pain Inventory (BPI) at 1 Year

"The participant is asked circle the one number that describes how much, during the past week pain has interfered with general activity, mood, walking ability, normal work (includes both work outside the home and housework), relations with other people, sleep, and enjoyment of life.~0=does not interference and 10 = completely interferes. The higher number indicates more interference from pain.~The scores for each subsection will be averaged." (NCT03084536)
Timeframe: At 1 year

Interventionscore on a scale (Median)
Preoperative PECS Blocks0
Placebo PECS Blocks0

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Worst Pain as Measured by the Brief Pain Inventory (BPI) at 1 Year

"The participant is asked to rate their pain by circling the one number that best describes their pain at its worst in the past week.~0=no pain and 10 = pain as bad as they can imagine. The higher number indicates worse pain." (NCT03084536)
Timeframe: At 1 year

Interventionscore on a scale (Median)
Preoperative PECS Blocks0
Placebo PECS Blocks0

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Average Pain as Measured by the Brief Pain Inventory (BPI) at 1 Year

"The participant is asked to rate their pain by circling the one number that best describes their pain on the average.~0=no pain and 10 = pain as bad as they can imagine. The higher number indicates worse pain." (NCT03084536)
Timeframe: At 1 year

Interventionscore on a scale (Median)
Preoperative PECS Blocks0
Placebo PECS Blocks0

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Patient/Parent and Provider Satisfaction With Sedation and Anxiolytic/Sedative.

"Patient/parent satisfaction will be assessed for all patients; child satisfaction will be assessed for patients over 12 years of age. Satisfaction will be measured on a scale of 1 to 5 (1 being not satisfied and 5 being very satisfied). Specifically, parents (and children when applicable) will be asked how satisfied with the means of sedation were you for the procedure performed. Research assistants will then ask the ED providers on a scale of 1 to 5 (1 being not satisfied and 5 being very satisfied) how satisfied with the means of sedation were you for the procedure performed." (NCT03085563)
Timeframe: Time of discharge, Approximately 2 hours

,
Interventionscore on a scale (Median)
Parent/PatientProvider
Intranasal Midazolam54.5
Nitrous Oxide55

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Adverse Events.

Number of adverse events observed. Adverse events will be classified and defined as hypoxia, need for administration of reversal agent, nausea, vomiting, paradoxical reaction, airway obstruction, laryngospasm, inadequate sedation, allergic reaction, and cardiac arrest. (NCT03085563)
Timeframe: Time of discharge, Approximately 2 hours

,
InterventionAdverse Events (Number)
hypoxianeed for administration of reversal agentnausea, vomitingparadoxical reactionairway obstructionlaryngospasminadequate sedationallergic reactioncardiac arrest
Intranasal Midazolam300100000
Nitrous Oxide000000000

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ED Length of Stay After Intranasal Midazolam or Nitrous Oxide Administration

The total length of Emergency Department (ED) stay will be defined as time from intranasal midazolam or nitrous oxide administration to time of discharge readiness, collected by the research assistants. Additional time periods measured will include: time from anxiolytic/sedative given to time of procedure completion, and total time for recovery. (NCT03085563)
Timeframe: From administration of intranasal midazolam or nitrous oxide, assessed over an estimated time of 2 hours.

,
Interventionminutes (Median)
Time from intranasal midazolam or nitrous oxide administration to time of discharge readinessTime from anxiolytic/sedative given to time of procedure completionTotal time for recovery
Intranasal Midazolam18.5108.5
Nitrous Oxide24.5915.5

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Surgeon Satisfaction

Surgeon satisfaction will be determined by completion of a 5 question satisfaction survey. The responses to each question will be graded on a scale from 1 to 6: 1 being the least satisfied and 6 being the most satisfied. After all answers are graded for one survey, they will be averaged to give an overall survey grade on the 1 to 6 scale per surgeon Higher mean scores are associated with higher levels of satisfaction. (NCT03246724)
Timeframe: The surgeon satisfaction survey will be administered immediately after the completion of the surgery. .

Interventionscore on a scale (Mean)
Cataract Procedures5.28
Retina Procedures5.57
Cornea Procedures5.34
Glaucoma Procedures4.6

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Surgical Complication Rates

The number of subjects in each arm that experienced a complication during the operative procedure after the initial sedation. (NCT03246724)
Timeframe: Information regarding surgical complications will be collected within 2 days of completion of the subjects surgical procedure.

InterventionParticipants (Count of Participants)
Cataract Procedures11
Retina Procedures8
Cornea Procedures1
Glaucoma Procedures6

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Patient Satisfaction

Patient satisfaction will be determined by completion of a 12 question satisfaction survey. The responses to each question will be graded on a scale from 1 to 6: 1 being the least satisfied and 6 being the most satisfied. After all answers are graded for one survey, they will be averaged to give an overall survey grade on the 1 to 6 scale per patient. Higher mean scores are associated with higher levels of satisfaction. (NCT03246724)
Timeframe: The patient satisfaction survey was administered up to two days after surgery.

Interventionscore on a scale (Mean)
Cataract Procedures5.37
Retina Procedures5.23
Cornea Procedures5.37
Glaucoma Procedures5.05

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Number of Participants Requiring Additional Anesthesia Intervention

The number of subjects in each arm that received additional anesthetic agents during the operative procedure after the initial sedation. (NCT03246724)
Timeframe: Information regarding additional anesthesia intervention will be collected within 2 days of completion of the subjects surgical procedure.

InterventionParticipants (Count of Participants)
Cataract Procedures11
Retina Procedures8
Cornea Procedures11
Glaucoma Procedures16

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Anesthesiologist/Certified Registered Nurse Anesthetist (CRNA) Satisfaction

Anesthesiologist/CRNA satisfaction will be determined by completion of a 5 question satisfaction survey. The responses to each question will be graded on a scale from 1 to 6: 1 being the least satisfied and 6 being the most satisfied. After all answers are graded for one survey, they will be averaged to give an overall survey grade on the 1 to 6 scale per anesthesiologist/CRNA. Higher mean scores are associated with higher levels of satisfaction. (NCT03246724)
Timeframe: The anesthesiologist/CRNA satisfaction survey will be administered immediately after the completion of the surgical case.

Interventionscore on a scale (Mean)
Cataract Procedures5.16
Retina Procedures5.14
Cornea Procedures5.33
Glaucoma Procedures4.9

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Reaction to Administration of Local Anesthesia

"To compare the groups regarding movement of the patient during the first injection of local anesthesia during the IVS at time of injection measured using the Behavioral Pain Scale - Non-Intubated patients.~The minimum value is 3 and the maximum value is 12. Higher scores mean a worse outcome (i.e., more pain and movement on injection)" (NCT03255824)
Timeframe: During the first injection of local anesthesia during surgery

Interventionscore on a scale (Mean)
Propofol Group3.9
Dexmedetomidine Group4.2

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Postoperative Recovery Time - Time to Discharge

"To assess whether a D/M combination increases postoperative recovery time when compared the MFP combination.~a. Time to discharge or virtual discharge (comparative statistic) - Aldrete score of ≥ 9 or pre-procedure score is met The minimum score is 0 and the maximum score is 10. A higher score indicates wakefulness, hemodynamically stable, and able to ambulate.~ii. All subjects are required to stay a minimum of 30 minutes after the end of the procedure. Therefore, at least two postoperative vital sign readings will be obtained. If the subject meets discharge criteria prior to 30 minutes, this time will be the virtual discharge time" (NCT03255824)
Timeframe: After the procedure until discharge, up to 45 minutes

Interventionminutes (Mean)
Propofol Group26.5
Dexmedetomidine Group29.9

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Postoperative Recovery Time - Duration of Procedure

"To assess whether a D/M combination increases postoperative recovery time when compared the MFP combination.~a. Duration of procedure will be recorded" (NCT03255824)
Timeframe: During the procedure, up to 40 minutes

InterventionMINUTES (Mean)
Propofol Group24.2
Dexmedetomidine Group22.1

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Postoperative Recovery Time - Ambulation

"To assess whether a D/M combination increases postoperative recovery time when compared the MFP combination.~a. Time to ambulation (to recovery room) will be recorded" (NCT03255824)
Timeframe: After the procedure until ambulation, up to 20 minutes

Interventionminutes (Mean)
Propofol Group10.8
Dexmedetomidine Group11.6

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Patient Satisfaction

"Visual Analog Scale was used to measure overall satisfaction with the IV sedation and memory of the procedure.~The minimum score is 0 (not satisfied at all) to a maximum score of 100 (completely satisfied).~A higher score is a better outcome." (NCT03255824)
Timeframe: 30 minutes following surgery

Interventionscore on a scale (Mean)
Propofol Group93.5
Dexmedetomidine Group86.6

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Hemodynamic Stability - Heart Rate

"To compare the differences in hemodynamic stability using a D/M combination compared to the MFP combination. (In this study, a deviation from baseline of both the blood pressure and heart rate by 20% or greater will be considered clinically significant)~a. Change in heart rate (change ≥ 20 BPM)" (NCT03255824)
Timeframe: During the procedure, up to 40 minutes

Interventionbeats per minute (Mean)
Propofol Group77
Dexmedetomidine Group62

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Respiratory Depression - Respiratory Rate

"To assess whether a D/M combination leads to a significant change in respiratory depression compared to the MFP combination.~a. Change in respiratory rate (change ≥ 20%)" (NCT03255824)
Timeframe: During the procedure, up to 40 minutes

Interventionbreaths per minute (Mean)
Propofol Group18
Dexmedetomidine Group18

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Respiratory Events Requiring Intervention

To compare the groups regarding the number of respiratory events requiring intervention, described as: Chin lift/jaw thrust, Tongue thrust, Yankauer suctioning, Positive pressure oxygen administration, Placement of an oral or nasal airway. (NCT03255824)
Timeframe: During surgery

InterventionParticipants (Count of Participants)
Propofol Group17
Dexmedetomidine Group2

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Surgeon Satisfaction - Survey

"Surgeon satisfaction was measured by the surgeon grading the Operating Conditions scale.~The minimum value was 0 and the maximum was 3. 0=very poor, 1=poor, 2=fair, 3=good" (NCT03255824)
Timeframe: 15 minutes following surgery

Interventionscore on a scale (Mean)
Propofol Group2.8
Dexmedetomidine Group2.9

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Cooperation Scale

Surgeon satisfaction is measured by the Cooperation Scale. Minimum score of 0 and maximum of 9. Higher indicates a worse outcome (i.e., discomfort and movement) (NCT03255824)
Timeframe: 15 minutes following surgery

Interventionscore on a scale (Mean)
Propofol Group2.07
Dexmedetomidine Group1.47

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Hemodynamic Stability - Blood Pressure

"To compare the differences in hemodynamic stability using a D/M combination compared to the MFP combination. (In this study, a deviation from baseline by 20% or greater will be considered clinically significant)~a. Change in blood pressure (NIBP) (change ≥ 20%) Blood pressure is presented as mean arterial pressure" (NCT03255824)
Timeframe: During the procedure, up to 40 minutes

Interventionmm Hg (Mean)
Propofol Group78
Dexmedetomidine Group88

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Respiratory Depression - Oxygen Saturation

"To assess whether a D/M combination leads to a significant change in respiratory depression compared to the MFP combination.~a. Change in arterial oxygen saturation (as measured by pulse oximeter) i. number of events of ≤92%" (NCT03255824)
Timeframe: During the procedure, up to 40 minutes

InterventionSaturation percent (Mean)
Propofol Group98.7
Dexmedetomidine Group98.9

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The Brief Psychiatric Rating Scale (BPRS)

"The BPRS measures psychotomimetic effects. The investigators will use the positive symptoms subscale of the Brief Psychiatric Rating Scale. The 4-item positive symptoms subscale measures suspiciousness, hallucinations, unusual thought content, and conceptual disorganisation. Each question is scored between 0-7. The maximum score in this 4-item questionnaire is 28. Higher scores indicate more severe psychotic symptoms.~Participants will have the BPRS performed before, during (+30mins) and after (+60mins) each of the four once-weekly infusions." (NCT03256162)
Timeframe: 4 weeks

Interventionscore on a scale (Mean)
Ketamine4.1
Midazolam4.0

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The Clinician-Administered Dissociative States Scale (CADSS)

"The CADSS measures dissociative symptoms. It will be administered before, during and after infusions in order to capture the range of possible subjective side effects of either agent. This consists of 23 questions and scores for each question range from 0-4. The maximum score is 92 with higher scores indicating more dissociative symptoms.~Participants will have the CADSS performed before, during (+30mins) and after (+60mins) each of the four once-weekly infusions." (NCT03256162)
Timeframe: 4 weeks

Interventionscore on a scale (Mean)
Ketamine5.3
Midazolam2.5

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The Quick Inventory of Depressive Symptoms, Self-report Version (QIDS-SR16)

"The QIDS-SR16 is a validated self-report measure of depressive symptoms. This consists of 16 questions rated 0-3. Its score range is 0-48, with higher scores reflecting greater burden of depressive symptoms.~Participants will have a baseline (T0) QIDS-SR16 score. This will be repeated one week after each of four once-weekly infusions (T1-4) and follow-up measures after another five (T9) and 11 (T15) weeks. Week 15 scores are reported." (NCT03256162)
Timeframe: 15 weeks

Interventionscore on a scale (Mean)
Ketamine9.1
Midazolam11.4

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The Patient-Rated Inventory of Side Effects (PRISE)

"The PRISE will be used to document other general adverse events by patients before, during and after infusions. This is a patient self-report used to qualify side effects by identifying and evaluating the tolerability of each symptom. It is a 9 item assessment of the side effects in the following symptom domains; Gastrointestinal, Heart, Skin, Nervous System, Eyes/Ears, Genital/Urinary, Sleep, Sexual Functioning, and Other. Each domain has multiple symptoms which can be endorsed. For each domain the patient rates whether or not the symptoms are tolerable or distressing. Data below represent the number of participants from which there was an endorsement of each listed event.~Participants will have the PRISE performed before, during (+30mins) and after (+60mins) each of the four once-weekly infusions." (NCT03256162)
Timeframe: 4 weeks

,
Interventionparticipants (Number)
dry mouthdiarrhoeaConstipationNausea / vomitingPalpitationChest painRashHeadacheTremorsPoor coordinationDizzinessBlurred visionDifficulty urinatingDifficulty sleepingSleeping too muchAnxietyPoor concentrationRestlessnessFatigue
Ketamine1000000001200002023
Midazolam1000000000000010101

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Young Mania Rating Scale (YMRS; Mood Item)

"Investigators will use the mood item of them YMRS to assess for psychotomimetic effects. This item is rated 0-4. The higher scores reflect elevated mood.~Participants will have the YMRS performed before, during (+30mins) and after (+60mins) each of the four once-weekly infusions." (NCT03256162)
Timeframe: 4 weeks

Interventionscore on a scale (Mean)
Ketamine0.1
Midazolam0.1

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The Hamilton Rating Scale for Depression-24 Item Version (HRSD-24)

"The HRSD assesses severity of depressive symptoms and is commonly used to measure depression severity. It was initially a 17-item format with the optional addition of 4 items making up the 21-item version. In addition to the original 21 items, the 24-item HRSD includes items on helplessness, hopelessness and worthlessness; its score range is 0-77, with higher scores reflecting greater burden of depressive symptoms.~Response to antidepressant treatment is defined as achieving ≥60% decrease from baseline HRSD-24 and score ≤16. Remission criteria are ≥60% decrease in HRSD from baseline and score ≤10. Criteria for relapse are ≥10 point increase in HRSD-24 compared to responder baseline score plus HRSD ≥16; in addition, increase in the HRSD should be maintained one week later.~Participants will have a baseline (T0) HRSD-24 score. This will be repeated 1 week after each of 4 once-weekly infusions (T1-4) and follow-up measures after another 5 (T9) and 11 (T15) weeks, week 15 is reported." (NCT03256162)
Timeframe: 15 weeks

Interventionscore on a scale (Mean)
Ketamine11.2
Midazolam16.6

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The Montreal Cognitive Assessment (MoCA)

"The MOCA was designed as a rapid screening instrument for mild cognitive dysfunction. It assesses different cognitive domains: attention and concentration, executive functions, memory, language, conceptual thinking, calculations, and orientation. It is scored out of a maximum of 30. The higher scores indicate better cognition.~The MOCA will be performed at baseline, one day after infusions 1 and 4 and 12 weeks after the final infusion." (NCT03256162)
Timeframe: 15 weeks

Interventionscore on a scale (Mean)
Ketamine26.4
Midazolam28.5

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Area Under the Concentration-time Curve of the Analyte BI 730357 in Plasma Over a Uniform Dosing Interval Tau After Administration of the First Dose (AUCtau,1)

"Area under the concentration-time curve of the analyte BI 730357 in plasma over a uniform dosing interval tau after administration of the first dose (AUCtau,1).~In this study AUCtau,1 = AUC0-24" (NCT03279978)
Timeframe: -0.5h before dosing and 0.25h, 0.5h, 1h, 1.5h, 2 h, 2.5h, 3h, 3.5h, 4h, 6h, 8h, 12h and 23.5h after first dosing on Day1.

InterventionNanomole (nmol)·hour (h)/ liter(L) (Geometric Mean)
BI 730357 25 mg Fast2150
BI 730357 50 mg Fast3590
BI 730357 50 mg Fed4620
BI 730357 100 mg Fast6650
BI 730357 200 mg Fast9240
BI 730357 200 mg Fed11900
BI 730357 400 mg Fed15600

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Area Under the Concentration-time Curve of BI 730357 in Plasma at Steady State Over a Uniform Dosing Interval τ (AUCτ,ss) After Last Dose Administration.

"Area under the concentration-time curve of BI 730357 in plasma at steady state over a uniform dosing interval τ (AUCτ,ss) after last dose administration is reported. τ for 25, 50, 100 , 200 and 400 mg dose groups is: 24 hours (h).~Time Frame: For 25, 50, and 100 mg dose groups: -0.5h before dosing and 0.25h, 0.5h, 1h, 1.5h, 2 h, 2.5h, 3h, 3.5h, 4h, 6h, 8h, 12h, 23.5h, 47.5 and 71.5 h after last dose on Day14. For 200 and 400 mg dose groups: -0.5h before last dose and 1.0h, 2.0h, 3.0h, 4.0h and 24.0h after last dose on Day28." (NCT03279978)
Timeframe: Day 14 and Day 28 (Please refer description for the time frame in detail)

InterventionNanomole (nmol)·hour (h)/ liter(L) (Geometric Mean)
BI 730357 25 mg Fast4200
BI 730357 50 mg Fast7550
BI 730357 50 mg Fed9950
BI 730357 100 mg Fast14100
BI 730357 200 mg Fast14600
BI 730357 200 mg Fed29700
BI 730357 400 mg Fed31400

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Maximum Measured Concentration of the Analyte BI 730357 in Plasma at Steady State Over a Uniform Dosing Interval τ After the Last Dose (Cmax,ss)

"Maximum measured concentration of BI 730357 in plasma at steady state over a uniform dosing interval τ (Cmax,ss) after last dose administration is reported. τ for 25, 50, 100 , 200 and 400 mg dose groups is: 24 hours (h).~Time Frame:~For 25, 50, and 100 mg dose groups:-0.5h before dosing and 0.25h, 0.5h, 1h, 1.5h, 2 h, 2.5h, 3h, 3.5h, 4h, 6h, 8h, 12h, 23.5h, 47.5 and 71.5 h after last dose on Day14.~For 200 and 400 mg dose groups: -0.5h before last dose and 1.0h, 2.0h, 3.0h, 4.0h and 24.0h after last dose on Day28." (NCT03279978)
Timeframe: Day 14 and Day 28 (Please refer description for the time frame in detail)

InterventionNanomole (nmol)/ liter(L) (Geometric Mean)
BI 730357 25 mg Fast277
BI 730357 50 mg Fast474
BI 730357 50 mg Fed697
BI 730357 100 mg Fast793
BI 730357 200 mg Fast948
BI 730357 200 mg Fed1840
BI 730357 400 mg Fed2260

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Maximum Measured Concentration of the Analyte BI 730357 in Plasma After Administration of the First Dose (Cmax)

Maximum measured concentration of the analyte BI 730357 in plasma after administration of the first dose (Cmax) (NCT03279978)
Timeframe: -0.5h before dosing and 0.25h, 0.5h, 1h, 1.5h, 2 h, 2.5h, 3h, 3.5h, 4h, 6h, 8h, 12h and 23.5h after first dosing on Day1.

InterventionNanomole (nmol)/liter(L) (Geometric Mean)
BI 730357 25 mg Fast143
BI 730357 50 mg Fast247
BI 730357 50 mg Fed368
BI 730357 100 mg Fast408
BI 730357 200 mg Fast537
BI 730357 200 mg Fed953
BI 730357 400 mg Fed1320

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Effect of Study Drug on Ability to Form Implicit Memory

Subjects will have a list of words read to them while under sedation and their ability to hear these words and form implicit memories of them will be assessed using a two-alternative forced choice task. Results will be reported as the average number of correct responses out of sixteen. (NCT03284307)
Timeframe: Intraoperative (During sedation-- up to 8 hours)

Interventioncorrect responses (Mean)
Dexmedetomidine8
Ketamine8.17
Propofol9

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Effect of Study Drug on Ability to Correctly Identify Images

The ability to match sounds and images measured by the predictive coding task. Will be reported by a proportion correct as a decimal. (NCT03284307)
Timeframe: Intraoperative (During sedation-- up to 8 hours)

,,
Interventionproportion correct (Mean)
Baseline Predictive Coding Task AccuracySedation Predictive Coding Task Accuracy
Dexmedetomidine0.9160.793
Ketamine0.8990.763
Propofol0.910.734

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Effect of Study Drug on Ability to Correctly Identify Shapes/Images

The ability to identify shapes/images in visual illusions measured by the NIH Toolbox. Will be reported by a computed score from NIH Toolbox for the Dimensional Change Card Sort Test (DCCS) and the Flanker Inhibitory Control & Attention Test (Flanker). Both Flanker and DCCS use a 2-vector scoring method that takes accuracy and reaction time (if accuracy >=80%) into account, resulting in a computed score that can range in value from 0-10. A higher score indicates better performance on the test. (NCT03284307)
Timeframe: Intraoperative (During sedation-- up to 8 hours)

,,
Interventionscore on a scale (Mean)
Baseline NIH Toolbox Card Sorting ScoreSedation NIH Toolbox Card Sorting ScoreBaseline NIH Toolbox Flanker ScoreSedation NIH Toolbox Flanker Score
Dexmedetomidine8.837.859.146.62
Ketamine9.298.28.998.47
Propofol9.456.949.488.36

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Number of Instances of Disconnected Conscious Experience (Dreaming) vs Connected Conscious Experience (Awareness of External World).

The number of instances of disconnected conscious experience (dreaming) versus connected conscious experience (awareness of the external world) during sedation is measured by subject self-report at the time of researcher initiated inquiry. (NCT03284307)
Timeframe: Intraoperative (During sedation-- up to 8 hours)

,,
Interventionnumber of instances (Number)
Instances of Connected ConsciousnessInstances of Disconnected Consciousness
Dexmedetomidine70226
Ketamine18030
Propofol5622

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Occipital Delta Power Spectral Density by Conscious State and Study Group.

The difference in spontaneous EEG slow wave activity over posterior cortex between states of consciousness measured with high-density EEG equipment and reported in spectral power in the delta band (1-4 Hz) at electrode Oz. Disconnected conscious experience (dreaming), connected conscious experience (awareness of the external world), and unconsciousness (no report) was assessed when participants were roused from sedation or sleep. (NCT03284307)
Timeframe: Intraoperative (During sedation-- up to 8 hours)

,,,
Interventionlog10(μV^2) (Least Squares Mean)
Connected ConsciousnessDisconnected ConsciousnessUnconsciousness
Dexmedetomidine2.372.572.68
Ketamine1.621.71.46
Propofol2.052.342.51
Sleep2.12.582.63

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Pharmacokinetic Analysis: Area Under the Curve to the Last Observable Concentration (AUClast) for Pexidartinib and ZAAD-1006a Metabolite

Plasma samples for pexidartinib and its metabolite were collected at predose, 0.5, 1, 2, 2.5, 3, 4, 6, 8, and 10 (±1) h after the first dose on Day 3, and at steady state when co-administered with midazolam and tolbutamide on Day 13. (NCT03291288)
Timeframe: Baseline to 13 days post treatment

,
Interventionng*hour/mL (Mean)
PexidartinibZAAD-1006a
Part 1: Pexidartinib (Cycle 1, Day 1)1440018300
Part 1: Pexidartinib (Cycle 1, Day 11)53200102000

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Pharmacokinetic Analysis: Area Under the Curve to the Last Observable Concentration (AUClast) for Midazolam

Plasma samples for midazolam were collected at predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 24, and 48 hours (h) (±10 minutes up to 1 h, ±10% thereafter) on Days 1 to 3, and also when co-administered with pexidartinib on Days 3 (to 5) and Days 13 (to 15). (NCT03291288)
Timeframe: Baseline to 15 days post treatment

Interventionng*hour/mL (Mean)
Part 1: Midazolam Only43.7
Part 1: Pexidartinib + Midazolam (Cycle 1, Day 1)31.6
Part 1: Pexidartinib + Midazolam (Cycle 1, Day 11)18.5

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Pharmacokinetic Analysis: Time to Maximum Concentration (Tmax) for Tolbutamide

Plasma samples for tolbutamide were collected at predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 24, and 48 h (±10 min up to 1 h, ±10% thereafter) on Days 1 to 3, and also when co-administered with pexidartinib on Days 3 (to 5) and Days 13 (to 15). (NCT03291288)
Timeframe: Baseline to 15 days post treatment

Interventionhours (Median)
Part 1: Tolbutamide Only2.90
Part 1: Pexidartinib + Tolbutamide (Cycle 1, Day 1)2.94
Part 1: Pexidartinib + Tolbutamide (Cycle 1, Day 11)3.17

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Pharmacokinetic Analysis: Area Under the Curve to the Last Observable Concentration (AUClast) for Midazolam Metabolite, 1-Hydroxy Midazolam

Plasma samples for midazolam and 1-hydroxy midazolam were to be collected at predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8 (±10 min up to 8 h), 10 (±2), 24 (±2), and 48 (±2) hours on Days 1 to 3 and also when co-administered with pexidartinib on Days 3 to 5 and Days 13 to 15. (NCT03291288)
Timeframe: Baseline to 13 days post treatment

Interventionng*hour/mL (Mean)
Part 1: Midazolam Only200
Part 1: Pexidartinib + Midazolam (Cycle 1, Day 1)206
Part 1: Pexidartinib + Midazolam (Cycle 1, Day 11)212

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Overall Summary of Treatment-emergent Adverse Events

Adverse events that emerge during treatment, having been absent pre-treatment, or worsens relative to the pre-treatment state. (NCT03291288)
Timeframe: Baseline to 1 year post treatment

,
InterventionParticipants (Count of Participants)
TEAEsPexidartinib-related TEAEsTreatment-emergent serious adverse events (SAEs)Pexidartinib-related SAEs
Part 1: Drug-drug Interaction Phase241651
Part 2: Pexidartinib Only232051

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Pharmacokinetic Analysis: Area Under the Curve to the Last Observable Concentration (AUClast) for Tolbutamide

Plasma samples for tolbutamide were collected at predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 24, and 48 h (±10 min up to 1 h, ±10% thereafter) on Days 1 to 3, and also when co-administered with pexidartinib on Days 3 (to 5) and Days 13 (to 15). (NCT03291288)
Timeframe: Baseline to 15 days post treatment

Interventionng*hour/mL (Mean)
Part 1: Tolbutamide Only500000
Part 1: Pexidartinib + Tolbutamide (Cycle 1, Day 1)585000
Part 1: Pexidartinib + Tolbutamide (Cycle 1, Day 11)700000

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Pharmacokinetic Analysis: Maximum Concentration (Cmax) for Midazolam

Plasma samples for midazolam were collected at predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 24, and 48 hours (h) (±10 minutes up to 1 h, ±10% thereafter) on Days 1 to 3, and also when co-administered with pexidartinib on Days 3 (to 5) and Days 13 (to 15). (NCT03291288)
Timeframe: Baseline to 15 days post treatment

Interventionng/mL (Mean)
Part 1: Midazolam Only13.6
Part 1: Pexidartinib + Midazolam (Cycle 1, Day 1)12.0
Part 1: Pexidartinib + Midazolam (Cycle 1, Day 11)9.7

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Pharmacokinetic Analysis: Maximum Concentration (Cmax) for Midazolam Metabolite, 1-Hydroxy Midazolam

Plasma samples for midazolam and 1-hydroxy midazolam were to be collected at predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8 (±10 min up to 8 h), 10 (±2), 24 (±2), and 48 (±2) hours on Days 1 to 3 and also when co-administered with pexidartinib on Days 3 to 5 and Days 13 to 15. (NCT03291288)
Timeframe: Baseline to 13 days post treatment

Interventionng/mL (Mean)
Part 1: Midazolam Only49.7
Part 1: Pexidartinib + Midazolam (Cycle 1, Day 1)52.1
Part 1: Pexidartinib + Midazolam (Cycle 1, Day 11)55.7

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Pharmacokinetic Analysis: Maximum Concentration (Cmax) for Tolbutamide

Plasma samples for tolbutamide were collected at predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 24, and 48 h (±10 min up to 1 h, ±10% thereafter) on Days 1 to 3, and also when co-administered with pexidartinib on Days 3 (to 5) and Days 13 (to 15). (NCT03291288)
Timeframe: Baseline to 15 days post treatment

Interventionng/mL (Mean)
Part 1: Tolbutamide Only44400
Part 1: Pexidartinib + Tolbutamide (Cycle 1, Day 1)46700
Part 1: Pexidartinib + Tolbutamide (Cycle 1, Day 11)44400

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Pharmacokinetic Analysis: Metabolite to Parent Ratio (MPR) for Midazolam

"Plasma samples for midazolam were collected at predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 24, and 48 hours (h) (±10 minutes up to 1 h, ±10% thereafter) on Days 1 to 3, and also when co-administered with pexidartinib on Days 3 (to 5) and Days 13 (to 15).~Plasma pharmacokinetic parameters calculated for Midazolam metabolite. 1-hydroxy midazolam and midazolam for the MPR value." (NCT03291288)
Timeframe: Baseline to 13 days post treatment

InterventionRatio (Mean)
Part 1: Midazolam Only587
Part 1: Pexidartinib + Midazolam (Cycle 1, Day 1)750
Part 1: Pexidartinib + Midazolam (Cycle 1, Day 11)1220

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Pharmacokinetic Analysis: Time to Maximum Concentration (Tmax) for Midazolam

Plasma samples for midazolam were collected at predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 24, and 48 hours (h) (±10 minutes up to 1 h, ±10% thereafter) on Days 1 to 3, and also when co-administered with pexidartinib on Days 3 (to 5) and Days 13 (to 15). (NCT03291288)
Timeframe: Baseline to 15 days post treatment

Interventionhours (Median)
Part 1: Midazolam Only0.525
Part 1: Pexidartinib + Midazolam (Cycle 1, Day 1)0.5
Part 1: Pexidartinib + Midazolam (Cycle 1, Day 11)0.5

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Pharmacokinetic Analysis: Time to Maximum Concentration (Tmax) for Midazolam Metabolite, 1-Hydroxy Midazolam

Plasma samples for midazolam and 1-hydroxy midazolam were to be collected at predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8 (±10 min up to 8 h), 10 (±2), 24 (±2), and 48 (±2) hours on Days 1 to 3 and also when co-administered with pexidartinib on Days 3 to 5 and Days 13 to 15. (NCT03291288)
Timeframe: Baseline to 13 days post treatment

Interventionhours (Median)
Part 1: Midazolam Only1.0
Part 1: Pexidartinib + Midazolam (Cycle 1, Day 1)0.933
Part 1: Pexidartinib + Midazolam (Cycle 1, Day 11)0.833

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Pharmacokinetic Analysis: Time to Maximum Concentration (Tmax) for Pexidartinib and ZAAD-1006a Metabolite

Plasma samples for pexidartinib and its metabolite were collected at predose, 0.5, 1, 2, 2.5, 3, 4, 6, 8, and 10 (±1) h after the first dose on Day 3, and at steady state when co-administered with midazolam and tolbutamide on Day 13. (NCT03291288)
Timeframe: Baseline to 13 days post treatment

,
Interventionhours (Median)
PexidartinibZAAD-1006a
Part 1: Pexidartinib (Cycle 1, Day 1)2.036.04
Part 1: Pexidartinib (Cycle 1, Day 11)1.932.53

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Pharmacokinetic Analysis: Maximum Concentration (Cmax) for Pexidartinib and ZAAD-1006a Metabolite

Plasma samples for pexidartinib and its metabolite were collected at predose, 0.5, 1, 2, 2.5, 3, 4, 6, 8, and 10 (±1) h after the first dose on Day 3, and at steady state when co-administered with midazolam and tolbutamide on Day 13. (NCT03291288)
Timeframe: Baseline to 13 days post treatment

,
Interventionng/mL (Mean)
PexidartinibZAAD-1006a
Part 1: Pexidartinib (Cycle 1, Day 1)31403330
Part 1: Pexidartinib (Cycle 1, Day 11)832013500

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Apparent Plasma Terminal Half-life (t1/2) Post-dose Period 1

T1/2 is the elimination half-life of study drug. T1/2 is the time it takes for half of the study drug in the blood plasma to dissipate. Plasma pharmacokinetic data presented in the table below are following the administration of a single oral dose of a microdose cocktail in healthy participants, participants with renal impairment, and 24 hours prior to hemodialysis in participants with end-stage renal disease requiring hemodialysis. (NCT03311841)
Timeframe: 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 32, 48, and 72 hours post-dose

,,,,
Interventionhours (Geometric Mean)
MidazolamDabigatranPitavastatinPitavastatin lactone (metabolite)AtorvastatinOrtho-hydroxyatorvastatin (metabolite)Rosuvastatin
End-Stage Renal Disease4.4141.411.811.08.0312.414.0
Healthy Control7.996.7517.818.514.921.216.2
Mild Impairment6.768.4019.320.516.722.815.5
Moderate Impairment10.311.922.422.018.624.624.9
Severe Impairment7.7924.020.418.117.521.918.8

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Effect of Rifampin on t1/2 Post-dose Period 2

To evaluate the effect of a single oral dose of rifampin on the t1/2 of midazolam, dabigatran, pitavastatin, pitavastatin lactone, atorvastatin, ortho-hydroxyatorvastatin, and rosuvatatin. T1/2 is the elimination half-life of study drug. T1/2 is the time it takes for half of the study drug in the blood plasma to dissipate. Plasma pharmacokinetic data presented in the table below are following the administration of a single oral dose of a microdose cocktail and rifampin in healthy participants and participants with renal impairment. As pre-specified in the protocol, this outcome measure does not include end-stage renal disease participants as they did not receive rifampin during Period 2. (NCT03311841)
Timeframe: Microdose cocktail: 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 32, 48, and 72 hours post-dose; rifampin: 0.5, 1, 1.5, 2, 3, 4, 6, 12, and 24 hours post-dose

,,,
Interventionhours (Geometric Least Squares Mean)
MidazolamDabigatranPitavastatinPitavastatin lactone (metabolite)AtorvastatinOrtho-hydroxyatorvastatin (metabolite)Rosuvastatin
Healthy Control (Period 2)4.976.486.5016.52.763.496.76
Mild Impairment (Period 2)4.127.578.4021.03.223.839.64
Moderate Impairment (Period 2)5.4911.311.517.72.994.257.48
Severe Impairment (Period 2)4.1419.46.9917.23.144.564.89

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Effect of Rifampin on Tmax Post-dose Period 2

To evaluate the effect of a single oral dose of rifampin on the Tmax of midazolam, dabigatran, pitavastatin, pitavastatin lactone, atorvastatin, ortho-hydroxyatorvastatin, and rosuvatatin. Tmax is the amount of time to reach maximum (peak) plasma drug concentration following drug administration. Plasma pharmacokinetic data presented in the table below are following the administration of a single oral dose of a microdose cocktail and rifampin in healthy participants and participants with renal impairment. As pre-specified in the protocol, this outcome measure does not include end-stage renal disease participants as they did not receive rifampin during Period 2. (NCT03311841)
Timeframe: Microdose cocktail: 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 32, 48, and 72 hours post-dose; rifampin: 0.5, 1, 1.5, 2, 3, 4, 6, 12, and 24 hours post-dose

,,,
Interventionhours (Median)
MidazolamDabigatranPitavastatinPitavastatin lactone (metabolite)AtorvastatinOrtho-hydroxyatorvastatin (metabolite)Rosuvastatin
Healthy Control (Period 2)1.002.501.002.001.503.002.00
Mild Impairment (Period 2)0.502.501.003.001.001.751.00
Moderate Impairment (Period 2)0.753.001.004.001.502.502.00
Severe Impairment (Period 2)0.503.501.003.000.501.751.00

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Effect of Rifampin on Vz/F Post-dose Period 2

To evaluate the effect of a single oral dose of rifampin on the Vz/F of midazolam, dabigatran, pitavastatin, pitavastatin lactone, atorvastatin, ortho-hydroxyatorvastatin, and rosuvatatin. Vz/F is the distribution of study drug between the plasma and the rest of the body after the dose. Plasma pharmacokinetic data presented in the table below are following the administration of a single oral dose of a microdose cocktail and rifampin in healthy participants and participants with renal impairment. As pre-specified in the protocol, this outcome measure does not include end-stage renal disease participants as they did not receive rifampin during Period 2. (NCT03311841)
Timeframe: Microdose cocktail: 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 32, 48, and 72 hours post-dose; rifampin: 0.5, 1, 1.5, 2, 3, 4, 6, 12, and 24 hours post-dose

,,,
Interventionliters (Geometric Least Squares Mean)
MidazolamDabigatranPitavastatinAtorvastatinRosuvastatin
Healthy Control (Period 2)30080049.2225565
Mild Impairment (Period 2)315101047.8272654
Moderate Impairment (Period 2)22063247.3177313
Severe Impairment (Period 2)24273336.0200272

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Maximum Plasma Concentration (Cmax) Post-dose Period 1

Cmax is the peak plasma concentration of study drug after administration. Plasma pharmacokinetic data presented in the table below are following the administration of a single oral dose of a microdose cocktail in healthy participants, participants with renal impairment, and 24 hours prior to hemodialysis in participants with end-stage renal disease requiring hemodialysis. (NCT03311841)
Timeframe: 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 32, 48, and 72 hours post-dose

,,,,
Interventionpg/mL (Geometric Mean)
MidazolamDabigatranPitavastatinPitavastatin lactone (metabolite)AtorvastatinOrtho-hydroxyatorvastatin (metabolite)Rosuvastatin
End-Stage Renal Disease39.913224278.563.78.5822.5
Healthy Control73.218316488.121.67.6721.5
Mild Impairment70.715324410531.98.5023.6
Moderate Impairment77.231230310655.09.5040.4
Severe Impairment68.431921895.446.77.2224.4

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Plasma Concentration at 24 Hours (C24) Post-dose Period 1

C24hr is a measure of the plasma study drug concentration 24 hours post-dose. Plasma pharmacokinetic data presented in the table below are following the administration of a single oral dose of a microdose cocktail in healthy participants, participants with renal impairment, and 24 hours prior to hemodialysis in participants with end-stage renal disease requiring hemodialysis. (NCT03311841)
Timeframe: 24 hours post-dose

,,,,
Interventionpg/mL (Geometric Mean)
MidazolamDabigatranPitavastatinPitavastatin lactone (metabolite)AtorvastatinOrtho-hydroxyatorvastatin (metabolite)Rosuvastatin
End-Stage Renal Disease0.28370.26.0712.94.283.672.64
Healthy Control1.577.704.1021.73.853.081.94
Mild Impairment0.73418.75.3222.45.045.023.59
Moderate Impairment2.6459.38.1332.86.034.436.01
Severe Impairment1.831074.0423.25.733.253.40

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Time to Maximum Plasma Concentration (Tmax) Post-dose Period 1

Tmax is the amount of time to reach maximum (peak) plasma drug concentration following drug administration. Plasma pharmacokinetic data presented in the table below are following the administration of a single oral dose of a microdose cocktail in healthy participants, participants with renal impairment, and 24 hours prior to hemodialysis in participants with end-stage renal disease requiring hemodialysis. (NCT03311841)
Timeframe: 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 32, 48, and 72 hours post-dose

,,,,
Interventionhours (Geometric Mean)
MidazolamDabigatranPitavastatinPitavastatin lactone (metabolite)AtorvastatinOrtho-hydroxyatorvastatin (metabolite)Rosuvastatin
End-Stage Renal Disease0.502.000.502.500.255.003.00
Healthy Control1.001.500.752.000.506.003.50
Mild Impairment0.501.500.522.000.256.002.00
Moderate Impairment0.502.501.002.500.256.004.00
Severe Impairment0.503.000.504.000.256.004.00

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Effect of Rifampin on AUC0-last Post-dose Period 2

To evaluate the effect of a single oral dose of rifampin on the AUC0-last of midazolam, dabigatran, pitavastatin, pitavastatin lactone, atorvastatin, ortho-hydroxyatorvastatin, and rosuvatatin. AUC0-last is the area under the plasma concentration-time curve from time zero to time of last measurable concentration. It is a measure of the amount of study drug in the blood plasma from pre-dose until the last measurable concentration of study drug could be determined. Plasma pharmacokinetic data presented in the table below are following the administration of a single oral dose of a microdose cocktail and rifampin in healthy participants and participants with renal impairment. As pre-specified in the protocol, this outcome measure does not include end-stage renal disease participants as they did not receive rifampin during Period 2. (NCT03311841)
Timeframe: Microdose cocktail: 0 hour (pre-dose) and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 32, 48, and 72 hours post-dose; rifampin: 0 hour (pre-dose) and 0.5, 1, 1.5, 2, 3, 4, 6, 12, and 24 hours post-dose

,,,
Interventionpg*hr/mL (Geometric Least Squares Mean)
MidazolamDabigatranPitavastatinPitavastatin lactone (metabolite)AtorvastatinOrtho-hydroxyatorvastatin (metabolite)Rosuvastatin
Healthy Control (Period 2)23131401890127017601630854
Mild Impairment (Period 2)182283025101850169017501040
Moderate Impairment (Period 2)353683034802380242018501740
Severe Impairment (Period 2)2361040028501470222016101150

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Effect of Rifampin on AUC0-inf Post-dose Period 2

To evaluate the effect of a single oral dose of rifampin on the AUC0-inf of midazolam, dabigatran, pitavastatin, pitavastatin lactone, atorvastatin, ortho-hydroxyatorvastatin, and rosuvatatin. AUC0-inf is the area under the plasma concentration versus time curve from time zero (pre-dose) to extrapolated infinite time. Plasma pharmacokinetic data presented in the table below are following the administration of a single oral dose of a microdose cocktail and rifampin in healthy participants and participants with renal impairment. As pre-specified in the protocol, this outcome measure does not include data from the end-stage renal disease participants as they did not receive rifampin during Period 2. (NCT03311841)
Timeframe: Microdose cocktail: 0 hour (pre-dose) and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 32, 48, and 72 hours post-dose; rifampin: 0 hour (pre-dose) and 0.5, 1, 1.5, 2, 3, 4, 6, 12, and 24 hours post-dose

,,,
Interventionpg*hr/mL (Geometric Least Squares Mean)
MidazolamDabigatranPitavastatinPitavastatin lactone (metabolite)AtorvastatinOrtho-hydroxyatorvastatin (metabolite)Rosuvastatin
Healthy Control (Period 2)23932901910134017701650830
Mild Impairment (Period 2)189304025301930171017601060
Moderate Impairment (Period 2)359724035002500243018701800
Severe Impairment (Period 2)2441070028501560224016201240

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Effect of Rifampin on AUC0-24 Post-dose Period 2

To evaluate the effect of a single oral dose of rifampin on the AUC0-24 of midazolam, dabigatran, pitavastatin, pitavastatin lactone, atorvastatin, ortho-hydroxyatorvastatin, and rosuvatatin. AUC0-24 is the area under the plasma concentration-time curve from time 0 to 24 hours post-dose. This is a measure of the average amount of study drug in the blood plasma over a period of 24 hours after the dose. Plasma pharmacokinetic data presented in the table below are following the administration of a single oral dose of a microdose cocktail and rifampin in healthy participants and participants with renal impairment. As pre-specified in the protocol, this outcome measure does not include end-stage renal disease participants as they did not receive rifampin during Period 2. (NCT03311841)
Timeframe: Microdose cocktail: 0 hour (pre-dose) and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, and 24 hours post-dose; rifampin: 0 hour (pre-dose) and 0.5, 1, 1.5, 2, 3, 4, 6, 12, and 24 hours post-dose

,,,
Interventionpg*hr/mL (Geometric Least Squares Mean)
MidazolamDabigatranPitavastatinPitavastatin lactone (metabolite)AtorvastatinOrtho-hydroxyatorvastatin (metabolite)Rosuvastatin
Healthy Control (Period 2)23430301860100017601620842
Mild Impairment (Period 2)186266024601490170017201010
Moderate Impairment (Period 2)346548033601780242018001670
Severe Impairment (Period 2)238654027601070223015801100

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Area Under the Plasma Concentration-time Curve From Time 0 to Last (AUC0-last) Post-dose Period 1

AUC0-last is the area under the plasma concentration-time curve from time zero to time of last measurable concentration. This is a measure of the amount of study drug in the blood plasma from pre-dose until the last measurable concentration of study drug could be determined. Plasma pharmacokinetic data presented in the table below are following the administration of a single oral dose of a microdose cocktail in healthy participants, participants with renal impairment, and 24 hours prior to hemodialysis in participants with end-stage renal disease requiring hemodialysis. (NCT03311841)
Timeframe: 0 hour (pre-dose) and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 32, 48, and 72 hours post-dose

,,,,
Interventionpg*hr/mL (Geometric Mean)
MidazolamDabigatranPitavastatinPitavastatin lactone (metabolite)AtorvastatinOrtho-hydroxyatorvastatin (metabolite)Rosuvastatin
End-Stage Renal Disease10537406491060298126171
Healthy Control26414104831450255152181
Mild Impairment16714406431490295221231
Moderate Impairment34442309502020459256479
Severe Impairment24874506021570419176269

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Area Under the Plasma Concentration-time Curve From Time 0 to Infinity (AUC0-inf) Post-dose Period 1

AUC0-inf is the area under the plasma concentration versus time curve from time zero (pre-dose) to extrapolated infinite time. Plasma pharmacokinetic data presented in the table below are following the administration of a single oral dose of a microdose cocktail in healthy participants, participants with renal impairment, and 24 hours prior to hemodialysis in participants with end-stage renal disease (ESRD) requiring hemodialysis. (NCT03311841)
Timeframe: 0 hour (pre-dose) and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 32, 48, and 72 hours post-dose

,,,,
Interventionpg*hr/mL (Geometric Least Squares Mean)
MidazolamDabigatranPitavastatinPitavastatin lactone (metabolite)AtorvastatinOrtho-hydroxyatorvastatin (metabolite)Rosuvastatin
End-Stage Renal Disease11053706761100329163208
Healthy Control27315805201540292208292
Mild Impairment17616106881610329286262
Moderate Impairment364455010202240511273575
Severe Impairment26079006481680476226365

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Area Under the Plasma Concentration-time Curve From Time 0 to 24 Hours (AUC0-24) Post-dose Period 1

AUC0-24 is the area under the plasma concentration-time curve from time 0 to 24 hours post-dose. This is a measure of the average amount of study drug in the blood plasma over a period of 24 hours after the dose. Plasma pharmacokinetic data presented in the table below are following the administration of a single oral dose of a microdose cocktail in healthy participants, participants with renal impairment, and 24 hours prior to hemodialysis in participants with end-stage renal disease requiring hemodialysis. (NCT03311841)
Timeframe: 0 hour (pre-dose) and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, and 24 hours post-dose

,,,,
Interventionpg*hr/mL (Geometric Mean)
MidazolamDabigatranPitavastatinPitavastatin lactone (metabolite)AtorvastatinOrtho-hydroxyatorvastatin (metabolite)Rosuvastatin
End-Stage Renal Disease1062100593858287115162
Healthy Control25214404151010198108153
Mild Impairment16813805431040219139191
Moderate Impairment31734407641280329143343
Severe Impairment23544705251100300112223

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Apparent Volume of Distribution During the Terminal Phase (Vz/F) Post-dose Period 1

Vz/F is the distribution of study drug between the plasma and the rest of the body after the dose. Plasma pharmacokinetic data presented in the table below are following the administration of a single oral dose of a microdose cocktail in healthy participants, participants with renal impairment, and 24 hours prior to hemodialysis in participants with end-stage renal disease requiring hemodialysis. Vz/F was to be calculated for the parent plasma analytes only, midazolam, dabigatran, pitavastatin, atorvastatin, and rosuvastatin. (NCT03311841)
Timeframe: 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 32, 48, and 72 hours post-dose

,,,,
Interventionliters (Geometric Mean)
MidazolamDabigatranPitavastatinAtorvastatinRosuvastatin
End-Stage Renal Disease579314025235204870
Healthy Control422173049573804010
Mild Impairment555212040573004270
Moderate Impairment409106031752403120
Severe Impairment433123045453103720

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Apparent Clearance After Extravascular Administration (CL/F) Post-dose Period 1

CL/F is the rate at which study drug was removed from the body. Plasma pharmacokinetic data presented in the table below are following the administration of a single oral dose of a microdose cocktail in healthy participants, participants with renal impairment, and 24 hours prior to hemodialysis in participants with end-stage renal disease requiring hemodialysis. CL/F was to be calculated for the parent plasma analytes only, midazolam, dabigatran, pitavastatin, atorvastatin, and rosuvastatin. (NCT03311841)
Timeframe: 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 32, 48, and 72 hours post-dose

,,,,
Interventionliters/hour (Geometric Mean)
MidazolamDabigatranPitavastatinAtorvastatinRosuvastatin
End-Stage Renal Disease90.852.514.8304240
Healthy Control36.617819.2343171
Mild Impairment56.917514.5304191
Moderate Impairment27.561.89.8419687.0
Severe Impairment38.535.715.4210137

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Effect of Rifampin on CL/F Post-dose Period 2

To evaluate the effect of a single oral dose of rifampin on the CL/F of midazolam, dabigatran, pitavastatin, atorvastatin, and rosuvatatin. CL/F is the rate at which study drug was removed from the body. Plasma pharmacokinetic data presented in the table below are following the administration of a single oral dose of a microdose cocktail and rifampin in healthy participants and participants with renal impairment. As pre-specified in the protocol, this outcome measure does not include end-stage renal disease participants as they did not receive rifampin during Period 2. (NCT03311841)
Timeframe: Microdose cocktail: 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 32, 48, and 72 hours post-dose; rifampin: 0.5, 1, 1.5, 2, 3, 4, 6, 12, and 24 hours post-dose

,,,
Interventionliters/hour (Geometric Least Squares Mean)
MidazolamDabigatranPitavastatinAtorvastatinRosuvastatin
Healthy Control (Period 2)41.885.65.2456.457.9
Mild Impairment (Period 2)53.092.83.9558.647.1
Moderate Impairment (Period 2)27.838.92.8641.128.9
Severe Impairment (Period 2)40.526.33.5744.238.6

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Effect of Rifampin on Cmax Post-dose Period 2

To evaluate the effect of a single oral dose of rifampin on the Cmax of midazolam, dabigatran, pitavastatin, pitavastatin lactone, atorvastatin, ortho-hydroxyatorvastatin, and rosuvatatin. Cmax is the peak plasma concentration of study drug after administration. Plasma pharmacokinetic data presented in the table below are following the administration of a single oral dose of a microdose cocktail and rifampin in healthy participants and participants with renal impairment. As pre-specified in the protocol, this outcome measure does not include end-stage renal disease participants as they did not receive rifampin during Period 2. (NCT03311841)
Timeframe: Microdose cocktail: 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 32, 48, and 72 hours post-dose; rifampin: 0.5, 1, 1.5, 2, 3, 4, 6, 12, and 24 hours post-dose

,,,
Interventionpg/mL (Geometric Least Squares Mean)
MidazolamDabigatranPitavastatinPitavastatin lactone (metabolite)AtorvastatinOrtho-hydroxyatorvastatin (metabolite)Rosuvastatin
Healthy Control (Period 2)81.4351599102405198236
Mild Impairment (Period 2)73.0243819131505215254
Moderate Impairment (Period 2)92.5443860119508174396
Severe Impairment (Period 2)75.442298188.4531150208

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Effect of Rifampin on C24 Post-dose Period 2

To evaluate the effect of a single oral dose of rifampin on the C24 of midazolam, dabigatran, pitavastatin, pitavastatin lactone, atorvastatin, ortho-hydroxyatorvastatin, and rosuvatatin. C24 is a measure of the plasma study drug concentration 24 hours post-dose. C24 is reported as median (minimum and maximum) in severe renal impairment arm due to zero values. Plasma pharmacokinetic data presented in the table below are following the administration of a single oral dose of a microdose cocktail and rifampin in healthy participants and participants with renal impairment. As pre-specified in the protocol, this outcome measure does not include end-stage renal disease participants as they did not receive rifampin during Period 2. (NCT03311841)
Timeframe: 24 hours post-dose

,,,
Interventionpg/mL (Geometric Least Squares Mean)
MidazolamDabigatranPitavastatinPitavastatin lactone (metabolite)AtorvastatinOrtho-hydroxyatorvastatin (metabolite)Rosuvastatin
Healthy Control (Period 2)0.60127.54.7217.11.355.572.42
Mild Impairment (Period 2)0.0031.14.7020.71.766.284.18
Moderate Impairment (Period 2)1.4210010.534.02.989.966.97
Severe Impairment (Period 2)0.3941747.0121.32.987.234.47

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Maximum Measured Concentration of Midazolam in Plasma (Cmax) After the First and Last Dose

"Maximum measured concentration of Midazolam in plasma (Cmax) after the first and last dose for Placebo Matching BI 705564 group and for dose groups 2 to 5 is reported." (NCT03325712)
Timeframe: 1.5 h prior midazolam administration and 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6 and 8 h after first midazolam dose on Day -1 and 1h prior midazolam administration and 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6 and 8 h after last midazolam dose on Day 17.

,,,,
Interventionpicomole/Liter (pmol/L) (Geometric Least Squares Mean)
After last dose: Midazolam +BI 705564 or Midazolam +Placebo (Treatment (T))After first dose: Midazolam alone (Reference (R))
Dose Group 2: BI 705564 20 mg1040.421232.26
Dose Group 3: BI 705564 40 mg1255.361147.40
Dose Group 4: BI 705564 80 mg1058.321175.41
Dose Group 5: BI 705564 60 mg984.141031.18
Placebo Matching BI 7055641197.891196.63

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Area Under the Concentration-time Curve of Midazolam in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz) After the First and Last Dose

"Area under the concentration-time curve of Midazolam in plasma over the time interval from 0 to the last quantifiable data point (AUC0-tz) after the first and last dose for Placebo Matching BI 705564 group and for dose groups 2 to 5 is reported." (NCT03325712)
Timeframe: 1.5 h prior midazolam administration and 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6 and 8 h after first midazolam dose on Day -1 and 1h prior midazolam administration and 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6 and 8 h after last midazolam dose on Day 17.

,,,,
Interventionpicomole*hour/Liter (pmol*h/L) (Geometric Least Squares Mean)
After last dose: Midazolam + BI705564 or Midazolam + Placebo (Treatment (T))After first dose: Midazolam alone (Reference (R))
Dose Group 2: BI 705564 20 mg3463.243721.70
Dose Group 3: BI 705564 40 mg4812.454382.24
Dose Group 4: BI 705564 80 mg3759.203445.42
Dose Group 5: BI 705564 60 mg3458.323191.16
Placebo Matching BI 7055644478.584356.03

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Maximum Measured Concentration of BI 705564 in Plasma at Steady State Over a Uniform Dosing Interval τ (Cmax,ss) After the Administration of the Last Dose

"Maximum measured concentration of BI 705564 in plasma at steady state over a uniform dosing interval τ (Cmax,ss) after the administration of the last dose.~As per the protocol, day is counted as Day 1 = 0:00." (NCT03325712)
Timeframe: 1 h before last dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 h after last BI 705564 dose on Day 17 (for dose groups 1 to 5); 1.5 h before last dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 23 h after last BI 705564 dose on Day 28 (for dose group 8).

Interventionnanomole/Liter (nmol/L) (Geometric Mean)
Dose Group 1: BI 705564 10 mg13.3
Dose Group 2: BI 705564 20 mg19.8
Dose Group 3: BI 705564 40 mg41.8
Dose Group 5: BI 705564 60 mg43.4
Dose Group 4: BI 705564 80 mg52.6
Dose Group 8: BI 705564 40 mg - SPT39.2

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Maximum Measured Concentration of BI 705564 in Plasma (Cmax) After the Administration of the First Dose

Maximum measured concentration of BI 705564 in plasma (Cmax) after the administration of the first dose of BI 705564 is reported. (NCT03325712)
Timeframe: 1 hour(s) (h) prior drug administration and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 h after first BI 705564 dose (for dose groups 1 to 5); 1.5 h prior drug administration and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 23 h after first BI 705564 dose (for dose group 8).

Interventionnanomole/Liter (nmol/L) (Geometric Mean)
Dose Group 1: BI 705564 10 mg11.4
Dose Group 2: BI 705564 20 mg18.8
Dose Group 3: BI 705564 40 mg36.5
Dose Group 5: BI 705564 60 mg41.0
Dose Group 4: BI 705564 80 mg58.1
Dose Group 8: BI 705564 40 mg - SPT31.7

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Area Under the Concentration-time Curve of BI 705564 in Plasma Over a Uniform Dosing Interval τ After Administration of the First Dose (AUCτ,1)

Area under the concentration-time curve of BI 705564 in plasma over a uniform dosing interval τ after administration of the first dose of BI 705564 (AUCτ,1) is reported. Here AUCτ,1 = AUC0-24. (NCT03325712)
Timeframe: 1 hour(s) (h) prior drug administration and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 h after first BI 705564 dose (for dose groups 1 to 5); 1.5 h prior drug administration and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 23 h after first BI 705564 dose (for dose group 8).

Interventionnanomole*hour/liter (nmol*h/L) (Geometric Mean)
Dose Group 1: BI 705564 10 mg42.1
Dose Group 2: BI 705564 20 mg70.8
Dose Group 3: BI 705564 40 mg131.0
Dose Group 5: BI 705564 60 mg168.0
Dose Group 4: BI 705564 80 mg238.0
Dose Group 8: BI 705564 40 mg - SPT120.0

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Area Under the Concentration-time Curve of BI 705564 in Plasma at Steady State Over a Uniform Dosing Interval τ (AUCτ,ss) After the Administration of the Last Dose

"Area under the concentration-time curve of BI 705564 in plasma at steady state over a uniform dosing interval τ (AUCτ,ss) after the administration of the last dose of BI 705564 is reported.~As per the protocol, day is counted as Day 1 = 0:00." (NCT03325712)
Timeframe: 1 h before last dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 h after last BI 705564 dose on Day 17 (for dose groups 1 to 5); 1.5 h before last dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 23 h after last BI 705564 dose on Day 28 (for dose group 8).

Interventionnanomole *hour/liter (nmol*h/L) (Geometric Mean)
Dose Group 1: BI 705564 10 mg45.9
Dose Group 2: BI 705564 20 mg84.8
Dose Group 3: BI 705564 40 mg164.0
Dose Group 5: BI 705564 60 mg170.0
Dose Group 4: BI 705564 80 mg204.0
Dose Group 8: BI 705564 40 mg - SPT138.0

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Safety: Number of Participants With Aspiration Pneumonia Reported as Treatment Emergent Adverse Events (TEAEs)

TEAEs was defined as adverse events (AEs) whose onset occurs, severity worsens or intensity increases on or after the date of SHP615 administration. Number of participants with aspiration pneumonia identified as TEAEs were reported. (NCT03336450)
Timeframe: From start of study drug administration up to follow-up (Day 8)

InterventionParticipants (Count of Participants)
SHP6150

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Safety: Number of Participants With Buccal Irritation Reported as Treatment Emergent Adverse Events (TEAEs)

TEAEs was defined as AEs whose onset occurs, severity worsens or intensity increases on or after the date of IP administration. Buccal cavity was examined for redness, inflammation and ulceration. Number of participants with buccal irritation reported as TEAEs were reported. (NCT03336450)
Timeframe: Up to 6 hours post-dose

InterventionParticipants (Count of Participants)
SHP6150

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Safety: Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters Reported as TEAEs

Clinical laboratory evaluations included biochemistry, endocrinology, hematology and urinalysis. Any change in clinical laboratory abnormalities which were deemed clinically significant by the investigator were recorded as TEAEs. (NCT03336450)
Timeframe: From start of study drug administration up to 24 hours post-dose

InterventionParticipants (Count of Participants)
SHP6150

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Safety: Number of Participants With Clinically Significant Change in Electrocardiogram (ECG) Reported as TEAEs

12-lead ECG were evaluated. Any change in ECG assessments which are deemed clinically significant by the investigator were reported as TEAEs. (NCT03336450)
Timeframe: From start of study drug administration up to 24 hours post-dose

InterventionParticipants (Count of Participants)
SHP6150

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Safety: Number of Participants With Clinically Significant Change in Vital Signs Reported as TEAEs

Vital sign assessments included blood pressure, pulse, respiratory rate and body temperature. Any change in vital signs which were deemed clinically significant by the investigator were recorded as TEAEs. (NCT03336450)
Timeframe: From start of study drug administration up to 24 hours post-dose

InterventionParticipants (Count of Participants)
SHP6150

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Safety: Number of Participants With Respiratory Depression

Respiratory depression, included the following measures within 24 hours after administration of the IP: i) Persistent decrease in oxygen saturation to <92 percent (%) measured up to 24 hours post-dose (i.e., <92% on room air for 2 minutes or more after dosing while monitoring [per healthcare setting protocol and/or the clinical judgment of the physician]. ii) Increase in respiratory effort such that assisted ventilation is used (bag-valve-mask ventilation or endotracheal intubation). Number of participants with respiratory depression were reported. (NCT03336450)
Timeframe: Up to 24 hours post-dose

InterventionParticipants (Count of Participants)
SHP6150

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Safety: Number of Participants With Treatment-emergent Adverse Events (TEAEs)

An AE was any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. TEAEs was defined as AEs whose onset occurs, severity worsens or intensity increases on or after the date of IP administration. Number of participants with TEAEs were reported. (NCT03336450)
Timeframe: From start of study drug administration up to follow-up (Day 8)

InterventionParticipants (Count of Participants)
SHP6152

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Efficacy: Number of Participants Who Had Sustained Absence of Seizure Activity for at Least 1, 4, and 6 Hours

Number of participants whose seizure event stopped within 10 minutes of single dose administration of SHP615 and who had sustained absence of seizure activity for at least 1, 4, and 6 hours were reported. (NCT03336450)
Timeframe: From start of study drug administration up to 1, 4, and 6 hours post-dose

InterventionParticipants (Count of Participants)
Sustained absence for at least 1 hourSustained absence for at least 4 hourSustained absence for at least 6 hour
SHP615301

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Efficacy: Time to Recovery of Consciousness

Time to recovery of consciousness in minutes was calculated only for participants who lost consciousness pre-dose as time from SHP615 administration to recovery of consciousness post-dose or administration of rescue anticonvulsant medication, whichever occurs first. Participant wise data was reported for this outcome. (NCT03336450)
Timeframe: From start of study drug administration up to follow-up (Day 8)

InterventionMinutes (Number)
Participant 1Participant 2Participant 3
SHP61541435

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Efficacy: Time to Resolution of Seizures (Convulsions)

Time to resolution of seizures (convulsions) was calculated as time from SHP615 administration to the end of the initial seizure or administration of rescue anticonvulsant medication, whichever occurs first. The initial seizure refers to the seizure which triggered the use of the IP. Participant wise data was reported for this outcome. (NCT03336450)
Timeframe: From start of study drug administration up to follow-up (Day 8)

InterventionMinutes (Number)
Participant 1Participant 2Participant 3
SHP615125

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Safety: Number of Participants Analyzed for Sedation or Agitation Measured by the Riker Sedation-Agitation Scale

"Sedation-Agitation was assessed, using the Riker Sedation-Agitation Scale (SAS) by the following 7-point scale: 7. dangerous agitation; 6. very agitated; 5. agitated; 4. calm, cooperative; 3. sedated; 2. very sedated; 1. unarousable. Number of participants analyzed for sedation or agitation measured by the riker sedation-agitation scale were reported." (NCT03336450)
Timeframe: 1, 4, 6, and 24 hours post-dose

InterventionParticipants (Count of Participants)
Participant with unarousableParticipant with very sedatedParticipant with sedatedParticipant with calm and cooperativeParticipant with agitatedParticipant with very agitatedParticipant with dangerous agitation
SHP6150113100

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Safety: Percentage of Participants With Normal Oxygen Saturation Values Collected During Hospital Setting

Oxygen saturation is the amount of oxygen that is in bloodstream and is measured as the percentage of blood hemoglobin that is carrying oxygen. Normal oxygen saturation levels are considered to be 95-100 percent; low oxygen saturation values indicate worse disease. Oxygen saturation was measured and recorded on room air. The investigator recorded the oxygen saturation as well as the oxygen delivery system and amount of oxygen administered during hospital setting. Percentage of participants with normal oxygen saturation values collected during hospital setting were reported. (NCT03336450)
Timeframe: 0.5, 1, 4, 6 and 24 hours post-dose

InterventionPercentage of participants (Number)
SHP615100

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Efficacy: Number of Participants With Therapeutic Success

Therapeutic success was defined as cessation of visible seizure activity within 10 minutes and sustained absence of visible seizure activity for 30 minutes following a single dose of SHP615 without the need for additional rescue medication. Number of participants with therapeutic success were reported. (NCT03336450)
Timeframe: From start of study drug administration up to 30 minutes post-dose

InterventionParticipants (Count of Participants)
SHP6153

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Efficacy: Percentage of Participants Who Failed to Respond to Treatment With SHP615

Treatment failure/non-responder was defined as continuing seizure activity and/or the need for any additional rescue medication according to the participating healthcare setting protocol or guideline 10 minutes after administration of SHP615 was reported. (NCT03336450)
Timeframe: 10 minutes post-dose

InterventionPercentage of participants (Number)
SHP6150

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Efficacy: Percentage of Participants Who Required Additional Anticonvulsant Medication for Ongoing Status Epilepticus (SE) 10 Minutes After Administration of SHP615

Percentage of participants who required additional anticonvulsant medication for ongoing SE according to the participating hospital protocol or guideline, 10 minutes after the administration of SHP615 were reported. (NCT03336450)
Timeframe: 10 minutes post-dose

InterventionPercentage of participants (Number)
SHP6150

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Time at Maximum Concentration (Tmax) of SHP615 in Plasma

Tmax of SHP615 in plasma were reported. (NCT03336645)
Timeframe: 1, 3, and 6 hours post-dose

Interventionminutes (Median)
SHP61520.5

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Number of Participants With Time to Recovery of Consciousness

Time to recovery of consciousness (in minutes) was calculated only for participants who lost consciousness pre-dose at time from investigational product administration to recovery of consciousness post-dose or administration of rescue anticonvulsant medication, whichever occurs first. Number of participants with time to recovery of consciousness were reported. (NCT03336645)
Timeframe: From start of study drug administration up to follow-up (Day 8)

InterventionParticipants (Count of Participants)
SHP61519

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Number of Participants With Time to Resolution of Seizures (Convulsions)

Time to resolution of seizures (convulsions) was calculated as time from IP administration to the end of the initial seizure or administration of rescue anti-convulsant medication, whichever occurs first. Initial seizure referred to the seizure that triggered the use of the IP. Number of participants with time to resolution of seizures (convulsions) from the administration of SHP615 were reported. (NCT03336645)
Timeframe: From start of study drug administration up to follow-up (Day 8)

InterventionParticipants (Count of Participants)
SHP61521

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Number of Participants With Respiratory Depression

Respiratory depression, included the following measures within 24 hours after administration of the IP: i) Persistent decrease in oxygen saturation to < 92 percent (%) measured at 10, 30 minutes, and 4, 6, and 24 hours post-dose (i.e, < 92 % on room air for 2 minutes or more after dosing while monitoring [per healthcare setting protocol and/or the clinical judgment of the physician]) ii) Increase in respiratory effort such that assisted ventilation is used (bag-valve-mask ventilation or endotracheal intubation). Number of participants with respiratory depression were reported. (NCT03336645)
Timeframe: From start of study drug administration up to follow-up (Day 8)

InterventionParticipants (Count of Participants)
Persistent Decrease in Oxygen SaturationIncrease in Respiratory Effort
SHP61501

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Number of Participants With Treatment-Emergent Adverse Events (TEAEs)

An adverse event (AE) was any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. TEAEs was defined as AEs that start or deteriorate on or after the date of the first dose of investigational product and no later than 3 days following the last dose of IP. Number of participants with TEAEs were reported. (NCT03336645)
Timeframe: From start of study drug administration up to follow-up (Day 8)

InterventionParticipants (Count of Participants)
SHP6159

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Percentage of Participants Who Failed to Respond to the Treatment With SHP615

Treatment failure/non-responder was defined as participants with continuing seizure activity and/or the need for any additional rescue medication according to the participating healthcare setting protocol or guideline, for 10 mins or more after a single dose of the IP. (NCT03336645)
Timeframe: 10 minutes post-dose

InterventionPercentage of participants (Number)
SHP61516.0

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Percentage of Participants Who Required Additional Anticonvulsant Medication for Ongoing Status Epilepticus (SE)

Percentage of participants who required additional anticonvulsant medication for ongoing SE, 10 minutes after a single dose of SHP615 were reported. (NCT03336645)
Timeframe: 10 minutes post-dose

InterventionPercentage of Participants (Number)
SHP61516.0

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Change From Baseline in Riker Sedation-Agitation Scale at 24 Hours Post-dose

"Sedation-Agitation was assessed, using the Riker Sedation-Agitation Scale (SAS) by the following 7-point scale: 7. dangerous agitation; 6. very agitated; 5. agitated; 4. calm, cooperative; 3. sedated; 2. very sedated; 1. unarousable. Change from baseline in riker sedation-agition scale at 24 hours post-dose were reported." (NCT03336645)
Timeframe: Baseline, 24 hours post-dose

InterventionScore on the scale (Mean)
SHP6152.2

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Percentage of Participants Who Had Sustained Absence of Seizure Activity for at Least 1, 4 and 6 Hours

Percentage of participants whose seizure event stopped within 10 minutes of single dose administration of SHP615 and who had sustained absence of seizure activity for at least 1, 4, and 6 hours were reported. (NCT03336645)
Timeframe: From start of study drug administration up to 1, 4 and 6 hours post-dose

InterventionPercentage of participants (Number)
Sustained Absence for at least 1 hourSustained Absence for at least 4 hoursSustained Absence for at least 6 hours
SHP61568.036.032.0

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Percentage of Participants With Response Rate

Response rate was defined as the percentage of participants with therapeutic success. Therapeutic success was defined as the cessation of visible seizure activity within 10 minutes with a sustained absence of visible seizure activity for 30 minutes following a single dose of MHOS/SHP615 without the need for additional rescue medication. (NCT03336645)
Timeframe: From start of study drug administration up to 30 minutes post-dose

InterventionPercentage of participants (Number)
SHP61580.0

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Area Under the Concentration-time Curve From Time Zero to 180 Minutes (AUC0-180) of SHP615 in Plasma

AUC0-180 of SHP615 in plasma were reported. (NCT03336645)
Timeframe: Pre-dose, 180 minutes post-dose

Interventionmin ng/mL (Mean)
SHP6154411

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Area Under the Concentration-time Curve From Time Zero to 60 Minutes (AUC0-60) of SHP615 in Plasma

AUC0-60 of SHP615 in plasma were reported. (NCT03336645)
Timeframe: Pre-dose, 60 minutes post-dose

Interventionmin ng/mL (Mean)
SHP6152965

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Area Under the Concentration-time Curve From Time Zero to Infinity (AUC0-inf) of SHP615 in Plasma

AUC(0-infinity) of SHP615 in plasma were reported. (NCT03336645)
Timeframe: Pre-dose, 1, 3, and 6 hours post-dose

Interventionmin ng/mL (Mean)
SHP6155847

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Change From Baseline in Oxygen Saturation Percentage at 24 Hours Post-dose

Oxygen saturation at baseline was measured and recorded on room air. The investigator had recorded the oxygen saturation, oxygen delivery system and amount of oxygen administered during the study. Change from baseline in oxygen saturation percentage at 24 hours post-dose were reported. (NCT03336645)
Timeframe: Baseline, 24 hours post-dose

InterventionPercentage of oxygen saturation (Mean)
SHP6153.7

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Area Under the Concentration-time Curve From Time Zero to 10 Minutes (AUC0-10) of SHP615 in Plasma

"AUC0-10 of SHP615 in plasma were reported. Here min ng/mL was minutes nanogram per milliliter." (NCT03336645)
Timeframe: Pre-dose, 10 minutes post-dose

Interventionmin ng/mL (Mean)
SHP615304

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Concentration of SHP615 in Plasma at 10 Minutes (C10)

Concentration of SHP615 in plasma at 10 minutes were reported. (NCT03336645)
Timeframe: 10 minutes post-dose

Interventionnanogram per milliliter (ng/mL) (Mean)
SHP61545.2

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Elimination Half-life (T1/2) of SHP615 in Plasma

T1/2 of SHP615 in plasma were reported. (NCT03336645)
Timeframe: 1, 3, and 6 hours post-dose

Interventionminutes (Median)
SHP615115

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Maximum Plasma Concentration (Cmax) of SHP615

Cmax of SHP615 in plasma were reported. (NCT03336645)
Timeframe: 1, 3, 6 hours post-dose

Interventionng/mL (Mean)
SHP61578.0

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Number of Participants With Aspiration Pneumonia Reported as Treatment Emergent Adverse Events (TEAEs)

TEAEs was defined as AEs that start or deteriorate on or after the date of the first dose of investigational product and no later than 3 days following the last dose of IP. Number of participants with aspiration pneumonia identified as TEAEs were reported. (NCT03336645)
Timeframe: From start of study drug administration up to follow-up (Day 8)

InterventionParticipants (Count of Participants)
SHP6150

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Patients' Satisfaction Using a Likert-type Scale

overall satisfaction with the procedure using the Likert-type scale (1. Very dissatisfied, 2. Dissatisfied, 3. Neither satisfied nor dissatisfied, 4. Satisfied, 5. Very satisfied). The patient may comment any cause which made the satisfaction score high or low and if the patient would like to receive the same method of sedation during a future bronchoscopy. (NCT03357393)
Timeframe: After patient has recovered after bronchoscopy and before discharge home, estimated period of time 0-24 hours.

Interventionunits on a scale (Median)
Midazolam and Morphine-scopolamine5
PCS (Propofol) With Morphine-scopolamine5
PCS (Propofol) With Glycopyrronium Bromide5

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Quality of Recovery (QoR-23)

"Modified version of Quality of Recovery (QoR-23) Minimum value 23. Maximum value 115. A higher score indicate a better quality of recovery.~The questionnaire Quality of Recovery (QoR-23) is a 23 item questionnaire to assess recovery after day surgery regarding the patients' emotional state, physical comfort and physical independence (see further appendix 4). Each item is rated on a five-point scale (1-5) and the scores are summed." (NCT03357393)
Timeframe: The assessment is done by the patient at home (or at ward if pro-longed hospital stay is necessary) in the morning the day after bronchoscopy. It takes less than 1 minute to complete the assessment.

Interventionscore on a scale (Median)
Midazolam and Morphine-scopolamine100
PCS (Propofol) With Morphine-scopolamine102
PCS (Propofol) With Glycopyrronium Bromide100

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Assessment of Self-rated Patient Questionaries' Using S-PSR

"Post-discharge Surgical Recovery Scale (S-PSR) The modified Swedish version S-PSR is based on the Post-discharge Surgical Recovery Scale and is a 14-item questionnaire to assess the recovery post-discharge regarding the patients' health status and activity (see further appendix 2). Each item is rated using a semantic differential scale and the total sum is multiplied by 100. The possible range is 10-100, with higher score indicating a more favourable postoperative recovery." (NCT03357393)
Timeframe: The assessment is done by the patient at home (or at ward if pro-longed hospital stay is necessary) in the evening on the day of bronchoscopy. It takes approximately 2 minutes to complete the questionnaire.

Interventionunits on a scale (Median)
Midazolam and Morphine-scopolamine55
PCS (Propofol) With Morphine-scopolamine56
PCS (Propofol) With Glycopyrronium Bromide54

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Bronchoscopist Evaluation Using a Likert-type Scale

the bronchoscopist assess their perception of cough, bronchial secretion respectively circumstances for a smooth performance of the bronchoscopy of procedure using the Likert-type scale (1. Very dissatisfied, 2. Dissatisfied, 3. Neither satisfied nor dissatisfied, 4. Satisfied, 5. Very satisfied). (NCT03357393)
Timeframe: Directly after completion of the procedure.

Interventionunits on a scale (Median)
Midazolam and Morphine-scopolamine5
PCS (Propofol) With Morphine-scopolamine4
PCS (Propofol) With Glycopyrronium Bromide4

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Discharge Assessment Using PADSS After 2 Hours Number of Patients Reaching PADSS Score 10 After 2 Hours

Post Anaesthetic Discharge Scoring System (PADSS).A measurement of the PADSS score is done by pulmonary nurse every 15 min after bronchoscopy is finished (when bronchoscope is removed) for 2 hours. The PADSS is used to clinically assess if the patient is ready to be discharged after anaesthesia/sedation and consist of five criteria: vital signs, ambulation, nausea and/or vomiting, pain and surgical bleeding. Each criterion is given a score ranging from 0 to 2. Only patients who achieve a total score of 10 are considered ready for discharge after 2 hours. (NCT03357393)
Timeframe: 2 hours after bronchoscopy is finished

InterventionParticipants (Count of Participants)
Midazolam and Morphine-scopolamine19
PCS (Propofol) With Morphine-scopolamine30
PCS (Propofol) With Glycopyrronium Bromide45

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Level of Sedation Using the Observer's Assessment of Alertness/Sedation (OAA/S) Scale

"Level of sedation is assessed every 5th minute during the procedure by the nurse anaesthetist using The Observer's Assessment of Alertness/Sedation (OAA/S) scale whereby a higher score represent a lighter sedation. Below is the scale descriped, Observation/score:~Responds readily to name spoken in normal tone/5 Lethargic response to name spoken in normal tone/4 Responds only after name is called loudly and/or repeatedly/3 Responds only after mild prodding or shaking/2 Does not respond to mild prodding or shaking/1" (NCT03357393)
Timeframe: Assessement are done every 5th minute from procedure start until end of procedure (extraction of bronchoscope), estimated period of time 0-60 minutes.

Interventionunits on a scale (Median)
Midazolam and Morphine-scopolamine3
PCS (Propofol) With Morphine-scopolamine2
PCS (Propofol) With Glycopyrronium Bromide2

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Number of Participants With Interventions Performed

Number of participants with interventions performed to maintain cardiovascular (if atropine or ephidrine has been given) and respiratory stability (if assisted ventilation, chin lift or painful stimulation has been performed). Assesed every five minutes during the procedure. (NCT03357393)
Timeframe: From procedure start until end of procedure (extraction of bronchoscope), estimated period of time 0-60 minutes.

InterventionParticipants (Count of Participants)
Midazolam and Morphine-scopolamine1
PCS (Propofol) With Morphine-scopolamine4
PCS (Propofol) With Glycopyrronium Bromide3

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Change in Brief Psychiatric Rating Scale (BPRS) Total Scores

BPRS is an 18-item clinician rated scale with 11 general symptom items, 5 positive-symptom items, and 2 negative symptom items scored on a 7-point scale (1=not present and 7=extremely severe), with higher score indicating greater severity of symptom. Total possible score range=18 to 126. (NCT03395314)
Timeframe: Timepoints: pre-infusion, during infusion +20, +40 minutes, post-infusion +40 minutes

,
Interventionscore on a scale (Least Squares Mean)
Baseline (pre-infusion)20 Minutes (during infusion)40 Minutes (during infusion)80 Minutes (post infusion)
Low Dose Ketamine33.7938.736.228.2
Midazolam29.3628.1828.025.9

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Change in Beck Depression Inventory Score

"The Beck Depression Inventory (BDI) consisted of twenty-one questions about how the subject has been feeling in the last week. Each question has a set of at least four possible answer choices, ranging in intensity.~When the test is scored, a value of 0 to 3 is assigned for each answer and then the total score is used to quantify the participant's degree of depression from 0 = no depression to 63 = maximally severe depression." (NCT03395314)
Timeframe: Timepoints will be baseline, 1hr post-infusion and at 1, 3, 7, 14, & 28 days after infusion.

,
Interventionscore on a scale (Least Squares Mean)
Baseline1hr post-infusionDay 1Day 3Day 7Day 14Day 28
Low Dose Ketamine34.913.312.28.912.614.518.73
Midazolam30.7511.1612.4110.9411.3317.4117.57

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Change in Beck Suicide Scale Total Score

The Beck Suicide Scale is a 23 item self report scale with items to specifically assess the presence and intensity of thoughts and actions related to suicidality. Each item response is on a 3 point likert (0-2) for each of 21 items, so possible totals range from 0-42. Higher scores indicate higher suicidality. The description was updated when results were entered. (NCT03395314)
Timeframe: Timepoints will be baseline, 1hr post-infusion and at 1, 3, 7, 14, & 28 days after infusion.

,
Interventionscore on a scale (Least Squares Mean)
Baseline1hr post-infusionDay 1Day 3Day 7Day 14Day 28
Low Dose Ketamine11.54.13.33.94.65.47.12
Midazolam7.663.53.132.923.085.664.51

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Change in Behavior in the Economic Trust Game - Cooperation

The trust game is a multi-round economic exchange game. There are two roles in the game: investor and trustee. Study participants will play as the trustee. Each round, the investor is given a set number of points and can send any amount to the trustee. The investment triples and the trustee decides how much to repay the investor. Outcome measures are cooperation (amount returned to the investor) and coaxing (amount returned to investor on trials when poor prior returns from trustee have led investor to decrease investment). Cooperation was used as part of the evaluation in this study- coaxing was not. Outcome measure description was updated at the time of results entry. (NCT03395314)
Timeframe: Timepoints will be at baseline and 3, 7, 14, 28 days after infusion

,
Interventionproportion of amount returned (Least Squares Mean)
BaselineDay 3Day 7Day 14Day 28
Low Dose Ketamine0.380.420.290.390.31
Midazolam0.390.360.420.340.31

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Change in Brief Pain Inventory Score - Intensity

"Self report inventory that assesses intensity of pain and its interference with everyday life.~Intensity: pain severity as measured by a 0 to 10 visual analogue scale. 0 = no pain, 10 = worst pain imaginable.~Interference score: Interference as measured by a 0 to 10 numerical rating scale. 0 = does not interfere, 10 = completely interferes" (NCT03395314)
Timeframe: Timepoints will be at baseline, and post-infusion 1hr, and days 1, 3, 7, 14, & 28.

,
Interventionscore on a scale (Least Squares Mean)
BaselinePost-infusion 1hrDay 1Day 3Day 7Day 14Day 28
Low Dose Ketamine6.322.564.464.465.924.145.11
Midazolam6.195.756.526.739.043.26.28

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Change in Adverse Events

Adverse events were tracked in a log of treatment emergent adverse events, EKG, pulse oximetry, vital signs. A count of any treatment emergent adverse events is presented through Day 28. The outcome measure description as updated when results were entered. (NCT03395314)
Timeframe: Timepoints: Continuous monitoring throughout infusion; post-infusion days 1, 3, 7, 14, 28.

InterventionParticipants (Count of Participants)
Midazolam0
Low Dose Ketamine0

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Change in Brief Pain Inventory Score - Interference

"Self report inventory that assesses intensity of pain and its interference with everyday life.~Intensity: pain severity as measured by a 0 to 10 visual analogue scale. 0 = no pain, 10 = worst pain imaginable.~Interference score: Interference as measured by a 0 to 10 numerical rating scale. 0 = does not interfere, 10 = completely interferes" (NCT03395314)
Timeframe: Timepoints will be at baseline, and post-infusion 1hr, and days 1, 3, 7, 14, & 28.

,
Interventionscore on a scale (Least Squares Mean)
BaselinePost-infusion 1hrDay 1Day 3Day 7Day 14Day 28
Low Dose Ketamine2.940.513.13.14.093.454.52
Midazolam3.491.224.793.414.062.214.23

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Change in Preferred Distance in Stop-distance Paradigm (SDP)

"The stop-distance paradigm is a measure of preferred interpersonal distance (PID). Subjects begin the task standing face-to-face and 6 feet away from a test confederate. On each of 3 trials, the confederate slowly approaches the subject. The subjects are instructed to say stop to indicate their 1) preferred conversational distance, then a closer distance 2) if you start to feel uncomfortable. After each stop, toe to toe distance is measured using a tape measure, and mean PID for the three trials is computed separately for conversational and uncomfortable distance. A computerized version of the task may also be implemented for remote visits and administered in place of the in-person task." (NCT03395314)
Timeframe: Timepoints will be at baseline and 3, 7, 14, 28 days after infusion

,
Interventiondistance in inches (Least Squares Mean)
BaselineDay 3Day 7Day 14Day 28
Low Dose Ketamine20.617.215.516.519.5
Midazolam18.617.314.719.417.2

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Change in Beck Anxiety Inventory Score

"The Beck Anxiety Inventory (BDI) consisted of twenty-one questions about how the subject has been feeling in the last week. Each question has a set of at least four possible answer choices, ranging in intensity.~When the test is scored, a value of 0 to 3 is assigned for each answer and then the total score is used to quantify the participant's degree of anxiety from 0 = no anxiety to 63 = maximally severe anxiety." (NCT03395314)
Timeframe: Timepoints will be baseline, 1hr post-infusion and at 1, 3, 7, 14, & 28 days after infusion.

,
Interventionscore on a scale (Least Squares Mean)
Baseline1hr post-infusionDay 1Day 3Day 7Day 14Day 28
Low Dose Ketamine21.77.38.35.58.211.018.23
Midazolam21.754.07.435.717.438.886.34

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Change in Clinician-Administered Dissociative States Scale (CADSS) Score

This scale captures the range of possible subjective side effects of ketamine or Midazolam. This consists of 23 questions and scores for each question range from 0-4. The maximum score is 92 with higher scores indicating more dissociative symptoms. (NCT03395314)
Timeframe: Timepoints: pre- infusion, during infusion +20, +40 minutes, and post-infusion 40 minutes.

,
Interventionscore on a scale (Least Squares Mean)
Baseline (pre-infusion)20 minutes (during infusion)40 minutes (during infusion)80 minutes (post infusion)
Low Dose Ketamine5.9225.416.83.0
Midazolam5.945.549.541.90

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Change in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score

The MADRS scale measures the depression level of a participant. The total score was derived by adding the scores of the following 10 items: 1, Apparent sadness; 2, Reported sadness; 3, Inner tension; 4, Reduced sleep; 5, Reduced appetite; 6, Concentration difficulties; 7, Lassitude; 8, Inability to feel; 9, Pessimistic thoughts; 10, Suicidal thoughts. Each item was scored using a scale of 0 to 6 (a higher score indicates increased severity). The maximum total score is 60; 0, no depression; 60, severely depressed. (NCT03395314)
Timeframe: Timepoints will be baseline, 1hr post-infusion and at 1, 3, 7, 14, & 28 days after infusion.

,
Interventionscore on a scale (Least Squares Mean)
Baseline1hr post-infusionDay 1Day 3Day 7Day 14Day 28
Low Dose Ketamine28.36.28.212.212.312.922.67
Midazolam26.753.669.2711.7012.519.2517.39

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Change in Social Adjustment Scale Self Report (SAS-SR) Short Version Score

This questionaire measures expressive and instrumental performance over the past two weeks in six role areas: (1) work, either as a paid worker, unpaid homemaker, or student, (2) social and leisure activities, (3) relationships with extended family, (4) role as a marital partner, (5) parental role, and (6) role within the family unit, including perceptions about economic functioning.Each question is rated on a five-point scale from which role area means and an overall mean can be obtained, with higher scores denoting greater impairment. Role areas not relevant to the respondent can be skipped. Overall means are based on all items completed by the respondent. Scores range from 0 = no difficulties to 125 = broad difficulties in multiple domains. An overall adjustment (NCT03395314)
Timeframe: Timepoints will be at baseline and 3, 7, 14, 28 days after infusion

,
Interventionscore on a scale (Least Squares Mean)
BaselineDay 3Day 7Day 14Day 28
Low Dose Ketamine2.741.952.022.072.12
Midazolam2.862.302.172.582.33

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Change in Suicidal Thoughts as Measured by Item 10 on the Montgomery-Asberg Depression Scale (MADRS)

The MADRS test includes 10 items and uses a 0 to 6 severity scale for each item, with higher scores indicating increasing depressive symptoms. Scores are averaged across items and can range from 0 to 6 (with 0 indicating enjoying life, and 6 indicating explicit plans for suicide). Outcome description updated when results were entered. (NCT03395314)
Timeframe: Timepoints will be baseline, 1hr post-infusion and at 1, 3, 7, 14, & 28 days after infusion.

,
Interventionunits on a scale (Least Squares Mean)
baseline1hr post-infusionDay 1 post-infusionDay 3 post-infusionDay 7 post-infusionDay 14 post-infusionDay 28 post-infusion
Low Dose Ketamine2.70.10.50.70.81.32.6
Midazolam2.660.00.590.890.831.661.29

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Change in 'Reading the Mind in the Eyes' Test (RMET) Score

The RMET is an advanced test of theory of mind. It is widely used to assess individual differences in social cognition and emotion recognition across different groups and cultures. This is a score from 0-36 where higher score indicates better performance. (NCT03395314)
Timeframe: Timepoints: at baseline and 3, 7, 14, 28 days after infusion.

,
Interventionscore on a scale (Least Squares Mean)
BaselineDay 3Day 7Day 14Day 28
Low Dose Ketamine25.627.326.625.125.4
Midazolam28.227.629.229.929.9

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Change in Suicidality as Measured by Item-12 on the Quick Inventory of Depressive Symptomatology (QIDS SR-16)

The Quick Inventory of Depressive Symptomatology (QIDS SR-16) is a a self-report measure of depression. Each item is scored from 0-3. Higher scores denote more severe load of depressive symptoms. Item 12 measures thoughts of death or suicide from 0 (no thoughts) to 3 (specific suicide plan or action.). Presented is the mean score across items with a range of 0 to 3 where the higher score indicates greater depressive symptoms. Outcome description was updated at the time of results entry. (NCT03395314)
Timeframe: Timepoints will be baseline, 1hr post-infusion and at 1, 3, 7, 14, & 28 days after infusion.

,
Interventionscore on a scale (Least Squares Mean)
baseline1hr post-infusionDay 1 post-infusionDay 3 post-infusionDay 7 post-infusionDay 14 post-infusionDay 28 post-infusion
Low Dose Ketamine1.50.20.10.30.50.71.21
Midazolam1.250.080.340.330.340.710.55

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Change in Suicidality as Measured by the Columbia Suicide Severity Rating Scale (C-SSRS)

Suicide Rating Scale from 1-5; higher numbers indicate increased suicidal thinking. (NCT03395314)
Timeframe: Timepoints will be baseline, 1hr post-infusion and at 1, 3, 7, 14, & 28 days after infusion.

,
Interventionscore on a scale (Least Squares Mean)
baseline1hr post-infusionDay 1 post-infusionDay 3 post-infusionDay 7 post-infusionDay 14 post-infusionDay 28 post-infusion
Low Dose Ketamine1.90.00.00.50.30.81.6
Midazolam1.58000.750.830.911.16

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Change in Zanarini Rating Scale for Borderline Personality Disorder

A dimensional self-report measure of BPD symptoms that consists of 9 items scored on a 4 point likert scale. Scores range of 0 = minimally symptomatic to 28 = maximally symptomatic for symptoms of Borderline Personality Disorder. Originally, 1hr post-infusion was included as a time frame but this was not collected at this time frame. (NCT03395314)
Timeframe: Timepoints will be baseline and at 1, 3, 7, 14, & 28 days after infusion.

,
Interventionscore on a scale (Least Squares Mean)
BaselineDay 1Day 3Day 7Day 14Day 28
Low Dose Ketamine15.45.25.26.87.211.42
Midazolam14.333.525.0456.757.16

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Change in Suicidality as Measured by Item 9 on Beck Depression Inventory

When the test is scored, a value of 0 to 3 is assigned for each answer and then the total score is used to quantify the participant's degree of depression from 0 = no depression to 63 = maximally severe depression. Item 9 measures degree of suicidal thoughts or wishes from 0 = no thoughts to 3 = suicidal intent. (NCT03395314)
Timeframe: Timepoints will be baseline, 1hr post-infusion and at 1, 3, 7, 14, & 28 days after infusion.

,
Interventionunits on a scale (Least Squares Mean)
baseline1hr post-infusionDay 1 post-infusionDay 3 post-infusionDay 7 post-infusionDay 14 post-infusionDay 28 post-infusion
Low Dose Ketamine1.20.10.30.30.30.30.56
Midazolam1.160.080.360.240.410.50.70

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Part A, Cmax: Maximum Observed Plasma Concentration for Midazolam

The statistical analysis was calculated via a mixed-effects ANOVA fitting terms for treatment (midazolam with or without brigatinib coadministration). (NCT03420742)
Timeframe: Cycle 1, Days 1 (Midazolam alone) and 21 (Midazolam + Brigatinib): pre-dose and at multiple timepoints (up to 24 hours) post-dose (Cycle length is 28 days)

Interventionnanogram per milliliter (ng/mL) (Geometric Mean)
Part A, Cycle 1 Day 1: Midazolam Alone19.7
Part A, Cycle 1 Day 21: Midazolam + Brigatinib16.5

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Part A, AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for Midazolam

The statistical analysis was calculated via a mixed-effects analysis of variance (ANOVA) fitting terms for treatment (midazolam with or without brigatinib coadministration). (NCT03420742)
Timeframe: Cycle 1, Days 1 (Midazolam alone) and 21 (Midazolam + Brigatinib): pre-dose and at multiple timepoints (up to 24 hours) post-dose (Cycle length is 28 days)

Interventionhour*nanogram per milliliter (h*ng/mL) (Geometric Mean)
Part A, Cycle 1 Day 1: Midazolam Alone57.2
Part A, Cycle 1 Day 21: Midazolam + Brigatinib42.1

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Part A, Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for Midazolam

(NCT03420742)
Timeframe: Cycle 1, Days 1 (Midazolam alone) and 21 (Midazolam + Brigatinib): pre-dose and at multiple timepoints (up to 24 hours) post-dose (Cycle length is 28 days)

Interventionhour (Median)
Part A, Cycle 1 Day 1: Midazolam Alone0.500
Part A, Cycle 1 Day 21: Midazolam + Brigatinib0.500

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PK of Inarigivir After Single and Multiple Oral Doses in Healthy Subjects (AUC)

A summary of the main plasma PK parameters for inarigivir, Rp-SB 9000, Sp-SB 9000, and Rp-SB 9000 and Sp-SB 9000 combined after a single oral dose of 400 mg inarigivir on Day 3 (Treatment B) and after the last of 14 consecutive daily oral doses of 400 mg inarigivir from Day 6 to 19 (Treatment D) (NCT03493698)
Timeframe: Day 3 and Day 6 to 19

Interventionh.ng/ml (Mean)
Day 19 AUC0-t (h.ng/mL)
Treatment D: Inarigivir With Midazolam0.951

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PK of Inarigivir After Single and Multiple Oral Doses in Healthy Subjects (Cmax)

A summary of the main plasma PK parameters for inarigivir, Rp-SB 9000, Sp-SB 9000, and Rp-SB 9000 and Sp-SB 9000 combined after a single oral dose of 400 mg inarigivir on Day 3 (Treatment B) and after the last of 14 consecutive daily oral doses of 400 mg inarigivir from Day 6 to 19 (Treatment D) (NCT03493698)
Timeframe: Day 3 and Day 6 to 19

Interventionng/mL (Mean)
Treatment B: Inarigivir0.886
Treatment D: Inarigivir With Midazolam0.991

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Number of Participants With Clinical Relevant Clinical Laboratory, Vital Signs, 12-lead ECG, or Physical Examination

Safety and tolerability were measured via clinical laboratory evaluations, vital signs, 12-lead ECG, or physical examination (NCT03493698)
Timeframe: Day -1 to Day 20 and Follow-up (5-9 days post-treatment)

InterventionParticipants (Count of Participants)
Treatment A: Midazolam0
Treatment B: Inarigivir0
Treatment C: Inarigivir0
Treatment D: Inarigivir With Midazolam0

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Effect of Steady-state Oral Inarigivir on the Single Dose Pharmacokinetics (PK) of Oral Midazolam in Healthy Subjects (Cmax)

Comparison of Cmax for midazolam between Treatments A and D. (NCT03493698)
Timeframe: Day 1 Treatment A and Day 19 Treatment D, respectively

Interventionng/mL (Mean)
Treatment A: Midazolam12.4
Treatment D: Inarigivir With Midazolam13.0

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Effect of Steady-state Oral Inarigivir on the Single Dose Pharmacokinetics (PK) of Oral Midazolam in Healthy Subjects (AUC0-t)

Comparison of AUC0-t for midazolam between Treatments A and D. (NCT03493698)
Timeframe: Day 1 Treatment A and Day 19 Treatment D, respectively

Interventionh.ng/ml (Mean)
Treatment A: Midazolam29.9
Treatment D: Inarigivir With Midazolam28.7

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Effect of Steady-state Oral Inarigivir on the Single Dose Pharmacokinetics (PK) of Oral Midazolam in Healthy Subjects (AUC0-inf )

Comparison of AUC0-inf for midazolam between Treatments A and D. (NCT03493698)
Timeframe: Day 1 Treatment A and Day 19 Treatment D, respectively

Interventionh.ng/ml (Mean)
Treatment A: Midazolam31.5
Treatment D: Inarigivir With Midazolam30.5

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PK of Inarigivir After Single and Multiple Oral Doses in Healthy Subjects (AUC)

A summary of the main plasma PK parameters for inarigivir, Rp-SB 9000, Sp-SB 9000, and Rp-SB 9000 and Sp-SB 9000 combined after a single oral dose of 400 mg inarigivir on Day 3 (Treatment B) and after the last of 14 consecutive daily oral doses of 400 mg inarigivir from Day 6 to 19 (Treatment D) (NCT03493698)
Timeframe: Day 3 and Day 6 to 19

Interventionh.ng/ml (Mean)
Day 3 AUC0-t (h.ng/mL)Day 3AUC0-inf (h.ng/mL)
Treatment B: Inarigivir0.9141.19

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Change in Daily Fatigue Severity Score

It is a single item question: 'how much fatigue (tiredness, weariness, problems thinking clearly) have you felt today?' with responses from 0 'None at all' to 10 'Extreme Fatigue'. Reported score changes are the average point/day score change. The mean score is reported based on this calculation: [(last day measure - baseline measure) / the number of days in the study]. (NCT03500289)
Timeframe: Baseline (infusion visit) through day 7

Interventionscore on a scale (Mean)
Ketamine-0.05
Midazolam-0.05

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Change in Epworth Sleepiness Scale Score

The Epworth Sleepiness Scale score can range from 0 to 24. The higher the score, the higher that person's average sleep propensity in daily life (ASP), or their 'daytime sleepiness'. Reported score changes are the average point/day score change. The mean score is reported based on this calculation: [(last day measure - baseline measure) / the number of days in the study]. (NCT03500289)
Timeframe: Baseline (infusion visit) through day 28 post-infusion

Interventionscore on a scale (Mean)
Ketamine0.03
Midazolam0.11

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Change in Fatigue Severity Scale (FSS) Score

The total score of the FSS ranges from 9 to 63. Higher scores denote more severe fatigue. Reported score changes are the average point/day score change. The mean score is reported based on this calculation: [(last day measure - baseline measure) / the number of days in the study]. (NCT03500289)
Timeframe: Baseline (infusion visit) through day 28 post-infusion

Interventionscore on a scale (Mean)
Ketamine0.03
Midazolam0.22

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Change in Beck Depression Inventory (BDI) Score

The total score of the BDI ranges from 0 to 63. Higher scores denote more severe depressive symptoms. Reported score changes are the average point/day score change. The mean score is reported based on this calculation: [(last day measure - baseline measure) / the number of days in the study]. (NCT03500289)
Timeframe: Baseline (infusion visit) through day 28 post-infusion

Interventionscore on a scale (Mean)
Ketamine0.07
Midazolam0.07

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Change in Quality of Life in Neurological Disorders (NeuroQol) Fatigue Item Bank Score

T-score distributions rescale raw scores into standardized scores with a mean of 50 and a standard deviation (SD) of 10. Higher T-scores denote more severe fatigue. Reported score changes are the average point/day score change. The mean score is reported based on this calculation: [(last day measure - baseline measure) / the number of days in the study]. (NCT03500289)
Timeframe: Baseline (infusion visit) through day 28 post-infusion

Interventionscore on a scale (Mean)
Ketamine-1.02
Midazolam-0.46

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Change in Modified Fatigue Impact Scale (MFIS) Score

The total score of the MFIS ranges from 0 to 84. Higher scores denote more severe fatigue. Reported score changes are the average point/day score change. The mean score is reported based on this calculation: [(last day measure - baseline measure) / the number of days in the study]. (NCT03500289)
Timeframe: Baseline (infusion visit) through Day 28 post-infusion

Interventionscore on a scale (Mean)
Ketamine-0.46
Midazolam0.02

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Nurse and Physician Satisfaction

Nurse and physician satisfaction will be assessed by a survey which will be filled in the end of the sedation. Response to overall experience question score on Likert scale where 1 is poor and 5 is Excellent. Proportion of responders giving answers of 4 or 5 will be calculated. (NCT03528512)
Timeframe: Up to 30 minutes

InterventionParticipants (Count of Participants)
IN Ketamine1
IN Midazolam and Fentanyl4

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Change in Vitals

Proportion of children who have any significant change in vitals during analgosedation (any desaturation - Oxygen saturation < 90, and hypotension per age-related norms) will be compared between the two groups. (NCT03528512)
Timeframe: up to 30 minutes

InterventionParticipants (Count of Participants)
IN Ketamine0
IN Midazolam and Fentanyl0

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Pain Scores During Laceration Repair

The effect of IN ketamine vs IN midazolam + IN fentanyl on pain scores during laceration repair using either Face, Legs, Activity, Cry, Consolability (FLACC) Scale or Faces Scale pain scale depending for patient age, each a Likert scale from 0 being no pain to 10 being worst pain, median scores for each group (NCT03528512)
Timeframe: Up to 30 minutes

Interventionunits on a scale (Median)
IN Ketamine4
IN Midazolam and Fentanyl0

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Proportion of Children With Maximum Sedation Score

The proportion of children who receive a maximum sedation score of either 1 or 2 (without distinguishing between those values) (NCT03528512)
Timeframe: Up to 30 minutes

InterventionParticipants (Count of Participants)
IN Ketamine2
IN Midazolam and Fentanyl2

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Rates of Failure

Rates of failure to repair laceration due to agitation or intolerable pain with the switch to intravenous medications will be compared between two groups. Percentage failure will be reported. (NCT03528512)
Timeframe: Up to 30 minutes

InterventionParticipants (Count of Participants)
IN Ketamine0
IN Midazolam and Fentanyl0

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Sedation Score

The primary outcome variable is the maximum sedation score as measured by the University of Michigan Sedation Scale. This scale consists of an ordinal scale from 0 being awake and alert and 4 being unarousable. Medians will be calculated for each group. (NCT03528512)
Timeframe: up to 30 minutes

Interventionunits on a scale (Median)
IN Ketamine1
IN Midazolam and Fentanyl1

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Number of Participants With Clinically Significant Changes in Vital Signs

Number of participants with clinically significant changes in vital signs were reported. Clinical significance was decided by Investigator. Vital signs included body temperature, blood pressure and pulse rate. (NCT03628339)
Timeframe: Day 1 (Treatment Period 1) up to the End of Trial visit (Day 20)

InterventionParticipants (Count of Participants)
Midazolam (Reference Treatment)0
Tepotinib + Midazolam (Test Treatment)0

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Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious TEAEs and TEAEs Leading to Death

Adverse event (AE) was defined as any untoward medical occurrence in participants which does not necessarily have causal relationship with treatment. AE was any unfavorable and unintended sign (including abnormal laboratory finding), symptom/disease temporally associated with use of medicinal product, whether/not considered related to medicinal product. A serious adverse event (SAE) was AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial/prolonged inpatient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. Term TEAE is defined as AEs starting/worsening after first intake of the study drug. TEAEs included both serious TEAEs and non-serious TEAEs. (NCT03628339)
Timeframe: Baseline (Day 1 of treatment period 1) up to the End of Trial visit (Day 20)

,
InterventionParticipants (Count of Participants)
TEAEsSerious TEAEsTEAEs Leading to Death
Midazolam (Reference Treatment)100
Tepotinib + Midazolam (Test Treatment)1000

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Maximum Observed Plasma Concentration (Cmax) of Midazolam

Cmax was obtained directly from concentration versus time curve. (NCT03628339)
Timeframe: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36 and 43 hours post-dose on Day 1 of period 1 and Day 11 of Period 2

Interventionpg/mL (Geometric Mean)
Midazolam (Reference Treatment)49172
Tepotinib + Midazolam (Test Treatment)50954

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Area Under the Plasma Concentration-Time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of Midazolam Metabolite (1-Hydroxymidazolam)

AUC0-inf was calculated as AUC0-t plus (+) AUCextra. AUCextra represents the extrapolated part of AUC0-inf calculated by Clastpred/Lambda z, where Clastpred is the predicted plasma concentration at the last sampling time point, calculated from the log-linear regression line for Lambda z determination at which the measured plasma concentration is at or above Lower limit of quantification (LLOQ). (NCT03628339)
Timeframe: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36 and 43 hours post-dose on Day 1 of period 1 and Day 11 of Period 2

Interventionh*pg/mL (Geometric Mean)
Midazolam (Reference Treatment)31269
Tepotinib + Midazolam (Test Treatment)33372

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Area Under the Plasma Concentration-Time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of Midazolam

AUC0-inf was calculated as AUC0-t plus (+) AUCextra. AUCextra represents the extrapolated part of AUC0-inf calculated by Clastpred/Lambda z, where Clastpred is the predicted plasma concentration at the last sampling time point, calculated from the log-linear regression line for Lambda z determination at which the measured plasma concentration is at or above Lower limit of quantification (LLOQ). (NCT03628339)
Timeframe: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36 and 43 hours post-dose on Day 1 of period 1 and Day 11 of Period 2

Interventionh*pg/mL (Geometric Mean)
Midazolam (Reference Treatment)109285
Tepotinib + Midazolam (Test Treatment)110550

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Area Under Plasma Concentration-time Curve From Time Zero to Last Sampling Time (Tlast) at Which the Concentration is at or Above the Lower Limit of Quantification (AUC0-t) of Midazolam Metabolite (1-Hydroxymidazolam)

AUC0-t a Pharmacokinetic (PK) parameter was calculated according to the mixed log linear trapezoidal rule. (NCT03628339)
Timeframe: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36 and 43 hours post-dose on Day 1 of period 1 and Day 11 of Period 2

Interventionh*pg/mL (Geometric Mean)
Midazolam (Reference Treatment)30589
Tepotinib + Midazolam (Test Treatment)32627

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Area Under Plasma Concentration-time Curve From Time Zero to Last Sampling Time (Tlast) at Which the Concentration is at or Above the Lower Limit of Quantification (AUC0-t) of Midazolam

AUC0-t a Pharmacokinetic (PK) parameter was calculated according to the mixed log linear trapezoidal rule. (NCT03628339)
Timeframe: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36 and 43 hours post-dose on Day 1 of period 1 and Day 11 of Period 2

Interventionhour*picogram per milliliter (h*pg/mL) (Geometric Mean)
Midazolam (Reference Treatment)107969
Tepotinib + Midazolam (Test Treatment)109477

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Time to Reach Maximum Plasma Concentration (Tmax) of Midazolam and Midazolam Metabolite (1-Hydroxymidazolam)

Tmax is time to reach maximum observed plasma concentration obtained directly from the concentration versus time curve. (NCT03628339)
Timeframe: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36 and 43 hours post-dose on Day 1 of period 1 and Day 11 of Period 2

,
InterventionHours (Median)
MidazolamMidazolam Metabolite (1- Hydroxymidazolam)
Midazolam (Reference Treatment)0.5000.500
Tepotinib + Midazolam (Test Treatment)0.5080.508

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Maximum Observed Plasma Concentration (Cmax) of Midazolam Metabolite (1-Hydroxymidazolam)

Cmax was obtained directly from concentration versus time curve. (NCT03628339)
Timeframe: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36 and 43 hours post-dose on Day 1 of period 1 and Day 11 of Period 2

Interventionpg/mL (Geometric Mean)
Midazolam (Reference Treatment)14909
Tepotinib + Midazolam (Test Treatment)15852

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Metabolic Ratio of Midazolam and Midazolam Metabolite (1-hydroxymidazolam)

Metabolic ratio was calculated as AUC 0-infinity of midazolam divided by AUC 0-infinity of 1-hydroxymidazolam. (NCT03628339)
Timeframe: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36 and 43 hours post-dose on Day 1 of period 1 and Day 11 of Period 2

Interventionratio (Geometric Mean)
Midazolam (Reference Treatment)0.286
Tepotinib + Midazolam (Test Treatment)0.302

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Number of Participants With Clinically Significant Changes in 12-Lead Electrocardiogram (ECG)

Number of participants with clinically significant changes in 12-lead ECG were reported. Clinical significance was decided by the investigator. The 12-lead ECGs were recorded after the participants have rested for at least 5 minute in supine position. (NCT03628339)
Timeframe: Day 1 (Treatment Period 1) up to the End of Trial visit (Day 20)

InterventionParticipants (Count of Participants)
Midazolam (Reference Treatment)0
Tepotinib + Midazolam (Test Treatment)0

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Number of Participants With Clinically Significant Changes in Laboratory Values

Number of participants with clinically significant changes in laboratory values were reported. Clinical significance was decided by the investigator. Laboratory investigation included hematology and urinalysis. (NCT03628339)
Timeframe: From Screening up to the End of Trial visit (Day 20)

InterventionParticipants (Count of Participants)
Midazolam (Reference Treatment)0
Tepotinib + Midazolam (Test Treatment)0

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Elimination Half Life (t1/2) of Midazolam and Midazolam Metabolite (1-Hydroxymidazolam)

Elimination Half Life (t1/2) was defined as the time required for the concentration or amount of drug in the body to be reduced by one-half. (NCT03628339)
Timeframe: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36 and 43 hours post-dose on Day 1 of period 1 and Day 11 of Period 2

,
InterventionHours (Geometric Mean)
MidazolamMidazolam Metabolite (1- Hydroxymidazolam)
Midazolam (Reference Treatment)5.526.34
Tepotinib + Midazolam (Test Treatment)4.816.90

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Heart Rate-2

The heart rate observed from EKG monitorization at the time operator warns the investigator just before the traction of the orbital muscle. Heart rate-2 is a data, not an assessing change, which is recorded during the operation at the time operator warns. The heart rate observed from EKG monitorization, before every orbital muscle traction at the time the operator's warning before traction. (NCT03806270)
Timeframe: 1 minute, at the strabismus surgery operation, through study completion an average of 6 months

Interventionbeats per minute (Mean)
Midazolam110.4
Midazolam&Hydroxyzine dihydrochloride1/2125.3
Midazolam&Hydroxyzine Dihydrochloride124.8

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Heart Rate-1

"The lowest heart rate observed from EKG monitorization at the time-out after the anesthesia induction, and just before the surgery starts. Heart rate-1 is a data, not an assessing change, which is recoded during the time-out. The time-out is when the patient's name, the procedure, the surgent name is repeated before the operation starts." (NCT03806270)
Timeframe: "1 minute, at the time out, through study completion an average of 6 months"

Interventionbeats per minute (Mean)
Midazolam114.4
Midazolam&Hydroxyzine dihydrochloride1/2125.8
Midazolam&Hydroxyzine Dihydrochloride122.3

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Heart Rate-3

The lowest heart rate observed from EKG monitorization, after every orbital muscle traction within 120 seconds. Heart rate-3 is a data, not an assessing change, which is recorded within 120 seconds after traction applied. (NCT03806270)
Timeframe: within 120 seconds after the orbital muscle traction, at the strabismus surgery operation, through study completion an average of 6 months

Interventionbeats per minute (Mean)
Midazolam90.8
Midazolam&Hydroxyzine dihydrochloride1/2113.4
Midazolam&Hydroxyzine Dihydrochloride117.9

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Number of Observed Oculocardiac Reflex(OCR)

The OCR is a heartbeat anomaly(bradycardia, any arrhythmia, or cardiac arrest) associated with traction applied to the extraocular muscles during strabismus surgery. The specific criteria were as follows: the lowest heart rate observed within 120 seconds from EKG monitorization, after every orbital muscle traction, was less than 20% of the heart rate observed directly preceding traction of the orbital muscle. Additionally, any kind of arrhythmia or cardiac arrest occurrence within 120 seconds after orbital muscle traction was also defined as an OCR. (NCT03806270)
Timeframe: 2 minutes, at the strabismus surgery operation after recording Heart Rate-3, through study completion an average of 6 months

Interventionorbital muscles (Count of Units)
Midazolam15
Midazolam&Hydroxyzine dihydrochloride1/26
Midazolam&Hydroxyzine Dihydrochloride1

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Number of Orbital Muscles of the Participants With Different Considerations Taken With Respect to the Treatment of OCR

The investigator records every OCR treatment like; pausing surgery, atropin 20mcg/kg intravenous treatment or cardiac resuscitation. (NCT03806270)
Timeframe: within 5 minutes after defining the OCR occurrence, at the strabismus surgery operation, through study completion an average of 6 months

,,
Interventionnumber of orbital muscle/s, OCR occured (Number)
pausing surgeryatropin administrationcardiac resuscitation
Midazolam1320
Midazolam&Hydroxyzine Dihydrochloride100
Midazolam&Hydroxyzine dihydrochloride1/2600

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Side Effects

drug side effects scale: severity scale from 1 (not at all) to 7 (extremely) for symptoms of nausea, dizziness, sleepiness, strange thoughts, hallucinations, confusion, anxiousness, and headache. The average score across all side effects is reported. (NCT03813121)
Timeframe: about 1 week post infusion

Interventionscore on a scale (Mean)
Placebo Intravenous Infusion1.3
Ketamine Intravenous Infusion1.4

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Tolerability of a Multiple-dosing Ketamine Infusion Paradigm (2 Infusions Per Week for 3 Weeks) Compared to Midazolam in Adolescents With Treatment Resistant Depression

Establish if repeated ketamine will be tolerated as measured by drop-out counts. (NCT03889756)
Timeframe: Day 18

InterventionParticipants (Count of Participants)
Ketamine0
Midazolam0

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Efficacy of a Multiple-dosing Ketamine Infusion Paradigm (2 Infusions Per Week for 3 Weeks) Compared to Midazolam in Adolescents With Treatment Resistant Depression Using the Children's Depression Rating Scale (CDRS)

Establish if repeated ketamine will be efficacious medically and psychiatrically, as measured by a significant reduction in CDRS score in those treated with ketamine at the end of the dosing paradigm. The Children's Depression Rating Scale (CDRS) is a clinician-rated instrument with 17 items scored on a 1 to 5 or 1 to 7 scale. A rating of 1 indicates normal, thus the minimum score is 17. The maximum score is 113. Scores of 20-30 suggest borderline depression. Scores of 40-60 indicate moderate depression. (NCT03889756)
Timeframe: Day 18

Interventionscore on a scale (Mean)
Ketamine42
Midazolam62

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Part 2: AUClast of Midazolam Metabolite (1-Hydroxy Midazolam) Alone and in Combination With Risdiplam

In Part 2 of the study, all study participants received a single oral dose of 2 mg midazolam on Day 1. On Day 3, the 14-day once daily (QD) treatment period with risdiplam began, with single dose administration of 2 mg midazolam again on Day 15 (1 hour after the thirteenth dose of risdiplam). The following treatment sequence was used in Part 2 of the study: Day 1: 2 mg midazolam; Days 3 to 14: 8 mg risdiplam QD; Day 15: 2 mg midazolam and 8 mg risdiplam QD; Day 16: 8 mg risdiplam QD. Blood samples for PK analysis were taken at defined timepoints on Day 1 for midazolam administered alone and on Day 15 for midazolam administered in combination with risdiplam. (NCT03988907)
Timeframe: Day 1 and Day 15: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24 hours postdose

Interventionh*ng/mL (Geometric Mean)
Day 15 midazolam + risdiplam
2 mg Midazolam + 8 mg Risdiplam QD (Test)9.43

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Part 2: Cmax of Risdiplam and M1 Risdiplam Following Multiple Oral Doses

In Part 2 of the study, all study participants received a single oral dose of 2 mg midazolam on Day 1. On Day 3, the 14-day once daily (QD) treatment period with risdiplam began, with single dose administration of 2 mg midazolam again on Day 15 (1 hour after the thirteenth dose of risdiplam). The following treatment sequence was used in Part 2 of the study: Day 1: 2 mg midazolam; Days 3 to 14: 8 mg risdiplam QD; Day 15: 2 mg midazolam and 8 mg risdiplam QD; Day 16: 8 mg risdiplam QD. (NCT03988907)
Timeframe: Day 3: Predose, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, and 12 hours postdose; Day 4 to Day 15: Predose; Day 16: Predose, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 96, and 144 hours postdose

,
Interventionng/mL (Geometric Mean)
Day 3Day 16
8 mg Risdiplam QD42.6113
M1 of Risdiplam7.3330.5

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Part 2: Maximum Observed Plasma Concentration (Cmax) of Midazolam Alone and in Combination With Risdiplam

In Part 2 of the study, all study participants received a single oral dose of 2 mg midazolam on Day 1. On Day 3, the 14-day once daily (QD) treatment period with risdiplam began, with single dose administration of 2 mg midazolam again on Day 15 (1 hour after the thirteenth dose of risdiplam). The following treatment sequence was used in Part 2 of the study: Day 1: 2 mg midazolam; Days 3 to 14: 8 mg risdiplam QD; Day 15: 2 mg midazolam and 8 mg risdiplam QD; Day 16: 8 mg risdiplam QD. Blood samples for PK analysis were taken at defined timepoints on Day 1 for midazolam administered alone and on Day 15 for midazolam administered in combination with risdiplam. (NCT03988907)
Timeframe: Day 1 and Day 15: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24 hours postdose

Interventionng/mL (Geometric Mean)
Day 1 midazolam alone
2 mg Midazolam (Reference)7.65

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Part 2: AUClast of Risdiplam and M1 Risdiplam Following Multiple Oral Doses

In Part 2 of the study, all study participants received a single oral dose of 2 mg midazolam on Day 1. On Day 3, the 14-day once daily (QD) treatment period with risdiplam began, with single dose administration of 2 mg midazolam again on Day 15 (1 hour after the thirteenth dose of risdiplam). The following treatment sequence was used in Part 2 of the study: Day 1: 2 mg midazolam; Days 3 to 14: 8 mg risdiplam QD; Day 15: 2 mg midazolam and 8 mg risdiplam QD; Day 16: 8 mg risdiplam QD. (NCT03988907)
Timeframe: Day 3: Predose, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, and 12 hours postdose; Day 4 to Day 15: Predose; Day 16: Predose, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 96, and 144 hours postdose

,
Interventionh*ng/mL (Geometric Mean)
Day 3Day 16
8 mg Risdiplam QD5974280
M1 of Risdiplam1301350

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Part 2: Cmax of Midazolam Metabolite (1-Hydroxy Midazolam) Alone and in Combination With Risdiplam

In Part 2 of the study, all study participants received a single oral dose of 2 mg midazolam on Day 1. On Day 3, the 14-day once daily (QD) treatment period with risdiplam began, with single dose administration of 2 mg midazolam again on Day 15 (1 hour after the thirteenth dose of risdiplam). The following treatment sequence was used in Part 2 of the study: Day 1: 2 mg midazolam; Days 3 to 14: 8 mg risdiplam QD; Day 15: 2 mg midazolam and 8 mg risdiplam QD; Day 16: 8 mg risdiplam QD. Blood samples for PK analysis were taken at defined timepoints on Day 1 for midazolam administered alone and on Day 15 for midazolam administered in combination with risdiplam. (NCT03988907)
Timeframe: Day 1 and Day 15: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24 hours postdose

Interventionng/mL (Geometric Mean)
Day 1 midazolam alone
2 mg Midazolam (Reference)3.18

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Part 2: Percentage of Participants With Adverse Events After Midazolam Administration Alone and in Combination With Risdiplam

An adverse event is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events. (NCT03988907)
Timeframe: Day 1 to Day 20 and up to 10+/-2 Days Post Final Dose or Early Termination

,
InterventionPercentage of Participants (Number)
With at least one AEWith at least one SAE
2 mg Midazolam (Reference)7.40.0
2 mg Midazolam + 8 mg Risdiplam QD (Test)7.70.0

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Part 2: Maximum Observed Plasma Concentration (Cmax) of Midazolam Alone and in Combination With Risdiplam

In Part 2 of the study, all study participants received a single oral dose of 2 mg midazolam on Day 1. On Day 3, the 14-day once daily (QD) treatment period with risdiplam began, with single dose administration of 2 mg midazolam again on Day 15 (1 hour after the thirteenth dose of risdiplam). The following treatment sequence was used in Part 2 of the study: Day 1: 2 mg midazolam; Days 3 to 14: 8 mg risdiplam QD; Day 15: 2 mg midazolam and 8 mg risdiplam QD; Day 16: 8 mg risdiplam QD. Blood samples for PK analysis were taken at defined timepoints on Day 1 for midazolam administered alone and on Day 15 for midazolam administered in combination with risdiplam. (NCT03988907)
Timeframe: Day 1 and Day 15: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24 hours postdose

Interventionng/mL (Geometric Mean)
Day 15 midazolam + risdiplam
2 mg Midazolam + 8 mg Risdiplam QD (Test)8.96

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Part 2: Cmax of Midazolam Metabolite (1-Hydroxy Midazolam) Alone and in Combination With Risdiplam

In Part 2 of the study, all study participants received a single oral dose of 2 mg midazolam on Day 1. On Day 3, the 14-day once daily (QD) treatment period with risdiplam began, with single dose administration of 2 mg midazolam again on Day 15 (1 hour after the thirteenth dose of risdiplam). The following treatment sequence was used in Part 2 of the study: Day 1: 2 mg midazolam; Days 3 to 14: 8 mg risdiplam QD; Day 15: 2 mg midazolam and 8 mg risdiplam QD; Day 16: 8 mg risdiplam QD. Blood samples for PK analysis were taken at defined timepoints on Day 1 for midazolam administered alone and on Day 15 for midazolam administered in combination with risdiplam. (NCT03988907)
Timeframe: Day 1 and Day 15: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24 hours postdose

Interventionng/mL (Geometric Mean)
Day 15 midazolam + risdiplam
2 mg Midazolam + 8 mg Risdiplam QD (Test)4.10

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Part 2: AUCtau of Risdiplam and M1 Risdiplam Following Multiple Oral Doses

In Part 2 of the study, all study participants received a single oral dose of 2 mg midazolam on Day 1. On Day 3, the 14-day once daily (QD) treatment period with risdiplam began, with single dose administration of 2 mg midazolam again on Day 15 (1 hour after the thirteenth dose of risdiplam). The following treatment sequence was used in Part 2 of the study: Day 1: 2 mg midazolam; Days 3 to 14: 8 mg risdiplam QD; Day 15: 2 mg midazolam and 8 mg risdiplam QD; Day 16: 8 mg risdiplam QD. (NCT03988907)
Timeframe: Day 3: Predose, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, and 12 hours postdose; Day 4 to Day 15: Predose; Day 16: Predose, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 96, and 144 hours postdose

,
Interventionh*ng/mL (Geometric Mean)
Day 3Day 16
8 mg Risdiplam QD6131730
M1 of Risdiplam131504

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Part 1: Cmax of Risdiplam and M1 Risdiplam Following Multiple Oral Doses

In Part 1 of the study, participants received a single oral dose of 5 mg risdiplam once daily (QD) for 14 consecutive days. Blood samples of risdiplam and its metabolite were taken at defined timepoints on Day 1 and on Day 14 for the PK analysis. (NCT03988907)
Timeframe: Day 1: Predose, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, and 12 hours postdose; Day 2 to Day 13: Predose; Day 14: Predose, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 96, and 144 hours postdose

,
Interventionng/mL (Geometric Mean)
Day 1Day 14
5 mg Risdiplam25.978.6
M1 Risdiplam4.3319.1

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Part 2: Area Under the Concentration-Time Curve From Time Zero Extrapolated to Infinity (AUCinf) of Midazolam Alone and in Combination With Risdiplam

In Part 2 of the study, all study participants received a single oral dose of 2 mg midazolam on Day 1. On Day 3, the 14-day once daily (QD) treatment period with risdiplam began, with single dose administration of 2 mg midazolam again on Day 15 (1 hour after the thirteenth dose of risdiplam). The following treatment sequence was used in Part 2 of the study: Day 1: 2 mg midazolam; Days 3 to 14: 8 mg risdiplam QD; Day 15: 2 mg midazolam and 8 mg risdiplam QD; Day 16: 8 mg risdiplam QD. Blood samples for pharmacokinetic (PK) analysis were taken at defined timepoints on Day 1 for midazolam administered alone and on Day 15 for midazolam administered in combination with risdiplam. (NCT03988907)
Timeframe: Day 1 and Day 15: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24 hours postdose

Interventionh*ng/mL (Geometric Mean)
Day 1 midazolam alone
2 mg Midazolam (Reference)22.6

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Part 2: Area Under the Concentration-Time Curve From Time Zero Extrapolated to Infinity (AUCinf) of Midazolam Alone and in Combination With Risdiplam

In Part 2 of the study, all study participants received a single oral dose of 2 mg midazolam on Day 1. On Day 3, the 14-day once daily (QD) treatment period with risdiplam began, with single dose administration of 2 mg midazolam again on Day 15 (1 hour after the thirteenth dose of risdiplam). The following treatment sequence was used in Part 2 of the study: Day 1: 2 mg midazolam; Days 3 to 14: 8 mg risdiplam QD; Day 15: 2 mg midazolam and 8 mg risdiplam QD; Day 16: 8 mg risdiplam QD. Blood samples for pharmacokinetic (PK) analysis were taken at defined timepoints on Day 1 for midazolam administered alone and on Day 15 for midazolam administered in combination with risdiplam. (NCT03988907)
Timeframe: Day 1 and Day 15: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24 hours postdose

Interventionh*ng/mL (Geometric Mean)
Day 15 midazolam + risdiplam
2 mg Midazolam + 8 mg Risdiplam QD (Test)25.1

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Part 2: Area Under the Plasma Concentration-Time Curve From Time Zero to the Time of Last Quantifiable Concentration (AUClast) of Midazolam Alone and in Combination With Risdiplam

In Part 2 of the study, all study participants received a single oral dose of 2 mg midazolam on Day 1. On Day 3, the 14-day once daily (QD) treatment period with risdiplam began, with single dose administration of 2 mg midazolam again on Day 15 (1 hour after the thirteenth dose of risdiplam). The following treatment sequence was used in Part 2 of the study: Day 1: 2 mg midazolam; Days 3 to 14: 8 mg risdiplam QD; Day 15: 2 mg midazolam and 8 mg risdiplam QD; Day 16: 8 mg risdiplam QD. Blood samples for PK analysis were taken at defined timepoints on Day 1 for midazolam administered alone and on Day 15 for midazolam administered in combination with risdiplam. (NCT03988907)
Timeframe: Day 1 and Day 15: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24 hours postdose

Interventionh*ng/mL (Geometric Mean)
Day 1 midazolam alone
2 mg Midazolam (Reference)19.9

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Part 2: Area Under the Plasma Concentration-Time Curve From Time Zero to the Time of Last Quantifiable Concentration (AUClast) of Midazolam Alone and in Combination With Risdiplam

In Part 2 of the study, all study participants received a single oral dose of 2 mg midazolam on Day 1. On Day 3, the 14-day once daily (QD) treatment period with risdiplam began, with single dose administration of 2 mg midazolam again on Day 15 (1 hour after the thirteenth dose of risdiplam). The following treatment sequence was used in Part 2 of the study: Day 1: 2 mg midazolam; Days 3 to 14: 8 mg risdiplam QD; Day 15: 2 mg midazolam and 8 mg risdiplam QD; Day 16: 8 mg risdiplam QD. Blood samples for PK analysis were taken at defined timepoints on Day 1 for midazolam administered alone and on Day 15 for midazolam administered in combination with risdiplam. (NCT03988907)
Timeframe: Day 1 and Day 15: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24 hours postdose

Interventionh*ng/mL (Geometric Mean)
Day 15 midazolam + risdiplam
2 mg Midazolam + 8 mg Risdiplam QD (Test)22.0

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Part 2: AUCinf of Midazolam Metabolite (1-Hydroxy Midazolam) Alone and in Combination With Risdiplam

In Part 2 of the study, all study participants received a single oral dose of 2 mg midazolam on Day 1. On Day 3, the 14-day once daily (QD) treatment period with risdiplam began, with single dose administration of 2 mg midazolam again on Day 15 (1 hour after the thirteenth dose of risdiplam). The following treatment sequence was used in Part 2 of the study: Day 1: 2 mg midazolam; Days 3 to 14: 8 mg risdiplam QD; Day 15: 2 mg midazolam and 8 mg risdiplam QD; Day 16: 8 mg risdiplam QD. Blood samples for PK analysis were taken at defined timepoints on Day 1 for midazolam administered alone and on Day 15 for midazolam administered in combination with risdiplam. (NCT03988907)
Timeframe: Day 1 and Day 15: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24 hours postdose

Interventionh*ng/mL (Geometric Mean)
Day 1 midazolam alone
2 mg Midazolam (Reference)8.66

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Part 2: AUCinf of Midazolam Metabolite (1-Hydroxy Midazolam) Alone and in Combination With Risdiplam

In Part 2 of the study, all study participants received a single oral dose of 2 mg midazolam on Day 1. On Day 3, the 14-day once daily (QD) treatment period with risdiplam began, with single dose administration of 2 mg midazolam again on Day 15 (1 hour after the thirteenth dose of risdiplam). The following treatment sequence was used in Part 2 of the study: Day 1: 2 mg midazolam; Days 3 to 14: 8 mg risdiplam QD; Day 15: 2 mg midazolam and 8 mg risdiplam QD; Day 16: 8 mg risdiplam QD. Blood samples for PK analysis were taken at defined timepoints on Day 1 for midazolam administered alone and on Day 15 for midazolam administered in combination with risdiplam. (NCT03988907)
Timeframe: Day 1 and Day 15: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24 hours postdose

Interventionh*ng/mL (Geometric Mean)
Day 15 midazolam + risdiplam
2 mg Midazolam + 8 mg Risdiplam QD (Test)9.41

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Part 2: AUClast of Midazolam Metabolite (1-Hydroxy Midazolam) Alone and in Combination With Risdiplam

In Part 2 of the study, all study participants received a single oral dose of 2 mg midazolam on Day 1. On Day 3, the 14-day once daily (QD) treatment period with risdiplam began, with single dose administration of 2 mg midazolam again on Day 15 (1 hour after the thirteenth dose of risdiplam). The following treatment sequence was used in Part 2 of the study: Day 1: 2 mg midazolam; Days 3 to 14: 8 mg risdiplam QD; Day 15: 2 mg midazolam and 8 mg risdiplam QD; Day 16: 8 mg risdiplam QD. Blood samples for PK analysis were taken at defined timepoints on Day 1 for midazolam administered alone and on Day 15 for midazolam administered in combination with risdiplam. (NCT03988907)
Timeframe: Day 1 and Day 15: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24 hours postdose

Interventionh*ng/mL (Geometric Mean)
Day 1 midazolam alone
2 mg Midazolam (Reference)7.75

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Part 1: AUClast of Risdiplam and M1 Risdiplam Following Multiple Oral Doses

In Part 1 of the study, participants received a single oral dose of 5 mg risdiplam once daily (QD) for 14 consecutive days. Blood samples of risdiplam and its metabolite were taken at defined timepoints on Day 1 and on Day 14 for the PK analysis. (NCT03988907)
Timeframe: Day 1: Predose, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, and 12 hours postdose; Day 2 to Day 13: Predose; Day 14: Predose, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 96, and 144 hours postdose

,
Interventionh*ng/mL (Geometric Mean)
Day 1Day 14
5 mg Risdiplam3993160
M1 Risdiplam78.2929

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Part 1: Area Under the Plasma Concentration-Time Curve From Time Zero to the End of the Dosing Interval (AUCtau) of Risdiplam and Its Metabolite (M1) Following Multiple Oral Doses

In Part 1 of the study, participants received a single oral dose of 5 mg risdiplam once daily (QD) for 14 consecutive days. Blood samples for risdiplam and its metabolite were taken at defined timepoints on Day 1 and on Day 14 for the PK analysis. (NCT03988907)
Timeframe: Day 1: Predose, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, and 12 hours postdose; Day 2 to Day 13: Predose; Day 14: Predose, 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 96, and 144 hours postdose

,
Interventionh*ng/mL (Geometric Mean)
Day 1Day 14
5 mg Risdiplam4041250
M1 Risdiplam78.4349

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Part 1 and Part 2: Percentage of Participants With Adverse Events After Administration of Multiple Doses of Risdiplam

An adverse event is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events. (NCT03988907)
Timeframe: Day 1 to Day 20 and up to 10+/-2 Days Post Final Dose or Early Termination

,
InterventionPercentage of Participants (Number)
With at least one AEWith at least one SAE
Part 125.00.0
Part 2: 8 mg Risdiplam QD51.90.0

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Number of Participants With Successful Sedation

Children's behavior during sedation is rated on the Houpt Behavior Rating Scale. A successful sedation is rated as Excellent, Very Good, or Good. A failed sedation is rated as Fair, Poor, or Aborted. (NCT04068948)
Timeframe: At completion of procedure

InterventionParticipants (Count of Participants)
Midazolam, Hydroxyzine, Meperidine11
Midazolam, Hydroxyzine9

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Part 1: Maximum Plasma Concentration (Cmax) of S-648414

(NCT04147715)
Timeframe: Day 1 and Day 14 (for participants in the 100 mg dose group only) predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 24, 48, 72 and 96 hours postdose.

Interventionng/mL (Geometric Mean)
Part 1: 10 mg S-648414151
Part 1: 30 mg S-648414498
Part 1: 100 mg S-648414 Fasted1620
Part 1: 100 mg S-648414 Fed1430
Part 1: 250 mg S-6484143820
Part 1: 500 mg S-6484149260
Part 1: 1000 mg S-64841412700

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Part 1: Mean Residence Time (MRT) of S-648414

Mean residence time, calculated as MRT = AUMC0-inf / AUC0-inf, where AUMC0-inf is the area under the first moment curve extrapolated to infinity. (NCT04147715)
Timeframe: Day 1 and Day 14 (for participants in the 100 mg dose group only) predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 24, 48, 72 and 96 hours postdose.

Interventionhours (Geometric Mean)
Part 1: 10 mg S-64841432.5
Part 1: 30 mg S-64841429.2
Part 1: 100 mg S-648414 Fasted31.5
Part 1: 100 mg S-648414 Fed33.8
Part 1: 250 mg S-64841434.2
Part 1: 500 mg S-64841432.6
Part 1: 1000 mg S-64841434.5

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Part 1: Renal Clearance (CLR) of S-648414

Renal clearance was estimated according to: CLR = cumulative amount of S-648414 excreted in urine from time zero to 96 hours postdose (Aeu0-96) / area under the concentration-time curve from time zero to the time of the last quantifiable concentration after dosing (AUC0-last). (NCT04147715)
Timeframe: Day 1 and Day 14 (for participants in the 100 mg dose group only) predose (-12 to 0 hours), 0 to 24 hours, 24 to 48 hours, 48 to 72 hours, and 72 to 96 hours postdose

InterventionL/hr (Geometric Mean)
Part 1: 10 mg S-6484140.884
Part 1: 30 mg S-6484140.721
Part 1: 100 mg S-648414 Fasted0.695
Part 1: 100 mg S-648414 Fed0.720
Part 1: 250 mg S-6484140.804
Part 1: 500 mg S-6484140.732
Part 1: 1000 mg S-6484140.720

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Part 1: Terminal Elimination Half-life (t1/2,z) of S-648414

Terminal elimination half-life calculated as t1/2,z = (ln2)/λz, where λz is the terminal elimination rate constant. (NCT04147715)
Timeframe: Day 1 and Day 14 (for participants in the 100 mg dose group only) predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 24, 48, 72 and 96 hours postdose.

Interventionhours (Geometric Mean)
Part 1: 10 mg S-64841423.0
Part 1: 30 mg S-64841420.7
Part 1: 100 mg S-648414 Fasted22.2
Part 1: 100 mg S-648414 Fed22.8
Part 1: 250 mg S-64841424.1
Part 1: 500 mg S-64841422.2
Part 1: 1000 mg S-64841423.7

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Part 1: Terminal Elimination Rate Constant (λz) of S-648414

(NCT04147715)
Timeframe: Day 1 and Day 14 (for participants in the 100 mg dose group only) predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 24, 48, 72 and 96 hours postdose.

Intervention1/hour (Geometric Mean)
Part 1: 10 mg S-6484140.0301
Part 1: 30 mg S-6484140.0336
Part 1: 100 mg S-648414 Fasted0.0313
Part 1: 100 mg S-648414 Fed0.0305
Part 1: 250 mg S-6484140.0288
Part 1: 500 mg S-6484140.0312
Part 1: 1000 mg S-6484140.0293

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Part 1: Time to Maximum Plasma Concentration (Tmax) of S-648414

(NCT04147715)
Timeframe: Day 1 and Day 14 (for participants in the 100 mg dose group only) predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 24, 48, 72 and 96 hours postdose.

Interventionhours (Median)
Part 1: 10 mg S-6484141.00
Part 1: 30 mg S-6484141.00
Part 1: 100 mg S-648414 Fasted1.25
Part 1: 100 mg S-648414 Fed3.00
Part 1: 250 mg S-6484141.50
Part 1: 500 mg S-6484141.50
Part 1: 1000 mg S-6484141.75

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Part 2: Apparent Total Clearance (CL/F) of S-648414 Following Multiple-dose Administration

Apparent total clearance estimated according to: CL/F = Dose/AUC0-τ on Day 14 (NCT04147715)
Timeframe: Day 14 predose (0 hours), 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, and 24 hours postdose.

InterventionL/hr (Geometric Mean)
Part 2: 30 mg S-648414 + Midazolam2.85
Part 2: 50 mg S-648414 + Midazolam2.72

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Part 2: Apparent Volume of Distribution in the Terminal Elimination Phase (Vz/F) of S-648414 Following Multiple-dose Administration

Apparent volume of distribution in the terminal elimination phase on Day 14, estimated according to: Vz /F = Dose/AUC0-τ/λz (NCT04147715)
Timeframe: Day 14 predose (0 hours), 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 24, 48, 72, and 96 hours postdose.

Interventionliters (Geometric Mean)
Part 2: 30 mg S-648414 + Midazolam88.7
Part 2: 50 mg S-648414 + Midazolam93.0

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Part 2: Area Under the Concentration-time Curve From Time Zero to Infinity (AUC0-inf) of Midazolam

"The effect of S-648414 on the PK of midazolam (a cytochrome P450 3A [CYP3A] substrate) was assessed in Part 2 following 5 mg midazolam administration alone (Day -2) and co-administration with S-648414 30 or 50 mg (Day 14).~Area under the concentration-time curve extrapolated from time zero to infinity defined as AUC0-last + (Clast/λz), where Clast is the last measurable plasma concentration and λz is the plasma terminal elimination rate constant." (NCT04147715)
Timeframe: Day -2 and Day 14 predose (0 hours), 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, and 24 hours postdose.

Interventionng*hr/mL (Geometric Mean)
Part 2: Midazolam (30 mg S-648414 Group)72.81
Part 2: 30 mg S-648414 + Midazolam61.68
Part 2: Midazolam (50 mg S-648414 Group)76.03
Part 2: 50 mg S-648414 + Midazolam67.02

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Part 1: Apparent Volume of Distribution in the Terminal Elimination Phase (Vz/F) of S-648414

Apparent volume of distribution in the terminal elimination phase was estimated according to: Vz /F = Dose / AUC0-inf / λz. (NCT04147715)
Timeframe: Day 1 and Day 14 (for participants in the 100 mg dose group only) predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 24, 48, 72 and 96 hours postdose.

Interventionliters (Geometric Mean)
Part 1: 10 mg S-64841491.7
Part 1: 30 mg S-64841481.0
Part 1: 100 mg S-648414 Fasted83.5
Part 1: 100 mg S-648414 Fed88.9
Part 1: 250 mg S-64841491.0
Part 1: 500 mg S-64841470.8
Part 1: 1000 mg S-64841489.3

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Part 2: Area Under the Concentration-time Curve From Time Zero to the Last Quantifiable Concentration After Dosing (AUC0-last) for Midazolam

"The effect of S-648414 on the PK of midazolam (a cytochrome P450 3A [CYP3A] substrate) was assessed in Part 2 following 5 mg midazolam administration alone (Day -2) and co-administration with S-648414 30 or 50 mg (Day 14).~Area under the concentration-time curve from time zero to the time of the last quantifiable concentration after dosing, calculated by linear up/log down trapezoidal method." (NCT04147715)
Timeframe: Day -2 and Day 14 predose (0 hours), 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, and 24 hours postdose.

Interventionng*hr/mL (Geometric Mean)
Part 2: Midazolam (30 mg S-648414 Group)70.17
Part 2: 30 mg S-648414 + Midazolam59.83
Part 2: Midazolam (50 mg S-648414 Group)73.28
Part 2: 50 mg S-648414 + Midazolam64.53

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Part 2: Fraction of S-648414 Dose Excreted in Urine Over the Dosing Interval (Feu0- τ) Following Multiple-dose Administration

Fraction of dose excreted in urine over the dosing interval τ (24 hours) on Day 14 calculated as Aeu0-τ/Dose × 100, where Aeu0-τ is the amount of drug excreted in urine over the dosing interval τ (24 hours). (NCT04147715)
Timeframe: Day 14 0-24 hours postdose

Interventionpercent excreted (Geometric Mean)
Part 2: 30 mg S-648414 + Midazolam33.3
Part 2: 50 mg S-648414 + Midazolam35.0

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Part 1: Apparent Total Clearance (CL/F) of S-648414

Apparent total clearance estimated according to: CL/F = Dose / AUC0-inf. (NCT04147715)
Timeframe: Day 1 and Day 14 (for participants in the 100 mg dose group only) predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 24, 48, 72 and 96 hours postdose.

InterventionL/hr (Geometric Mean)
Part 1: 10 mg S-6484142.76
Part 1: 30 mg S-6484142.72
Part 1: 100 mg S-648414 Fasted2.61
Part 1: 100 mg S-648414 Fed2.71
Part 1: 250 mg S-6484142.62
Part 1: 500 mg S-6484142.21
Part 1: 1000 mg S-6484142.62

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Part 1: Area Under the Concentration-time Curve From Time Zero to Infinity (AUC0-inf) of S-648414

Area under the concentration-time curve extrapolated from time zero to infinity defined as AUC0-last + (Clast/λz), where Clast is the last measurable plasma concentration and λz is the plasma terminal elimination rate constant. (NCT04147715)
Timeframe: Day 1 and Day 14 (for participants in the 100 mg dose group only) predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 24, 48, 72 and 96 hours postdose.

Interventionng*hr/mL (Geometric Mean)
Part 1: 10 mg S-6484143620
Part 1: 30 mg S-64841411040
Part 1: 100 mg S-648414 Fasted38300
Part 1: 100 mg S-648414 Fed36940
Part 1: 250 mg S-64841495510
Part 1: 500 mg S-648414226600
Part 1: 1000 mg S-648414382000

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Part 1: Area Under the Concentration-time Curve From Time Zero to the Last Quantifiable Concentration After Dosing (AUC0-last) of S-648414

Area under the concentration-time curve from time zero to the time of the last quantifiable concentration after dosing, calculated by the linear trapezoidal method when concentrations are increasing and by the logarithmic trapezoidal method when concentrations are decreasing (linear up/log down trapezoidal method). (NCT04147715)
Timeframe: Day 1 and Day 14 (for participants in the 100 mg dose group only) predose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 24, 48, 72 and 96 hours postdose.

Interventionng*hr/mL (Geometric Mean)
Part 1: 10 mg S-6484143431
Part 1: 30 mg S-64841410610
Part 1: 100 mg S-648414 Fasted36370
Part 1: 100 mg S-648414 Fed34910
Part 1: 250 mg S-64841489330
Part 1: 500 mg S-648414215300
Part 1: 1000 mg S-648414359300

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Part 1: Fraction of S-648414 Dose Excreted in Urine From 0 to 96 Hours Postdose (Feu0-96)

"The fraction of S-648414 dose excreted in urine from 0 to 96 hours postdose was calculated as:~Cumulative amount of S-648414 excreted in urine from time zero to 96 hours postdose (Aeu0-96) / Dose × 100" (NCT04147715)
Timeframe: Day 1 and Day 14 (for participants in the 100 mg dose group only) predose (-12 to 0 hours), 0 to 24 hours, 24 to 48 hours, 48 to 72 hours, and 72 to 96 hours postdose

Interventionpercent excreted (Geometric Mean)
Part 1: 10 mg S-64841430.3
Part 1: 30 mg S-64841425.5
Part 1: 100 mg S-648414 Fasted25.3
Part 1: 100 mg S-648414 Fed25.1
Part 1: 250 mg S-64841428.7
Part 1: 500 mg S-64841431.5
Part 1: 1000 mg S-64841425.9

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Parts 1: Change From Baseline in Heart Rate (HR)

"Continuous 12-lead digital electrocardiogram (ECG) recording was performed on Day 1. ECGs were analyzed at a blinded, central ECG laboratory. At each specified time point, ten 14-second 12-lead ECG tracings were extracted from the continuous recordings. The median HR in each replicate was calculated; the mean of available medians was used as the participant's reportable value at that time point.~Baseline was defined as the average of the measured ECG values from the 3 pre-dose time points (45, 30, and 15 minutes before dosing) on Day 1.~Change from Baseline in HR (ΔHR) was calculated based on a linear mixed-effects model with time (categorical), treatment, and time-by-treatment interaction as fixed effects and Baseline HR as covariate." (NCT04147715)
Timeframe: Day 1: Predose at 3 time points (-45, -30 and -15 minutes), and 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, and 24 hours postdose.

,,,,,,
Interventionbeats per minute (Least Squares Mean)
0.5 hours postdose1 hour postdose1.5 hours postdose2 hours postdose2.5 hours postdose3 hours postdose4 hours postdose6 hours postdose8 hours postdose12 hours postdose24 hours postdose
Part 1: 10 mg S-648414-0.2-2.7-3.0-3.2-1.2-3.0-1.24.61.71.1-1.7
Part 1: 100 mg S-648414-1.1-2.1-3.0-2.5-2.2-2.1-2.84.2-0.21.1-1.4
Part 1: 1000 mg S-648414-1.6-0.8-0.4-0.3-0.7-0.63.37.53.53.43.3
Part 1: 250 mg S-648414-0.10.4-0.5-1.7-0.7-1.80.83.71.82.40.8
Part 1: 30 mg S-648414-1.4-1.9-0.3-2.4-3.0-1.60.72.40.71.9-0.4
Part 1: 500 mg S-648414-0.7-1.00.20.42.72.02.17.34.69.10.3
Part 1: Placebo0.91.5-0.4-0.50.8-0.90.25.21.52.70.4

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Part 3: Number of Participants With Treatment-emergent Adverse Events

"A TEAE is any event not present before exposure to study drug or any event already present that worsens after exposure to study drug.~A serious adverse event is any untoward medical occurrence that resulted in death, was life-threatening, required or prolonged inpatient hospitalization, resulted in persistent disability/incapacity, was a congenital anomaly/birth defect, or other event that may have jeopardized the participant or required intervention to prevent one of the outcomes above.~The investigator assessed the intensity of each AE according to the following:~Grade 1 (Mild): No or minimal interference with usual activities.~Grade 2 (Moderate): More than minimal interference with usual activities, intervention indicated.~Grade 3 (Severe): Inability to perform usual activities, intervention or hospitalization indicated.~Grade 4 (Potentially life-threatening): Inability to perform self-care, intervention indicated to prevent permanent impairment, disability, or death." (NCT04147715)
Timeframe: From the first dose up to Day 36; A TEAE was summarized to a given treatment if the event onset/worsening occurred any time after the dose of that treatment and before the dose of the next treatment.

,,,,,
InterventionParticipants (Count of Participants)
Any TEAEAny treatment-related TEAEAny TEAE with severity Grade 2 to 4Any TEAE with severity Grade 3 to 4Any gastrointestinal AEsAny ocular AEsAny serious adverse eventsAny treatment-related SAEAny TEAE leading to study discontinuationAny TEAE leading to study drug discontinuationDeaths
Part 3: 100 mg S-64841430200000000
Part 3: 100 mg S-648414 + Dolutegravir40200000000
Part 3: 200 mg S-64841452300200000
Part 3: 200 mg S-648414 + Dolutegravir21101000000
Part 3: Dolutegravir (100 mg S-648414 Group)30200000000
Part 3: Dolutegravir (200 mg S-648414 Group)20200000000

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Part 2: Time to Maximum Plasma Concentration (Tmax) of S-648414 Following Single and Multiple-dose Administration

(NCT04147715)
Timeframe: Day 1 predose (0 hours), 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, and 24 hours postdose; Day 14 predose (0 hours), 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 24, 48, 72, and 96 hours postdose.

,
Interventionhours (Median)
Day 1Day 14
Part 2: 30 mg S-648414 + Midazolam3.022.03
Part 2: 50 mg S-648414 + Midazolam4.501.25

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Part 2: Number of Participants With Treatment-emergent Adverse Events

"A TEAE is any event not present before exposure to study drug or any event already present that worsens after exposure to study drug.~A serious adverse event is any untoward medical occurrence that resulted in death, was life-threatening, required or prolonged inpatient hospitalization, resulted in persistent disability/incapacity, was a congenital anomaly/birth defect, or other event that may have jeopardized the participant or required intervention to prevent one of the outcomes above.~The investigator assessed the intensity of each AE according to the following:~Grade 1 (Mild): No or minimal interference with usual activities.~Grade 2 (Moderate): More than minimal interference with usual activities, intervention indicated.~Grade 3 (Severe): Inability to perform usual activities, intervention or hospitalization indicated.~Grade 4 (Potentially life-threatening): Inability to perform self-care, intervention indicated to prevent permanent impairment, disability, or death." (NCT04147715)
Timeframe: From the first dose up to 10 days after end of dosing (25 days); A TEAE was summarized to a given treatment if the event onset/worsening occurred any time after the dose of that treatment and before the dose of the next treatment.

,,,,,,
InterventionParticipants (Count of Participants)
Any TEAEAny treatment-related TEAEAny TEAE with severity Grade 2 to 4Any TEAE with severity Grade 3 to 4Any gastrointestinal AEsAny ocular AEsAny serious adverse eventsAny treatment-related SAEsAny TEAE leading to study discontinuationAny TEAE leading to study drug discontinuationDeaths
Part 2: 30 mg S-648414 (Days 1-13)32100200000
Part 2: 30 mg S-648414 + Midazolam (Day 14)10000000000
Part 2: 50 mg S-648414 (Days 1-13)22200000110
Part 2: 50 mg S-648414 + Midazolam (Day 14)11000000000
Part 2: Midazolam (Day -2)00000000000
Part 2: Placebo (Days 1-13)22200100220
Part 2: Placebo + Midazolam (Day 14)00000000000

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Part 2: Maximum Plasma Concentration (Cmax) of S-648414 Following Single and Multiple-dose Administration

(NCT04147715)
Timeframe: Day 1 predose (0 hours), 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, and 24 hours postdose; Day 14 predose (0 hours), 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 24, 48, 72, and 96 hours postdose.

,
Interventionng/mL (Geometric Mean)
Day 1Day 14
Part 2: 30 mg S-648414 + Midazolam411719
Part 2: 50 mg S-648414 + Midazolam6231320

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Part 2: Area Under the Concentration-time Curve Over the Dosing Interval τ (AUC0-τ) of S-648414 Following Single and Multiple-dose Administration

Area under the concentration-time curve over the dosing interval (24 hours) on Day 1 and Day 14, calculated by the linear up/log down trapezoidal method. (NCT04147715)
Timeframe: Day 1 and day 14 predose (0 hours), 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, and 24 hours postdose.

,
Interventionng*hr/mL (Geometric Mean)
Day 1Day 14
Part 2: 30 mg S-648414 + Midazolam551910540
Part 2: 50 mg S-648414 + Midazolam898318400

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Part 1: Placebo-corrected Change From Baseline in QRS Duration

"Continuous 12-lead digital electrocardiogram (ECG) recording was performed on Day 1. ECGs were analyzed at a blinded, central ECG laboratory. At each specified time point, ten 14-second 12-lead ECG tracings were extracted from the continuous recordings. The median QRS duration in each replicate was calculated; the mean of available medians was used as the participant's reportable value at that time point.~Baseline was defined as the average of the measured ECG intervals from the 3 pre-dose time points (45, 30, and 15 minutes before dosing) on Day 1.~Change from Baseline in QRS duration (ΔQRS) was calculated based on a linear mixed-effects model with time (categorical), treatment, and time-by-treatment interaction as fixed effects and Baseline QRS as covariate.~Placebo-corrected ΔQRS (ΔΔQRS) was calculated as the adjusted mean ΔQRS in the S-648414 group minus adjusted mean ΔQRS in the placebo group at each time point." (NCT04147715)
Timeframe: Day 1: Predose at 3 time points (-45, -30 and -15 minutes), and 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, and 24 hours postdose.

,,,,,
Interventionms (Least Squares Mean)
0.5 hours postdose1 hour postdose1.5 hours postdose2 hours postdose2.5 hours postdose3 hours postdose4 hours postdose6 hours postdose8 hours postdose12 hours postdose24 hours postdose
Part 1: 10 mg S-6484140.20.3-0.70.50.10.2-0.3-0.30.21.40.8
Part 1: 100 mg S-6484140.50.6-0.11.1-0.10.30.3-0.20.51.11.1
Part 1: 1000 mg S-6484140.20.80.01.10.40.30.81.30.31.90.0
Part 1: 250 mg S-6484140.20.7-0.10.50.30.50.1-0.80.51.10.6
Part 1: 30 mg S-648414-0.10.5-0.60.40.30.40.00.00.71.40.8
Part 1: 500 mg S-6484140.40.6-0.30.70.10.50.81.11.11.90.7

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Part 1: Placebo-corrected Change From Baseline in PR Interval

"Continuous 12-lead digital electrocardiogram (ECG) recording was performed on Day 1. ECGs were analyzed at a blinded, central ECG laboratory. At each specified time point, ten 14-second 12-lead ECG tracings were extracted from the continuous recordings. The median PR interval in each replicate was calculated; the mean of available medians was used as the participant's reportable value at that time point.~Baseline was defined as the average of the measured ECG intervals from the 3 pre-dose time points (45, 30, and 15 minutes before dosing) on Day 1.~Change from Baseline (ΔPR) was calculated based on a linear mixed-effects model with time (categorical), treatment, and time-by-treatment interaction as fixed effects and Baseline PR as covariate.~Placebo-corrected ΔPR (ΔΔPR) was calculated as the adjusted mean ΔPR in the S-648414 group minus adjusted mean ΔPR in the placebo group at each time point." (NCT04147715)
Timeframe: Day 1: Predose at 3 time points (-45, -30 and -15 minutes), and 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, and 24 hours postdose.

,,,,,
Interventionms (Least Squares Mean)
0.5 hours postdose1 hour postdose1.5 hours postdose2 hours postdose2.5 hours postdose3 hours postdose4 hours postdose6 hours postdose8 hours postdose12 hours postdose24 hours postdose
Part 1: 10 mg S-6484140.60.23.02.00.43.82.51.21.41.31.6
Part 1: 100 mg S-648414-0.50.50.5-3.1-0.81.8-1.50.5-1.3-0.42.0
Part 1: 1000 mg S-648414-0.40.20.5-0.6-1.6-0.5-2.2-0.11.40.4-1.6
Part 1: 250 mg S-6484140.91.01.8-2.2-0.2-1.4-0.51.9-2.6-0.1-2.7
Part 1: 30 mg S-6484141.83.20.62.63.83.82.73.56.84.52.2
Part 1: 500 mg S-648414-4.3-7.20.4-2.9-5.9-5.2-7.4-4.1-2.6-6.9-0.7

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Part 1: Placebo-corrected Change From Baseline in Heart Rate

"Continuous 12-lead digital electrocardiogram (ECG) recording was performed on Day 1. ECGs were analyzed at a blinded, central ECG laboratory. At each specified time point, ten 14-second 12-lead ECG tracings were extracted from the continuous recordings. The median HR in each replicate was calculated; the mean of available medians was used as the participant's reportable value at that time point.~Baseline was defined as the average of the measured values from the 3 pre-dose time points (45, 30, and 15 minutes before dosing) on Day 1.~Change from Baseline (ΔHR) was calculated based on a linear mixed-effects model with time (categorical), treatment, and time-by-treatment interaction as fixed effects and Baseline HR as covariate.~Placebo-corrected ΔHR (ΔΔHR) was calculated as the adjusted mean ΔHR in the S-648414 group minus adjusted mean ΔHR in the placebo group at each time point." (NCT04147715)
Timeframe: Day 1: Predose at 3 time points (-45, -30 and -15 minutes), and 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, and 24 hours postdose.

,,,,,
Interventionbeats per minute (Least Squares Mean)
0.5 hours postdose1 hour postdose1.5 hours postdose2 hours postdose2.5 hours postdose3 hours postdose4 hours postdose6 hours postdose8 hours postdose12 hours postdose24 hours postdose
Part 1: 10 mg S-648414-1.1-4.2-2.6-2.7-2.0-2.1-1.4-0.60.1-1.6-2.2
Part 1: 100 mg S-648414-2.0-3.5-2.6-2.1-3.0-1.2-3.1-1.0-1.7-1.5-1.9
Part 1: 1000 mg S-648414-2.5-2.20.00.1-1.50.43.12.32.00.72.9
Part 1: 250 mg S-648414-1.0-1.10.0-1.3-1.5-0.80.6-1.50.3-0.30.4
Part 1: 30 mg S-648414-2.3-3.40.1-2.0-3.8-0.70.4-2.8-0.9-0.7-0.9
Part 1: 500 mg S-648414-1.6-2.50.60.92.02.91.92.03.16.4-0.1

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Part 1: Placebo-corrected Change From Baseline in Fridericia's Corrected QT Interval

"Continuous 12-lead digital electrocardiogram (ECG) recording was performed on Day 1. ECGs were analyzed at a blinded, central ECG laboratory. At each specified time point, ten 14-second 12-lead ECG tracings were extracted from the continuous recordings. The median QT in each replicate was calculated; the mean of available medians was used as the participant's reportable value at that time point.~QT interval was corrected for heart rate using Fridericia's correction (QTcF). Baseline was defined as the average of the measured ECG intervals from the 3 pre-dose time points (45, 30, and 15 minutes before dosing) on Day 1.~Change from Baseline (ΔQTcF) was calculated based on a linear mixed-effects model with time (categorical), treatment, and time-by-treatment interaction as fixed effects and Baseline QTcF as covariate.~Placebo-corrected ΔQTcF (ΔΔQTcF) was calculated as the adjusted mean ΔQTcF in the S-648414 group minus adjusted mean ΔQTcF in the placebo group at each time point." (NCT04147715)
Timeframe: Day 1: Predose at 3 time points (-45, -30 and -15 minutes), and 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, and 24 hours postdose.

,,,,,
Interventionms (Least Squares Mean)
0.5 hours postdose1 hour postdose1.5 hours postdose2 hours postdose2.5 hours postdose3 hours postdose4 hours postdose6 hours postdose8 hours postdose12 hours postdose24 hours postdose
Part 1: 10 mg S-6484140.01.7-0.1-2.00.84.12.1-6.7-2.7-1.0-3.6
Part 1: 100 mg S-648414-1.6-1.00.0-1.81.41.22.44.00.91.8-0.7
Part 1: 1000 mg S-6484145.27.06.06.410.412.014.38.19.19.68.8
Part 1: 250 mg S-648414-0.91.23.0-1.12.84.52.50.7-1.8-0.50.5
Part 1: 30 mg S-648414-2.4-0.2-1.5-0.91.00.51.73.03.71.80.2
Part 1: 500 mg S-648414-2.41.14.22.55.01.45.90.60.7-2.1-0.4

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Part 1: Number of Participants With Treatment-emergent Changes for T-wave Morphology and U-wave Presence

"T-wave abnormalities were categorized as follows:~Normal T wave: Any positive T wave not meeting any criterion below~Flat T wave: T amplitude < 1 mm (either positive or negative) including flat isoelectric line~Notched T wave (+): Presence of notch(es) of at least 0.05 mV amplitude on ascending or descending arm of the positive T wave~Biphasic: T wave that contains a second component with an opposite phase that is at least 0.1 mV deep (both positive/negative and negative/positive and polyphasic T waves included)~Normal T wave (-): T amplitude that is negative, without biphasic T wave or notches~Notched T wave (-): Presence of notch(es) of at least 0.05 mV amplitude on descending or ascending arm of the negative T wave~U waves: Presence of abnormal U waves" (NCT04147715)
Timeframe: Day 1: Predose at 3 time points (-45, -30 and -15 minutes), and 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, and 24 hours postdose.

,,,,,,
InterventionParticipants (Count of Participants)
FlatNotched (+)BiphasicNormal (-)Notched (-)U-Wave presence
Part 1: 10 mg S-648414110010
Part 1: 100 mg S-648414000000
Part 1: 1000 mg S-648414000000
Part 1: 250 mg S-648414000000
Part 1: 30 mg S-648414000000
Part 1: 500 mg S-648414000000
Part 1: Placebo000000

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Part 1: Number of Participants With Treatment-emergent Adverse Events (TEAEs)

"A TEAE is any event not present before exposure to study drug or any event already present that worsens after exposure to study drug.~A serious adverse event is any untoward medical occurrence that resulted in death, was life-threatening, required or prolonged inpatient hospitalization, resulted in persistent disability/incapacity, was a congenital anomaly/birth defect, or other event that may have jeopardized the participant or required intervention to prevent one of the outcomes above.~The investigator assessed the intensity of each AE according to the following:~Grade 1 (Mild): No or minimal interference with usual activities.~Grade 2 (Moderate): More than minimal interference with usual activities, intervention indicated.~Grade 3 (Severe): Inability to perform usual activities, intervention or hospitalization indicated.~Grade 4 (Potentially life-threatening): Inability to perform self-care, intervention indicated to prevent permanent impairment, disability, or death." (NCT04147715)
Timeframe: From dosing on Day 1 or Day 14 up to 10 days post dose

,,,,,,,,
InterventionParticipants (Count of Participants)
Any treatment-emergent adverse event (TEAE)Any treatment-related TEAEAny TEAE with severity Grade 2 to 4Any TEAE with severity Grade 3 to 4Any gastrointestinal AEsAny ocular AEsSerious adverse events (SAEs)Any treatment-related SAEAny TEAE leading to study discontinuationAny TEAE leading to study drug discontinuationDeaths
Part 1: 10 mg S-64841400000000000
Part 1: 100 mg S-648414 Fasted21101000000
Part 1: 100 mg S-648414 Fed21101000000
Part 1: 1000 mg S-64841422002000000
Part 1: 250 mg S-64841410000000000
Part 1: 30 mg S-64841410000000000
Part 1: 500 mg S-64841410000000000
Part 1: Placebo - Fasted21001000000
Part 1: Placebo - Fed00000000000

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Part 1: Number of Participants With Recorded Outlier Values for QTcF, HR, PR, and QRS

"A participant was determined as an outlier if the following criteria (assessed separately) were met for the ECG intervals at any time point:~QTcF:~Treatment-emergent value of > 450 and ≤ 480 ms when not present at Baseline (new onset)~Treatment-emergent value of > 480 and ≤ 500 ms when not present at Baseline (new onset)~Treatment-emergent value of > 500 ms when not present at Baseline (new onset)~Increase of QTcF (ΔQTcF) from Baseline of > 30 and ≤ 60 ms~Increase of QTcF from Baseline > 60 ms~HR:~Decrease of HR from Baseline > 25% resulting in HR < 50 bpm~Increase of HR from Baseline > 25% resulting in HR > 100 bpm~PR:~Increase of PR from Baseline > 25% resulting in PR > 200 ms~QRS:~Increase of QRS from Baseline > 25% resulting in QRS > 120 ms" (NCT04147715)
Timeframe: Day 1: Predose at 3 time points (-45, -30 and -15 minutes), and 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, and 24 hours postdose.

,,,,,,
InterventionParticipants (Count of Participants)
QTcF > 450 and ≤ 480 msQTcF > 480 and ≤ 500 msQTcF > 500 msΔQTcF > 30 and ≤ 60 msΔQTcF > 60 msHR < 50 (bpm) with a decrease in ΔHR > 25%HR > 100 (bpm) with an increase in ΔHR > 25%PR > 200 (ms) with an increase in ΔPR > 25%QRS > 120 (ms) with an increase in ΔQRS > 25%
Part 1: 10 mg S-648414000001000
Part 1: 100 mg S-648414000000000
Part 1: 1000 mg S-648414000000000
Part 1: 250 mg S-648414000000000
Part 1: 30 mg S-648414000000000
Part 1: 500 mg S-648414000000000
Part 1: Placebo000000000

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Part 1: Change From Baseline in QRS Interval

"Continuous 12-lead digital electrocardiogram (ECG) recording was performed on Day 1. The QRS complex is a combination of the Q wave, R wave and S wave on an ECG tracing, and represents ventricular depolarization. ECGs were analyzed at a blinded, central ECG laboratory. At each specified time point, ten 14-second 12-lead ECG tracings were extracted from the continuous recordings. The median QRS in each replicate was calculated; the mean of available medians was used as the participant's reportable value at that time point.~Baseline was defined as the average of the measured ECG intervals from the 3 pre-dose time points (45, 30, and 15 minutes before dosing) on Day 1.~Change from Baseline in QRS interval (ΔQRS) was calculated based on a linear mixed-effects model with time (categorical), treatment, and time-by-treatment interaction as fixed effects and Baseline QRS as covariate." (NCT04147715)
Timeframe: Day 1: Predose at 3 time points (-45, -30 and -15 minutes), and 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, and 24 hours postdose.

,,,,,,
Interventionms (Least Squares Mean)
0.5 hours postdose1 hour postdose1.5 hours postdose2 hours postdose2.5 hours postdose3 hours postdose4 hours postdose6 hours postdose8 hours postdose12 hours postdose24 hours postdose
Part 1: 10 mg S-6484140.0-0.1-0.20.20.00.0-0.1-0.8-0.60.00.1
Part 1: 100 mg S-6484140.20.20.40.7-0.20.10.5-0.7-0.3-0.30.4
Part 1: 1000 mg S-648414-.10.40.60.80.30.21.00.8-0.50.5-0.7
Part 1: 250 mg S-648414-0.10.30.50.10.20.40.3-1.3-0.3-0.3-0.1
Part 1: 30 mg S-648414-0.40.10.00.10.20.20.2-0.5-0.20.00.1
Part 1: 500 mg S-6484140.10.20.30.40.00.40.90.60.20.50.0
Part 1: Placebo-0.3-0.40.5-0.3-0.1-0.20.2-0.5-0.8-1.4-0.7

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Part 1: Change From Baseline in PR Interval

"Continuous 12-lead digital electrocardiogram (ECG) recording was performed on Day 1. The PR interval is the time from the onset of the P-wave to the start of the next QRS complex. ECGs were analyzed at a blinded, central ECG laboratory. At each specified time point, ten 14-second 12-lead ECG tracings were extracted from the continuous recordings. The median PR in each replicate was calculated; the mean of available medians was used as the participant's reportable value at that time point.~Baseline was defined as the average of the measured ECG intervals from the 3 pre-dose time points (45, 30, and 15 minutes before dosing) on Day 1.~Change from Baseline in PR interval (ΔPR) was calculated based on a linear mixed-effects model with time (categorical), treatment, and time-by-treatment interaction as fixed effects and Baseline PR as covariate." (NCT04147715)
Timeframe: Day 1: Predose at 3 time points (-45, -30 and -15 minutes), and 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, and 24 hours postdose.

,,,,,,
Interventionms (Least Squares Mean)
0.5 hours postdose1 hour postdose1.5 hours postdose2 hours postdose2.5 hours postdose3 hours postdose4 hours postdose6 hours postdose8 hours postdose12 hours postdose24 hours postdose
Part 1: 10 mg S-6484141.01.03.42.81.13.63.0-1.6-1.80.40.1
Part 1: 100 mg S-648414-0.11.30.9-2.3-0.11.7-1.0-2.3-4.5-1.30.5
Part 1: 1000 mg S-6484140.01.00.90.2-0.9-0.7-1.7-3.0-1.8-0.5-3.1
Part 1: 250 mg S-6484141.31.92.2-1.40.5-1.5-0.1-0.9-5.8-1.0-4.2
Part 1: 30 mg S-6484142.24.01.03.44.53.73.10.73.63.50.8
Part 1: 500 mg S-648414-3.9-6.40.8-2.1-5.2-5.3-6.9-7.0-5.8-7.8-2.2
Part 1: Placebo0.40.90.40.80.7-0.10.5-2.8-3.2-0.9-1.5

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Part 1: Change From Baseline in Fridericia's Corrected QT Interval (QTcF)

"Continuous 12-lead digital electrocardiogram (ECG) recording was performed on Day 1. The QT interval is a measure between Q and T wave in heart's electrical cycle. ECGs were analyzed at a blinded, central ECG laboratory. At each specified time point, ten 14-second 12-lead ECG tracings were extracted from the continuous recordings. The median QT in each replicate was calculated; the mean of available medians was used as the participant's reportable value at that time point.~QT interval was corrected for heart rate using Fridericia's correction (QTcF). Baseline was defined as the average of the measured ECG intervals from the 3 pre-dose time points (45, 30, and 15 minutes before dosing) on Day 1.~Change from Baseline (ΔQTcF) was calculated based on a linear mixed-effects model with time (categorical), treatment, and time-by-treatment interaction as fixed effects and Baseline QTcF as covariate." (NCT04147715)
Timeframe: Day 1: Predose at 3 time points (-45, -30 and -15 minutes), and 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, and 24 hours postdose.

,,,,,,
Interventionms (Least Squares Mean)
0.5 hours postdose1 hour postdose1.5 hours postdose2 hours postdose2.5 hours postdose3 hours postdose4 hours postdose6 hours postdose8 hours postdose12 hours postdose24 hours postdose
Part 1: 10 mg S-648414-3.2-0.4-1.2-2.1-1.72.3-0.2-12.0-6.7-1.8-4.9
Part 1: 100 mg S-648414-4.8-3.2-1.1-1.9-1.1-0.60.1-1.2-3.21.0-2.1
Part 1: 1000 mg S-6484142.04.94.96.38.010.112.02.95.08.87.5
Part 1: 250 mg S-648414-4.1-0.91.8-1.20.42.60.2-4.6-5.9-1.3-0.8
Part 1: 30 mg S-648414-5.6-2.4-2.6-1.0-1.5-1.3-0.6-2.3-0.30.9-1.2
Part 1: 500 mg S-648414-5.6-1.03.12.42.5-0.43.6-4.6-3.4-3.0-1.8
Part 1: Placebo-3.2-2.2-1.1-0.1-2.5-1.9-2.3-5.3-4.1-0.9-1.4

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Part 3: Time to Maximum Plasma Concentration (Tmax) of S-648414

The effect of dolutegravir on the pharmacokinetics (PK) of S-648414 was assessed after administration of multiple oral doses of S-648414 alone (Day 21) and after administration of multiple oral doses of S-648414 co-administered with dolutegravir (Day 28). (NCT04147715)
Timeframe: Day 21 predose (0 hours), 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8 and 12 hours postdose. Day 28 predose (0 hours), 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, and 24 hours postdose.

Interventionhours (Median)
Part 3: 100 mg S-6484142.00
Part 3: 100 mg S-648414 + Dolutegravir2.25
Part 3: 200 mg S-6484142.50
Part 3: 200 mg S-648414 + Dolutegravir2.25

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Part 3: Time to Maximum Plasma Concentration (Tmax) of Dolutegravir

The effect of S-648414 on the PK of dolutegravir was assessed after administration of multiple oral doses of dolutegravir alone and after administration of multiple oral doses of S-648414 co-administered with dolutegravir. (NCT04147715)
Timeframe: Day 7 and Day 28 predose (0 hours), 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12 and 24 hours postdose.

Interventionhours (Median)
Part 3: Dolutegravir (100 mg S-648414 Group)3.50
Part 3: 100 mg S-648414 + Dolutegravir2.75
Part 3: Dolutegravir (200 mg S-648414 Group)3.50
Part 3: 200 mg S-648414 + Dolutegravir4.00

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Part 3: Plasma Concentration of S-648414 at the End of the Dosing Interval τ (Cτ)

The effect of dolutegravir on the pharmacokinetics (PK) of S-648414 was assessed after administration of multiple oral doses of S-648414 alone (Day 21) and after administration of multiple oral doses of S-648414 co-administered with dolutegravir (Day 28). (NCT04147715)
Timeframe: Day 22 and Day 29 (24 hours post-dosing on Days 21 and 28)

Interventionng/mL (Geometric Mean)
Part 3: 100 mg S-6484141210
Part 3: 100 mg S-648414 + Dolutegravir1250
Part 3: 200 mg S-6484142590
Part 3: 200 mg S-648414 + Dolutegravir2360

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Part 3: Plasma Concentration of Dolutegravir at the End of the Dosing Interval τ (Cτ)

The effect of S-648414 on the PK of dolutegravir was assessed after administration of multiple oral doses of dolutegravir alone and after administration of multiple oral doses of S-648414 co-administered with dolutegravir. (NCT04147715)
Timeframe: Day 8 and Day 29 (24 hours post-dosing on Day 7 and Day 28).

Interventionng/mL (Geometric Mean)
Part 3: Dolutegravir (100 mg S-648414 Group)1980
Part 3: 100 mg S-648414 + Dolutegravir2660
Part 3: Dolutegravir (200 mg S-648414 Group)1850
Part 3: 200 mg S-648414 + Dolutegravir2000

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Part 3: Maximum Plasma Concentration (Cmax) of S-648414

The effect of dolutegravir on the pharmacokinetics (PK) of S-648414 was assessed after administration of multiple oral doses of S-648414 alone (Day 21) and after administration of multiple oral doses of S-648414 co-administered with dolutegravir (Day 28). (NCT04147715)
Timeframe: Day 21 predose (0 hours), 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8 and 12 hours postdose. Day 28 predose (0 hours), 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, and 24 hours postdose.

Interventionng/mL (Geometric Mean)
Part 3: 100 mg S-6484142740
Part 3: 100 mg S-648414 + Dolutegravir2720
Part 3: 200 mg S-6484145150
Part 3: 200 mg S-648414 + Dolutegravir5020

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Part 3: Maximum Plasma Concentration (Cmax) of Dolutegravir

The effect of S-648414 on the PK of dolutegravir was assessed after administration of multiple oral doses of dolutegravir alone and after administration of multiple oral doses of S-648414 co-administered with dolutegravir. (NCT04147715)
Timeframe: Day 7 and Day 28 predose (0 hours), 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12 and 24 hours postdose.

Interventionng/mL (Geometric Mean)
Part 3: Dolutegravir (100 mg S-648414 Group)4910
Part 3: 100 mg S-648414 + Dolutegravir5800
Part 3: Dolutegravir (200 mg S-648414 Group)4720
Part 3: 200 mg S-648414 + Dolutegravir4950

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Part 3: Area Under the Concentration-time Curve Over the Dosing Interval τ (AUC0-τ) for S-648414

"The effect of dolutegravir on the pharmacokinetics (PK) of S-648414 was assessed after administration of multiple oral doses of S-648414 alone (Day 21) and after administration of multiple oral doses of S-648414 co-administered with dolutegravir (Day 28).~Area under the concentration-time curve over the dosing interval τ (24 hours) was calculated by the linear up/log down trapezoidal method." (NCT04147715)
Timeframe: Day 21 predose (0 hours), 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8 and 12 hours postdose. Day 28 predose (0 hours), 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, and 24 hours postdose.

Interventionng*hr/mL (Geometric Mean)
Part 3: 100 mg S-64841440800
Part 3: 100 mg S-648414 + Dolutegravir41080
Part 3: 200 mg S-64841481010
Part 3: 200 mg S-648414 + Dolutegravir79820

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Part 3: Area Under the Concentration-time Curve Over the Dosing Interval τ (AUC0-τ) for Dolutegravir

"The effect of S-648414 on the PK of dolutegravir was assessed after administration of multiple oral doses of dolutegravir alone and after administration of multiple oral doses of S-648414 co-administered with dolutegravir.~Area under the concentration-time curve over the dosing interval τ (24 hours) was calculated by the linear up/log down trapezoidal method." (NCT04147715)
Timeframe: Day 7 and Day 28 predose (0 hours), 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12 and 24 hours postdose.

Interventionng*hr/mL (Geometric Mean)
Part 3: Dolutegravir (100 mg S-648414 Group)74790
Part 3: 100 mg S-648414 + Dolutegravir89290
Part 3: Dolutegravir (200 mg S-648414 Group)69850
Part 3: 200 mg S-648414 + Dolutegravir73210

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Part 3: Apparent Total Clearance (CL/F) of S-648414

"The effect of dolutegravir on the pharmacokinetics (PK) of S-648414 was assessed after administration of multiple oral doses of S-648414 alone (Day 21) and after administration of multiple oral doses of S-648414 co-administered with dolutegravir (Day 28).~Apparent total clearance was calculated as CL/F = Dose/AUC0-τ" (NCT04147715)
Timeframe: Day 21 predose (0 hours), 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8 and 12 hours postdose. Day 28 predose (0 hours), 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, and 24 hours postdose.

InterventionL/hr (Geometric Mean)
Part 3: 100 mg S-6484142.45
Part 3: 100 mg S-648414 + Dolutegravir2.43
Part 3: 200 mg S-6484142.47
Part 3: 200 mg S-648414 + Dolutegravir2.51

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Part 3: Apparent Total Clearance (CL/F) of Dolutegravir

"The effect of S-648414 on the PK of dolutegravir was assessed after administration of multiple oral doses of dolutegravir alone and after administration of multiple oral doses of S-648414 co-administered with dolutegravir.~Apparent total clearance calculated as CL/F =Dose/AUC0-τ" (NCT04147715)
Timeframe: Day 7 and Day 28 predose (0 hours), 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12 and 24 hours postdose.

InterventionL/hr (Geometric Mean)
Part 3: Dolutegravir (100 mg S-648414 Group)0.669
Part 3: 100 mg S-648414 + Dolutegravir0.560
Part 3: Dolutegravir (200 mg S-648414 Group)0.716
Part 3: 200 mg S-648414 + Dolutegravir0.683

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Part 2: Time to Maximum Plasma Concentration of Midazolam

The effect of S-648414 on the PK of midazolam (a cytochrome P450 3A [CYP3A] substrate) was assessed in Part 2 following 5 mg midazolam administration alone (Day -2) and co-administration with S-648414 30 or 50 mg (Day 14). (NCT04147715)
Timeframe: Day -2 and Day 14 predose (0 hours), 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, and 24 hours postdose.

Interventionhours (Median)
Part 2: Midazolam (30 mg S-648414 Group)0.76
Part 2: 30 mg S-648414 + Midazolam1.00
Part 2: Midazolam (50 mg S-648414 Group)0.50
Part 2: 50 mg S-648414 + Midazolam0.50

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Part 2: Terminal Elimination Rate Constant for Midazolam

The effect of S-648414 on the PK of midazolam (a cytochrome P450 3A [CYP3A] substrate) was assessed in Part 2 following 5 mg midazolam administration alone (Day -2) and co-administration with S-648414 30 or 50 mg (Day 14). (NCT04147715)
Timeframe: Day -2 and Day 14 predose (0 hours), 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, and 24 hours postdose.

Intervention1/hour (Geometric Mean)
Part 2: Midazolam (30 mg S-648414 Group)0.1366
Part 2: 30 mg S-648414 + Midazolam0.1494
Part 2: Midazolam (50 mg S-648414 Group)0.1570
Part 2: 50 mg S-648414 + Midazolam0.1528

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Part 2: Terminal Elimination Rate Constant (λz) of S-648414 Following Multiple-dose Administration

Terminal elimination rate constant, where λz is the magnitude of the slope of the linear regression of the log concentration versus time profile during the terminal phase on Day 14. (NCT04147715)
Timeframe: Day 14 predose (0 hours), 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 24, 48, 72, and 96 hours postdose.

Intervention1/hours (Geometric Mean)
Part 2: 30 mg S-648414 + Midazolam0.0321
Part 2: 50 mg S-648414 + Midazolam0.0292

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Part 2: Terminal Elimination Half-life for Midazolam

The effect of S-648414 on the PK of midazolam (a cytochrome P450 3A [CYP3A] substrate) was assessed in Part 2 following 5 mg midazolam administration alone (Day -2) and co-administration with S-648414 30 or 50 mg (Day 14). (NCT04147715)
Timeframe: Day -2 and Day 14 predose (0 hours), 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, and 24 hours postdose.

Interventionhours (Geometric Mean)
Part 2: Midazolam (30 mg S-648414 Group)5.07
Part 2: 30 mg S-648414 + Midazolam4.64
Part 2: Midazolam (50 mg S-648414 Group)4.41
Part 2: 50 mg S-648414 + Midazolam4.54

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Part 2: Terminal Elimination Half-life (t1/2,z) of S-648414 Following Multiple-dose Administration

Terminal elimination half-life, where t1/2,z = (ln2)/λz on Day 14. (NCT04147715)
Timeframe: Day 14 predose (0 hours), 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 24, 48, 72, and 96 hours postdose.

Interventionhours (Geometric Mean)
Part 2: 30 mg S-648414 + Midazolam21.6
Part 2: 50 mg S-648414 + Midazolam23.7

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Part 2: Renal Clearance (CLR) of S-648414 Following Multiple-dose Administration

Renal clearance on Day 14, calculated as CLR = Aeu0-τ/AUC0-τ, where Aeu0-τ is the amount of drug excreted in urine over the dosing interval τ (24 hours) (NCT04147715)
Timeframe: Day 14 0-24 hours postdose

InterventionL/hr (Geometric Mean)
Part 2: 30 mg S-648414 + Midazolam0.948
Part 2: 50 mg S-648414 + Midazolam0.952

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Part 2: Mean Residence Time for Midazolam

"The effect of S-648414 on the PK of midazolam (a cytochrome P450 3A [CYP3A] substrate) was assessed in Part 2 following 5 mg midazolam administration alone (Day -2) and co-administration with S-648414 30 or 50 mg (Day 14).~Mean residence time was calculated as MRT = AUMC0-inf/AUC0-inf where AUMC0-inf is the area under the first moment curve extrapolated to infinity." (NCT04147715)
Timeframe: Day -2 and Day 14 predose (0 hours), 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, and 24 hours postdose.

Interventionhours (Geometric Mean)
Part 2: Midazolam (30 mg S-648414 Group)5.30
Part 2: 30 mg S-648414 + Midazolam4.44
Part 2: Midazolam (50 mg S-648414 Group)4.93
Part 2: 50 mg S-648414 + Midazolam4.40

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Part 2: Maximum Plasma Concentration (Cmax) of Midazolam

The effect of S-648414 on the PK of midazolam (a cytochrome P450 3A [CYP3A] substrate) was assessed in Part 2 following 5 mg midazolam administration alone (Day -2) and co-administration with S-648414 30 or 50 mg (Day 14). (NCT04147715)
Timeframe: Day -2 and Day 14 predose (0 hours), 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, and 24 hours postdose.

Interventionng/mL (Geometric Mean)
Part 2: Midazolam (30 mg S-648414 Group)18.0
Part 2: 30 mg S-648414 + Midazolam16.8
Part 2: Midazolam (50 mg S-648414 Group)19.5
Part 2: 50 mg S-648414 + Midazolam19.3

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Change in Positive and Negative Affect Scale (PANAS)

Change from pre- to post-TSST in The Positive and Negative Affect Scale (PANAS) measures both positive and negative affect and is utilized within clinical and non-clinical populations. The PANAS is a 20-item instrument, each item is scored on a 5-likert scale from 1 (very slightly or not at all) to 5 (extremely). Positive Affect Score - total score from 10-50, with higher score indicating higher levels of positive affect. Negative Affect Score - total score from 10-50, with lower scores representing lower levels of negative affect. (NCT04173962)
Timeframe: baseline and 1 week after infusion

,
Interventionscore on a scale (Mean)
Negative Affect ScorePositive Affect Score
Ketamine Group2.2-2.2
Midazolam Group4.61.2

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Change in Visual Analog Scale: Stressed (VAS-Stressed)

"Change from pre- to post-TSST in The Visual Analog Scales are scored in millimeters from the left-hand side of a 100-mm line to a perpendicular mark made by the patient at a point corresponding to the apparent magnitude of the feeling state. Full range: 0 (not at all) to 100 (most ever), with higher score indicating poorer health status. The VAS-Stressed prompts participants to rate their level of stress in that exact moment on the visual analog scale." (NCT04173962)
Timeframe: baseline and 1 week after infusion

Interventionscore on a scale (Mean)
Ketamine Group12.8
Midazolam Group12.1

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Change in The Profile of Mood States - Bipolar Version (POMS - Bi) Composed-Anxious Subscale

"Change from pre- to post-TSST in The Profile of Mood States - Bipolar Version (POMS - Bi) scale measures moods and feelings primarily in clinical rather than nonclinical settings. The POMS-Bi consists of 72 adjectives that form six bipolar sub-scale scores (Composed - Anxious, Clear - Confused, Confident - Unsure, Agreeable - Hostile, Energetic - Tired, Elated - Depressed). Each of the 12 adjectives within each subscale is rated on a 4-point Likert scale with anchors of 0 = much unlike this, 1 = slightly unlike this, 2 = slightly like this, and 3 = much like this. The Composed-Anxious Subscale score is the sum of positive minus the sum of negative responses plus a constant of 18. The subscale score range is from 0 to 36. Higher score indicates higher functioning. Each subscale is separate and there is no overall score." (NCT04173962)
Timeframe: baseline and 1 week after infusion

Interventionscore on a scale (Mean)
Ketamine Group-6.8
Midazolam Group-11.9

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Change in Systolic Blood Pressure

Change from pre- to post-TSST in Cardiovascular response to stressor during assessment visit (NCT04173962)
Timeframe: baseline and 1 week after infusion

InterventionmmHg (Mean)
Ketamine Group4.3
Midazolam Group12.9

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Change in Salivary Cortisol

Change from pre- to post-TSST in salivary cortisol level. Salivary cortisol level to assess effect on the hypothalamic-pituitary-adrenal axis (HPA axis). (NCT04173962)
Timeframe: baseline and 1 week after infusion

Interventionug/dL (Mean)
Ketamine Group0.1
Midazolam Group0.0

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Change in Salivary Alpha-amylase Level

Change from pre- to post-TSST in Salivary alpha-amylase level to assess effect on the adrenaline-noradrenaline axis (ANS axis). (NCT04173962)
Timeframe: baseline and 1 week after infusion

InterventionU/mL (Mean)
Ketamine Group109.0
Midazolam Group141.7

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Change in Heart Rate

Change from pre- to post-TSST in Cardiovascular response to stressor during assessment visit (NCT04173962)
Timeframe: baseline and 1 week after infusion

Interventionbeats per minute (bpm) (Mean)
Ketamine Group-0.33
Midazolam Group3.83

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Change in Diastolic Blood Pressure

Change from pre- to post-TSST in Cardiovascular response to stressor during assessment visit (NCT04173962)
Timeframe: baseline and 1 week after infusion

InterventionmmHg (Mean)
Ketamine Group4.17
Midazolam Group6.58

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Change in Beck Anxiety Inventory (BAI)

Change from pre- to post-TSST in Beck Anxiety Inventory (BAI). This is a 21-question multiple-choice self-report inventory that is used for measuring the severity of anxiety in adults. The questions used in this measure ask about common symptoms of anxiety (such as numbness and tingling, sweating not due to heat, and fear of the worst happening). It is designed for individuals who are of 17 years of age or older and takes 5 to 10 minutes to complete. Total score range of 0-63, with higher score indicating more severe anxiety symptoms. (NCT04173962)
Timeframe: baseline and 1 week after infusion

Interventionscore on a scale (Mean)
Ketamine Group0.8
Midazolam Group2.6

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Improvement in the Severity of PTSD as Measured by the Clinician Administered PTSD Scale DSM5 (CAPS-5)

Improvement in PTSD severity is measured by the Clinician Administered PTSD Scale DSM-5 (CAPS-5). It measures frequency and intensity of PTSD-related symptoms. For the CAPS-5 the minimum units are 0 and maximum units are 80. The higher the number on the CAPS-5, the more severe the PTSD symptoms. Response is defined as a change in the CAPS-5 of at least 12 points, which represents meaningful improvement in clinical PTSD symptoms. (NCT04378426)
Timeframe: 1 week

Interventionunits on a scale (Mean)
Nitrous Oxide46

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Mitragynine Half Life

Time to reach one-half of the concentration of mitragynine. (NCT04392011)
Timeframe: 0, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8,12, 24, 48, 72, 96, and 120 hours

Interventionh (Median)
Kratom Alone45.3

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Midazolam and Dextromethorphan Cmax

Maximum concentration (Cmax) of midazolam and dextromethorphan (NCT04392011)
Timeframe: 0, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8,12, 24, 48, 72, 96,120, and 144 hours

,
InterventionnM (Geometric Mean)
midazolamdextromethorphan
Drug Cocktail21.14.57
Kratom + Drug Cocktail31.64.30

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Midazolam and Dextromethorphan Half-life

Time to reach one-half of the concentration of midazolam and dextromethorphan (NCT04392011)
Timeframe: 0, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8,12, 24, 48, 72, 96,120, and 144 hours

,
Interventionh (Geometric Mean)
midazolamdextromethorphan
Drug Cocktail3.856.87
Kratom + Drug Cocktail4.126.84

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Dextromethorphan Area Under the Concentration vs. Time Curve (AUC)

Area under the plasma concentration time curve (AUC) of dextromethorphan (NCT04392011)
Timeframe: 0, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8,12, 24, 48, 72, 96, 120, and 144 hours

InterventionnM*h (Geometric Mean)
Drug Cocktail46.5
Kratom + Drug Cocktail46.2

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Mitragynine Cmax

Maximum plasma concentration of mitragynine. (NCT04392011)
Timeframe: 0, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8,12, 24, 48, 72, 96, and 120 hours

InterventionnM (Median)
Kratom Alone81.9

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Mitragynine Area Under the Concentration vs. Time Curve (AUC)

Area under the concentration vs. time curve (AUC) of mitragynine. (NCT04392011)
Timeframe: 0, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8,12, 24, 48, 72, 96, and 120 hours

InterventionnM x h (Median)
Kratom Alone388

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Midazolam Area Under the Concentration vs. Time Curve (AUC)

Area under the plasma concentration time curve (AUC) of midazolam (NCT04392011)
Timeframe: 0, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8,12, 24, 48, 72 , 96, 120, and 144 hours

InterventionnM * hr (Geometric Mean)
Drug Cocktail58.3
Kratom + Drug Cocktail80.8

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Treatment C: Change From Baseline in Erythrocytes

Blood samples were collected to analyze the hematology parameter: erythrocytes. Baseline for treatment C was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits (Day 20), before the dose of Treatment C. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value. (NCT04425902)
Timeframe: Baseline (Day 20), Days 22 and 25

Intervention10^12 cells per liter (Mean)
Day 22Day 25
Treatment C: Probe Substrates + GSK3640254 200 mg-0.161-0.013

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Treatment C: Change From Baseline in Erythrocytes Mean Corpuscular Hemoglobin

Blood samples were collected to analyze the hematology parameter: erythrocytes mean corpuscular hemoglobin. Baseline for treatment C was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits (Day 20), before the dose of Treatment C. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value. (NCT04425902)
Timeframe: Baseline (Day 20), Days 22 and 25

InterventionPicograms (Mean)
Day 22Day 25
Treatment C: Probe Substrates + GSK3640254 200 mg-0.23-0.39

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Treatment C: Change From Baseline in Erythrocytes Mean Corpuscular Volume

Blood samples were collected to analyze the hematology parameter: erythrocytes mean corpuscular volume. Baseline for treatment C was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits (Day 20), before the dose of Treatment C. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value. (NCT04425902)
Timeframe: Baseline (Day 20), Days 22 and 25

InterventionFemtoliter (Mean)
Day 22Day 25
Treatment C: Probe Substrates + GSK3640254 200 mg-1.64-1.28

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Treatment C: Change From Baseline in Glucose, Carbon Dioxide, Cholesterol, Triglycerides, Anion Gap, Calcium, Chloride, Phosphate, Potassium, Sodium, Urea

Blood samples were collected to analyze the chemistry parameters: glucose, carbon dioxide, cholesterol, triglycerides, anion gap, calcium, chloride, phosphate, potassium, sodium and urea. Baseline for treatment C was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits (Day 20), before the dose of Treatment C. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value. (NCT04425902)
Timeframe: Baseline (Day 20), Days 22 and 25

InterventionMillimoles per liter (Mean)
Day 22: GlucoseDay 25: GlucoseDay 22: Carbon DioxideDay 25: Carbon DioxideDay 22: CholesterolDay 25: CholesterolDay 22: TriglyceridesDay 25: TriglyceridesDay 22: Anion GapDay 25: Anion GapDay 22: CalciumDay 25: CalciumDay 22: ChlorideDay 25: ChlorideDay 22: PhosphateDay 25: PhosphateDay 22: PotassiumDay 25: PotassiumDay 22: SodiumDay 25: SodiumDay 22: UreaDay 25: Urea
Treatment C: Probe Substrates + GSK3640254 200 mg0.08760.15190.51.2-0.4355-0.29260.00540.0291-0.6-0.1-0.04070.03021.4-0.8-0.06800.0816-0.04-0.031.20.4-0.8286-0.4265

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Treatment C: Change From Baseline in Hematocrit

Blood samples were collected to analyze the hematology parameter: hematocrit. Baseline for treatment C was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits (Day 20), before the dose of Treatment C. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value. (NCT04425902)
Timeframe: Baseline (Day 20), Days 22 and 25

InterventionProportion of red blood cells in blood (Mean)
Day 22Day 25
Treatment C: Probe Substrates + GSK3640254 200 mg-0.0217-0.0071

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Treatment C: Change From Baseline in Hemoglobin

Blood samples were collected to analyze the hematology parameter: hemoglobin. Baseline for treatment C was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits (Day 20), before the dose of Treatment C. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value. (NCT04425902)
Timeframe: Baseline (Day 20), Days 22 and 25

InterventionGrams per liter (Mean)
Day 22Day 25
Treatment C: Probe Substrates + GSK3640254 200 mg-5.8-2.3

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Treatment C: Change From Baseline in Oral Temperature

Oral temperature was measured in the supine position after at least 5 minutes of rest for the participant in a quiet setting without distractions. Baseline for treatment C was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits (Day 21, Pre-Dose), before the first dose in Treatment C. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value. (NCT04425902)
Timeframe: Baseline (Day 21, Pre-Dose), Days 22 and 25

InterventionDegrees Celsius (Mean)
Day 22Day 25
Treatment C: Probe Substrates + GSK3640254 200 mg-0.130.01

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Treatment C: Change From Baseline in Platelet Count, Leukocyte Count, Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils

Blood samples were collected to analyze the hematology parameters: platelet count, leukocyte count, neutrophils, lymphocytes, monocytes, eosinophils and basophils. Baseline for treatment C was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits (Day 20), before the dose of Treatment C. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value. (NCT04425902)
Timeframe: Baseline (Day 20), Days 22 and 25

Intervention10^9 cells per liter (Mean)
Day 22: Platelet countDay 25: Platelet countDay 22: Leukocyte countDay 25: Leukocyte countDay 22: NeutrophilsDay 25: NeutrophilsDay 22: LymphocytesDay 25: LymphocytesDay 22: MonocytesDay 25: MonocytesDay 22: EosinophilsDay 25: EosinophilsDay 22: BasophilsDay 25: Basophils
Treatment C: Probe Substrates + GSK3640254 200 mg-13.1-1.6-0.050.12-0.12540.13510.03510.08430.0184-0.09290.0329-0.0115-0.0094-0.0066

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Treatment C: Change From Baseline in Pulse Rate

Pulse rate was measured in the supine position after at least 5 minutes of rest for the participant in a quiet setting without distractions. Baseline for treatment C was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits (Day 21, Pre-Dose), before the first dose in Treatment C. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value. (NCT04425902)
Timeframe: Baseline (Day 21, Pre-Dose), Days 22 and 25

InterventionBeats per minute (Mean)
Day 22Day 25
Treatment C: Probe Substrates + GSK3640254 200 mg-7.1-1.5

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Treatment C: Change From Baseline in Respiratory Rate

Respiratory rate was measured in the supine position after at least 5 minutes of rest for the participant in a quiet setting without distractions. Baseline for treatment C was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits (Day 21, Pre-Dose), before the first dose in Treatment C. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value. (NCT04425902)
Timeframe: Baseline (Day 21, Pre-Dose), Days 22 and 25

InterventionBreaths per minute (Mean)
Day 22Day 25
Treatment C: Probe Substrates + GSK3640254 200 mg-0.10.8

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Treatment C: Change From Baseline in SBP and DBP

SBP and DBP were measured in the supine position after at least 5 minutes of rest for the participant in a quiet setting without distractions. Baseline for treatment C was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits (Day 21, Pre-Dose), before the first dose in Treatment C. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value. (NCT04425902)
Timeframe: Baseline (Day 21, Pre-Dose), Days 22 and 25

InterventionMillimeters of mercury (Mean)
Day 22: SBPDay 25: SBPDay 22: DBPDay 25: DBP
Treatment C: Probe Substrates + GSK3640254 200 mg-1.92.2-4.3-0.5

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Treatment C: Change From Baseline in Urate, Creatinine, Bilirubin, Direct Bilirubin

Blood samples were collected to analyze the chemistry parameters: urate, creatinine, bilirubin and direct bilirubin. Baseline for treatment C was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits (Day 20), before the dose of Treatment C. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value. (NCT04425902)
Timeframe: Baseline (Day 20), Days 22 and 25

InterventionMicromoles per liter (Mean)
Day 22: UrateDay 25: UrateDay 22: CreatinineDay 25: CreatinineDay 22: BilirubinDay 25: BilirubinDay 22: Direct bilirubinDay 25: Direct bilirubin
Treatment C: Probe Substrates + GSK3640254 200 mg-40.0707-2.5044-4.7922-1.58191.13400.28800.23400.1530

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Treatment A: Change From Baseline in Urate, Creatinine, Bilirubin, Direct Bilirubin

Blood samples were collected to analyze the chemistry parameters: urate, creatinine, bilirubin and direct bilirubin. Baseline for treatment A was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits (Day -1), before the dose of Treatment A. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value. (NCT04425902)
Timeframe: Baseline (Day -1) and Day 10

InterventionMicromoles per liter (Mean)
UrateCreatinineBilirubinDirect bilirubin
Treatment A: Probe Substrates18.14141.4586-1.8297-0.3506

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Treatment A: Change From Baseline in SBP and DBP

SBP and DBP were measured in the supine position after at least 5 minutes of rest for the participant in a quiet setting without distractions. Baseline for treatment A was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits (Day 1, Pre-Dose), before the dose in Treatment A. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value. (NCT04425902)
Timeframe: Baseline (Day 1, Pre-dose) and Day 10

InterventionMillimeters of mercury (Mean)
SBPDBP
Treatment A: Probe Substrates-3.3-5.4

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Treatment A: Change From Baseline in Glucose, Carbon Dioxide, Cholesterol, Triglycerides, Anion Gap, Calcium, Chloride, Phosphate, Potassium, Sodium, Urea

Blood samples were collected to analyze the chemistry parameters: glucose, carbon dioxide, cholesterol, triglycerides, anion gap, calcium, chloride, phosphate, potassium, sodium, and urea. Baseline for treatment A was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits (Day -1), before the dose of Treatment A. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value. (NCT04425902)
Timeframe: Baseline (Day -1) and Day 10

InterventionMillimoles per liter (Mean)
GlucoseCarbon DioxideCholesterolTriglyceridesAnion GapCalciumChloridePhosphatePotassiumSodiumUrea
Treatment A: Probe Substrates-0.2137-78.7-0.6452-0.04185.9-0.062478.00.0678-0.050.71.1263

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Treatment A: Change From Baseline in ECG Parameters: PR Interval, QRS Duration, QT Interval, QTcF

Twelve-lead ECGs were obtained to measure PR Interval, QRS Duration, QT Interval and QTcF Interval. Twelve-lead ECGs were performed with the participant in a supine position after a rest of at least 10 minutes. Baseline for treatment A was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits (Day 1, Pre-Dose), before the dose in Treatment A. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value. (NCT04425902)
Timeframe: Baseline (Day 1, Pre-dose) and Day 10

InterventionMilliseconds (Mean)
PR IntervalQRS DurationQT IntervalQTcF Interval
Treatment A: Probe Substrates3.42.57.14.8

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Treatment A: Change From Baseline in Creatine Kinase, Lactate Dehydrogenase, ALT, ALP, AST, Gamma-glutamyl Transferase

Blood samples were collected to analyze the chemistry parameters: creatine kinase, lactate dehydrogenase, ALT, ALP, AST and gamma-glutamyl transferase. Baseline for treatment A was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits (Day -1), before the dose of Treatment A. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value. (NCT04425902)
Timeframe: Baseline (Day -1) and Day 10

InterventionInternational units per liter (Mean)
Creatine kinaseLactate dehydrogenaseALTALPASTGamma-glutamyl transferase
Treatment A: Probe Substrates-36.9-16.54.5-1.91.0-0.2

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Treatment A: Change From Baseline in Amylase, Lipase

Blood samples were collected to analyze the chemistry parameters: amylase and lipase. Baseline for treatment A was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits (Day -1), before the dose of Treatment A. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value. (NCT04425902)
Timeframe: Baseline (Day -1) and Day 10

InterventionUnits per liter (Mean)
LipaseAmylase
Treatment A: Probe Substrates2.2-2.6

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Treatment A: Change From Baseline in Albumin, Globulin, Protein

Blood samples were collected to analyze the chemistry parameters: albumin, globulin and protein. Baseline for treatment A was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits (Day -1), before the dose of Treatment A. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value. (NCT04425902)
Timeframe: Baseline (Day -1) and Day 10

InterventionGrams per liter (Mean)
AlbuminGlobulinProtein
Treatment A: Probe Substrates-0.7-1.5-2.2

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Treatment A: Absolute Values of Urate, Creatinine, Bilirubin, Direct Bilirubin

Blood samples were collected to analyze the chemistry parameters: urate, creatinine, bilirubin and direct bilirubin. Baseline for treatment A was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits (Day -1), before the dose of Treatment A. (NCT04425902)
Timeframe: Baseline (Day -1) and Day 10

InterventionMicromoles per liter (Mean)
Baseline (Day -1): UrateDay 10: UrateBaseline (Day -1): CreatinineDay 10: CreatinineBaseline (Day -1): BilirubinDay 10: BilirubinBaseline (Day -1): Direct bilirubinDay 10: Direct bilirubin
Treatment A: Probe Substrates347.3632365.504684.952486.41109.83258.00282.05201.7015

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Treatment A: Absolute Values of Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)

SBP and DBP were measured in the supine position after at least 5 minutes of rest for the participant in a quiet setting without distractions. Baseline for treatment A was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits (Day 1, Pre-Dose), before the dose in Treatment A. (NCT04425902)
Timeframe: Baseline (Day 1, Pre-dose) and Day 10

InterventionMillimeters of mercury (Mean)
Baseline (Day 1, Pre-dose): SBPDay 10: SBPBaseline (Day 1, Pre-dose): DBPDay 10: DBP
Treatment A: Probe Substrates111.0107.765.159.7

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Treatment A: Absolute Values of Respiratory Rate

Respiratory rate was measured in the supine position after at least 5 minutes of rest for the participant in a quiet setting without distractions. Baseline for treatment A was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits (Day 1, Pre-Dose), before the dose in Treatment A. (NCT04425902)
Timeframe: Baseline (Day 1, Pre-dose) and Day 2

InterventionBreaths per minute (Mean)
Baseline (Day 1, Pre-dose)Day 2
Treatment A: Probe Substrates16.115.8

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Treatment A: Absolute Values of Pulse Rate

Pulse rate was measured in the supine position after at least 5 minutes of rest for the participant in a quiet setting without distractions. Baseline for treatment A was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits (Day 1, Pre-Dose), before the dose in Treatment A. (NCT04425902)
Timeframe: Baseline (Day 1, Pre-dose) and Day 10

InterventionBeats per minute (Mean)
Baseline (Day 1, Pre-dose)Day 10
Treatment A: Probe Substrates64.565.0

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Treatment A: Absolute Values of Platelet Count, Leukocyte Count, Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils

Blood samples were collected to analyze the hematology parameters: platelet count, leukocyte count, neutrophils, lymphocytes, monocytes, eosinophils and basophils. Baseline for treatment A was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits (Day -1), before the dose of Treatment A. (NCT04425902)
Timeframe: Baseline (Day -1) and Day 10

Intervention10^9 cells per liter (Mean)
Baseline (Day -1): Platelet countDay 10: Platelet countBaseline (Day -1): Leukocyte countDay 10: Leukocyte countBaseline (Day -1): NeutrophilsDay 10: NeutrophilsBaseline (Day -1): LymphocytesDay 10: LymphocytesBaseline (Day -1): MonocytesDay 10: MonocytesBaseline (Day -1): EosinophilsDay 10: EosinophilsBaseline (Day -1): BasophilsDay 10: Basophils
Treatment A: Probe Substrates258.6265.95.646.303.15043.74301.82171.89650.48900.45150.14610.16100.03310.0440

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Treatment A: Absolute Values of Oral Temperature

Oral temperature was measured in the supine position after at least 5 minutes of rest for the participant in a quiet setting without distractions. Baseline for treatment A was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits (Day 1, Pre-Dose), before the dose in Treatment A. (NCT04425902)
Timeframe: Baseline (Day 1, Pre-dose) and Day 10

InterventionDegrees Celsius (Mean)
Baseline (Day 1, Pre-dose)Day 10
Treatment A: Probe Substrates36.3836.26

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Treatment A: Absolute Values of Hemoglobin

Blood samples were collected to analyze the hematology parameter: hemoglobin. Baseline for treatment A was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits (Day -1), before the dose of Treatment A. (NCT04425902)
Timeframe: Baseline (Day -1) and Day 10

InterventionGrams per liter (Mean)
Baseline (Day -1)Day 10
Treatment A: Probe Substrates141.9137.7

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Treatment A: Absolute Values of Hematocrit

Blood samples were collected to analyze the hematology parameter: hematocrit. Baseline for treatment A was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits (Day -1), before the dose of Treatment A. (NCT04425902)
Timeframe: Baseline (Day -1) and Day 10

InterventionProportion of red blood cells in blood (Mean)
Baseline (Day -1)Day 10
Treatment A: Probe Substrates0.41880.4098

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Treatment A: Absolute Values of Glucose, Carbon Dioxide, Cholesterol, Triglycerides, Anion Gap, Calcium, Chloride, Phosphate, Potassium, Sodium, Urea

Blood samples were collected to analyze the chemistry parameters: glucose, carbon dioxide, cholesterol, triglycerides, anion gap, calcium, chloride, phosphate, potassium, sodium, urea. Baseline for treatment A was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits (Day -1), before the dose of Treatment A. (NCT04425902)
Timeframe: Baseline (Day -1) and Day 10

InterventionMillimoles per liter (Mean)
Baseline (Day -1): GlucoseDay 10: GlucoseBaseline (Day -1): Carbon DioxideDay 10: Carbon DioxideBaseline (Day -1): CholesterolDay 10: CholesterolBaseline (Day -1): TriglyceridesDay 10: TriglyceridesBaseline (Day -1): Anion GapDay 10: Anion GapBaseline (Day -1): CalciumDay 10: CalciumBaseline (Day -1): ChlorideDay 10: ChlorideBaseline (Day -1): PhosphateDay 10: PhosphateBaseline (Day -1): PotassiumDay 10: PotassiumBaseline (Day -1): SodiumDay 10: SodiumBaseline (Day -1): UreaDay 10: Urea
Treatment A: Probe Substrates5.03484.8211104.125.44.45703.81181.22321.18147.913.82.37652.314125.8103.71.10751.17544.484.43137.7138.44.81955.9458

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Treatment A: Absolute Values of Erythrocytes Mean Corpuscular Volume

Blood samples were collected to analyze the hematology parameter: erythrocytes mean corpuscular volume. Baseline for treatment A was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits (Day -1), before the dose of Treatment A. (NCT04425902)
Timeframe: Baseline (Day -1) and Day 10

InterventionFemtoliter (Mean)
Baseline (Day -1)Day 10
Treatment A: Probe Substrates86.7188.02

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Treatment A: Absolute Values of Erythrocytes Mean Corpuscular Hemoglobin

Blood samples were collected to analyze the hematology parameter: erythrocytes mean corpuscular hemoglobin. Baseline for treatment A was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits (Day -1), before the dose of Treatment A. (NCT04425902)
Timeframe: Baseline (Day -1) and Day 10

InterventionPicograms (Mean)
Baseline (Day -1)Day 10
Treatment A: Probe Substrates29.3729.57

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Treatment A: Absolute Values of Erythrocytes

Blood samples were collected to analyze the hematology parameter: erythrocytes. Baseline for treatment A was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits (Day -1), before the dose of Treatment A. (NCT04425902)
Timeframe: Baseline (Day -1) and Day 10

Intervention10^12 cells per liter (Mean)
Baseline (Day -1)Day 10
Treatment A: Probe Substrates4.8364.664

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Treatment A: Absolute Values of Creatine Kinase, Lactate Dehydrogenase, Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST), Gamma-glutamyl Transferase

Blood samples were collected to analyze the chemistry parameters: creatine kinase, lactate dehydrogenase, ALT, ALP, AST and gamma-glutamyl transferase. Baseline for treatment A was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits (Day -1), before the dose of Treatment A. (NCT04425902)
Timeframe: Baseline (Day -1) and Day 10

InterventionInternational units per liter (Mean)
Baseline (Day -1): Creatine kinaseDay 10: Creatine kinaseBaseline (Day -1): Lactate dehydrogenaseDay 10: Lactate dehydrogenaseBaseline (Day -1): ALTDay 10: ALTBaseline (Day -1): ALPDay 10: ALPBaseline (Day -1): ASTDay 10: ASTBaseline (Day -1): Gamma-glutamyl transferaseDay 10: Gamma-glutamyl transferase
Treatment A: Probe Substrates103.766.9131.3114.815.620.162.760.814.615.619.118.9

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Treatment A: Absolute Values of Amylase, Lipase

Blood samples were collected to analyze the chemistry parameters: amylase and lipase. Baseline for treatment A was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits (Day -1), before the dose of Treatment A. (NCT04425902)
Timeframe: Baseline (Day -1) and Day 10

InterventionUnits per liter (Mean)
Baseline (Day -1): LipaseDay 10: LipaseBaseline (Day -1): AmylaseDay 10: Amylase
Treatment A: Probe Substrates29.431.659.556.9

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Treatment A: Absolute Values of Albumin, Globulin, Protein

Blood samples were collected to analyze the chemistry parameters: albumin, globulin and protein. Baseline for treatment A was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits (Day -1), before the dose of Treatment A. (NCT04425902)
Timeframe: Baseline (Day -1) and Day 10

InterventionGrams per liter (Mean)
Baseline (Day -1): AlbuminDay 10: AlbuminBaseline (Day -1): GlobulinDay 10: GlobulinBaseline (Day -1): ProteinDay 10: Protein
Treatment A: Probe Substrates42.942.227.425.970.368.1

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Treatment A: Absolute Values for Electrocardiogram (ECG) Parameters: PR Interval, QRS Duration, QT Interval, Corrected QT Interval Using Fridericia's Formula (QTcF)

Twelve-lead ECGs were obtained to measure PR Interval, QRS Duration, QT Interval and QTcF Interval. Twelve-lead ECGs were performed with the participant in a supine position after a rest of at least 10 minutes. Baseline for treatment A was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits (Day 1, Pre-Dose), before the dose in Treatment A. (NCT04425902)
Timeframe: Baseline (Day 1, Pre-Dose) and Day 10

InterventionMilliseconds (Mean)
Baseline (Day 1, Pre-dose): PR IntervalDay 10: PR IntervalBaseline (Day 1, Pre-dose): QRS DurationDay 10: QRS DurationBaseline (Day 1, Pre-dose): QT IntervalDay 10: QT IntervalBaseline (Day 1, Pre-dose): QTcF IntervalDay 10: QTcF Interval
Treatment A: Probe Substrates154.8158.292.595.0391.2398.3401.0405.8

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Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)

An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. SAE was defined as any untoward medical occurrence that, at any dose, results in death, was life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect and other situations according to medical or scientific judgement. (NCT04425902)
Timeframe: Up to Day 26

,,
InterventionParticipants (Count of Participants)
AEsSAEs
Treatment A: Probe Substrates10
Treatment B: GSK3640254 200 mg50
Treatment C: Probe Substrates + GSK3640254 200 mg50

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Treatment C: Tmax for GSK3640254

Blood samples were collected at the indicated time points for steady-state pharmacokinetic analysis of GSK3640254. (NCT04425902)
Timeframe: Pre-dose and at 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 12, 24, 48, 72, 96, and 120 hours post-dose in treatment period 3

InterventionHours (Median)
Treatment C: Probe Substrates + GSK3640254 200 mg4.500

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Treatment C: t1/2 for GSK3640254

Blood samples were collected at the indicated time points for steady-state pharmacokinetic analysis of GSK3640254. (NCT04425902)
Timeframe: Pre-dose and at 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 12, 24, 48, 72, 96, and 120 hours post-dose in treatment period 3

InterventionHours (Geometric Mean)
Treatment C: Probe Substrates + GSK3640254 200 mg29.556

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Treatment C: Plasma Concentration at the End of the Dosing Interval (Ctau) for GSK3640254

Blood samples were collected at the indicated time points for steady-state pharmacokinetic analysis of GSK3640254. (NCT04425902)
Timeframe: Pre-dose and at 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 12, 24, 48, 72, 96, and 120 hours post-dose in treatment period 3

Interventionng/mL (Geometric Mean)
Treatment C: Probe Substrates + GSK3640254 200 mg729.5

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Treatment C: Cmax for GSK3640254

Blood samples were collected at the indicated time points for steady-state pharmacokinetic analysis of GSK3640254. (NCT04425902)
Timeframe: Pre-dose and at 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 12, 24, 48, 72, 96, and 120 hours post-dose in treatment period 3

Interventionng/mL (Geometric Mean)
Treatment C: Probe Substrates + GSK3640254 200 mg1450

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Treatment C: AUC(0-t) for GSK3640254

Blood samples were collected at the indicated time points for steady-state pharmacokinetic analysis of GSK3640254. The AUC(0-t) was determined using the linear trapezoidal rule for each incremental trapezoid and the log trapezoidal rule for each decremental trapezoid. (NCT04425902)
Timeframe: Pre-dose and at 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 12, 24, 48, 72, 96, and 120 hours post-dose in treatment period 3

Interventionh*ng/mL (Geometric Mean)
Treatment C: Probe Substrates + GSK3640254 200 mg51840

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Treatment C: AUC From Time Zero to the End of the Dosing Interval at Steady State (AUC[0-tau]) for GSK3640254

Blood samples were collected at the indicated time points for steady-state pharmacokinetic analysis of GSK3640254. (NCT04425902)
Timeframe: Pre-dose and at 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 12, 24, 48, 72, 96, and 120 hours post-dose in treatment period 3

Interventionh*ng/mL (Geometric Mean)
Treatment C: Probe Substrates + GSK3640254 200 mg22920

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Treatment B: Change From Baseline in Respiratory Rate

Respiratory rate was measured in the supine position after at least 5 minutes of rest for the participant in a quiet setting without distractions. Baseline for treatment B was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits (Day 11, Pre-Dose), before the first dose in Treatment B. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value. (NCT04425902)
Timeframe: Baseline (Day 11, Pre-Dose) and Day 20

InterventionBreaths per minute (Mean)
Treatment B: GSK3640254 200 mg-0.3

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Treatment B: Change From Baseline in Pulse Rate

Pulse rate was measured in the supine position after at least 5 minutes of rest for the participant in a quiet setting without distractions. Baseline for treatment B was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits (Day 11, Pre-Dose), before the first dose in Treatment B. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value. (NCT04425902)
Timeframe: Baseline (Day 11, Pre-Dose) and Day 20

InterventionBeats per minute (Mean)
Treatment B: GSK3640254 200 mg1.3

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Treatment B: Change From Baseline in Oral Temperature

Oral temperature was measured in the supine position after at least 5 minutes of rest for the participant in a quiet setting without distractions. Baseline for treatment B was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits (Day 11, Pre-Dose), before the first dose in Treatment B. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value. (NCT04425902)
Timeframe: Baseline (Day 11, Pre-Dose) and Day 20

InterventionDegrees Celsius (Mean)
Treatment B: GSK3640254 200 mg-0.03

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Treatment B: Change From Baseline in Hemoglobin

Blood samples were collected to analyze the hematology parameter: hemoglobin. Baseline for treatment B was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits (Day 10), before the first dose of Treatment B. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value. (NCT04425902)
Timeframe: Baseline (Day 10) and Day 20

InterventionGrams per liter (Mean)
Treatment B: GSK3640254 200 mg2.3

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Treatment B: Change From Baseline in Hematocrit

Blood samples were collected to analyze the hematology parameter: hematocrit. Baseline for treatment B was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits (Day 10), before the first dose of Treatment B. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value. (NCT04425902)
Timeframe: Baseline (Day 10) and Day 20

InterventionProportion of red blood cells in blood (Mean)
Treatment B: GSK3640254 200 mg0.0118

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Treatment B: Change From Baseline in Erythrocytes Mean Corpuscular Volume

Blood samples were collected to analyze the hematology parameter: erythrocytes mean corpuscular volume. Baseline for treatment B was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits (Day 10), before the first dose of Treatment B. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value. (NCT04425902)
Timeframe: Baseline (Day 10) and Day 20

InterventionFemtoliter (Mean)
Treatment B: GSK3640254 200 mg0.94

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Treatment B: Change From Baseline in Erythrocytes Mean Corpuscular Hemoglobin

Blood samples were collected to analyze the hematology parameter: erythrocytes mean corpuscular hemoglobin. Baseline for treatment B was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits (Day 10), before the first dose of Treatment B. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value. (NCT04425902)
Timeframe: Baseline (Day 10) and Day 20

InterventionPicograms (Mean)
Treatment B: GSK3640254 200 mg-0.05

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Treatment B: Change From Baseline in Erythrocytes

Blood samples were collected to analyze the hematology parameter: erythrocytes. Baseline for treatment B was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits (Day 10), before the first dose of Treatment B. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value. (NCT04425902)
Timeframe: Baseline (Day 10) and Day 20

Intervention10^12 cells per liter (Mean)
Treatment B: GSK3640254 200 mg0.083

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Treatment A: Change From Baseline in Respiratory Rate

Respiratory rate was measured in the supine position after at least 5 minutes of rest for the participant in a quiet setting without distractions. Baseline for treatment A was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits (Day 1, Pre-Dose), before the dose in Treatment A. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value. (NCT04425902)
Timeframe: Baseline (Day 1, Pre-dose) and Day 2

InterventionBreaths per minute (Mean)
Treatment A: Probe Substrates-0.3

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Treatment A: Change From Baseline in Pulse Rate

Pulse rate was measured in the supine position after at least 5 minutes of rest for the participant in a quiet setting without distractions. Baseline for treatment A was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits (Day 1, Pre-Dose), before the dose in Treatment A. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value. (NCT04425902)
Timeframe: Baseline (Day 1, Pre-dose) and Day 10

InterventionBeats per minute (Mean)
Treatment A: Probe Substrates0.5

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Treatment A: Change From Baseline in Oral Temperature

Oral temperature was measured in the supine position after at least 5 minutes of rest for the participant in a quiet setting without distractions. Baseline for treatment A was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits (Day 1, Pre-Dose), before the dose in Treatment A. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value. (NCT04425902)
Timeframe: Baseline (Day 1, Pre-dose) and Day 10

InterventionDegrees Celsius (Mean)
Treatment A: Probe Substrates-0.12

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Treatment A: Change From Baseline in Hemoglobin

Blood samples were collected to analyze the hematology parameter: hemoglobin. Baseline for treatment A was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits (Day -1), before the dose of Treatment A. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value. (NCT04425902)
Timeframe: Baseline (Day -1) and Day 10

InterventionGrams per liter (Mean)
Treatment A: Probe Substrates-4.2

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Treatment A: Change From Baseline in Hematocrit

Blood samples were collected to analyze the hematology parameter: hematocrit. Baseline for treatment A was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits (Day -1), before the dose of Treatment A. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value. (NCT04425902)
Timeframe: Baseline (Day -1) and Day 10

InterventionProportion of red blood cells in blood (Mean)
Treatment A: Probe Substrates-0.0090

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Treatment A: Change From Baseline in Erythrocytes Mean Corpuscular Volume

Blood samples were collected to analyze the hematology parameter: erythrocytes mean corpuscular volume. Baseline for treatment A was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits (Day -1), before the dose of Treatment A. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value. (NCT04425902)
Timeframe: Baseline (Day -1) and Day 10

InterventionFemtoliter (Mean)
Treatment A: Probe Substrates1.31

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Treatment A: Change From Baseline in Erythrocytes Mean Corpuscular Hemoglobin

Blood samples were collected to analyze the hematology parameter: erythrocytes mean corpuscular hemoglobin. Baseline for treatment A was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits (Day -1), before the dose of Treatment A. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value. (NCT04425902)
Timeframe: Baseline (Day -1) and Day 10

InterventionPicograms (Mean)
Treatment A: Probe Substrates0.20

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Treatment A: Change From Baseline in Erythrocytes

Blood samples were collected to analyze the hematology parameter: erythrocytes. Baseline for treatment A was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits (Day -1), before the dose of Treatment A. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value. (NCT04425902)
Timeframe: Baseline (Day -1) and Day 10

Intervention10^12 cells per liter (Mean)
Treatment A: Probe Substrates-0.172

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Tmax for Pravastatin

Blood samples were collected at the indicated time points for pharmacokinetic analysis of pravastatin. (NCT04425902)
Timeframe: Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 96, and 120 hours post-dose in treatment period 1 and 3

InterventionHours (Median)
Treatment A: Probe Substrates1.500
Treatment C: Probe Substrates + GSK3640254 200 mg3.000

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Tmax for Omeprazole

Blood samples were collected at the indicated time points for pharmacokinetic analysis of omeprazole. (NCT04425902)
Timeframe: Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 96, and 120 hours post-dose in treatment period 1 and 3

InterventionHours (Median)
Treatment A: Probe Substrates6.000
Treatment C: Probe Substrates + GSK3640254 200 mg6.000

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Tmax for Montelukast

Blood samples were collected at the indicated time points for pharmacokinetic analysis of montelukast. (NCT04425902)
Timeframe: Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 96, and 120 hours post-dose in treatment period 1 and 3

InterventionHours (Median)
Treatment A: Probe Substrates5.000
Treatment C: Probe Substrates + GSK3640254 200 mg6.000

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Tmax for Midazolam

Blood samples were collected at the indicated time points for pharmacokinetic analysis of midazolam. (NCT04425902)
Timeframe: Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 96, and 120 hours post-dose in treatment period 1 and 3

InterventionHours (Median)
Treatment A: Probe Substrates1.000
Treatment C: Probe Substrates + GSK3640254 200 mg1.000

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Tmax for Metoprolol

Blood samples were collected at the indicated time points for pharmacokinetic analysis of metoprolol. (NCT04425902)
Timeframe: Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 96, and 120 hours post-dose in treatment period 1 and 3

InterventionHours (Median)
Treatment A: Probe Substrates2.000
Treatment C: Probe Substrates + GSK3640254 200 mg3.000

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Tmax for Flurbiprofen

Blood samples were collected at the indicated time points for pharmacokinetic analysis of flurbiprofen. (NCT04425902)
Timeframe: Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 96, and 120 hours post-dose in treatment period 1 and 3

InterventionHours (Median)
Treatment A: Probe Substrates3.000
Treatment C: Probe Substrates + GSK3640254 200 mg4.000

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Tmax for Digoxin

Blood samples were collected at the indicated time points for pharmacokinetic analysis of digoxin. (NCT04425902)
Timeframe: Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 96, and 120 hours post-dose in treatment period 1 and 3

InterventionHours (Median)
Treatment A: Probe Substrates3.000
Treatment C: Probe Substrates + GSK3640254 200 mg2.000

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Tmax for Alpha-hydroxymetoprolol

Blood samples were collected at the indicated time points for pharmacokinetic analysis of alpha-hydroxymetoprolol. Alpha-hydroxymetoprolol is a metabolite of metoprolol. (NCT04425902)
Timeframe: Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 96, and 120 hours post-dose in treatment period 1 and 3

InterventionHours (Median)
Treatment A: Probe Substrates3.033
Treatment C: Probe Substrates + GSK3640254 200 mg4.000

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Tmax for 5-hydroxyomeprazole

Blood samples were collected at the indicated time points for pharmacokinetic analysis of 5-hydroxyomeprazole. 5-hydroxyomeprazole is a metabolite of omeprazole. (NCT04425902)
Timeframe: Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 96, and 120 hours post-dose in treatment period 1 and 3

InterventionHours (Median)
Treatment A: Probe Substrates6.000
Treatment C: Probe Substrates + GSK3640254 200 mg6.000

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Tmax for 36-hydroxymontelukast

Blood samples were collected at the indicated time points for pharmacokinetic analysis of 36-hydroxymontelukast. 36-hydroxymontelukast is a metabolite of montelukast. (NCT04425902)
Timeframe: Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 96, and 120 hours post-dose in treatment period 1 and 3

InterventionHours (Median)
Treatment A: Probe Substrates6.000
Treatment C: Probe Substrates + GSK3640254 200 mg6.000

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Tmax for 1-hydroxymidazolam

Blood samples were collected at the indicated time points for pharmacokinetic analysis of 1-hydroxymidazolam. 1-hydroxymidazolam is a metabolite of midazolam. (NCT04425902)
Timeframe: Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 96, and 120 hours post-dose in treatment period 1 and 3

InterventionHours (Median)
Treatment A: Probe Substrates1.000
Treatment C: Probe Substrates + GSK3640254 200 mg1.000

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Time to Cmax (Tmax) for Caffeine

Blood samples were collected at the indicated time points for pharmacokinetic analysis of caffeine. (NCT04425902)
Timeframe: Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 96, and 120 hours post-dose in treatment period 1 and 3

InterventionHours (Median)
Treatment A: Probe Substrates2.000
Treatment C: Probe Substrates + GSK3640254 200 mg3.000

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t1/2 for Pravastatin

Blood samples were collected at the indicated time points for pharmacokinetic analysis of pravastatin. (NCT04425902)
Timeframe: Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 96, and 120 hours post-dose in treatment period 1 and 3

InterventionHours (Geometric Mean)
Treatment A: Probe Substrates3.189
Treatment C: Probe Substrates + GSK3640254 200 mg3.156

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t1/2 for Omeprazole

Blood samples were collected at the indicated time points for pharmacokinetic analysis of omeprazole. (NCT04425902)
Timeframe: Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 96, and 120 hours post-dose in treatment period 1 and 3

InterventionHours (Geometric Mean)
Treatment A: Probe Substrates1.439
Treatment C: Probe Substrates + GSK3640254 200 mg1.219

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t1/2 for Montelukast

Blood samples were collected at the indicated time points for pharmacokinetic analysis of montelukast. (NCT04425902)
Timeframe: Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 96, and 120 hours post-dose in treatment period 1 and 3

InterventionHours (Geometric Mean)
Treatment A: Probe Substrates5.035
Treatment C: Probe Substrates + GSK3640254 200 mg5.135

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t1/2 for Midazolam

Blood samples were collected at the indicated time points for pharmacokinetic analysis of midazolam. (NCT04425902)
Timeframe: Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 96, and 120 hours post-dose in treatment period 1 and 3

InterventionHours (Geometric Mean)
Treatment A: Probe Substrates5.756
Treatment C: Probe Substrates + GSK3640254 200 mg5.222

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t1/2 for Metoprolol

Blood samples were collected at the indicated time points for pharmacokinetic analysis of metoprolol. (NCT04425902)
Timeframe: Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 96, and 120 hours post-dose in treatment period 1 and 3

InterventionHours (Geometric Mean)
Treatment A: Probe Substrates4.872
Treatment C: Probe Substrates + GSK3640254 200 mg5.342

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t1/2 for Flurbiprofen

Blood samples were collected at the indicated time points for pharmacokinetic analysis of flurbiprofen. (NCT04425902)
Timeframe: Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 96, and 120 hours post-dose in treatment period 1 and 3

InterventionHours (Geometric Mean)
Treatment A: Probe Substrates6.123
Treatment C: Probe Substrates + GSK3640254 200 mg6.088

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t1/2 for Digoxin

Blood samples were collected at the indicated time points for pharmacokinetic analysis of digoxin. (NCT04425902)
Timeframe: Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 96, and 120 hours post-dose in treatment period 1 and 3

InterventionHours (Geometric Mean)
Treatment A: Probe Substrates40.279
Treatment C: Probe Substrates + GSK3640254 200 mg38.784

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t1/2 for Alpha-hydroxymetoprolol

Blood samples were collected at the indicated time points for pharmacokinetic analysis of alpha-hydroxymetoprolol. Alpha-hydroxymetoprolol is a metabolite of metoprolol. (NCT04425902)
Timeframe: Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 96, and 120 hours post-dose in treatment period 1 and 3

InterventionHours (Geometric Mean)
Treatment A: Probe Substrates8.040
Treatment C: Probe Substrates + GSK3640254 200 mg8.339

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t1/2 for 5-hydroxyomeprazole

Blood samples were collected at the indicated time points for pharmacokinetic analysis of 5-hydroxyomeprazole. 5-hydroxyomeprazole is a metabolite of omeprazole. (NCT04425902)
Timeframe: Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 96, and 120 hours post-dose in treatment period 1 and 3

InterventionHours (Geometric Mean)
Treatment A: Probe Substrates1.580
Treatment C: Probe Substrates + GSK3640254 200 mg1.569

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t1/2 for 36-hydroxymontelukast

Blood samples were collected at the indicated time points for pharmacokinetic analysis of 36-hydroxymontelukast. 36-hydroxymontelukast is a metabolite of montelukast. (NCT04425902)
Timeframe: Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 96, and 120 hours post-dose in treatment period 1 and 3

InterventionHours (Geometric Mean)
Treatment A: Probe Substrates5.310
Treatment C: Probe Substrates + GSK3640254 200 mg5.644

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t1/2 for 1-hydroxymidazolam

Blood samples were collected at the indicated time points for pharmacokinetic analysis of 1-hydroxymidazolam. 1-hydroxymidazolam is a metabolite of midazolam. (NCT04425902)
Timeframe: Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 96, and 120 hours post-dose in treatment period 1 and 3

InterventionHours (Geometric Mean)
Treatment A: Probe Substrates3.632
Treatment C: Probe Substrates + GSK3640254 200 mg3.717

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Ratio of Cmax of Alpha-hydroxymetoprolol to Metoprolol

Blood samples were collected at the indicated time points for pharmacokinetic analysis of parent drug (metoprolol) and its metabolite (alpha-hydroxymetoprolol). Ratio of Cmax of metabolite to parent drug has been presented. (NCT04425902)
Timeframe: Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 96, and 120 hours post-dose in treatment period 1 and 3

InterventionRatio (Mean)
Treatment A: Probe Substrates0.7869
Treatment C: Probe Substrates + GSK3640254 200 mg0.7066

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Ratio of Cmax of 5-hydroxyomeprazole to Omeprazole

Blood samples were collected at the indicated time points for pharmacokinetic analysis of parent drug (omeprazole) and its metabolite (5-hydroxyomeprazole). Ratio of Cmax of metabolite to parent drug has been presented. (NCT04425902)
Timeframe: Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 96, and 120 hours post-dose in treatment period 1 and 3

InterventionRatio (Mean)
Treatment A: Probe Substrates0.9461
Treatment C: Probe Substrates + GSK3640254 200 mg0.8810

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Ratio of Cmax of 36-hydroxymontelukast to Montelukast

Blood samples were collected at the indicated time points for pharmacokinetic analysis of parent drug (montelukast) and its metabolite (36-hydroxymontelukast). Ratio of Cmax of metabolite to parent drug has been presented. (NCT04425902)
Timeframe: Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 96, and 120 hours post-dose in treatment period 1 and 3

InterventionRatio (Mean)
Treatment A: Probe Substrates0.06766
Treatment C: Probe Substrates + GSK3640254 200 mg0.06308

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Ratio of Cmax of 1-hydroxymidazolam to Midazolam

Blood samples were collected at the indicated time points for pharmacokinetic analysis of parent drug (midazolam) and its metabolite (1-hydroxymidazolam). Ratio of Cmax of metabolite to parent drug has been presented. (NCT04425902)
Timeframe: Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 96, and 120 hours post-dose in treatment period 1 and 3

InterventionRatio (Mean)
Treatment A: Probe Substrates0.5286
Treatment C: Probe Substrates + GSK3640254 200 mg0.4955

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Ratio of AUC(0-infinity) of Alpha-hydroxymetoprolol to Metoprolol

Blood samples were collected at the indicated time points for pharmacokinetic analysis of parent drug (metoprolol) and its metabolite (alpha-hydroxymetoprolol). Ratio of AUC(0-infinity) of metabolite to parent drug has been presented. (NCT04425902)
Timeframe: Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 96, and 120 hours post-dose in treatment period 1 and 3

InterventionRatio (Mean)
Treatment A: Probe Substrates1.733
Treatment C: Probe Substrates + GSK3640254 200 mg1.449

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Ratio of AUC(0-infinity) of 5-hydroxyomeprazole to Omeprazole

Blood samples were collected at the indicated time points for pharmacokinetic analysis of parent drug (omeprazole) and its metabolite (5-hydroxyomeprazole). Ratio of AUC(0-infinity) of metabolite to parent drug has been presented. (NCT04425902)
Timeframe: Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 96, and 120 hours post-dose in treatment period 1 and 3

InterventionRatio (Mean)
Treatment A: Probe Substrates1.151
Treatment C: Probe Substrates + GSK3640254 200 mg1.077

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Ratio of AUC(0-infinity) of 36-hydroxymontelukast to Montelukast

Blood samples were collected at the indicated time points for pharmacokinetic analysis of parent drug (montelukast) and its metabolite (36-hydroxymontelukast). Ratio of AUC(0-infinity) of metabolite to parent drug has been presented. (NCT04425902)
Timeframe: Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 96, and 120 hours post-dose in treatment period 1 and 3

InterventionRatio (Mean)
Treatment A: Probe Substrates0.09182
Treatment C: Probe Substrates + GSK3640254 200 mg0.08562

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Ratio of AUC(0-infinity) of 1-hydroxymidazolam to Midazolam

Blood samples were collected at the indicated time points for pharmacokinetic analysis of parent drug (midazolam) and its metabolite (1-hydroxymidazolam). Ratio of AUC(0-infinity) of metabolite to parent drug has been presented. (NCT04425902)
Timeframe: Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 96, and 120 hours post-dose in treatment period 1 and 3

InterventionRatio (Mean)
Treatment A: Probe Substrates0.4677
Treatment C: Probe Substrates + GSK3640254 200 mg0.4618

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Apparent Terminal Phase Half-life (t1/2) for Caffeine

Blood samples were collected at the indicated time points for pharmacokinetic analysis of caffeine. (NCT04425902)
Timeframe: Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 96, and 120 hours post-dose in treatment period 1 and 3

InterventionHours (Geometric Mean)
Treatment A: Probe Substrates5.380
Treatment C: Probe Substrates + GSK3640254 200 mg6.085

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Area Under the Plasma Concentration-time Curve (AUC) From Time Zero to Time t (AUC[0-t]) for Caffeine

Blood samples were collected at the indicated time points for pharmacokinetic analysis of caffeine. Area under the plasma concentration-time curve from time zero to time t, to be calculated using the linear trapezoidal rule for each incremental trapezoid and the log trapezoidal rule for each decremental trapezoid. (NCT04425902)
Timeframe: Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 96, and 120 hours post-dose in treatment period 1 and 3

InterventionHour*nanograms per milliliter (h*ng/mL) (Geometric Mean)
Treatment A: Probe Substrates37970
Treatment C: Probe Substrates + GSK3640254 200 mg42230

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Treatment A: Change From Baseline in Platelet Count, Leukocyte Count, Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils

Blood samples were collected to analyze the hematology parameters: platelet count, leukocyte count, neutrophils, lymphocytes, monocytes, eosinophils and basophils. Baseline for treatment A was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits (Day -1), before the dose of Treatment A. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value. (NCT04425902)
Timeframe: Baseline (Day -1) and Day 10

Intervention10^9 cells per liter (Mean)
Platelet countLeukocyte countNeutrophilsLymphocytesMonocytesEosinophilsBasophils
Treatment A: Probe Substrates7.30.660.59260.0748-0.03750.01500.0110

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AUC From Time Zero Extrapolated to Infinity (AUC[0-infinity]) for Caffeine

Blood samples were collected at the indicated time points for pharmacokinetic analysis of caffeine. The AUC(0-infinity) was determined using the linear trapezoidal rule for each incremental trapezoid and the log trapezoidal rule for each decremental trapezoid. (NCT04425902)
Timeframe: Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 96, and 120 hours post-dose in treatment period 1 and 3

Interventionh*ng/mL (Geometric Mean)
Treatment A: Probe Substrates39720
Treatment C: Probe Substrates + GSK3640254 200 mg44440

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AUC(0-infinity) for 1-hydroxymidazolam

Blood samples were collected at the indicated time points for pharmacokinetic analysis of 1-hydroxymidazolam. 1-hydroxymidazolam is a metabolite of midazolam. The AUC(0-infinity) was determined using the linear trapezoidal rule for each incremental trapezoid and the log trapezoidal rule for each decremental trapezoid. (NCT04425902)
Timeframe: Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 96, and 120 hours post-dose in treatment period 1 and 3

Interventionh*ng/mL (Geometric Mean)
Treatment A: Probe Substrates31.86
Treatment C: Probe Substrates + GSK3640254 200 mg28.99

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AUC(0-infinity) for 36-hydroxymontelukast

Blood samples were collected at the indicated time points for pharmacokinetic analysis of 36-hydroxymontelukast. 36-hydroxymontelukast is a metabolite of montelukast. The AUC(0-infinity) was determined using the linear trapezoidal rule for each incremental trapezoid and the log trapezoidal rule for each decremental trapezoid. (NCT04425902)
Timeframe: Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 96, and 120 hours post-dose in treatment period 1 and 3

Interventionh*ng/mL (Geometric Mean)
Treatment A: Probe Substrates252.5
Treatment C: Probe Substrates + GSK3640254 200 mg249.3

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AUC(0-infinity) for 5-hydroxyomeprazole

Blood samples were collected at the indicated time points for pharmacokinetic analysis of 5-hydroxyomeprazole. 5-hydroxyomeprazole is a metabolite of omeprazole. The AUC(0-infinity) was determined using the linear trapezoidal rule for each incremental trapezoid and the log trapezoidal rule for each decremental trapezoid. (NCT04425902)
Timeframe: Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 96, and 120 hours post-dose in treatment period 1 and 3

Interventionh*ng/mL (Geometric Mean)
Treatment A: Probe Substrates767.4
Treatment C: Probe Substrates + GSK3640254 200 mg762.0

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AUC(0-infinity) for Alpha-hydroxymetoprolol

Blood samples were collected at the indicated time points for pharmacokinetic analysis of alpha-hydroxymetoprolol. Alpha-hydroxymetoprolol is a metabolite of metoprolol. The AUC(0-infinity) was determined using the linear trapezoidal rule for each incremental trapezoid and the log trapezoidal rule for each decremental trapezoid. (NCT04425902)
Timeframe: Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 96, and 120 hours post-dose in treatment period 1 and 3

Interventionh*ng/mL (Geometric Mean)
Treatment A: Probe Substrates682.8
Treatment C: Probe Substrates + GSK3640254 200 mg632.8

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AUC(0-infinity) for Digoxin

Blood samples were collected at the indicated time points for pharmacokinetic analysis of digoxin. The AUC(0-infinity) was determined using the linear trapezoidal rule for each incremental trapezoid and the log trapezoidal rule for each decremental trapezoid. (NCT04425902)
Timeframe: Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 96, and 120 hours post-dose in treatment period 1 and 3

Interventionh*pg/mL (Geometric Mean)
Treatment A: Probe Substrates19180
Treatment C: Probe Substrates + GSK3640254 200 mg20090

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AUC(0-infinity) for Flurbiprofen

Blood samples were collected at the indicated time points for pharmacokinetic analysis of flurbiprofen. The AUC(0-infinity) was determined using the linear trapezoidal rule for each incremental trapezoid and the log trapezoidal rule for each decremental trapezoid. (NCT04425902)
Timeframe: Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 96, and 120 hours post-dose in treatment period 1 and 3

Interventionh*ng/mL (Geometric Mean)
Treatment A: Probe Substrates66700
Treatment C: Probe Substrates + GSK3640254 200 mg68660

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AUC(0-infinity) for Metoprolol

Blood samples were collected at the indicated time points for pharmacokinetic analysis of metoprolol. The AUC(0-infinity) was determined using the linear trapezoidal rule for each incremental trapezoid and the log trapezoidal rule for each decremental trapezoid. (NCT04425902)
Timeframe: Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 96, and 120 hours post-dose in treatment period 1 and 3

Interventionh*ng/mL (Geometric Mean)
Treatment A: Probe Substrates659.1
Treatment C: Probe Substrates + GSK3640254 200 mg813.1

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AUC(0-infinity) for Midazolam

Blood samples were collected at the indicated time points for pharmacokinetic analysis of midazolam. The AUC(0-infinity) was determined using the linear trapezoidal rule for each incremental trapezoid and the log trapezoidal rule for each decremental trapezoid. (NCT04425902)
Timeframe: Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 96, and 120 hours post-dose in treatment period 1 and 3

Interventionh*ng/mL (Geometric Mean)
Treatment A: Probe Substrates70.08
Treatment C: Probe Substrates + GSK3640254 200 mg65.46

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AUC(0-infinity) for Montelukast

Blood samples were collected at the indicated time points for pharmacokinetic analysis of montelukast. The AUC(0-infinity) was determined using the linear trapezoidal rule for each incremental trapezoid and the log trapezoidal rule for each decremental trapezoid. (NCT04425902)
Timeframe: Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 96, and 120 hours post-dose in treatment period 1 and 3

Interventionh*ng/mL (Geometric Mean)
Treatment A: Probe Substrates2859
Treatment C: Probe Substrates + GSK3640254 200 mg3109

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Treatment B: Absolute Values of Erythrocytes Mean Corpuscular Volume

Blood samples were collected to analyze the hematology parameter: erythrocytes mean corpuscular volume. Baseline for treatment B was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits (Day 10), before the first dose of Treatment B. (NCT04425902)
Timeframe: Baseline (Day 10) and Day 20

InterventionFemtoliter (Mean)
Baseline (Day 10)Day 20
Treatment B: GSK3640254 200 mg88.0288.96

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Treatment B: Absolute Values of Erythrocytes Mean Corpuscular Hemoglobin

Blood samples were collected to analyze the hematology parameter: erythrocytes mean corpuscular hemoglobin. Baseline for treatment B was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits (Day 10), before the first dose of Treatment B. (NCT04425902)
Timeframe: Baseline (Day 10) and Day 20

InterventionPicograms (Mean)
Baseline (Day 10)Day 20
Treatment B: GSK3640254 200 mg29.5729.52

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Treatment B: Absolute Values of Erythrocytes

Blood samples were collected to analyze the hematology parameter: erythrocytes. Baseline for treatment B was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits (Day 10), before the first dose of Treatment B. (NCT04425902)
Timeframe: Baseline (Day 10) and Day 20

Intervention10^12 cells per liter (Mean)
Baseline (Day 10)Day 20
Treatment B: GSK3640254 200 mg4.6644.746

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Treatment B: Absolute Values of Creatine Kinase, Lactate Dehydrogenase, ALT, ALP, AST, Gamma-glutamyl Transferase

Blood samples were collected to analyze the chemistry parameters: creatine kinase, lactate dehydrogenase, ALT, ALP, AST, and gamma-glutamyl transferase. Baseline for treatment B was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits (Day 10), before the first dose of Treatment B. (NCT04425902)
Timeframe: Baseline (Day 10) and Day 20

InterventionInternational units per liter (Mean)
Baseline (Day 10): Creatine kinaseDay 20: Creatine kinaseBaseline (Day 10): Lactate dehydrogenaseDay 20: Lactate dehydrogenaseBaseline (Day 10): ALTDay 20: ALTBaseline (Day 10): ALPDay 20: ALPBaseline (Day 10): ASTDay 20: ASTBaseline (Day 10): Gamma-glutamyl transferaseDay 20: Gamma-glutamyl transferase
Treatment B: GSK3640254 200 mg66.968.9114.8115.920.120.360.858.515.616.118.918.3

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Treatment B: Absolute Values of Amylase, Lipase

Blood samples were collected to analyze the chemistry parameters: amylase and lipase. Baseline for treatment B was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits (Day 10), before the first dose of Treatment B. (NCT04425902)
Timeframe: Baseline (Day 10) and Day 20

InterventionUnits per liter (Mean)
Baseline (Day 10): LipaseDay 20: LipaseBaseline (Day 10): AmylaseDay 20: Amylase
Treatment B: GSK3640254 200 mg31.632.456.960.1

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Treatment B: Absolute Values of Albumin, Globulin, Protein

Blood samples were collected to analyze the chemistry parameters: albumin, globulin and protein. Baseline for treatment B was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits (Day 10), before the first dose of Treatment B. (NCT04425902)
Timeframe: Baseline (Day 10) and Day 20

InterventionGrams per liter (Mean)
Baseline (Day 10): AlbuminDay 20: AlbuminBaseline (Day 10): GlobulinDay 20: GlobulinBaseline (Day 10): ProteinDay 20: Protein
Treatment B: GSK3640254 200 mg42.241.425.926.868.168.2

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Treatment B: Absolute Values for ECG Parameters: PR Interval, QRS Duration, QT Interval, QTcF Interval

Twelve-lead ECGs were obtained to measure PR Interval, QRS Duration, QT Interval and QTcF Interval. Twelve-lead ECGs were performed with the participant in a supine position after a rest of at least 10 minutes. Baseline for treatment B was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits (Day 11, Pre-Dose), before the first dose in Treatment B. (NCT04425902)
Timeframe: Baseline (Day 11, Pre-Dose) and Day 20

InterventionMilliseconds (Mean)
Baseline (Day 11, Pre-dose): PR IntervalDay 20: PR IntervalBaseline (Day 11, Pre-dose): QRS DurationDay 20: QRS DurationBaseline (Day 11, Pre-dose): QT IntervalDay 20: QT IntervalBaseline (Day 11, Pre-dose): QTcF IntervalDay 20: QTcF Interval
Treatment B: GSK3640254 200 mg158.6161.894.296.4403.1408.8403.5408.6

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AUC(0-infinity) for Omeprazole

Blood samples were collected at the indicated time points for pharmacokinetic analysis of omeprazole. The AUC(0-infinity) was determined using the linear trapezoidal rule for each incremental trapezoid and the log trapezoidal rule for each decremental trapezoid. (NCT04425902)
Timeframe: Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 96, and 120 hours post-dose in treatment period 1 and 3

Interventionh*ng/mL (Geometric Mean)
Treatment A: Probe Substrates1127
Treatment C: Probe Substrates + GSK3640254 200 mg1093

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AUC(0-infinity) for Pravastatin

Blood samples were collected at the indicated time points for pharmacokinetic analysis of pravastatin. The AUC(0-infinity) was determined using the linear trapezoidal rule for each incremental trapezoid and the log trapezoidal rule for each decremental trapezoid. (NCT04425902)
Timeframe: Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 96, and 120 hours post-dose in treatment period 1 and 3

Interventionh*ng/mL (Geometric Mean)
Treatment A: Probe Substrates72.09
Treatment C: Probe Substrates + GSK3640254 200 mg43.70

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AUC(0-t) for 1-hydroxymidazolam

Blood samples were collected at the indicated time points for pharmacokinetic analysis of 1-hydroxymidazolam. 1-hydroxymidazolam is a metabolite of midazolam. The AUC(0-t) was determined using the linear trapezoidal rule for each incremental trapezoid and the log trapezoidal rule for each decremental trapezoid. (NCT04425902)
Timeframe: Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 96, and 120 hours post-dose in treatment period 1 and 3

Interventionh*ng/mL (Geometric Mean)
Treatment A: Probe Substrates31.07
Treatment C: Probe Substrates + GSK3640254 200 mg28.07

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AUC(0-t) for 36-hydroxymontelukast

Blood samples were collected at the indicated time points for pharmacokinetic analysis of 36-hydroxymontelukas. 36-hydroxymontelukast is a metabolite of montelukast. The AUC(0-t) was determined using the linear trapezoidal rule for each incremental trapezoid and the log trapezoidal rule for each decremental trapezoid. (NCT04425902)
Timeframe: Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 96, and 120 hours post-dose in treatment period 1 and 3

Interventionh*ng/mL (Geometric Mean)
Treatment A: Probe Substrates234.2
Treatment C: Probe Substrates + GSK3640254 200 mg230.9

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AUC(0-t) for 5-hydroxyomeprazole

Blood samples were collected at the indicated time points for pharmacokinetic analysis of 5-hydroxyomeprazole. 5-hydroxyomeprazole is a metabolite of omeprazole. The AUC(0-t) was determined using the linear trapezoidal rule for each incremental trapezoid and the log trapezoidal rule for each decremental trapezoid. (NCT04425902)
Timeframe: Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 96, and 120 hours post-dose in treatment period 1 and 3

Interventionh*ng/mL (Geometric Mean)
Treatment A: Probe Substrates713.5
Treatment C: Probe Substrates + GSK3640254 200 mg785.1

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AUC(0-t) for Alpha-hydroxymetoprolol

Blood samples were collected at the indicated time points for pharmacokinetic analysis of alpha-hydroxymetoprolol. Alpha-hydroxymetoprolol is a metabolite of metoprolol. The AUC(0-t) was determined using the linear trapezoidal rule for each incremental trapezoid and the log trapezoidal rule for each decremental trapezoid. (NCT04425902)
Timeframe: Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 96, and 120 hours post-dose in treatment period 1 and 3

Interventionh*ng/mL (Geometric Mean)
Treatment A: Probe Substrates531.3
Treatment C: Probe Substrates + GSK3640254 200 mg487.9

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AUC(0-t) for Digoxin

Blood samples were collected at the indicated time points for pharmacokinetic analysis of digoxin. The AUC(0-t) was determined using the linear trapezoidal rule for each incremental trapezoid and the log trapezoidal rule for each decremental trapezoid. (NCT04425902)
Timeframe: Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 96, and 120 hours post-dose in treatment period 1 and 3

InterventionHours*picogram per milliliter (h*pg/mL) (Geometric Mean)
Treatment A: Probe Substrates16690
Treatment C: Probe Substrates + GSK3640254 200 mg17840

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AUC(0-t) for Flurbiprofen

Blood samples were collected at the indicated time points for pharmacokinetic analysis of flurbiprofen. The AUC(0-t) was determined using the linear trapezoidal rule for each incremental trapezoid and the log trapezoidal rule for each decremental trapezoid. (NCT04425902)
Timeframe: Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 96, and 120 hours post-dose in treatment period 1 and 3

Interventionh*ng/mL (Geometric Mean)
Treatment A: Probe Substrates64930
Treatment C: Probe Substrates + GSK3640254 200 mg66170

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AUC(0-t) for Metoprolol

Blood samples were collected at the indicated time points for pharmacokinetic analysis of metoprolol. The AUC(0-t) was determined using the linear trapezoidal rule for each incremental trapezoid and the log trapezoidal rule for each decremental trapezoid. (NCT04425902)
Timeframe: Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 96, and 120 hours post-dose in treatment period 1 and 3

Interventionh*ng/mL (Geometric Mean)
Treatment A: Probe Substrates655.0
Treatment C: Probe Substrates + GSK3640254 200 mg807.3

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AUC(0-t) for Midazolam

Blood samples were collected at the indicated time points for pharmacokinetic analysis of midazolam. The AUC(0-t) was determined using the linear trapezoidal rule for each incremental trapezoid and the log trapezoidal rule for each decremental trapezoid. (NCT04425902)
Timeframe: Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 96, and 120 hours post-dose in treatment period 1 and 3

Interventionh*ng/mL (Geometric Mean)
Treatment A: Probe Substrates67.11
Treatment C: Probe Substrates + GSK3640254 200 mg62.95

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AUC(0-t) for Montelukast

Blood samples were collected at the indicated time points for pharmacokinetic analysis of montelukast. The AUC(0-t) was determined using the linear trapezoidal rule for each incremental trapezoid and the log trapezoidal rule for each decremental trapezoid. (NCT04425902)
Timeframe: Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 96, and 120 hours post-dose in treatment period 1 and 3

Interventionh*ng/mL (Geometric Mean)
Treatment A: Probe Substrates2724
Treatment C: Probe Substrates + GSK3640254 200 mg2940

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AUC(0-t) for Omeprazole

Blood samples were collected at the indicated time points for pharmacokinetic analysis of omeprazole. The AUC(0-t) was determined using the linear trapezoidal rule for each incremental trapezoid and the log trapezoidal rule for each decremental trapezoid. (NCT04425902)
Timeframe: Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 96, and 120 hours post-dose in treatment period 1 and 3

Interventionh*ng/mL (Geometric Mean)
Treatment A: Probe Substrates728.1
Treatment C: Probe Substrates + GSK3640254 200 mg817.9

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AUC(0-t) for Pravastatin

Blood samples were collected at the indicated time points for pharmacokinetic analysis of pravastatin. The AUC(0-t) was determined using the linear trapezoidal rule for each incremental trapezoid and the log trapezoidal rule for each decremental trapezoid. (NCT04425902)
Timeframe: Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 96, and 120 hours post-dose in treatment period 1 and 3

Interventionh*ng/mL (Geometric Mean)
Treatment A: Probe Substrates69.92
Treatment C: Probe Substrates + GSK3640254 200 mg51.03

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Cmax for 1-hydroxymidazolam

Blood samples were collected at the indicated time points for pharmacokinetic analysis of 1-hydroxymidazolam. 1-hydroxymidazolam is a metabolite of midazolam. (NCT04425902)
Timeframe: Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 96, and 120 hours post-dose in treatment period 1 and 3

Interventionng/mL (Geometric Mean)
Treatment A: Probe Substrates7.933
Treatment C: Probe Substrates + GSK3640254 200 mg6.722

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Cmax for 36-hydroxymontelukast

Blood samples were collected at the indicated time points for pharmacokinetic analysis of 36-hydroxymontelukast. 36-hydroxymontelukast is a metabolite of montelukast. (NCT04425902)
Timeframe: Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 96, and 120 hours post-dose in treatment period 1 and 3

Interventionng/mL (Geometric Mean)
Treatment A: Probe Substrates24.62
Treatment C: Probe Substrates + GSK3640254 200 mg23.22

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Cmax for 5-hydroxyomeprazole

Blood samples were collected at the indicated time points for pharmacokinetic analysis of 5-hydroxyomeprazole. 5-hydroxyomeprazole is a metabolite of omeprazole. (NCT04425902)
Timeframe: Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 96, and 120 hours post-dose in treatment period 1 and 3

Interventionng/mL (Geometric Mean)
Treatment A: Probe Substrates181.1
Treatment C: Probe Substrates + GSK3640254 200 mg203.3

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Cmax for Alpha-hydroxymetoprolol

Blood samples were collected at the indicated time points for pharmacokinetic analysis of alpha-hydroxymetoprolol. Alpha-hydroxymetoprolol is a metabolite of metoprolol. (NCT04425902)
Timeframe: Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 96, and 120 hours post-dose in treatment period 1 and 3

Interventionng/mL (Geometric Mean)
Treatment A: Probe Substrates45.70
Treatment C: Probe Substrates + GSK3640254 200 mg39.21

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Cmax for Digoxin

Blood samples were collected at the indicated time points for pharmacokinetic analysis of digoxin. (NCT04425902)
Timeframe: Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 96, and 120 hours post-dose in treatment period 1 and 3

InterventionPicogram per milliliter (pg/mL) (Geometric Mean)
Treatment A: Probe Substrates1026
Treatment C: Probe Substrates + GSK3640254 200 mg1282

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Cmax for Flurbiprofen

Blood samples were collected at the indicated time points for pharmacokinetic analysis of flurbiprofen. (NCT04425902)
Timeframe: Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 96, and 120 hours post-dose in treatment period 1 and 3

Interventionng/mL (Geometric Mean)
Treatment A: Probe Substrates10220
Treatment C: Probe Substrates + GSK3640254 200 mg10710

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Cmax for Metoprolol

Blood samples were collected at the indicated time points for pharmacokinetic analysis of metoprolol. (NCT04425902)
Timeframe: Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 96, and 120 hours post-dose in treatment period 1 and 3

Interventionng/mL (Geometric Mean)
Treatment A: Probe Substrates127.4
Treatment C: Probe Substrates + GSK3640254 200 mg141.1

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Cmax for Midazolam

Blood samples were collected at the indicated time points for pharmacokinetic analysis of midazolam. (NCT04425902)
Timeframe: Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 96, and 120 hours post-dose in treatment period 1 and 3

Interventionng/mL (Geometric Mean)
Treatment A: Probe Substrates15.44
Treatment C: Probe Substrates + GSK3640254 200 mg13.95

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Cmax for Montelukast

Blood samples were collected at the indicated time points for pharmacokinetic analysis of montelukast. (NCT04425902)
Timeframe: Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 96, and 120 hours post-dose in treatment period 1 and 3

InterventionNanograms per milliliter (ng/mL) (Geometric Mean)
Treatment A: Probe Substrates379.8
Treatment C: Probe Substrates + GSK3640254 200 mg393.5

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Treatment B: Absolute Values of Glucose, Carbon Dioxide, Cholesterol, Triglycerides, Anion Gap, Calcium, Chloride, Phosphate, Potassium, Sodium, Urea

Blood samples were collected to analyze the chemistry parameters: glucose, carbon dioxide, cholesterol, triglycerides, anion gap, calcium, chloride, phosphate, potassium, sodium, and urea. Baseline for treatment B was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits (Day 10), before the first dose of Treatment B. (NCT04425902)
Timeframe: Baseline (Day 10) and Day 20

InterventionMillimoles per liter (Mean)
Baseline (Day 10): GlucoseDay 20: GlucoseBaseline (Day 10): Carbon DioxideDay 20: Carbon DioxideBaseline (Day 10): CholesterolDay 20: CholesterolBaseline (Day 10): TriglyceridesDay 20: TriglyceridesBaseline (Day 10): Anion GapDay 20: Anion GapBaseline (Day 10): CalciumDay 20: CalciumBaseline (Day 10): ChlorideDay 20: ChlorideBaseline (Day 10): PhosphateDay 20: PhosphateBaseline (Day 10): PotassiumDay 20: PotassiumBaseline (Day 10): SodiumDay 20: SodiumBaseline (Day 10): UreaDay 20: Urea
Treatment B: GSK3640254 200 mg4.82114.737825.424.93.81183.69151.18141.082513.814.52.31412.3141103.7103.61.17541.25934.434.39138.4138.65.94585.6335

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Treatment B: Absolute Values of Hematocrit

Blood samples were collected to analyze the hematology parameter: hematocrit. Baseline for treatment B was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits (Day 10), before the first dose of Treatment B. (NCT04425902)
Timeframe: Baseline (Day 10) and Day 20

InterventionProportion of red blood cells in blood (Mean)
Baseline (Day 10)Day 20
Treatment B: GSK3640254 200 mg0.40980.4216

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Treatment B: Absolute Values of Hemoglobin

Blood samples were collected to analyze the hematology parameter: hemoglobin. Baseline for treatment B was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits (Day 10), before the first dose of Treatment B. (NCT04425902)
Timeframe: Baseline (Day 10) and Day 20

InterventionGrams per liter (Mean)
Baseline (Day 10)Day 20
Treatment B: GSK3640254 200 mg137.7140.0

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Treatment B: Absolute Values of Oral Temperature

Oral temperature was measured in the supine position after at least 5 minutes of rest for the participant in a quiet setting without distractions. Baseline for treatment B was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits (Day 11, Pre-Dose), before the first dose in Treatment B. (NCT04425902)
Timeframe: Baseline (Day 11, Pre-Dose) and Day 20

InterventionDegrees Celsius (Mean)
Baseline (Day 11, Pre-dose)Day 20
Treatment B: GSK3640254 200 mg36.3136.28

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Treatment B: Absolute Values of Platelet Count, Leukocyte Count, Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils

Blood samples were collected to analyze the hematology parameters: platelet count, leukocyte count, neutrophils, lymphocytes, monocytes, eosinophils and basophils. Baseline for treatment B was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits (Day 10), before the first dose of Treatment B. (NCT04425902)
Timeframe: Baseline (Day 10) and Day 20

Intervention10^9 cells per liter (Mean)
Baseline (Day 10): Platelet countDay 20: Platelet countBaseline (Day 10): Leukocyte countDay 20: Leukocyte countBaseline (Day 10): NeutrophilsDay 20: NeutrophilsBaseline (Day 10): LymphocytesDay 20: LymphocytesBaseline (Day 10): MonocytesDay 20: MonocytesBaseline (Day 10): EosinophilsDay 20: EosinophilsBaseline (Day 10): BasophilsDay 20: Basophils
Treatment B: GSK3640254 200 mg265.9261.96.305.793.74303.26801.89651.83550.45150.44350.16100.19200.04400.0460

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Treatment B: Absolute Values of Pulse Rate

Pulse rate was measured in the supine position after at least 5 minutes of rest for the participant in a quiet setting without distractions. Baseline for treatment B was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits (Day 11, Pre-Dose), before the first dose in Treatment B. (NCT04425902)
Timeframe: Baseline (Day 11, Pre-Dose) and Day 20

InterventionBeats per minute (Mean)
Baseline (Day 11, Pre-dose)Day 20
Treatment B: GSK3640254 200 mg61.662.8

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Treatment B: Absolute Values of Respiratory Rate

Respiratory rate was measured in the supine position after at least 5 minutes of rest for the participant in a quiet setting without distractions. Baseline for treatment B was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits (Day 11, Pre-Dose), before the first dose in Treatment B. (NCT04425902)
Timeframe: Baseline (Day 11, Pre-Dose) and Day 20

InterventionBreaths per minute (Mean)
Baseline (Day 11, Pre-dose)Day 20
Treatment B: GSK3640254 200 mg15.014.7

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Treatment B: Absolute Values of SBP and DBP

SBP and DBP were measured in the supine position after at least 5 minutes of rest for the participant in a quiet setting without distractions. Baseline for treatment B was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits (Day 11, Pre-Dose), before the first dose in Treatment B. (NCT04425902)
Timeframe: Baseline (Day 11, Pre-Dose) and Day 20

InterventionMillimeters of mercury (Mean)
Baseline (Day 11, Pre-dose): SBPDay 20: SBPBaseline (Day 11, Pre-dose): DBPDay 20: DBP
Treatment B: GSK3640254 200 mg107.7107.261.659.6

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Cmax for Omeprazole

Blood samples were collected at the indicated time points for pharmacokinetic analysis of omeprazole. (NCT04425902)
Timeframe: Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 96, and 120 hours post-dose in treatment period 1 and 3

Interventionng/mL (Geometric Mean)
Treatment A: Probe Substrates224.4
Treatment C: Probe Substrates + GSK3640254 200 mg256.6

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Cmax for Pravastatin

Blood samples were collected at the indicated time points for pharmacokinetic analysis of pravastatin. (NCT04425902)
Timeframe: Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 96, and 120 hours post-dose in treatment period 1 and 3

Interventionng/mL (Geometric Mean)
Treatment A: Probe Substrates19.45
Treatment C: Probe Substrates + GSK3640254 200 mg15.19

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Maximum Observed Plasma Concentration (Cmax) for Caffeine

Blood samples were collected at the indicated time points for pharmacokinetic analysis of caffeine. (NCT04425902)
Timeframe: Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 96, and 120 hours post-dose in treatment period 1 and 3

InterventionNanograms per milliliter (ng/mL) (Geometric Mean)
Treatment A: Probe Substrates4340
Treatment C: Probe Substrates + GSK3640254 200 mg4110

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Treatment B: Absolute Values of Urate, Creatinine, Bilirubin, Direct Bilirubin

Blood samples were collected to analyze the chemistry parameters: urate, creatinine, bilirubin and direct bilirubin. Baseline for treatment B was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits (Day 10), before the first dose of Treatment B. (NCT04425902)
Timeframe: Baseline (Day 10) and Day 20

InterventionMicromoles per liter (Mean)
Baseline (Day 10): UrateDay 20: UrateBaseline (Day 10): CreatinineDay 20: CreatinineBaseline (Day 10): BilirubinDay 20: BilirubinBaseline (Day 10): Direct bilirubinDay 20: Direct bilirubin
Treatment B: GSK3640254 200 mg365.5046337.846486.411090.78688.00288.61841.70151.8126

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Treatment B: Change From Baseline in Albumin, Globulin, Protein

Blood samples were collected to analyze the chemistry parameters: albumin, globulin and protein. Baseline for treatment B was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits (Day 10), before the first dose of Treatment B. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value. (NCT04425902)
Timeframe: Baseline (Day 10) and Day 20

InterventionGrams per liter (Mean)
AlbuminGlobulinProtein
Treatment B: GSK3640254 200 mg-0.90.90.1

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Treatment B: Change From Baseline in Amylase, Lipase

Blood samples were collected to analyze the chemistry parameters: amylase and lipase. Baseline for treatment B was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits (Day 10), before the first dose of Treatment B. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value. (NCT04425902)
Timeframe: Baseline (Day 10) and Day 20

InterventionUnits per liter (Mean)
LipaseAmylase
Treatment B: GSK3640254 200 mg0.93.2

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Treatment B: Change From Baseline in Creatine Kinase, Lactate Dehydrogenase, ALT, ALP, AST, Gamma-glutamyl Transferase

Blood samples were collected to analyze the chemistry parameters: creatine kinase, lactate dehydrogenase, ALT, ALP, AST, and gamma-glutamyl transferase. Baseline for treatment B was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits (Day 10), before the first dose of Treatment B. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value. (NCT04425902)
Timeframe: Baseline (Day 10) and Day 20

InterventionInternational units per liter (Mean)
Creatine kinaseLactate dehydrogenaseALTALPASTGamma-glutamyl transferase
Treatment B: GSK3640254 200 mg2.11.10.3-2.40.6-0.6

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Treatment B: Change From Baseline in ECG Parameters: PR Interval, QRS Duration, QT Interval, QTcF

Twelve-lead ECGs were obtained to measure PR Interval, QRS Duration, QT Interval and QTcF Interval. Twelve-lead ECGs were performed with the participant in a supine position after a rest of at least 10 minutes. Baseline for treatment B was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits (Day 11, Pre-Dose), before the first dose in Treatment B. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value. (NCT04425902)
Timeframe: Baseline (Day 11, Pre-Dose) and Day 20

InterventionMilliseconds (Mean)
PR IntervalQRS DurationQT IntervalQTcF Interval
Treatment B: GSK3640254 200 mg3.22.35.75.1

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Treatment B: Change From Baseline in Glucose, Carbon Dioxide, Cholesterol, Triglycerides, Anion Gap, Calcium, Chloride, Phosphate, Potassium, Sodium, Urea

Blood samples were collected to analyze the chemistry parameters: glucose, carbon dioxide, cholesterol, triglycerides, anion gap, calcium, chloride, phosphate, potassium, sodium, and urea. Baseline for treatment B was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits (Day 10), before the first dose of Treatment B. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value. (NCT04425902)
Timeframe: Baseline (Day 10) and Day 20

InterventionMillimoles per liter (Mean)
GlucoseCarbon DioxideCholesterolTriglyceridesAnion GapCalciumChloridePhosphatePotassiumSodiumUrea
Treatment B: GSK3640254 200 mg-0.0833-0.6-0.1203-0.09890.80.0000-0.10.0840-0.050.3-0.3124

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Treatment B: Change From Baseline in Platelet Count, Leukocyte Count, Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils

Blood samples were collected to analyze the hematology parameters: platelet count, leukocyte count, neutrophils, lymphocytes, monocytes, eosinophils and basophils. Baseline for treatment B was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits (Day 10), before the first dose of Treatment B. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value. (NCT04425902)
Timeframe: Baseline (Day 10) and Day 20

Intervention10^9 cells per liter (Mean)
Platelet countLeukocyte countNeutrophilsLymphocytesMonocytesEosinophilsBasophils
Treatment B: GSK3640254 200 mg-4.1-0.51-0.4750-0.0610-0.00800.03100.0020

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Treatment B: Change From Baseline in SBP and DBP

SBP and DBP were measured in the supine position after at least 5 minutes of rest for the participant in a quiet setting without distractions. Baseline for treatment B was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits (Day 11, Pre-Dose), before the first dose in Treatment B. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value. (NCT04425902)
Timeframe: Baseline (Day 11, Pre-Dose) and Day 20

InterventionMillimeters of mercury (Mean)
SBPDBP
Treatment B: GSK3640254 200 mg-0.5-2.0

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Treatment B: Change From Baseline in Urate, Creatinine, Bilirubin, Direct Bilirubin

Blood samples were collected to analyze the chemistry parameters: urate, creatinine, bilirubin and direct bilirubin. Baseline for treatment B was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits (Day 10), before the first dose of Treatment B. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value. (NCT04425902)
Timeframe: Baseline (Day 10) and Day 20

InterventionMicromoles per liter (Mean)
UrateCreatinineBilirubinDirect bilirubin
Treatment B: GSK3640254 200 mg-27.65824.37580.61560.1112

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Treatment C: Absolute Values for ECG Parameters: PR Interval, QRS Duration, QT Interval, QTcF Interval

Twelve-lead ECGs were obtained to measure PR Interval, QRS Duration, QT Interval and QTcF Interval. Twelve-lead ECGs were performed with the participant in a supine position after a rest of at least 10 minutes. Baseline for treatment C was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits (Day 21, Pre-Dose), before the first dose in Treatment C. (NCT04425902)
Timeframe: Baseline (Day 21, Pre-Dose), Days 22 and 25

InterventionMilliseconds (Mean)
Baseline (Day 21, Pre-dose): PR IntervalDay 22: PR IntervalDay 25: PR IntervalBaseline (Day 21, Pre-dose): QRS DurationDay 22: QRS DurationDay 25: QRS DurationBaseline (Day 21, Pre-dose): QT IntervalDay 22: QT IntervalDay 25: QT IntervalBaseline (Day 21, Pre-dose): QTcF IntervalDay 22: QTcF IntervalDay 25: QTcF Interval
Treatment C: Probe Substrates + GSK3640254 200 mg160.8162.3159.695.898.796.8402.6420.6398.7408.7407.3402.5

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Treatment C: Absolute Values of Albumin, Globulin, Protein

Blood samples were collected to analyze the chemistry parameters: albumin, globulin and protein. Baseline for treatment C was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits (Day 20), before the dose of Treatment C. (NCT04425902)
Timeframe: Baseline (Day 20), Days 22 and 25

InterventionGrams per liter (Mean)
Baseline (Day 20): AlbuminDay 22: AlbuminDay 25: AlbuminBaseline (Day 20): GlobulinDay 22: GlobulinDay 25: GlobulinBaseline (Day 20): ProteinDay 22: ProteinDay 25: Protein
Treatment C: Probe Substrates + GSK3640254 200 mg41.640.542.026.925.126.668.565.668.6

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Treatment C: Absolute Values of Amylase, Lipase

Blood samples were collected to analyze the chemistry parameters: amylase and lipase. Baseline for treatment C was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits (Day 20), before the dose of Treatment C. (NCT04425902)
Timeframe: Baseline (Day 20), Days 22 and 25

InterventionUnits per liter (Mean)
Baseline (Day 20): LipaseDay 22: LipaseDay 25: LipaseBaseline (Day 20): AmylaseDay 22: AmylaseDay 25: Amylase
Treatment C: Probe Substrates + GSK3640254 200 mg32.933.533.162.264.760.7

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Treatment C: Absolute Values of Creatine Kinase, Lactate Dehydrogenase, ALT, ALP, AST, Gamma-glutamyl Transferase

Blood samples were collected to analyze the chemistry parameters: creatine kinase, lactate dehydrogenase, ALT, ALP, AST, gamma-glutamyl transferase. Baseline for treatment C was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits (Day 20), before the dose of Treatment C. (NCT04425902)
Timeframe: Baseline (Day 20), Days 22 and 25

InterventionInternational units per liter (Mean)
Baseline (Day 20): Creatine kinaseDay 22: Creatine kinaseDay 25: Creatine kinaseBaseline (Day 20): Lactate dehydrogenaseDay 22: Lactate dehydrogenaseDay 25: Lactate dehydrogenaseBaseline (Day 20): ALTDay 22: ALTDay 25: ALTBaseline (Day 20): ALPDay 22: ALPDay 25:ALPBaseline (Day 20): ASTDay 22: ASTDay 25: ASTBaseline (Day 20): Gamma-glutamyl transferaseDay 22: Gamma-glutamyl transferaseDay 25: Gamma-glutamyl transferase
Treatment C: Probe Substrates + GSK3640254 200 mg71.365.763.8116.6120.6119.320.417.320.958.557.658.616.214.716.418.517.118.7

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Treatment C: Absolute Values of Erythrocytes

Blood samples were collected to analyze the hematology parameter: erythrocytes. Baseline for treatment C was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits (Day 20), before the dose of Treatment C. (NCT04425902)
Timeframe: Baseline (Day 20), Days 22 and 25

Intervention10^12 cells per liter (Mean)
Baseline (Day 20)Day 22Day 25
Treatment C: Probe Substrates + GSK3640254 200 mg4.7694.6084.756

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Treatment C: Absolute Values of Erythrocytes Mean Corpuscular Hemoglobin

Blood samples were collected to analyze the hematology parameter: erythrocytes mean corpuscular hemoglobin. Baseline for treatment C was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits (Day 20), before the dose of Treatment C. (NCT04425902)
Timeframe: Baseline (Day 20), Days 22 and 25

InterventionPicograms (Mean)
Baseline (Day 20)Day 22Day 25
Treatment C: Probe Substrates + GSK3640254 200 mg29.5129.2829.12

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Treatment C: Absolute Values of Erythrocytes Mean Corpuscular Volume

Blood samples were collected to analyze the hematology parameter: erythrocytes mean corpuscular volume. Baseline for treatment C was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits (Day 20), before the dose of Treatment C. (NCT04425902)
Timeframe: Baseline (Day 20), Days 22 and 25

InterventionFemtoliter (Mean)
Baseline (Day 20)Day 22Day 25
Treatment C: Probe Substrates + GSK3640254 200 mg89.0387.3887.74

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Treatment C: Absolute Values of Glucose, Carbon Dioxide, Cholesterol, Triglycerides, Anion Gap, Calcium, Chloride, Phosphate, Potassium, Sodium, Urea

Blood samples were collected to analyze the chemistry parameters: glucose, carbon dioxide, cholesterol, triglycerides, anion gap, calcium, chloride, phosphate, potassium, sodium and urea. Baseline for treatment C was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits (Day 20), before the dose of Treatment C. (NCT04425902)
Timeframe: Baseline (Day 20), Days 22 and 25

InterventionMillimoles per liter (Mean)
Baseline (Day 20): GlucoseDay 22: GlucoseDay 25: GlucoseBaseline (Day 20): Carbon DioxideDay 22: Carbon DioxideDay 25: Carbon DioxideBaseline (Day 20): CholesterolDay 22: CholesterolDay 25: CholesterolBaseline (Day 20): TriglyceridesDay 22: TriglyceridesDay 25: TriglyceridesBaseline (Day 20): Anion GapDay 22: Anion GapDay 25: Anion GapBaseline (Day 20): CalciumDay 22: CalciumDay 25: CalciumBaseline (Day 20): ChlorideDay 22: ChlorideDay 25: ChlorideBaseline (Day 20): PhosphateDay 22: PhosphateDay 25: PhosphateBaseline (Day 20): PotassiumDay 22: PotassiumDay 25: PotassiumBaseline (Day 20): SodiumDay 22: SodiumDay 25: SodiumBaseline (Day 20): UreaDay 22: UreaDay 25: Urea
Treatment C: Probe Substrates + GSK3640254 200 mg4.71844.80604.870324.925.426.23.68983.25433.39721.07831.08361.107414.613.914.52.32172.28102.3519103.4104.8102.61.26611.19811.34774.384.344.35138.6139.8139.05.73644.90785.3099

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Treatment C: Absolute Values of Hematocrit

Blood samples were collected to analyze the hematology parameter: hematocrit. Baseline for treatment C was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits (Day 20), before the dose of Treatment C. (NCT04425902)
Timeframe: Baseline (Day 20), Days 22 and 25

InterventionProportion of red blood cells in blood (Mean)
Baseline (Day 20)Day 22Day 25
Treatment C: Probe Substrates + GSK3640254 200 mg0.42390.40220.4168

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Treatment C: Absolute Values of Hemoglobin

Blood samples were collected to analyze the hematology parameter: hemoglobin. Baseline for treatment C was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits (Day 20), before the dose of Treatment C. (NCT04425902)
Timeframe: Baseline (Day 20), Days 22 and 25

InterventionGrams per liter (Mean)
Baseline (Day 20)Day 22Day 25
Treatment C: Probe Substrates + GSK3640254 200 mg140.6134.7138.3

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Treatment C: Absolute Values of Oral Temperature

Oral temperature was measured in the supine position after at least 5 minutes of rest for the participant in a quiet setting without distractions. Baseline for treatment C was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits (Day 21, Pre-Dose), before the first dose in Treatment C. (NCT04425902)
Timeframe: Baseline (Day 21, Pre-Dose), Days 22 and 25

InterventionDegrees Celsius (Mean)
Baseline (Day 21, Pre-dose)Day 22Day 25
Treatment C: Probe Substrates + GSK3640254 200 mg36.3136.1836.31

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Treatment C: Absolute Values of Platelet Count, Leukocyte Count, Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils

Blood samples were collected to analyze the hematology parameters: platelet count, leukocyte count, neutrophils, lymphocytes, monocytes, eosinophils and basophils. Baseline for treatment C was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits (Day 20), before the dose of Treatment C. (NCT04425902)
Timeframe: Baseline (Day 20), Days 22 and 25

Intervention10^9 cells per liter (Mean)
Baseline (Day 20): Platelet countDay 22: Platelet countDay 25: Platelet countBaseline (Day 20): Leukocyte countDay 22: Leukocyte countDay 25: Leukocyte countBaseline (Day 20): NeutrophilsDay 22: NeutrophilsDay 25: NeutrophilsBaseline (Day 20): LymphocytesDay 22: LymphocytesDay 25: LymphocytesBaseline (Day 20): MonocytesDay 22: MonocytesDay 25: MonocytesBaseline (Day 20): EosinophilsDay 22: EosinophilsDay 25: EosinophilsBaseline (Day 20): BasophilsDay 22: BasophilsDay 25: Basophils
Treatment C: Probe Substrates + GSK3640254 200 mg262.3249.2260.75.865.815.983.31793.19253.45291.84371.87871.92800.45050.46890.35760.19530.22820.18370.04740.03800.0408

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Treatment C: Absolute Values of Pulse Rate

Pulse rate was measured in the supine position after at least 5 minutes of rest for the participant in a quiet setting without distractions. Baseline for treatment C was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits (Day 21, Pre-Dose), before the first dose in Treatment C. (NCT04425902)
Timeframe: Baseline (Day 21, Pre-Dose), Days 22 and 25

InterventionBeats per minute (Mean)
Baseline (Day 21, Pre-dose)Day 22Day 25
Treatment C: Probe Substrates + GSK3640254 200 mg63.256.261.7

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Treatment C: Absolute Values of Respiratory Rate

Respiratory rate was measured in the supine position after at least 5 minutes of rest for the participant in a quiet setting without distractions. Baseline for treatment C was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits (Day 21, Pre-Dose), before the first dose in Treatment C. (NCT04425902)
Timeframe: Baseline (Day 21, Pre-Dose), Days 22 and 25

InterventionBreaths per minute (Mean)
Baseline (Day 21, Pre-dose)Day 22Day 25
Treatment C: Probe Substrates + GSK3640254 200 mg15.715.716.5

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Treatment C: Absolute Values of SBP and DBP

SBP and DBP were measured in the supine position after at least 5 minutes of rest for the participant in a quiet setting without distractions. Baseline for treatment C was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits (Day 21, Pre-Dose), before the first dose in Treatment C. (NCT04425902)
Timeframe: Baseline (Day 21, Pre-Dose), Days 22 and 25

InterventionMillimeters of mercury (Mean)
Baseline (Day 21, Pre-dose): SBPDay 22: SBPDay 25: SBPBaseline (Day 21, Pre-dose): DBPDay 22: DBPDay 25: DBP
Treatment C: Probe Substrates + GSK3640254 200 mg107.5105.6109.762.758.462.2

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Treatment C: Absolute Values of Urate, Creatinine, Bilirubin, Direct Bilirubin

Blood samples were collected to analyze the chemistry parameters: urate, creatinine, bilirubin and direct bilirubin. Baseline for treatment C was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits (Day 20), before the dose of Treatment C. (NCT04425902)
Timeframe: Baseline (Day 20), Days 22 and 25

InterventionMicromoles per liter (Mean)
Baseline (Day 20): UrateDay 22: UrateDay 25: UrateBaseline (Day 20): CreatinineDay 22: CreatinineDay 25: CreatinineBaseline (Day 20): BilirubinDay 22: BilirubinDay 25: BilirubinBaseline (Day 20): Direct bilirubinDay 22: Direct bilirubinDay 25: Direct bilirubin
Treatment C: Probe Substrates + GSK3640254 200 mg343.1057303.0349340.601392.168687.376490.58678.74809.88209.03601.84502.07901.9980

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Treatment C: Change From Baseline in Albumin, Globulin, Protein

Blood samples were collected to analyze the chemistry parameters: albumin, globulin and protein. Baseline for treatment C was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits (Day 20), before the dose of Treatment C. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value. (NCT04425902)
Timeframe: Baseline (Day 20), Days 22 and 25

InterventionGrams per liter (Mean)
Day 22: AlbuminDay 25: AlbuminDay 22: GlobulinDay 25: GlobulinDay 22: ProteinDay 25: Protein
Treatment C: Probe Substrates + GSK3640254 200 mg-1.10.4-1.8-0.3-2.90.2

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Treatment C: Change From Baseline in Amylase, Lipase

Blood samples were collected to analyze the chemistry parameters: amylase and lipase. Baseline for treatment C was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits (Day 20), before the dose of Treatment C. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value. (NCT04425902)
Timeframe: Baseline (Day 20), Days 22 and 25

InterventionUnits per liter (Mean)
Day 22: LipaseDay 25: LipaseDay 22: AmylaseDay 25: Amylase
Treatment C: Probe Substrates + GSK3640254 200 mg0.60.22.5-1.5

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Treatment C: Change From Baseline in Creatine Kinase, Lactate Dehydrogenase, ALT, ALP, AST, Gamma-glutamyl Transferase

Blood samples were collected to analyze the chemistry parameters: creatine kinase, lactate dehydrogenase, ALT, ALP, AST, gamma-glutamyl transferase. Baseline for treatment C was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits (Day 20), before the dose of Treatment C. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value. (NCT04425902)
Timeframe: Baseline (Day 20), Days 22 and 25

InterventionInternational units per liter (Mean)
Day 22: Creatine kinaseDay 25: Creatine kinaseDay 22: Lactate dehydrogenaseDay 25: Lactate dehydrogenaseDay 22: ALTDay 25: ALTDay 22: ALPDay 25:ALPDay 22: ASTDay 25: ASTDay 22: Gamma-glutamyl transferaseDay 25: Gamma-glutamyl transferase
Treatment C: Probe Substrates + GSK3640254 200 mg-5.6-7.54.02.6-3.10.5-0.90.1-1.50.2-1.50.2

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Treatment C: Change From Baseline in ECG Parameters: PR Interval, QRS Duration, QT Interval, QTcF

Twelve-lead ECGs were obtained to measure PR Interval, QRS Duration, QT Interval and QTcF Interval. Twelve-lead ECGs were performed with the participant in a supine position after a rest of at least 10 minutes. Baseline for treatment C was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits (Day 21, Pre-Dose), before the first dose in Treatment C. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value. (NCT04425902)
Timeframe: Baseline (Day 21, Pre-Dose), Days 22 and 25

InterventionMilliseconds (Mean)
Day 22: PR IntervalDay 25: PR IntervalDay 22: QRS DurationDay 25: QRS DurationDay 22: QT IntervalDay 25: QT IntervalDay 22: QTcF IntervalDay 25: QTcF Interval
Treatment C: Probe Substrates + GSK3640254 200 mg1.5-1.22.91.018.0-3.9-1.4-6.3

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Cohort 3: Tmax of Gepotidacin in Plasma After the First Dose of 3000 mg (First Dose)

Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. (NCT04493931)
Timeframe: Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3, 4, 6, 8, 12 Hours, 12 Hours 30 minutes, 13 Hours, 13 Hours 30 Hours, 14 Hours, 14 Hours 30 Hours, 15, 16,18,20,24,36, 48, 60 Hours post-dose in each Treatment Periods 1 and 2

InterventionHours (Median)
Cohort 3:Gepotidacin 3000 mg + Digoxin 0.5 mg + Midazolam 2 mg2.500

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Cohort 4: AUC(0-t) of Gepotidacin in Plasma Following Two 3000 mg Doses (First Dose + Second Dose)-Fed State

Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. (NCT04493931)
Timeframe: Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3, 4, 6, 8, 12 Hours, 12 Hours 30 minutes, 13 Hours, 13 Hours 30 minutes, 14 Hours, 14 Hours 30 minutes, 15, 16, 18, 20, 24, 36, 48, 60 Hours post-dose in Treatment Period 3

InterventionHours*micrograms per milliliter (Geometric Mean)
Cohort 4: Gepotidacin 3000 mg Fed91.4

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Cohort 4: AUC(0-t) of Gepotidacin Following Single Dose of 1500 mg in Plasma - Food Effect in Japanese Participants

Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. Analysis was performed using a linear mixed-effect model with treatment as a fixed effect and participant as a random effect. Geometric LS mean and 90 % CI of the geometric LS means have been presented. (NCT04493931)
Timeframe: Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hour, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours, 36 Hours, 48 Hours post-dose in each Treatment Periods 1 and 2

InterventionHours*Micrograms per milliliter (Geometric Least Squares Mean)
Cohort 4: Gepotidacin 1500 mg Fed21.9
Cohort 4: Gepotidacin 1500 mg Fasted20.0

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Cohort 4: AUC(0-t) of Gepotidacin Following Single Dose of 1500 mg in Plasma

Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. (NCT04493931)
Timeframe: Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hour, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours, 36 Hours, 48 Hours post-dose in each Treatment Periods 1 and 2

InterventionHours*micrograms per milliliter (Geometric Mean)
Cohort 4: Gepotidacin 1500 mg Fed21.9
Cohort 4: Gepotidacin 1500 mg Fasted20.0

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Cohort 4: AUC(0-infinity) of Gepotidacin Following Single Dose of 1500 mg in Plasma - Food Effect in Japanese Participants

Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. Analysis was performed using a linear mixed-effect model with treatment as a fixed effect and participant as a random effect. Geometric LS mean and 90 % CI of the geometric LS means have been presented. (NCT04493931)
Timeframe: Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hour, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours, 36 Hours, 48 Hours post-dose in each Treatment Periods 1 and 2

InterventionHours*Micrograms per milliliter (Geometric Least Squares Mean)
Cohort 4: Gepotidacin 1500 mg Fed22.3
Cohort 4: Gepotidacin 1500 mg Fasted20.4

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Cohort 4: AUC(0-infinity) of Gepotidacin Following Single Dose of 1500 mg in Plasma

Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. (NCT04493931)
Timeframe: Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hour, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours, 36 Hours, 48 Hours post-dose in each Treatment Periods 1 and 2

InterventionHours*micrograms per milliliter (Geometric Mean)
Cohort 4: Gepotidacin 1500 mg Fed22.3
Cohort 4: Gepotidacin 1500 mg Fasted20.4

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Cohort 4: AUC(0-48) of Gepotidacin in Urine Following Two 3000 mg Doses-Fed State

Urine samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. (NCT04493931)
Timeframe: Pre-dose, 0-2 Hours, 2-4 Hours, 4-6 Hours, 6-8 Hours, 8-12 Hours, 12-14 Hours, 14-16 Hours, 16-18 Hours, 18-20 Hours, 20-24 Hours, 24-36 Hours, 36-48 Hours post-dose in Treatment Period 3

InterventionHours*micrograms per milliliter (Geometric Mean)
Cohort 4: Gepotidacin 3000 mg Fed15768.2

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Cohort 4: AUC(0-48) of Gepotidacin in Plasma Following Two 3000 mg Doses (First Dose + Second Dose)-Fed State

Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. (NCT04493931)
Timeframe: Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3, 4, 6, 8, 12 Hours, 12 Hours 30 minutes, 13 Hours, 13 Hours 30 minutes, 14 Hours, 14 Hours 30 minutes, 15, 16, 18, 20, 24, 36, 48 Hours post-dose in Treatment Period 3

InterventionHours*micrograms per milliliter (Geometric Mean)
Cohort 4: Gepotidacin 3000 mg Fed90.8

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Cohort 4: AUC(0-48) of Gepotidacin Following Single Dose of 1500 mg Under Fed Condition in Urine

Urine samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. (NCT04493931)
Timeframe: Pre-dose, 0-2 Hours, 2-4 Hours, 4-6 Hours, 6-8 Hours, 8-12 Hours, 12-24 Hours, 24-36 Hours, 36-48 Hours post-dose in each Treatment Periods 1 and 2

InterventionHours*micrograms per milliliter (Geometric Mean)
Cohort 4: Gepotidacin 1500 mg Fed2293.7

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Cohort 4: AUC(0-24) of Gepotidacin in Urine Following Two 3000 mg Doses-Fed State

Urine samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. (NCT04493931)
Timeframe: Pre-dose, 0-2 Hours, 2-4 Hours, 4-6 Hours, 6-8 Hours, 8-12 Hours, 12-14 Hours, 14-16 Hours, 16-18 Hours, 18-20 Hours, 20-24 Hours post-dose in Treatment Period 3

InterventionHours*micrograms per milliliter (Geometric Mean)
Cohort 4: Gepotidacin 3000 mg Fed14729.5

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Cohort 4: AUC(0-24) of Gepotidacin in Plasma Following Two 3000 mg Doses (First Dose + Second Dose)-Fed State

Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. (NCT04493931)
Timeframe: Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3, 4, 6, 8, 12 Hours, 12 Hours 30 minutes, 13 Hours, 13 Hours 30 minutes, 14 Hours, 14 Hours 30 minutes, 15, 16, 18, 20, 24 Hours post-dose in Treatment Period 3

InterventionHours*micrograms per milliliter (Geometric Mean)
Cohort 4: Gepotidacin 3000 mg Fed84.6

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Cohort 4: AUC(0-24) of Gepotidacin Following Single Dose of 1500 mg Under Fed Condition in Urine

Urine samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. (NCT04493931)
Timeframe: Pre-dose, 0-2 Hours, 2-4 Hours, 4-6 Hours, 6-8 Hours, 8-12 Hours, 12-24 Hours post-dose in each Treatment Periods 1 and 2

InterventionHours*micrograms per milliliter (Geometric Mean)
Cohort 4: Gepotidacin 1500 mg Fed2142.4

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Cohort 4: AUC From Time 0 (Predose) to Time Tau (AUC[0-tau]) of Gepotidacin in Plasma After the First Dose of 3000 Mg-Fed State

Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. (NCT04493931)
Timeframe: Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3, 4, 6, 8, 12 Hours, 12 Hours 30 minutes, 13 Hours, 13 Hours 30 minutes, 14 Hours, 14 Hours 30 minutes, 15, 16, 18, 20, 24, 36, 48, 60 Hours post-dose in Treatment Period 3

InterventionHours*micrograms per milliliter (Geometric Mean)
Cohort 4: Gepotidacin 3000 mg Fed37.3

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Cohort 4: Area Under the Concentration-time Curve From Time 0 (Pre-dose) to the Concentration at 48 Hours Post-dose (AUC[0-48]) of Gepotidacin Following Single Dose of 1500 mg in Plasma

Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. (NCT04493931)
Timeframe: Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hour, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours, 36 Hours, 48 Hours post-dose in each Treatment Periods 1 and 2

InterventionHours*micrograms per milliliter (Geometric Mean)
Cohort 4: Gepotidacin 1500 mg Fed21.9
Cohort 4: Gepotidacin 1500 mg Fasted20.0

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Cohort 4: Area Under the Concentration-time Curve From Time 0 (Pre-dose) to the Concentration at 24 Hours Post-dose (AUC[0-24]) of Gepotidacin Following Single Dose of 1500 mg in Plasma

Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. (NCT04493931)
Timeframe: Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hour, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours post-dose in each Treatment Periods 1 and 2

InterventionHours*micrograms per milliliter (Geometric Mean)
Cohort 4: Gepotidacin 1500 mg Fed20.9
Cohort 4: Gepotidacin 1500 mg Fasted19.0

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Cohort 4: Ae Total of Gepotidacin in Urine Following Two 3000 mg Doses-Fed State

Urine samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. Ae total was calculated by adding all the fractions of drug collected over all the allotted time intervals. (NCT04493931)
Timeframe: Pre-dose, 0-2 Hours, 2-4 Hours, 4-6 Hours, 6-8 Hours, 8-12 Hours, 12-14 Hours, 14-16 Hours, 16-18 Hours, 18-20 Hours, 20-24 Hours, 24-36 Hours, 36-48 Hours, 48-60 Hours post-dose in Treatment Period 3

InterventionMilligrams (Geometric Mean)
Cohort 4: Gepotidacin 3000 mg Fed1334.42

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Cohort 4: Accumulation Ratio Based on Cmax (RoCmax) of Gepotidacin in Plasma After the Second Dose of 3000 mg (Second Dose)-Fed State

Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. Accumulation ratio was calculated as Cmax after the second dose divided by Cmax after the first dose. (NCT04493931)
Timeframe: Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3, 4, 6, 8, 12 Hours, 12 Hours 30 minutes, 13 Hours, 13 Hours 30 minutes, 14 Hours, 14 Hours 30 minutes, 15, 16, 18, 20, 24, 36, 48, 60 Hours post-dose in Treatment Period 3

InterventionRatio (Geometric Mean)
Cohort 4: Gepotidacin 3000 mg Fed1.103

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Cohort 4: Accumulation Ratio Based on AUC(0-tau) (RoAUC) of Gepotidacin in Plasma After the Second Dose of 3000 mg (Second Dose)-Fed State

Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. Accumulation ratio was calculated as AUC(0-tau) after the second dose, where 0 is the timepoint prior to second dose, divided by AUC(0-tau) after the first dose, where 0 is the predose timepoint prior to the first dose. (NCT04493931)
Timeframe: Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3, 4, 6, 8, 12 Hours, 12 Hours 30 minutes, 13 Hours, 13 Hours 30 minutes, 14 Hours, 14 Hours 30 minutes, 15, 16, 18, 20, 24, 36, 48, 60 Hours post-dose in Treatment Period 3

InterventionRatio (Geometric Mean)
Cohort 4: Gepotidacin 3000 mg Fed1.254

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Cohort 3: Vz/F of Midazolam in Plasma

Blood samples were collected at indicated time points. Pharmacokinetic analysis of midazolam was conducted using standard non-compartmental analysis. Analysis was performed using a linear mixed-effect model with treatment as a fixed effect and participant as a random effect. Geometric LS mean and 90 % CI of the geometric LS means have been presented. (NCT04493931)
Timeframe: Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours, 36 Hours, 48 Hours post-dose in each Treatment Periods 1 and 2

InterventionLiters (Geometric Least Squares Mean)
Cohort 3: Digoxin 0.5 mg + Midazolam 2 mg615.36
Cohort 3:Gepotidacin 3000 mg + Digoxin 0.5 mg + Midazolam 2 mg371.24

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Cohort 3: Vz/F of Gepotidacin in Plasma Following Two 3000 mg Doses (First Dose + Second Dose)

Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. (NCT04493931)
Timeframe: Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3, 4, 6, 8, 12 Hours, 12 Hours 30 minutes, 13 Hours, 13 Hours 30 Hours, 14 Hours, 14 Hours 30 Hours, 15, 16,18,20,24,36, 48, 60 Hours post-dose in each Treatment Periods 1 and 2

InterventionLiters (Geometric Mean)
Cohort 3:Gepotidacin 3000 mg + Digoxin 0.5 mg + Midazolam 2 mg959.42

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Cohort 3: Vz/F of Digoxin in Plasma

Blood samples were collected at indicated time points. Pharmacokinetic analysis of digoxin was conducted using standard non-compartmental analysis. Analysis was performed using a linear mixed-effect model with treatment as a fixed effect and participant as a random effect. Geometric LS mean and 90 % CI of the geometric LS means have been presented. (NCT04493931)
Timeframe: Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 24 Hours, 36 Hours, 48 Hours, 72 Hours, 96 Hours post-dose in each Treatment Periods 1 and 2

InterventionLiters (Geometric Least Squares Mean)
Cohort 3: Digoxin 0.5 mg + Midazolam 2 mg923.75
Cohort 3:Gepotidacin 3000 mg + Digoxin 0.5 mg + Midazolam 2 mg688.49

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Cohort 3: Tmax of Midazolam in Plasma

Blood samples were collected at indicated time points. Pharmacokinetic analysis of midazolam was conducted using standard non-compartmental analysis. (NCT04493931)
Timeframe: Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours, 36 Hours, 48 Hours Post-dose in each Treatment Periods 1 and 2

InterventionHours (Median)
Cohort 3: Digoxin 0.5 mg + Midazolam 2 mg0.650
Cohort 3:Gepotidacin 3000 mg + Digoxin 0.5 mg + Midazolam 2 mg0.500

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Cohort 3: Tmax of Gepotidacin in Plasma After the Second Dose of 3000 mg (Second Dose)

Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. (NCT04493931)
Timeframe: Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3, 4, 6, 8, 12 Hours, 12 Hours 30 minutes, 13 Hours, 13 Hours 30 Hours, 14 Hours, 14 Hours 30 Hours, 15, 16,18,20,24,36, 48, 60 Hours post-dose in each Treatment Periods 1 and 2

InterventionHours (Median)
Cohort 3:Gepotidacin 3000 mg + Digoxin 0.5 mg + Midazolam 2 mg2.000

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Cohort 3: AUC(0-tau) of Gepotidacin in Plasma After the Second Dose of 3000 mg (Second Dose)

Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. (NCT04493931)
Timeframe: Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3, 4, 6, 8, 12 Hours, 12 Hours 30 minutes, 13 Hours, 13 Hours 30 Hours, 14 Hours, 14 Hours 30 Hours, 15, 16,18,20,24,36, 48, 60 Hours post-dose in each Treatment Periods 1 and 2

InterventionHours* micrograms per milliliter (Geometric Mean)
Cohort 3:Gepotidacin 3000 mg + Digoxin 0.5 mg + Midazolam 2 mg41.9

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Cohort 3: Tmax of Digoxin in Plasma

Blood samples were collected at indicated time points. Pharmacokinetic analysis of digoxin was conducted using standard non-compartmental analysis. (NCT04493931)
Timeframe: Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 24 Hours, 36 Hours, 48 Hours, 72 Hours, 96 Hours Post-dose in each Treatment Periods 1 and 2

InterventionHours (Median)
Cohort 3: Digoxin 0.5 mg + Midazolam 2 mg2.000
Cohort 3:Gepotidacin 3000 mg + Digoxin 0.5 mg + Midazolam 2 mg1.275

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Cohort 3: Tlag of Midazolam in Plasma

Blood samples were collected at indicated time points. Pharmacokinetic analysis of midazolam was conducted using standard non-compartmental analysis. (NCT04493931)
Timeframe: Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours, 36 Hours, 48 Hours Post-dose in each Treatment Periods 1 and 2

InterventionHours (Median)
Cohort 3: Digoxin 0.5 mg + Midazolam 2 mg0.000
Cohort 3:Gepotidacin 3000 mg + Digoxin 0.5 mg + Midazolam 2 mg0.000

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Cohort 3: Tlag of Gepotidacin in Plasma After the First Dose of 3000 mg (First Dose)

Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. (NCT04493931)
Timeframe: Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3, 4, 6, 8, 12 Hours, 12 Hours 30 minutes, 13 Hours, 13 Hours 30 Hours, 14 Hours, 14 Hours 30 Hours, 15, 16,18,20,24,36, 48, 60 Hours post-dose in each Treatment Periods 1 and 2

InterventionHours (Median)
Cohort 3:Gepotidacin 3000 mg + Digoxin 0.5 mg + Midazolam 2 mg0.250

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Cohort 3: Tlag of Digoxin in Plasma

Blood samples were collected at indicated time points. Pharmacokinetic analysis of digoxin was conducted using standard non-compartmental analysis. (NCT04493931)
Timeframe: Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 24 Hours, 36 Hours, 48 Hours, 72 Hours, 96 Hours Post-dose in each Treatment Periods 1 and 2

InterventionHours (Median)
Cohort 3: Digoxin 0.5 mg + Midazolam 2 mg0.000
Cohort 3:Gepotidacin 3000 mg + Digoxin 0.5 mg + Midazolam 2 mg0.000

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Cohort 3: T1/2 of Midazolam in Plasma

Blood samples were collected at indicated time points. Pharmacokinetic analysis of midazolam was conducted using standard non-compartmental analysis. Analysis was performed using a linear mixed-effect model with treatment as a fixed effect and participant as a random effect. Geometric LS mean and 90 % CI of the geometric LS means have been presented. (NCT04493931)
Timeframe: Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours, 36 Hours, 48 Hours post-dose in each Treatment Periods 1 and 2

InterventionHours (Geometric Least Squares Mean)
Cohort 3: Digoxin 0.5 mg + Midazolam 2 mg5.320
Cohort 3:Gepotidacin 3000 mg + Digoxin 0.5 mg + Midazolam 2 mg6.075

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Cohort 3: T1/2 of Gepotidacin in Plasma Following Two 3000 mg Doses (First Dose+ Second Dose)

Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. (NCT04493931)
Timeframe: Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3, 4, 6, 8, 12 Hours, 12 Hours 30 minutes, 13 Hours, 13 Hours 30 Hours, 14 Hours, 14 Hours 30 Hours, 15, 16,18,20,24,36, 48, 60 Hours post-dose in each Treatment Periods 1 and 2

InterventionHours (Geometric Mean)
Cohort 3:Gepotidacin 3000 mg + Digoxin 0.5 mg + Midazolam 2 mg9.501

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Cohort 3: T1/2 of Digoxin in Plasma

Blood samples were collected at indicated time points. Pharmacokinetic analysis of digoxin was conducted using standard non-compartmental analysis. Analysis was performed using a linear mixed-effect model with treatment as a fixed effect and participant as a random effect. Geometric LS mean and 90 % CI of the geometric LS means have been presented. (NCT04493931)
Timeframe: Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 24 Hours, 36 Hours, 48 Hours, 72 Hours, 96 Hours post-dose in each Treatment Periods 1 and 2

InterventionHours (Geometric Least Squares Mean)
Cohort 3: Digoxin 0.5 mg + Midazolam 2 mg39.367
Cohort 3:Gepotidacin 3000 mg + Digoxin 0.5 mg + Midazolam 2 mg32.777

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Cohort 3: RoCmax of Gepotidacin in Plasma After the Second Dose of 3000 mg (Second Dose)

Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. Accumulation ratio was calculated as Cmax after the second dose divided by Cmax after the first dose. (NCT04493931)
Timeframe: Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3, 4, 6, 8, 12 Hours, 12 Hours 30 minutes, 13 Hours, 13 Hours 30 Hours, 14 Hours, 14 Hours 30 Hours, 15, 16,18,20,24,36, 48, 60 Hours post-dose in each Treatment Periods 1 and 2

InterventionRatio (Geometric Mean)
Cohort 3:Gepotidacin 3000 mg + Digoxin 0.5 mg + Midazolam 2 mg1.278

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Cohort 3: RoAUC of Gepotidacin in Plasma After the Second Dose of 3000 mg (Second Dose)

Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. Accumulation ratio was calculated as AUC(0-tau) after the second dose, where 0 is the timepoint prior to second dose, divided by AUC(0-tau) after the first dose, where 0 is the predose timepoint prior to the first dose. (NCT04493931)
Timeframe: Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3, 4, 6, 8, 12 Hours, 12 Hours 30 minutes, 13 Hours, 13 Hours 30 Hours, 14 Hours, 14 Hours 30 Hours, 15, 16,18,20,24,36, 48, 60 Hours post-dose in each Treatment Periods 1 and 2

InterventionRatio (Geometric Mean)
Cohort 3:Gepotidacin 3000 mg + Digoxin 0.5 mg + Midazolam 2 mg1.406

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Cohort 3: Percentage of the Given Dose of Drug Excreted in Urine (fe%) Following Two 3000 mg Doses of Gepotidacin (First Dose + Second Dose )

Urine samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. fe% was calculated as: (Ae total divided by Dose) multiplied by 100 %. (NCT04493931)
Timeframe: Pre-dose, 0-2 Hours, 2-4 Hours, 4-6 Hours, 6-8 Hours, 8-12 Hours, 12-14 Hours, 14-16 Hours, 16-18 Hours, 18-20 Hours, 20-24 Hours, 24-36 Hours, 36-48 Hours, 48-60 Hours post-dose in each Treatment Periods 1 and 2

InterventionPercent dose excreted (Geometric Mean)
Cohort 3:Gepotidacin 3000 mg + Digoxin 0.5 mg + Midazolam 2 mg17.77

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Cohort 3: Minimum Observed Concentration (Cmin) of Digoxin in Plasma

Blood samples were collected at indicated time points. Pharmacokinetic analysis of digoxin was conducted using standard non-compartmental analysis. Analysis was performed using a linear mixed-effect model with treatment as a fixed effect and participant as a random effect. Geometric LS mean and 90 % CI of the geometric LS means have been presented. (NCT04493931)
Timeframe: Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 24 Hours, 36 Hours, 48 Hours, 72 Hours, 96 Hours post-dose in each Treatment Periods 1 and 2

InterventionPicograms per milliliter (Geometric Least Squares Mean)
Cohort 3: Digoxin 0.5 mg + Midazolam 2 mg44.127
Cohort 3:Gepotidacin 3000 mg + Digoxin 0.5 mg + Midazolam 2 mg77.447

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Cohort 3: Cmin of Midazolam in Plasma

Blood samples were collected at indicated time points. Pharmacokinetic analysis of midazolam was conducted using standard non-compartmental analysis. Analysis was performed using a linear mixed-effect model with treatment as a fixed effect and participant as a random effect. Geometric LS mean and 90 % CI of the geometric LS means have been presented. (NCT04493931)
Timeframe: Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours, 36 Hours, 48 Hours post-dose in each Treatment Periods 1 and 2

InterventionNanograms per milliliter (Geometric Least Squares Mean)
Cohort 3: Digoxin 0.5 mg + Midazolam 2 mg0.192
Cohort 3:Gepotidacin 3000 mg + Digoxin 0.5 mg + Midazolam 2 mg0.222

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Cohort 3: Cmax of Midazolam in Plasma

Blood samples were collected at indicated time points. Pharmacokinetic analysis of midazolam was conducted using standard non-compartmental analysis. Analysis was performed using a linear mixed-effect model with treatment as a fixed effect and participant as a random effect. Geometric LS mean and 90 % CI of the geometric LS means have been presented. (NCT04493931)
Timeframe: Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours, 36 Hours, 48 Hours Post-dose in each Treatment Periods 1 and 2

InterventionNanograms per milliliter (Geometric Least Squares Mean)
Cohort 3: Digoxin 0.5 mg + Midazolam 2 mg5.238
Cohort 3:Gepotidacin 3000 mg + Digoxin 0.5 mg + Midazolam 2 mg6.507

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Cohort 3: Cmax of Gepotidacin in Plasma After the Second Dose of 3000 mg (Second Dose)

Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. (NCT04493931)
Timeframe: Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3, 4, 6, 8, 12 Hours, 12 Hours 30 minutes, 13 Hours, 13 Hours 30 Hours, 14 Hours, 14 Hours 30 Hours, 15, 16,18,20,24,36, 48, 60 Hours post-dose in each Treatment Periods 1 and 2

InterventionMicrograms per milliliter (Geometric Mean)
Cohort 3:Gepotidacin 3000 mg + Digoxin 0.5 mg + Midazolam 2 mg10.051

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Cohort 3: Cmax of Gepotidacin in Plasma After the First Dose of 3000 mg (First Dose)

Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. (NCT04493931)
Timeframe: Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3, 4, 6, 8, 12 Hours, 12 Hours 30 minutes, 13 Hours, 13 Hours 30 Hours, 14 Hours, 14 Hours 30 Hours, 15, 16,18,20,24,36, 48, 60 Hours post-dose in each Treatment Periods 1 and 2

InterventionMicrograms per milliliter (Geometric Mean)
Cohort 3:Gepotidacin 3000 mg + Digoxin 0.5 mg + Midazolam 2 mg7.867

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Cohort 3: Cmax of Digoxin in Plasma

Blood samples were collected at indicated time points. Pharmacokinetic analysis of digoxin was conducted using standard non-compartmental analysis. Analysis was performed using a linear mixed-effect model with treatment as a fixed effect and participant as a random effect. Geometric LS mean and 90 % CI of the geometric LS means have been presented. (NCT04493931)
Timeframe: Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 24 Hours, 36 Hours, 48 Hours, 72 Hours, 96 Hours Post-dose in each Treatment Periods 1 and 2

InterventionPicograms per milliliter (Geometric Least Squares Mean)
Cohort 3: Digoxin 0.5 mg + Midazolam 2 mg1553.135
Cohort 3:Gepotidacin 3000 mg + Digoxin 0.5 mg + Midazolam 2 mg2381.259

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Cohort 3: CLr of Gepotidacin Following Two 3000 mg Doses (First Dose + Second Dose)

Urine samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. (NCT04493931)
Timeframe: Pre-dose, 0-2 Hours, 2-4 Hours, 4-6 Hours, 6-8 Hours, 8-12 Hours, 12-14 Hours, 14-16 Hours, 16-18 Hours, 18-20 Hours, 20-24 Hours, 24-36 Hours, 36-48 Hours, 48-60 Hours post-dose in each Treatment Periods 1 and 2

InterventionLiters per Hour (Geometric Mean)
Cohort 3:Gepotidacin 3000 mg + Digoxin 0.5 mg + Midazolam 2 mg13.19

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Cohort 3: CL/F of Midazolam in Plasma

Blood samples were collected at indicated time points. Pharmacokinetic analysis of midazolam was conducted using standard non-compartmental analysis. Analysis was performed using a linear mixed-effect model with treatment as a fixed effect and participant as a random effect. Geometric LS mean and 90 % CI of the geometric LS means have been presented. (NCT04493931)
Timeframe: Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours, 36 Hours, 48 Hours post-dose in each Treatment Periods 1 and 2

InterventionLiters per Hour (Geometric Least Squares Mean)
Cohort 3: Digoxin 0.5 mg + Midazolam 2 mg80.17
Cohort 3:Gepotidacin 3000 mg + Digoxin 0.5 mg + Midazolam 2 mg42.16

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Cohort 3: CL/F of Gepotidacin in Plasma Following Two 3000 mg Doses (First Dose + Second Dose)

Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. (NCT04493931)
Timeframe: Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3, 4, 6, 8, 12 Hours, 12 Hours 30 minutes, 13 Hours, 13 Hours 30 Hours, 14 Hours, 14 Hours 30 Hours, 15, 16,18,20,24,36, 48, 60 Hours post-dose in each Treatment Periods 1 and 2

InterventionLiters per Hour (Geometric Mean)
Cohort 3:Gepotidacin 3000 mg + Digoxin 0.5 mg + Midazolam 2 mg69.99

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Cohort 3: CL/F of Digoxin in Plasma

Blood samples were collected at indicated time points. Pharmacokinetic analysis of digoxin was conducted using standard non-compartmental analysis. Analysis was performed using a linear mixed-effect model with treatment as a fixed effect and participant as a random effect. Geometric LS mean and 90 % CI of the geometric LS means have been presented. (NCT04493931)
Timeframe: Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 24 Hours, 36 Hours, 48 Hours, 72 Hours, 96 Hours post-dose in each Treatment Periods 1 and 2

InterventionLiters per Hour (Geometric Least Squares Mean)
Cohort 3: Digoxin 0.5 mg + Midazolam 2 mg16.26
Cohort 3:Gepotidacin 3000 mg + Digoxin 0.5 mg + Midazolam 2 mg14.51

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Cohort 3: AUC(0-tau) of Gepotidacin in Urine Following Two 3000 mg Doses (First Dose + Second Dose)

Urine samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. (NCT04493931)
Timeframe: Pre-dose, 0-2 Hours, 2-4 Hours, 4-6 Hours, 6-8 Hours, 8-12 Hours, 12-14 Hours, 14-16 Hours, 16-18 Hours, 18-20 Hours, 20-24 Hours, 24-36 Hours, 36-48 Hours, 48-60 Hours post-dose in each Treatment Periods 1 and 2

InterventionHours*micrograms per milliliter (Geometric Mean)
Cohort 3:Gepotidacin 3000 mg + Digoxin 0.5 mg + Midazolam 2 mg4770.8

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Cohort 3: AUC(0-tau) of Gepotidacin in Plasma First Dose of 3000 mg (First Dose)

Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. (NCT04493931)
Timeframe: Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3, 4, 6, 8, 12 Hours, 12 Hours 30 minutes, 13 Hours, 13 Hours 30 Hours, 14 Hours, 14 Hours 30 Hours, 15, 16,18,20,24,36, 48, 60 Hours post-dose in each Treatment Periods 1 and 2

InterventionHours*micrograms per milliliter (Geometric Mean)
Cohort 3:Gepotidacin 3000 mg + Digoxin 0.5 mg + Midazolam 2 mg29.8

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Cohort 4: AUC(0-tau) of Gepotidacin in Plasma After the Second Dose of 3000 mg (Evening Dose)-Fed State

Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. (NCT04493931)
Timeframe: Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3, 4, 6, 8, 12 Hours, 12 Hours 30 minutes, 13 Hours, 13 Hours 30 minutes, 14 Hours, 14 Hours 30 minutes, 15, 16, 18, 20, 24, 36, 48, 60 Hours post-dose in Treatment Period 3

InterventionHours*micrograms per milliliter (Geometric Mean)
Cohort 4: Gepotidacin 3000 mg Fed46.7

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Cohort 3: AUC(0-t) of Midazolam in Plasma

Blood samples were collected at indicated time points. Pharmacokinetic analysis of midazolam was conducted using standard non-compartmental analysis. Analysis was performed using a linear mixed-effect model with treatment as a fixed effect and participant as a random effect. Geometric LS mean and 90 % CI of the geometric LS means have been presented. (NCT04493931)
Timeframe: Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours, 36 Hours, 48 Hours Post-dose in each Treatment Periods 1 and 2

InterventionHours*nanograms per milliliter (Geometric Least Squares Mean)
Cohort 3: Digoxin 0.5 mg + Midazolam 2 mg23.3
Cohort 3:Gepotidacin 3000 mg + Digoxin 0.5 mg + Midazolam 2 mg44.8

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Cohort 3: AUC(0-t) of Gepotidacin in Plasma Following Two 3000 mg Doses (First Dose + Second Dose)

Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. (NCT04493931)
Timeframe: Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3, 4, 6, 8, 12 Hours, 12 Hours 30 minutes, 13 Hours, 13 Hours 30 Hours, 14 Hours, 14 Hours 30 Hours, 15, 16,18,20,24,36, 48, 60 Hours post-dose in each Treatment Periods 1 and 2

InterventionHours*micrograms per milliliter (Geometric Mean)
Cohort 3:Gepotidacin 3000 mg + Digoxin 0.5 mg + Midazolam 2 mg85.2

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Cohort 3: AUC(0-t) of Digoxin in Plasma

Blood samples were collected at indicated time points. Pharmacokinetic analysis of digoxin was conducted using standard non-compartmental analysis. Analysis was performed using a linear mixed-effect model with treatment as a fixed effect and participant as a random effect. Geometric LS mean and 90 % CI of the geometric LS means have been presented. (NCT04493931)
Timeframe: Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 24 Hours, 36 Hours, 48 Hours, 72 Hours, 96 Hours Post-dose in each Treatment Periods 1 and 2

InterventionHours*picograms per milliliter (Geometric Least Squares Mean)
Cohort 3: Digoxin 0.5 mg + Midazolam 2 mg25353.1
Cohort 3:Gepotidacin 3000 mg + Digoxin 0.5 mg + Midazolam 2 mg30842.3

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Cohort 3: AUC(0-infinity) of Midazolam in Plasma

Blood samples were collected at indicated time points. Pharmacokinetic analysis of midazolam was conducted using standard non-compartmental analysis. Analysis was performed using a linear mixed-effect model with treatment as a fixed effect and participant as a random effect. Geometric LS mean and 90 % CI of the geometric LS means have been presented. (NCT04493931)
Timeframe: Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours, 36 Hours, 48 Hours Post-dose in each Treatment Periods 1 and 2

InterventionHours*nanograms per milliliter (Geometric Least Squares Mean)
Cohort 3: Digoxin 0.5 mg + Midazolam 2 mg24.9
Cohort 3:Gepotidacin 3000 mg + Digoxin 0.5 mg + Midazolam 2 mg47.4

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Cohort 3: AUC(0-infinity) of Digoxin in Plasma

Blood samples were collected at indicated time points. Pharmacokinetic analysis of digoxin was conducted using standard non-compartmental analysis. Analysis was performed using a linear mixed-effect model with treatment as a fixed effect and participant as a random effect. Geometric LS mean and 90 % CI of the geometric LS means have been presented. (NCT04493931)
Timeframe: Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 24 Hours, 36 Hours, 48 Hours, 72 Hours, 96 Hours Post-dose in each Treatment Periods 1 and 2

InterventionHours*picograms per milliliter (Geometric Least Squares Mean)
Cohort 3: Digoxin 0.5 mg + Midazolam 2 mg30743.6
Cohort 3:Gepotidacin 3000 mg + Digoxin 0.5 mg + Midazolam 2 mg34456.5

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Cohort 3: AUC(0-48) of Gepotidacin in Plasma Following Two 3000 mg Doses (First Dose + Second Dose)

Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. (NCT04493931)
Timeframe: Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3, 4, 6, 8, 12 Hours, 12 Hours 30 minutes, 13 Hours, 13 Hours 30 Hours, 14 Hours, 14 Hours 30 Hours, 15, 16,18,20,24,36, 48 Hours post-dose in each Treatment Periods 1 and 2

InterventionHours*micrograms per milliliter (Geometric Mean)
Cohort 3:Gepotidacin 3000 mg + Digoxin 0.5 mg + Midazolam 2 mg81.2

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Cohort 4: AUC(0-tau) of Gepotidacin Following Single Dose of 1500 mg Under Fed Condition in Urine

Urine samples were collected at indicated time points. AUC(0-tau) can be calculated only for multiple doses and not for single dose as tau refers to the dosing interval. Hence, AUC(0-tau) could not be calculated for Gepotidacin 1500 mg single dose as mentioned in Reporting and Analysis Plan. The results for this outcome measure will never be posted. (NCT04493931)
Timeframe: Pre-dose, 0-2 Hours, 2-4 Hours, 4-6 Hours, 6-8 Hours, 8-12 Hours, 12-24 Hours, 24-36 Hours, 36-48 Hours post-dose in each Treatment Periods 1 and 2

InterventionHours*micrograms per milliliter (Geometric Mean)
Cohort 4: Gepotidacin 1500 mg FedNA

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Cohort 3: AUC(0-24) of Gepotidacin in Plasma Following Two 3000 mg Doses (First Dose + Second Dose)

Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. (NCT04493931)
Timeframe: Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3, 4, 6, 8, 12 Hours, 12 Hours 30 minutes, 13 Hours, 13 Hours 30 Hours, 14 Hours, 14 Hours 30 Hours, 15, 16,18,20,24 Hours post-dose in each Treatment Periods 1 and 2

InterventionHours*micrograms per milliliter (Geometric Mean)
Cohort 3:Gepotidacin 3000 mg + Digoxin 0.5 mg + Midazolam 2 mg73.2

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Cohort 3: AUC (0-48) of Gepotidacin in Urine Following Two 3000 mg Doses (First Dose + Second Dose)

Urine samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. (NCT04493931)
Timeframe: Pre-dose, 0-2 Hours, 2-4 Hours, 4-6 Hours, 6-8 Hours, 8-12 Hours, 12-14 Hours, 14-16 Hours, 16-18 Hours, 18-20 Hours, 20-24 Hours, 24-36 Hours, 36-48 Hours post-dose in each Treatment Periods 1 and 2

InterventionHours*micrograms per milliliter (Geometric Mean)
Cohort 3:Gepotidacin 3000 mg + Digoxin 0.5 mg + Midazolam 2 mg16682.1

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Cohort 3: Ae Total of Gepotidacin in Urine Following Two 3000 mg Doses (First Dose + Second Dose )

Urine samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. Ae total was calculated by adding all the fractions of drug collected over all the allotted time intervals. (NCT04493931)
Timeframe: Pre-dose, 0-2 Hours, 2-4 Hours, 4-6 Hours, 6-8 Hours, 8-12 Hours, 12-14 Hours, 14-16 Hours, 16-18 Hours, 18-20 Hours, 20-24 Hours, 24-36 Hours, 36-48 Hours, 48-60 Hours post-dose in each Treatment Periods 1 and 2

InterventionMilligrams (Geometric Mean)
Cohort 3:Gepotidacin 3000 mg + Digoxin 0.5 mg + Midazolam 2 mg1066.21

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Cohort 2: Vz/F of Gepotidacin in Plasma

Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. (NCT04493931)
Timeframe: Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hour, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours, 36 Hours, 48 Hours post-dose in each Treatment Periods 1 and 2

InterventionLiters (Geometric Mean)
Cohort 2:Period 1: Gepotidacin 1500 mg1217.45
Cohort 2: Period 2: Gepotidacin 1500 mg + Rifampicin 600 mg2460.46

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Cohort 2: Tmax of Gepotidacin in Plasma

Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. (NCT04493931)
Timeframe: Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hour, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours, 36 Hours, 48 Hours Post-dose in each Treatment Periods 1 and 2

InterventionHours (Median)
Cohort 2:Period 1: Gepotidacin 1500 mg2.500
Cohort 2: Period 2: Gepotidacin 1500 mg + Rifampicin 600 mg2.000

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Cohort 2: T1/2 of Gepotidacin in Plasma

Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. (NCT04493931)
Timeframe: Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hour, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours, 36 Hours, 48 Hours post-dose in each Treatment Periods 1 and 2

InterventionHours (Geometric Mean)
Cohort 2:Period 1: Gepotidacin 1500 mg10.882
Cohort 2: Period 2: Gepotidacin 1500 mg + Rifampicin 600 mg10.972

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Cohort 2: Percentage of the Given Dose of Drug Excreted in Urine (fe%) of Gepotidacin

Urine samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. fe% was calculated as: (Ae total divided by Dose) multiplied by 100 %. (NCT04493931)
Timeframe: Pre-dose, 0-2 Hours, 2-4 Hours, 4-6 Hours, 6-8 Hours, 8-12 Hours, 12-24 Hours, 24-36 Hours, 36-48 Hours post-dose in each Treatment Periods 1 and 2

InterventionPercent dose excreted (Geometric Mean)
Cohort 2:Period 1: Gepotidacin 1500 mg20.85
Cohort 2: Period 2: Gepotidacin 1500 mg + Rifampicin 600 mg10.42

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Cohort 2: Lag Time Before Observation of Drug Concentrations (Tlag) of Gepotidacin in Plasma

Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. (NCT04493931)
Timeframe: Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hour, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours, 36 Hours, 48 Hours Post-dose in each Treatment Periods 1 and 2

InterventionHours (Median)
Cohort 2:Period 1: Gepotidacin 1500 mg0.000
Cohort 2: Period 2: Gepotidacin 1500 mg + Rifampicin 600 mg0.000

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Cohort 2: Cmax of Gepotidacin in Plasma

Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. Analysis was performed using a linear mixed-effect model with treatment as a fixed effect and participant as a random effect. Geometric LS mean and 90% CI of the geometric LS means have been presented. (NCT04493931)
Timeframe: Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hour, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours, 36 Hours, 48 Hours Post-dose in each Treatment Periods 1 and 2

InterventionMicrograms per milliliter (Geometric Least Squares Mean)
Cohort 2:Period 1: Gepotidacin 1500 mg3.735
Cohort 2: Period 2: Gepotidacin 1500 mg + Rifampicin 600 mg2.728

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Cohort 2: CLr of Gepotidacin

Urine samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. Analysis was performed using a linear mixed-effect model with treatment as a fixed effect and participant as a random effect. Geometric LS mean and 90 % CI of the geometric LS means have been presented. (NCT04493931)
Timeframe: Pre-dose, 0-2 Hours, 2-4 Hours, 4-6 Hours, 6-8 Hours, 8-12 Hours, 12-24 Hours, 24-36 Hours, 36-48 Hours post-dose in each Treatment Periods 1 and 2

InterventionLiters per Hour (Geometric Least Squares Mean)
Cohort 2:Period 1: Gepotidacin 1500 mg16.49
Cohort 2: Period 2: Gepotidacin 1500 mg + Rifampicin 600 mg17.07

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Cohort 2: CL/F of Gepotidacin in Plasma

Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. (NCT04493931)
Timeframe: Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hour, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours, 36 Hours, 48 Hours post-dose in each Treatment Periods 1 and 2

InterventionLiters per Hour (Geometric Mean)
Cohort 2:Period 1: Gepotidacin 1500 mg77.55
Cohort 2: Period 2: Gepotidacin 1500 mg + Rifampicin 600 mg155.43

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Cohort 2: AUC(0-t) of Gepotidacin in Plasma

Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. Analysis was performed using a linear mixed-effect model with treatment as a fixed effect and participant as a random effect. Geometric LS mean and 90% CI of the geometric LS means have been presented. (NCT04493931)
Timeframe: Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hour, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours, 36 Hours, 48 Hours Post-dose in each Treatment Periods 1 and 2

InterventionHours*micrograms per milliliter (Geometric Least Squares Mean)
Cohort 2:Period 1: Gepotidacin 1500 mg19.0
Cohort 2: Period 2: Gepotidacin 1500 mg + Rifampicin 600 mg9.0

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Cohort 2: AUC(0-infinity) of Gepotidacin in Plasma

Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. Analysis was performed using a linear mixed-effect model with treatment as a fixed effect and participant as a random effect. Geometric LS mean and 90 % CI of the geometric LS means have been presented. (NCT04493931)
Timeframe: Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hour, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours, 36 Hours, 48 Hours Post-dose in each Treatment Periods 1 and 2

InterventionHours*micrograms per milliliter (Geometric Least Squares Mean)
Cohort 2:Period 1: Gepotidacin 1500 mg19.3
Cohort 2: Period 2: Gepotidacin 1500 mg + Rifampicin 600 mg9.3

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Cohort 2: AUC(0-48) of Gepotidacin in Urine

Urine samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. Analysis was performed using a linear mixed-effect model with treatment as a fixed effect and participant as a random effect. Geometric LS mean and 90 % CI of the geometric LS means have been presented. (NCT04493931)
Timeframe: Pre-dose, 0-2 Hours, 2-4 Hours, 4-6 Hours, 6-8 Hours, 8-12 Hours, 12-24 Hours, 24-36 Hours, 36-48 Hours post-dose in each Treatment Periods 1 and 2

InterventionHours*micrograms per milliliter (Geometric Least Squares Mean)
Cohort 2:Period 1: Gepotidacin 1500 mg3370.1
Cohort 2: Period 2: Gepotidacin 1500 mg + Rifampicin 600 mg1476.8

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Cohort 2: AUC(0-48) of Gepotidacin in Plasma

Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. (NCT04493931)
Timeframe: Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hour, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours, 36 Hours, 48 Hours post-dose in each Treatment Periods 1 and 2

InterventionHours*micrograms per milliliter (Geometric Mean)
Cohort 2:Period 1: Gepotidacin 1500 mg19.0
Cohort 2: Period 2: Gepotidacin 1500 mg + Rifampicin 600 mg9.5

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Cohort 2: AUC(0-24) of Gepotidacin in Urine

Urine samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. Analysis was performed using a linear mixed-effect model with treatment as a fixed effect and participant as a random effect. Geometric LS mean and 90 % CI of the geometric LS means have been presented. (NCT04493931)
Timeframe: Pre-dose, 0-2 Hours, 2-4 Hours, 4-6 Hours, 6-8 Hours, 8-12 Hours, 12-24 Hours post-dose in each Treatment Periods 1 and 2

InterventionHours*micrograms per milliliter (Geometric Least Squares Mean)
Cohort 2:Period 1: Gepotidacin 1500 mg3081.3
Cohort 2: Period 2: Gepotidacin 1500 mg + Rifampicin 600 mg1352.4

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Cohort 2: AUC(0-24) of Gepotidacin in Plasma

Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. (NCT04493931)
Timeframe: Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hour, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours post-dose in each Treatment Periods 1 and 2

InterventionHours*micrograms per milliliter (Geometric Mean)
Cohort 2:Period 1: Gepotidacin 1500 mg17.9
Cohort 2: Period 2: Gepotidacin 1500 mg + Rifampicin 600 mg8.9

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Cohort 2: Ae Total of Gepotidacin in Urine

Urine samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. Ae total was calculated by adding all the fractions of drug collected over all the allotted time intervals. Analysis was performed using a linear mixed-effect model with treatment as a fixed effect and participant as a random effect. Geometric LS mean and 90 % CI of the geometric LS means have been presented. (NCT04493931)
Timeframe: Pre-dose, 0-2 Hours, 2-4 Hours, 4-6 Hours, 6-8 Hours, 8-12 Hours, 12-24 Hours, 24-36 Hours, 36-48 Hours post-dose in each Treatment Periods 1 and 2

InterventionMilligrams (Geometric Least Squares Mean)
Cohort 2:Period 1: Gepotidacin 1500 mg312.73
Cohort 2: Period 2: Gepotidacin 1500 mg + Rifampicin 600 mg156.05

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Cohort 1: Total Unchanged Drug (Ae Total) of Gepotidacin in Urine

Urine samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. Ae total was calculated by adding all the fractions of drug collected over all the allotted time intervals. Analysis was performed using a linear mixed-effect model with treatment as a fixed effect and participant as a random effect. Geometric LS mean and 90 % CI of the geometric LS means have been presented. (NCT04493931)
Timeframe: Pre-dose, 0-2 Hours, 2-4 Hours, 4-6 Hours, 6-8 Hours, 8-12 Hours, 12-24 Hours, 24-36 Hours, 36-48 Hours Post-dose in each Treatment periods 1 and 2

InterventionMilligrams (Geometric Least Squares Mean)
Cohort 1: Gepotidacin 1500 mg337.92
Cohort 1: Gepotidacin 1500 mg + Cimetidine 400 mg410.10

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Cohort 1: Tlag of Gepotidacin in Plasma

Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. (NCT04493931)
Timeframe: Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hour, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours, 36 Hours, 48 Hours Post-dose in each Treatment Periods 1 and 2

InterventionHours (Median)
Cohort 1: Gepotidacin 1500 mg0.000
Cohort 1: Gepotidacin 1500 mg + Cimetidine 400 mg0.000

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Cohort 1: Time to Reach Maximum Observed Concentration (Tmax) of Gepotidacin in Plasma

Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. (NCT04493931)
Timeframe: Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hour, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours, 36 Hours, 48 Hours Post-dose in each Treatment Periods 1 and 2

InterventionHours (Median)
Cohort 1: Gepotidacin 1500 mg2.500
Cohort 1: Gepotidacin 1500 mg + Cimetidine 400 mg2.500

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Cohort 1: Terminal Phase Half-life (t1/2) of Gepotidacin in Plasma

Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. Analysis was performed using a linear mixed-effect model with treatment as a fixed effect and participant as a random effect. Geometric LS mean and 90% CI of the geometric LS means have been presented. (NCT04493931)
Timeframe: Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hour, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours, 36 Hours, 48 Hours Post-dose in each Treatment Periods 1 and 2

InterventionHours (Geometric Least Squares Mean)
Cohort 1: Gepotidacin 1500 mg11.344
Cohort 1: Gepotidacin 1500 mg + Cimetidine 400 mg12.415

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Cohort 1: Renal Clearance (CLr) of Gepotidacin

Urine samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. Analysis was performed using a linear mixed-effect model with treatment as a fixed effect and participant as a random effect. Geometric LS mean and 90% CI of the geometric LS means have been presented. (NCT04493931)
Timeframe: Pre-dose, 0-2 Hours, 2-4 Hours, 4-6 Hours, 6-8 Hours, 8-12 Hours, 12-24 Hours, 24-36 Hours, 36-48 Hours Post-dose in each Treatment periods 1 and 2

InterventionLiters per Hour (Geometric Least Squares Mean)
Cohort 1: Gepotidacin 1500 mg16.06
Cohort 1: Gepotidacin 1500 mg + Cimetidine 400 mg17.59

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Cohort 1: Percentage of the Given Dose of Drug Excreted in Urine (fe%) of Gepotidacin

Urine samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. fe% was calculated as: (Ae total divided by Dose) multiplied by 100 percent (%). (NCT04493931)
Timeframe: Pre-dose, 0-2 Hours, 2-4 Hours, 4-6 Hours, 6-8 Hours, 8-12 Hours, 12-24 Hours, 24-36 Hours, 36-48 Hours Post-dose in each Treatment periods 1 and 2

InterventionPercent dose excreted (Geometric Mean)
Cohort 1: Gepotidacin 1500 mg22.72
Cohort 1: Gepotidacin 1500 mg + Cimetidine 400 mg26.90

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Cohort 1: Maximum Observed Concentration (Cmax) of Gepotidacin in Plasma

Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. Analysis was performed using a linear mixed-effect model with treatment as a fixed effect and participant as a random effect. Geometric least square (LS) mean and 90 percent (%) confidence interval (CI) of the geometric LS means have been presented. (NCT04493931)
Timeframe: Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hour, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours, 36 Hours, 48 Hours Post-dose in each Treatment Periods 1 and 2

InterventionMicrograms per milliliter (Geometric Least Squares Mean)
Cohort 1: Gepotidacin 1500 mg4.817
Cohort 1: Gepotidacin 1500 mg + Cimetidine 400 mg4.548

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Cohort 1: AUC(0-48) of Gepotidacin in Urine

Urine samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. Analysis was performed using a linear mixed-effect model with treatment as a fixed effect and participant as a random effect. Geometric LS mean and 90% CI of the geometric LS means have been presented. (NCT04493931)
Timeframe: Pre-dose, 0-2 Hours, 2-4 Hours, 4-6 Hours, 6-8 Hours, 8-12 Hours, 12-24 Hours, 24-36 Hours, 36-48 Hours Post-dose in each Treatment periods 1 and 2

InterventionHours*micrograms per milliliter (Geometric Least Squares Mean)
Cohort 1: Gepotidacin 1500 mg3578.2
Cohort 1: Gepotidacin 1500 mg + Cimetidine 400 mg3831.1

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Cohort 1: AUC(0-48) of Gepotidacin in Plasma

Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. (NCT04493931)
Timeframe: Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hour, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours, 36 Hours, 48 Hours Post-dose in each Treatment Periods 1 and 2

InterventionHours*micrograms per milliliter (Geometric Mean)
Cohort 1: Gepotidacin 1500 mg20.3
Cohort 1: Gepotidacin 1500 mg + Cimetidine 400 mg23.0

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Cohort 1: AUC(0-24) of Gepotidacin in Urine

Urine samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. Analysis was performed using a linear mixed-effect model with treatment as a fixed effect and participant as a random effect. Geometric LS mean and 90% CI of the geometric LS means have been presented. (NCT04493931)
Timeframe: Pre-dose, 0-2 Hours, 2-4 Hours, 4-6 Hours, 6-8 Hours, 8-12 Hours, 12-24 Hours Post-dose in each Treatment periods 1 and 2

InterventionHours*micrograms per milliliter (Geometric Least Squares Mean)
Cohort 1: Gepotidacin 1500 mg3292.1
Cohort 1: Gepotidacin 1500 mg + Cimetidine 400 mg3612.4

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Cohort 1: AUC From Time 0 (Pre-dose) Extrapolated to Infinite Time (AUC[0-infinity]) of Gepotidacin in Plasma

Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. Analysis was performed using a linear mixed-effect model with treatment as a fixed effect and participant as a random effect. Geometric LS mean and 90% CI of the geometric LS means have been presented. (NCT04493931)
Timeframe: Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hour, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours, 36 Hours, 48 Hours Post-dose in each Treatment Periods 1 and 2

InterventionHours* micrograms per milliliter (Geometric Least Squares Mean)
Cohort 1: Gepotidacin 1500 mg20.6
Cohort 1: Gepotidacin 1500 mg + Cimetidine 400 mg23.9

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Cohort 1: AUC (0-24) of Gepotidacin in Plasma

Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. (NCT04493931)
Timeframe: Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hour, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours Post-dose in each Treatment Periods 1 and 2

InterventionHours*micrograms per milliliter (Geometric Mean)
Cohort 1: Gepotidacin 1500 mg19.3
Cohort 1: Gepotidacin 1500 mg + Cimetidine 400 mg21.9

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Cohort 1: Area Under the Concentration-time Curve From Time 0 (Pre-dose) to the Time of the Last Quantifiable Concentration (AUC [0-t]) of Gepotidacin in Plasma

Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. Analysis was performed using a linear mixed-effect model with treatment as a fixed effect and participant as a random effect. Geometric LS mean and 90% CI of the geometric LS means have been presented. (NCT04493931)
Timeframe: Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hour, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours, 36 Hours, 48 Hours Post-dose in each Treatment Periods 1 and 2

InterventionHours*micrograms per milliliter (Geometric Least Squares Mean)
Cohort 1: Gepotidacin 1500 mg20.3
Cohort 1: Gepotidacin 1500 mg + Cimetidine 400 mg23.4

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Cohort 1: Apparent Volume of Distribution (Vz/F) of Gepotidacin in Plasma

Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. (NCT04493931)
Timeframe: Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hour, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours, 36 Hours, 48 Hours Post-dose in each Treatment Periods 1 and 2

InterventionLiters (Geometric Mean)
Cohort 1: Gepotidacin 1500 mg1190.16
Cohort 1: Gepotidacin 1500 mg + Cimetidine 400 mg1143.29

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Cohort 1: Apparent Oral Clearance (CL/F) of Gepotidacin in Plasma

Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. (NCT04493931)
Timeframe: Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hour, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours, 36 Hours, 48 Hours Post-dose in each Treatment Periods 1 and 2

InterventionLiters per Hour (Geometric Mean)
Cohort 1: Gepotidacin 1500 mg72.72
Cohort 1: Gepotidacin 1500 mg + Cimetidine 400 mg64.14

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Cohort 4: Number of Participants With Worst Case Hematology Results Relative to Normal Range Post-Baseline Relative to Baseline

Blood samples were collected at indicated time points for analysis of hematology parameters including Basophils, Eosinophils, Erythrocyte Mean Corpuscular Hemoglobin (MCH), Erythrocyte Mean Corpuscular Volume (MCV), Erythrocytes, Hematocrit, Hemoglobin, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets. Participants were counted in the worst case category that their value changes to (low, normal or high), unless there was no change in their category. Participants whose laboratory (lab) value category was unchanged (e.g., High to High), or whose value became normal, are recorded in the 'To Normal or No Change' category. Participants were counted twice if the participant had values that changed 'To Low' and 'To High', so the percentages may not add to 100 (%). High and low indicated that participants had values flagged as high and low respectively for the particular parameter any time on-treatment. (NCT04493931)
Timeframe: Up to 22 days

,,,
InterventionParticipants (Count of Participants)
Basophils; To LowBasophils; To Normal or No ChangeBasophils; To HighEosinophils; To LowEosinophils; To Normal or No ChangeEosinophils; To HighMCH; To LowMCH; To Normal or No ChangeMCH; To HighMCV; To LowMCV; To Normal or No ChangeMCV; To HighErythrocytes; To LowErythrocytes; To Normal or No ChangeErythrocytes; To HighHematocrit; To LowHematocrit; To Normal or No ChangeHematocrit; To HighHemoglobin; To LowHemoglobin; To Normal or No ChangeHemoglobin; To HighLeukocytes; To LowLeukocytes; To Normal or No ChangeLeukocytes; To HighLymphocytes; To LowLymphocytes; To Normal or No ChangeLymphocytes; To HighMonocytes; To LowMonocytes; To Normal or No ChangeMonocytes; To HighNeutrophils; To LowNeutrophils; To Normal or No ChangeNeutrophils; To HighPlatelets; To LowPlatelets; To Normal or No ChangePlatelets; To High
Cohort 4: Gepotidacin 1500 mg Fasted09201010110010101100110011001100110011011000110
Cohort 4: Gepotidacin 1500 mg Fed011001010110010101010101010101100110011001100110
Cohort 4: Gepotidacin 3000 mg Fed01010101011009211000101011011000110011011001100
Cohort 4: Placebo030030030021030030030030030030030030

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Cohort 4: Number of Participants With Worst Case Urinalysis Results Relative to Normal Range Post-Baseline Relative to Baseline

Urine samples were collected at indicated time points for the analysis of urinalysis parameters including potential of hydrogen (pH) of urine, presence of glucose, protein, blood, ketones, bilirubin, nitrite, leukocyte esterase in urine by dipstick. Specific gravity of urine was measured by microscopic examination. Participants were counted in the worst case category that their value changes to (low, normal, high, or abnormal), unless there is no change in their category. Participants whose lab value category was unchanged (e.g., High to High), or whose value became normal, are recorded in the 'To Normal or No Change' category. Participants were counted twice if the participant has values that changed 'To Low' and 'To High', so the percentages may not add to 100%. High and low indicated that participants had values flagged as high and low respectively for the particular parameter any time on-treatment. (NCT04493931)
Timeframe: Up to 22 days

,,,
InterventionParticipants (Count of Participants)
Bilirubin; To Normal or No ChangeBilirubin; To AbnormalGlucose; To Normal or No ChangeGlucose; To AbnormalKetones; To Normal or No ChangeKetones; To AbnormalLeukocyte Esterase; To Normal or No ChangeLeukocyte Esterase; To AbnormalNitrite; To Normal or No ChangeNitrite; To AbnormalOccult Blood; To Normal or No ChangeOccult Blood; To AbnormalProtein; To Normal or No ChangeProtein; To AbnormalpH; To LowpH; To Normal or No ChangepH; To HighSpecific Gravity; To LowSpecific Gravity; To Normal or No ChangeSpecific Gravity; To High
Cohort 4: Gepotidacin 1500 mg Fasted11011011011011010111001100110
Cohort 4: Gepotidacin 1500 mg Fed1101101109211011011001100110
Cohort 4: Gepotidacin 3000 mg Fed1101101109210110111001100110
Cohort 4: Placebo30302121302130030030

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Cohort 4: Number of Participants With Worst Case Vital Sign Results Relative to Normal Range Post-Baseline Relative to Baseline

Vital signs including systolic blood pressure (SBP), diastolic blood pressure (DBP) and pulse rate were measured in a semi-supine position after 5 minutes rest. Participants were counted in the worst case category that their value changes to (low, normal or high), unless there was no change in their category. Participants whose value category was unchanged (e.g., High to High), or whose value became normal, were recorded in the 'To Normal or No Change' category. Participants were counted twice if the participant had values that changed 'To Low' and 'To High', so the percentages may not add to 100%. High and low indicated that participants had values flagged as high and low respectively for the particular parameter any time on-treatment. (NCT04493931)
Timeframe: Up to 22 days

,,,
InterventionParticipants (Count of Participants)
DBP; To LowDBP; To Normal or No ChangeDBP; To HighSBP; To LowSBP; To Normal or No ChangeSBP; To HighPulse rate; To LowPulse rate; To Normal or No ChangePulse rate; To High
Cohort 4: Gepotidacin 1500 mg Fasted011011000110
Cohort 4: Gepotidacin 1500 mg Fed110011000110
Cohort 4: Gepotidacin 3000 mg Fed011001100110
Cohort 4: Placebo030030030

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Cohort 4: CL/F of Gepotidacin in Plasma Following Two 3000 mg Doses (First Dose + Second Dose)-Fed State

Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. (NCT04493931)
Timeframe: Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3, 4, 6, 8, 12 Hours, 12 Hours 30 minutes, 13 Hours, 13 Hours 30 minutes, 14 Hours, 14 Hours 30 minutes, 15, 16, 18, 20, 24, 36, 48, 60 Hours post-dose in Treatment Period 3

InterventionLiters per Hour (Geometric Mean)
Cohort 4: Gepotidacin 3000 mg Fed68.83

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Cohort 4: Number of Participants With Worst Case Clinical Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline

Blood samples were collected at indicated time points for analysis of clinical chemistry parameters including Alanine Aminotransferase (ALT), Albumin, Alkaline Phosphatase (Alk Phos), Aspartate Aminotransferase (AST), Bilirubin, Calcium, Carbon Dioxide, Chloride, Creatine Kinase, Creatinine, Direct Bilirubin, Glucose, Magnesium, Potassium, Protein, Sodium, Blood Urea Nitrogen (BUN). Participants were counted in the worst case category that their value changes to (low, normal or high), unless there was no change in their category. Participants whose lab value category was unchanged (e.g., High to High), or whose value became normal, are recorded in the 'To Normal or No Change' category. Participants were counted twice if the participant had values that changed 'To Low' and 'To High', so the percentages may not add to 100%. High and low indicated that participants had values flagged as high and low respectively for the particular parameter any time on-treatment. (NCT04493931)
Timeframe: Up to 22 days

,,,
InterventionParticipants (Count of Participants)
ALT; To LowALT; To Normal or No ChangeALT; To HighAlbumin; To LowAlbumin; To Normal or No ChangeAlbumin; To HighAlk Phos; To LowAlk Phos; To Normal or No ChangeAlk Phos; To HighAST; To LowAST; To Normal or No ChangeAST; To HighBilirubin; To LowBilirubin; To Normal or No ChangeBilirubin; To HighCalcium; To LowCalcium; To Normal or No ChangeCalcium; To HighCarbon Dioxide; To LowCarbon Dioxide; To Normal or No ChangeCarbon Dioxide; To HighChloride; To LowChloride; To Normal or No ChangeChloride; To HighCreatine Kinase; To LowCreatine Kinase; To Normal or No ChangeCreatine Kinase; To HighCreatinine; To LowCreatinine; To Normal or No ChangeCreatinine;To HighDirect Bilirubin; To LowDirect Bilirubin; To Normal or No ChangeDirect Bilirubin; To HighGlucose; To LowGlucose; To Normal or No ChangeGlucose; To HighMagnesium; To LowMagnesium; To Normal or No ChangeMagnesium; To HighPotassium; To LowPotassium; To Normal or No ChangePotassium; To HighProtein; To LowProtein; To Normal or No ChangeProtein; To HighSodium; To LowSodium; To Normal or No ChangeSodium; To HighBUN; To LowBUN; To Normal or No ChangeBUN; To High
Cohort 4: Gepotidacin 1500 mg Fasted01100110011001100110011011000110011001100110011001100110011001100110
Cohort 4: Gepotidacin 1500 mg Fed01100110011001100110011001100110011001100110011001100110011001100110
Cohort 4: Gepotidacin 3000 mg Fed0110011001100110011001100110011019101100110011001100110011001100110
Cohort 4: Placebo030120030030021030030030120030021030030021030030030

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Cohort 4: Number of Participants With Serious Adverse Events (SAE) and Non-serious Adverse Events (Non-SAE)

An adverse event (AE) is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. An SAE is defined as any serious adverse event that, at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or any other situations as per Medical or scientific judgment. (NCT04493931)
Timeframe: Up to 22 days

,,,
InterventionParticipants (Count of Participants)
Any SAEAny non-SAE
Cohort 4: Gepotidacin 1500 mg Fasted02
Cohort 4: Gepotidacin 1500 mg Fed01
Cohort 4: Gepotidacin 3000 mg Fed04
Cohort 4: Placebo00

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Cohort 4: Number of Participants With Any Increase in Maximum Post-Baseline Electrocardiogram (ECG) Parameter Corrected QT (QTc) Interval

A 12-lead ECG was recorded with the participant in a semi-supine position after a rest of at least 10 minutes using an ECG machine that automatically calculated the QTc interval. Number of participants with any increase of >450 milliseconds in corrected QT interval using the Bazett formula (QTcB) Interval and corrected QT interval using the Fridericia formula (QTcF) Interval has been reported. (NCT04493931)
Timeframe: Up to 22 days

,,,
InterventionParticipants (Count of Participants)
QTcB IntervalQTcF Interval
Cohort 4: Gepotidacin 1500 mg Fasted30
Cohort 4: Gepotidacin 1500 mg Fed81
Cohort 4: Gepotidacin 3000 mg Fed92
Cohort 4: Placebo11

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Cohort 4: Ae(t1-t2) of Gepotidacin in Urine Following Two 3000 mg Doses-Fed State

Urine samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. Ae(t1-t2) measured the amount of drug excreted in urine at defined time intervals. (NCT04493931)
Timeframe: Pre-dose, 0-2 Hours, 2-4 Hours, 4-6 Hours, 6-8 Hours, 8-12 Hours, 12-14 Hours, 14-16 Hours, 16-18 Hours, 18-20 Hours, 20-24 Hours, 24-36 Hours, 36-48 Hours, 48-60 Hours post-dose in Treatment Period 3

InterventionMilligrams (Geometric Mean)
Ae (0-2); n=11Ae (2-4); n=10Ae (4-6); n=11Ae (6-8); n=11Ae (8-12); n=11Ae (12-14); n=11Ae (14-16); n=11Ae (16-18); n=11Ae (18-20); n=11Ae (20-24); n=11Ae (24-36); n=11Ae (36-48); n=11Ae (48-60); n=10
Cohort 4: Gepotidacin 3000 mg FedNA221.19103.6867.5865.06112.83174.62136.6690.8180.5457.6214.479.67

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Cohort 4: Ae(t1-t2) of Gepotidacin Following Single Dose of 1500 mg Under Fed Condition in Urine

Urine samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. Ae(t1-t2) measured the amount of drug excreted in urine at defined time intervals. (NCT04493931)
Timeframe: Pre-dose, 0-2 Hours, 2-4 Hours, 4-6 Hours, 6-8 Hours, 8-12 Hours, 12-24 Hours, 24-36 Hours, 36-48 Hours post-dose in each Treatment Periods 1 and 2

InterventionMilligrams (Geometric Mean)
Ae (0-2)Ae (2-4)Ae (4-6)Ae (6-8)Ae (8-12)Ae (12-24)Ae (24-36)Ae (36-48)
Cohort 4: Gepotidacin 1500 mg FedNA102.2360.0531.6116.5117.165.724.28

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Cohort 3: Number of Participants With Worst Case Vital Sign Results Relative to Normal Range Post-Baseline Relative to Baseline

Vital signs including SBP, DBP and pulse rate were measured in a semi-supine position after 5 minutes rest. Participants were counted in the worst case category that their value changes to (low, normal or high), unless there was no change in their category. Participants whose value category was unchanged (e.g., High to High), or whose value became normal, were recorded in the 'To Normal or No Change' category. Participants were counted twice if the participant had values that changed 'To Low' and 'To High', so the percentages may not add to 100%. High and low indicated that participants had values flagged as high and low respectively for the particular parameter any time on-treatment. (NCT04493931)
Timeframe: Up to 30 days

,
InterventionParticipants (Count of Participants)
DBP; To LowDBP; To Normal or No ChangeDBP; To HighSBP; To LowSBP; To Normal or No ChangeSBP; To HighPulse rate; To LowPulse rate; To Normal or No ChangePulse rate; To High
Cohort 3: Digoxin 0.5 mg + Midazolam 2 mg019001900190
Cohort 3:Gepotidacin 3000 mg + Digoxin 0.5 mg + Midazolam 2 mg018001800180

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Cohort 3: Number of Participants With Worst Case Urinalysis Results Relative to Normal Range Post-Baseline Relative to Baseline

Urine samples were collected at indicated time points for the analysis of urinalysis parameters including pH of urine, presence of glucose, protein, blood, ketones, bilirubin, nitrite, leukocyte esterase in urine by dipstick. Specific gravity of urine was measured by microscopic examination. Participants were counted in the worst case category that their value changes to (low, normal, high, or abnormal), unless there is no change in their category. Participants whose lab value category was unchanged (e.g., High to High), or whose value became normal, are recorded in the 'To Normal or No Change' category. Participants were counted twice if the participant has values that changed 'To Low' and 'To High', so the percentages may not add to 100%. High and low indicated that participants had values flagged as high and low respectively for the particular parameter any time on-treatment. (NCT04493931)
Timeframe: Up to 30 days

,
InterventionParticipants (Count of Participants)
Bilirubin; To Normal or No ChangeBilirubin; To AbnormalGlucose; To Normal or No ChangeGlucose; To AbnormalKetones; To Normal or No ChangeKetones; To AbnormalLeukocyte Esterase; To Normal or No ChangeLeukocyte Esterase; To AbnormalNitrite; To Normal or No ChangeNitrite; To AbnormalOccult Blood; To Normal or No ChangeOccult Blood; To AbnormalProtein; To Normal or No ChangeProtein; To AbnormalpH; To LowpH; To Normal or No ChangepH; To HighSpecific Gravity; To LowSpecific Gravity; To Normal or No ChanSpecific Gravity; To High
Cohort 3: Digoxin 0.5 mg + Midazolam 2 mg19019016313619014516301900163
Cohort 3:Gepotidacin 3000 mg + Digoxin 0.5 mg + Midazolam 2 mg18018017113518013516201800108

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Cohort 3: Number of Participants With Worst Case Hematology Results Relative to Normal Range Post-Baseline Relative to Baseline

Blood samples were collected at indicated time points for analysis of hematology parameters including Basophils, Eosinophils, MCH, MCV, Erythrocytes, Hematocrit, Hemoglobin, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets. Participants were counted in the worst case category that their value changes to (low, normal or high), unless there was no change in their category. Participants whose lab value category was unchanged (e.g., High to High), or whose value became normal, are recorded in the 'To Normal or No Change' category. Participants were counted twice if the participant had values that changed 'To Low' and 'To High', so the percentages may not add to 100%. High and low indicated that participants had values flagged as high and low respectively for the particular parameter any time on-treatment. (NCT04493931)
Timeframe: Up to 30 days

,
InterventionParticipants (Count of Participants)
Basophils; To LowBasophils; To Normal or No ChangeBasophils; To HighEosinophils; To LowEosinophils; To Normal or No ChangeEosinophils; To HighMCH; To LowMCH; To Normal or No ChangeMCH; To HighMCV; To LowMCV; To Normal or No ChangeMCV; To HighErythrocytes; To LowErythrocytes; To Normal or No ChangeErythrocytes; To HighHematocrit; To LowHematocrit; To Normal or No ChangeHematocrit; To HighHemoglobin; To LowHemoglobin; To Normal or No ChangeHemoglobin; To HighLeukocytes; To LowLeukocytes; To Normal or No ChangeLeukocytes; To HighLymphocytes; To LowLymphocytes; To Normal or No ChangeLymphocytes; To HighMonocytes; To LowMonocytes; To Normal or No ChangeMonocytes; To HighNeutrophils; To LowNeutrophils; To Normal or No ChangeNeutrophils; To HighPlatelets; To LowPlatelets; To Normal or No ChangePlatelets; To High
Cohort 3: Digoxin 0.5 mg + Midazolam 2 mg019001900190018121701171018101900190018101900190
Cohort 3:Gepotidacin 3000 mg + Digoxin 0.5 mg + Midazolam 2 mg018001620180018011702142115201710171117001710180

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Cohort 3: Number of Participants With Worst Case Clinical Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline

Blood samples were collected at indicated time points for analysis of clinical chemistry parameters including ALT, Albumin, Alk Phos, AST, Bilirubin, Calcium, Carbon Dioxide, Chloride, Creatine Kinase, Creatinine, Direct Bilirubin, Glucose, Magnesium, Potassium, Protein, Sodium, BUN. Participants were counted in the worst case category that their value changes to (low, normal or high), unless there was no change in their category. Participants whose lab value category was unchanged (e.g., High to High), or whose value became normal, are recorded in the 'To Normal or No Change' category. Participants were counted twice if the participant had values that changed 'To Low' and 'To High', so the percentages may not add to 100%. High and low indicated that participants had values flagged as high and low respectively for the particular parameter any time on-treatment. (NCT04493931)
Timeframe: Up to 30 days

,
InterventionParticipants (Count of Participants)
ALT; To LowALT; To Normal or No ChangeALT; To HighAlbumin; To LowAlbumin; To Normal or No ChangeAlbumin; To HighAlk Phos; To LowAlk Phos; To Normal or No ChangeAlk Phos; To HighAST; To LowAST; To Normal or No ChangeAST; To HighBilirubin; To LowBilirubin; To Normal or No ChangeBilirubin; To HighCalcium; To LowCalcium; To Normal or No ChangeCalcium; To HighCarbon Dioxide; To LowCarbon Dioxide; To Normal or No ChangeCarbon Dioxide; To HighChloride; To LowChloride; To Normal or No ChangeChloride; To HighCreatine Kinase; To LowCreatine Kinase; To Normal or No ChangeCreatine Kinase; To HighCreatinine; To LowCreatinine; To Normal or No ChangeCreatinine; To HighDirect Bilirubin; To LowDirect Bilirubin; To Normal or No ChangeDirect Bilirubin; To HighGlucose; To LowGlucose; To Normal or No ChangeGlucose; To HighMagnesium; To LowMagnesium; To Normal or No ChangeMagnesium; To HighPotassium; To LowPotassium; To Normal or No ChangePotassium; To HighProtein; To LowProtein; To Normal or No ChangeProtein; To HighSodium; To LowSodium; To Normal or No ChangeSodium; To HighBUN; To LowBUN; To Normal or No ChangeBUN; To High
Cohort 3: Digoxin 0.5 mg + Midazolam 2 mg01901180019001810190118001900190018101900190019001900181019001900190
Cohort 3:Gepotidacin 3000 mg + Digoxin 0.5 mg + Midazolam 2 mg01710171018001800180117001800171018001800180018001800180018001801170

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Cohort 3: AUC(0-24) of Gepotidacin in Urine Following Two 3000 mg Doses (First Dose + Second Dose)

Urine samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. (NCT04493931)
Timeframe: Pre-dose, 0-2 Hours, 2-4 Hours, 4-6 Hours, 6-8 Hours, 8-12 Hours, 12-14 Hours, 14-16 Hours, 16-18 Hours, 18-20 Hours, 20-24 Hours post-dose in each Treatment Periods 1 and 2

InterventionHours*micrograms per milliliter (Geometric Mean)
Cohort 3:Gepotidacin 3000 mg + Digoxin 0.5 mg + Midazolam 2 mg14333.9

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Cohort 4: Ae Total of Gepotidacin Following Single Dose of 1500 mg Under Fed Condition in Urine

Urine samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. Ae total was calculated by adding all the fractions of drug collected over all the allotted time intervals. (NCT04493931)
Timeframe: Pre-dose, 0-2 Hours, 2-4 Hours, 4-6 Hours, 6-8 Hours, 8-12 Hours, 12-24 Hours, 24-36 Hours, 36-48 Hours post-dose in each Treatment Periods 1 and 2

InterventionMilligrams (Geometric Mean)
Cohort 4: Gepotidacin 1500 mg Fed293.50

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Cohort 3: Number of Participants With SAE and Non-SAE

An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. An SAE is defined as any serious adverse event that, at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or any other situations as per Medical or scientific judgment. (NCT04493931)
Timeframe: Up to 30 days

,
InterventionParticipants (Count of Participants)
Any SAEAny non-SAE
Cohort 3: Digoxin 0.5 mg + Midazolam 2 mg01
Cohort 3:Gepotidacin 3000 mg + Digoxin 0.5 mg + Midazolam 2 mg011

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Cohort 3: Number of Participants With Any Increase in Maximum Post-Baseline ECG Parameter QTc Interval

A 12-lead ECG was recorded with the participant in a semi-supine position after a rest of at least 10 minutes using an ECG machine that automatically calculated the QTc interval. Number of participants with any increase of >450 milliseconds in corrected QT interval using the QTcB Interval and QTcF Interval has been reported. (NCT04493931)
Timeframe: Up to 30 days

,
InterventionParticipants (Count of Participants)
QTcB IntervalQTcF Interval
Cohort 3: Digoxin 0.5 mg + Midazolam 2 mg20
Cohort 3:Gepotidacin 3000 mg + Digoxin 0.5 mg + Midazolam 2 mg50

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Cohort 3: Amount of Drug Excreted in Urine in a Time Interval (Ae[t1-t2]) of Gepotidacin Following Two 3000 mg Doses (First Dose + Second Dose)

Urine samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. Ae(t1-t2) measured the amount of drug excreted in urine at defined time intervals. (NCT04493931)
Timeframe: Pre-dose, 0-2 Hours, 2-4 Hours, 4-6 Hours, 6-8 Hours, 8-12 Hours, 12-14 Hours, 14-16 Hours, 16-18 Hours, 18-20 Hours, 20-24 Hours, 24-36 Hours, 36-48 Hours, 48-60 Hours post-dose in each Treatment Periods 1 and 2

InterventionMilligrams (Geometric Mean)
Ae (0-2), n=17Ae (2-4), n=18Ae (4-6), n=16Ae (6-8); n=16Ae (8-12), n=18Ae (12-14), n=17Ae (14-16), n=15Ae (16-18), n=14Ae (18-20), n=15Ae (20-24), n=17Ae (24-36), n=18Ae (36-48); n=18Ae (48-60), n=18
Cohort 3:Gepotidacin 3000 mg + Digoxin 0.5 mg + Midazolam 2 mgNA117.61103.1170.9867.4264.49142.36146.8993.0574.4470.0120.168.51

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Cohort 2: Number of Participants With Worst Case Vital Sign Results Relative to Normal Range Post-Baseline Relative to Baseline

Vital signs including SBP, DBP and pulse rate were measured in a semi-supine position after 5 minutes rest. Participants were counted in the worst case category that their value changes to (low, normal or high), unless there was no change in their category. Participants whose value category was unchanged (e.g., High to High), or whose value became normal, were recorded in the 'To Normal or No Change' category. Participants were counted twice if the participant had values that changed 'To Low' and 'To High', so the percentages may not add to 100%. High and low indicated that participants had values flagged as high and low respectively for the particular parameter any time on-treatment. (NCT04493931)
Timeframe: Up to 26 days

,
InterventionParticipants (Count of Participants)
DBP; To LowDBP; To Normal or No ChangeDBP; To HighSBP; To LowSBP; To Normal or No ChangeSBP; To HighPulse rate; To LowPulse rate; To Normal or No ChangePulse rate; To High
Cohort 2: Period 1: Gepotidacin 1500 mg016101700170
Cohort 2: Period 2: Gepotidacin 1500 mg + Rifampicin 600 mg014001400140

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Cohort 2: Number of Participants With Worst Case Urinalysis Results Relative to Normal Range Post-Baseline Relative to Baseline

Urine samples were collected at indicated time points for the analysis of urinalysis parameters including pH of urine, presence of glucose, protein, blood, ketones, bilirubin, nitrite, leukocyte esterase in urine by dipstick. Specific gravity of urine was measured by microscopic examination. Participants were counted in the worst case category that their value changes to (low, normal, high, or abnormal), unless there is no change in their category. Participants whose lab value category was unchanged (e.g., High to High), or whose value became normal, are recorded in the 'To Normal or No Change' category. Participants were counted twice if the participant has values that changed 'To Low' and 'To High', so the percentages may not add to 100%. High and low indicated that participants had values flagged as high and low respectively for the particular parameter any time on-treatment. (NCT04493931)
Timeframe: Up to 26 days

,
InterventionParticipants (Count of Participants)
Bilirubin; To Normal or No ChangeBilirubin; To AbnormalGlucose; To Normal or No ChangeGlucose; To AbnormalKetones; To Normal or No ChangeKetones; To AbnormalLeukocyte Esterase; To Normal or No ChangeLeukocyte Esterase; To AbnormalNitrite; To Normal or No ChangeNitrite; To AbnormalOccult Blood; To Normal or No ChangeOccult Blood; To AbnormalProtein; To Normal or No ChangeProtein; To AbnormalpH; To LowpH; To Normal or No ChangepH; To HighSpecific Gravity; To LowSpecific Gravity; To Normal or No ChangeSpecific Gravity; To High
Cohort 2: Period 1: Gepotidacin 1500 mg17017017016117017017001700143
Cohort 2: Period 2: Gepotidacin 1500 mg + Rifampicin 600 mg16016016014215114216001600151

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Cohort 2: Number of Participants With Worst Case Hematology Results Relative to Normal Range Post-Baseline Relative to Baseline

Blood samples were collected at indicated time points for analysis of hematology parameters including Basophils, Eosinophils, MCH, MCV, Erythrocytes, Hematocrit, Hemoglobin, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets. Participants were counted in the worst case category that their value changes to (low, normal or high), unless there was no change in their category. Participants whose lab value category was unchanged (e.g., High to High), or whose value became normal, are recorded in the 'To Normal or No Change' category. Participants were counted twice if the participant had values that changed 'To Low' and 'To High', so the percentages may not add to 100%. High and low indicated that participants had values flagged as high and low respectively for the particular parameter any time on-treatment. (NCT04493931)
Timeframe: Up to 26 days

,
InterventionParticipants (Count of Participants)
Basophils; To LowBasophils; To Normal or No ChangeBasophils; To HighEosinophils; To LowEosinophils; To Normal or No ChangeEosinophils; To HighMCH; To LowMCH; To Normal or No ChangeMCH; To HighMCV; To LowMCV; To Normal or No ChangeMCV; To HighErythrocytes; To LowErythrocytes; To Normal or No ChangeErythrocytes; To HighHematocrit; To LowHematocrit; To Normal or No ChangeHematocrit; To HighHemoglobin; To LowHemoglobin; To Normal or No ChangeHemoglobin; To HighLeukocytes; To LowLeukocytes; To Normal or No ChangeLeukocytes; To HighLymphocytes; To LowLymphocytes; To Normal or No ChangeLymphocytes; To HighMonocytes; To LowMonocytes; To Normal or No ChangeMonocytes; To HighNeutrophils; To LowNeutrophils; To Normal or No ChangeNeutrophils; To HighPlatelets; To LowPlatelets; To Normal or No ChangePlatelets; To High
Cohort 2: Period 1: Gepotidacin 1500 mg017001520170017001700143017001700170115101700170
Cohort 2: Period 2: Gepotidacin 1500 mg + Rifampicin 600 mg016101430170017001700152017011600152314041300161

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Cohort 2: Number of Participants With Worst Case Clinical Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline

Blood samples were collected at indicated time points for analysis of clinical chemistry parameters including ALT, Albumin, Alk Phos, AST, Bilirubin, Calcium, Carbon Dioxide, Chloride, Creatine Kinase, Creatinine, Direct Bilirubin, Glucose, Magnesium, Potassium, Protein, Sodium, BUN. Participants were counted in the worst case category that their value changes to (low, normal or high), unless there was no change in their category. Participants whose lab value category was unchanged (e.g., High to High), or whose value became normal, are recorded in the 'To Normal or No Change' category. Participants were counted twice if the participant had values that changed 'To Low' and 'To High', so the percentages may not add to 100%. High and low indicated that participants had values flagged as high and low respectively for the particular parameter any time on-treatment. (NCT04493931)
Timeframe: Up to 26 days

,
InterventionParticipants (Count of Participants)
ALT; To LowALT; To Normal or No ChangeALT; To HighAlbumin; To LowAlbumin; To Normal or No ChangeAlbumin; To HighAlk Phos; To LowAlk Phos; To Normal or No ChangeAlk Phos; To HighAST; To LowAST; To Normal or No ChangeAST; To HighBilirubin; To LowBilirubin; To Normal or No ChangeBilirubin; To HighCalcium; To LowCalcium; To Normal or No ChangeCalcium; To HighCarbon Dioxide; To LowCarbon Dioxide; To Normal or No ChangeCarbon Dioxide; To HighChloride; To LowChloride; To Normal or No ChangeChloride; To HighCreatine Kinase; To LowCreatine Kinase; To Normal or No ChangeCreatine Kinase; To HighCreatinine; To LowCreatinine; To Normal or No ChangeCreatinine; To HighDirect Bilirubin; To LowDirect Bilirubin; To Normal or No ChangeDirect Bilirubin; To HighGlucose; To LowGlucose; To Normal or No ChangeGlucose; To HighMagnesium; To LowMagnesium; To Normal or No ChangeMagnesium; To HighPotassium; To LowPotassium; To Normal or No ChangePotassium; To HighProtein; To LowProtein; To Normal or No ChangeProtein; To HighSodium; To LowSodium; To Normal or No ChangeSodium; To HighBUN; To LowBUN; To Normal or No ChangeBUN; To High
Cohort 2: Period 1: Gepotidacin 1500 mg01700170017001700170017001700170017001610170017001700161017001700170
Cohort 2: Period 2: Gepotidacin 1500 mg + Rifampicin 600 mg01520170017001612150017031400170017001610170016101700152017001700170

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Cohort 2: Number of Participants With SAE and Non-SAE

An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. An SAE is defined as any serious adverse event that, at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or any other situations as per Medical or scientific judgment. (NCT04493931)
Timeframe: Up to 26 days

,,
InterventionParticipants (Count of Participants)
Any SAEAny non-SAE
Cohort 2: Period 1: Gepotidacin 1500 mg03
Cohort 2: Period 2 (Days 1 to 7) Rifampicin 600 mg02
Cohort 2: Period 2 (Days 8 to 9) Gepotidacin 1500 mg + Rifampicin 600 mg02

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Cohort 4: Vz/F of Gepotidacin in Plasma Following Two 3000 mg Doses (First Dose + Second Dose)-Fed State

Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. (NCT04493931)
Timeframe: Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3, 4, 6, 8, 12 Hours, 12 Hours 30 minutes, 13 Hours, 13 Hours 30 minutes, 14 Hours, 14 Hours 30 minutes, 15, 16, 18, 20, 24, 36, 48, 60 Hours post-dose in Treatment Period 3

InterventionLiters (Geometric Mean)
Cohort 4: Gepotidacin 3000 mg Fed1251.05

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Cohort 2: Number of Participants With Any Increase in Maximum Post-Baseline ECG Parameter QTc Interval

A 12-lead ECG was recorded with the participant in a semi-supine position after a rest of at least 10 minutes using an ECG machine that automatically calculated the QTc interval. Number of participants with any increase of >450 milliseconds in corrected QT interval using the QTcB Interval and QTcF Interval has been reported. (NCT04493931)
Timeframe: Up to 26 days

,
InterventionParticipants (Count of Participants)
QTcB IntervalQTcF Interval
Cohort 2: Period 1: Gepotidacin 1500 mg20
Cohort 2: Period 2: Gepotidacin 1500 mg + Rifampicin 600 mg21

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Cohort 2: Ae(t1-t2) of Gepotidacin

Urine samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. Ae(t1-t2) measured the amount of drug excreted in urine at defined time intervals. (NCT04493931)
Timeframe: 0-2 Hours, 2-4 Hours, 4-6 Hours, 6-8 Hours, 8-12 Hours, 12-24 Hours, 24-36 Hours, 36-48 Hours post-dose in each Treatment Periods 1 and 2

,
InterventionMilligrams (Geometric Mean)
Ae (0-2)Ae (2-4)Ae (4-6)Ae (6-8)Ae (8-12)Ae (12-24)Ae (24-36)Ae (36-48)
Cohort 2: Period 2: Gepotidacin 1500 mg + Rifampicin 600 mgNA55.8121.6613.829.1911.514.742.75
Cohort 2:Period 1: Gepotidacin 1500 mg12.6779.8467.4833.9227.5921.1711.043.61

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Cohort 1: Number of Participants With Worst Case Vital Sign Results Relative to Normal Range Post-Baseline Relative to Baseline

Vital signs including SBP, DBP and pulse rate were measured in a semi-supine position after 5 minutes rest. Participants were counted in the worst case category that their value changes to (low, normal or high), unless there was no change in their category. Participants whose value category was unchanged (e.g., High to High), or whose value became normal, were recorded in the 'To Normal or No Change' category. Participants were counted twice if the participant had values that changed 'To Low' and 'To High', so the percentages may not add to 100%. High and low indicated that participants had values flagged as high and low respectively for the particular parameter any time on-treatment. (NCT04493931)
Timeframe: Up to 17 days

,
InterventionParticipants (Count of Participants)
DBP; To LowDBP; To Normal or No ChangeDBP; To HighSBP; To LowSBP; To Normal or No ChangeSBP; To HighPulse rate; To LowPulse rate; To Normal or No ChangePulse rate; To High
Cohort 1: Gepotidacin 1500 mg014001400140
Cohort 1: Gepotidacin 1500 mg + Cimetidine 400 mg013001300130

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Cohort 1: Number of Participants With Worst Case Urinalysis Results Relative to Normal Range Post-Baseline Relative to Baseline

Urine samples were collected at indicated time points for the analysis of urinalysis parameters including pH of urine, presence of glucose, protein, blood, ketones, bilirubin, nitrite, leukocyte esterase in urine by dipstick. Specific gravity of urine was measured by microscopic examination. Participants were counted in the worst case category that their value changes to (low, normal, high, or abnormal), unless there is no change in their category. Participants whose lab value category was unchanged (e.g., High to High), or whose value became normal, are recorded in the 'To Normal or No Change' category. Participants were counted twice if the participant has values that changed 'To Low' and 'To High', so the percentages may not add to 100%. High and low indicated that participants had values flagged as high and low respectively for the particular parameter any time on-treatment. (NCT04493931)
Timeframe: Up to 17 days

,
InterventionParticipants (Count of Participants)
Bilirubin; To Normal or No ChangeBilirubin; To AbnormalGlucose; To Normal or No ChangeGlucose; To AbnormalKetones; To Normal or No ChangeKetones; To AbnormalLeukocyte Esterase; To Normal or No ChangeLeukocyte Esterase; To AbnormalNitrite; To Normal or No ChangeNitrite; To AbnormalOccult Blood; To Normal or No ChangeOccult Blood; To AbnormalProtein; To Normal or No ChangeProtein; To AbnormalpH; To LowpH; To Normal or No ChangepH; To HighSpecific Gravity; To LowSpecific Gravity; To Normal or No ChangeSpecific Gravity; To High
Cohort 1: Gepotidacin 1500 mg14014014012214013114001400131
Cohort 1: Gepotidacin 1500 mg + Cimetidine 400 mg13013013013013011213001300130

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Cohort 1: Number of Participants With Worst Case Hematology Results Relative to Normal Range Post-Baseline Relative to Baseline

Blood samples were collected at indicated time points for analysis of hematology parameters including Basophils, Eosinophils, MCH, MCV, Erythrocytes, Hematocrit, Hemoglobin, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets. Participants were counted in the worst case category that their value changes to (low, normal or high), unless there was no change in their category. Participants whose lab value category was unchanged (e.g., High to High), or whose value became normal, are recorded in the 'To Normal or No Change' category. Participants were counted twice if the participant had values that changed 'To Low' and 'To High', so the percentages may not add to 100 %. High and low indicated that participants had values flagged as high and low respectively for the particular parameter any time on-treatment. (NCT04493931)
Timeframe: Up to 17 days

,
InterventionParticipants (Count of Participants)
Basophils; To LowBasophils; To Normal or No ChangeBasophils; To HighEosinophils; To LowEosinophils; To Normal or No ChangeEosinophils; To HighMCH; To LowMCH; To Normal or No ChangeMCH; To HighMCV; To LowMCV; To Normal or No ChangeMCV; To HighErythrocytes; To LowErythrocytes; To Normal or No ChangeErythrocytes; To HighHematocrit; To LowHematocrit; To Normal or No ChangeHematocrit; To HighHemoglobin; To LowHemoglobin; To Normal or No ChangeHemoglobin; To HighLeukocytes; To LowLeukocytes; To Normal or No ChangeLeukocytes; To HighLymphocytes; To LowLymphocytes; To Normal or No ChangeLymphocytes; To HighMonocytes; To LowMonocytes; To Normal or No ChangeMonocytes; To HighNeutrophils; To LowNeutrophils; To Normal or No ChangeNeutrophils; To HighPlatelets; To LowPlatelets; To Normal or No ChangePlatelets; To High
Cohort 1: Gepotidacin 1500 mg014001400140013101400131014001310140013101310140
Cohort 1: Gepotidacin 1500 mg + Cimetidine 400 mg011201300130013021101120013001300121013011200130

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Cohort 1: Number of Participants With Worst Case Clinical Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline

Blood samples were collected at indicated time points for analysis of clinical chemistry parameters including ALT, Albumin, Alk Phos, AST, Bilirubin, Calcium, Carbon Dioxide, Chloride, Creatine Kinase, Creatinine, Direct Bilirubin, Glucose, Magnesium, Potassium, Protein, Sodium, BUN. Participants were counted in the worst case category that their value changes to (low, normal or high), unless there was no change in their category. Participants whose lab value category was unchanged (e.g., High to High), or whose value became normal, are recorded in the 'To Normal or No Change' category. Participants were counted twice if the participant had values that changed 'To Low' and 'To High', so the percentages may not add to 100%. High and low indicated that participants had values flagged as high and low respectively for the particular parameter any time on-treatment. (NCT04493931)
Timeframe: Up to 17 days

,
InterventionParticipants (Count of Participants)
ALT; To LowALT; To Normal or No ChangeALT; To HighAlbumin; To LowAlbumin; To Normal or No ChangeAlbumin; To HighAlk Phos; To LowAlk Phos; To Normal or No ChangeAlk Phos; To HighAST; To LowAST; To Normal or No ChangeAST; To HighBilirubin; To LowBilirubin; To Normal or No ChangeBilirubin; To HighCalcium; To LowCalcium; To Normal or No ChangeCalcium; To HighCarbon Dioxide; To LowCarbon Dioxide; To Normal or No ChangeCarbon Dioxide; To HighChloride; To LowChloride; To Normal or No ChangeChloride; To HighCreatine Kinase; To LowCreatine Kinase; To Normal or No ChangeCreatine Kinase; To HighCreatinine; To LowCreatinine; To Normal or No ChangeCreatinine; To HighDirect Bilirubin; To LowDirect Bilirubin; To Normal or No ChangeDirect Bilirubin; To HighGlucose; To LowGlucose; To Normal or No ChangeGlucose; To HighMagnesium; To LowMagnesium; To Normal or No ChangeMagnesium; To HighPotassium; To LowPotassium; To Normal or No ChangePotassium; To HighProtein; To LowProtein; To Normal or No ChangeProtein; To HighSodium; To LowSodium; To Normal or No ChangeSodium; To HighBUN; To LowBUN; To Normal or No ChangeBUN; To High
Cohort 1: Gepotidacin 1500 mg01400140014001400140014011300140113001400140014001400140014001400140
Cohort 1: Gepotidacin 1500 mg + Cimetidine 400 mg01121120013001211120013001300121013001030130013001300121013001300130

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Cohort 1: Number of Participants With SAE and Non-SAE

An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. An SAE is defined as any serious adverse event that, at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or any other situations as per Medical or scientific judgment. (NCT04493931)
Timeframe: Up to 17 days

,
InterventionParticipants (Count of Participants)
Any SAEAny non-SAE
Cohort 1: Gepotidacin 1500 mg00
Cohort 1: Gepotidacin 1500 mg + Cimetidine 400 mg00

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Cohort 1: Number of Participants With Any Increase in Maximum Post-Baseline ECG Parameter QTc Interval

A 12-lead ECG was recorded with the participant in a semi-supine position after a rest of at least 10 minutes using an ECG machine that automatically calculated the QTc interval. Number of participants with any increase of >450 milliseconds in corrected QT interval using the QTcB Interval and QTcF Interval has been reported. (NCT04493931)
Timeframe: Up to 17 days

,
InterventionParticipants (Count of Participants)
QTcB IntervalQTcF Interval
Cohort 1: Gepotidacin 1500 mg30
Cohort 1: Gepotidacin 1500 mg + Cimetidine 400 mg41

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Cohort 1: Amount of Drug Excreted in Urine in a Time Interval (Ae[t1-t2]) of Gepotidacin

Urine samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. Ae(t1-t2) measured the amount of drug excreted in urine at defined time intervals. (NCT04493931)
Timeframe: 0-2 Hours, 2-4 Hours, 4-6 Hours, 6-8 Hours, 8-12 Hours, 12-24 Hours, 24-36 Hours, 36-48 Hours post-dose in each Treatment periods 1 and 2

,
InterventionMilligrams (Geometric Mean)
Ae (0-2), n=14, 13Ae (2-4), n=14, 12Ae (4-6), n=14, 13Ae (6-8); n=14, 13Ae (8-12), n=12, 13Ae (12-24), n=14, 13Ae (24-36), n=14, 13Ae (36-48), n=14, 13
Cohort 1: Gepotidacin 1500 mg28.6689.1850.5234.3829.9025.4410.884.50
Cohort 1: Gepotidacin 1500 mg + Cimetidine 400 mgNA142.9982.7746.2230.9722.048.764.08

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Cohort 4: Vz/F of Gepotidacin Following Single Dose of 1500 mg in Plasma

Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. (NCT04493931)
Timeframe: Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hour, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours, 36 Hours, 48 Hours post-dose in each Treatment Periods 1 and 2

InterventionLiters (Geometric Mean)
Cohort 4: Gepotidacin 1500 mg Fed1246.70
Cohort 4: Gepotidacin 1500 mg Fasted1329.83

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Cohort 4: Tmax of Gepotidacin in Plasma After the Second Dose of 3000 mg (Second Dose)-Fed State

Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. (NCT04493931)
Timeframe: Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3, 4, 6, 8, 12 Hours, 12 Hours 30 minutes, 13 Hours, 13 Hours 30 minutes, 14 Hours, 14 Hours 30 minutes, 15, 16, 18, 20, 24, 36, 48, 60 Hours post-dose in Treatment Period 3

InterventionHours (Median)
Cohort 4: Gepotidacin 3000 mg Fed2.000

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Cohort 4: Tmax of Gepotidacin in Plasma After the First Dose of 3000 mg -Fed State

Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. (NCT04493931)
Timeframe: Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3, 4, 6, 8, 12 Hours, 12 Hours 30 minutes, 13 Hours, 13 Hours 30 minutes, 14 Hours, 14 Hours 30 minutes, 15, 16, 18, 20, 24, 36, 48, 60 Hours post-dose in Treatment Period 3

InterventionHours (Median)
Cohort 4: Gepotidacin 3000 mg Fed2.000

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Cohort 4: Tmax of Gepotidacin Following Single Dose of 1500 mg in Plasma - Food Effect in Japanese Participants

Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. (NCT04493931)
Timeframe: Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hour, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours, 36 Hours, 48 Hours post-dose in each Treatment Periods 1 and 2

InterventionHours (Median)
Cohort 4: Gepotidacin 1500 mg Fed2.000
Cohort 4: Gepotidacin 1500 mg Fasted1.500

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Cohort 4: Tmax of Gepotidacin Following Single Dose of 1500 mg in Plasma

Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. (NCT04493931)
Timeframe: Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hour, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours, 36 Hours, 48 Hours post-dose in each Treatment Periods 1 and 2

InterventionHours (Median)
Cohort 4: Gepotidacin 1500 mg Fed2.000
Cohort 4: Gepotidacin 1500 mg Fasted1.500

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Cohort 4: Tlag of Gepotidacin in Plasma After the First Dose of 3000 mg (First Dose)-Fed State

Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. (NCT04493931)
Timeframe: Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3, 4, 6, 8, 12 Hours, 12 Hours 30 minutes, 13 Hours, 13 Hours 30 minutes, 14 Hours, 14 Hours 30 minutes, 15, 16, 18, 20, 24, 36, 48, 60 Hours post-dose in Treatment Period 3

InterventionHours (Median)
Cohort 4: Gepotidacin 3000 mg Fed0

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Cohort 4: Tlag of Gepotidacin Following Single Dose of 1500 mg in Plasma - Food Effect in Japanese Participants

Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. (NCT04493931)
Timeframe: Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hour, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours, 36 Hours, 48 Hours post-dose in each Treatment Periods 1 and 2

InterventionHours (Median)
Cohort 4: Gepotidacin 1500 mg Fed0.000
Cohort 4: Gepotidacin 1500 mg Fasted0.000

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Cohort 4: T1/2 of Gepotidacin in Plasma Following Two 3000 mg Doses (First Dose + Second Dose )-Fed State

Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. (NCT04493931)
Timeframe: Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3, 4, 6, 8, 12 Hours, 12 Hours 30 minutes, 13 Hours, 13 Hours 30 minutes, 14 Hours, 14 Hours 30 minutes, 15, 16, 18, 20, 24, 36, 48, 60 Hours post-dose in Treatment Period 3

InterventionHours (Geometric Mean)
Cohort 4: Gepotidacin 3000 mg Fed12.599

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Cohort 4: T1/2 of Gepotidacin Following Single Dose of 1500 mg in Plasma

Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. (NCT04493931)
Timeframe: Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hour, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours, 36 Hours, 48 Hours post-dose in each Treatment Periods 1 and 2

InterventionHours (Geometric Mean)
Cohort 4: Gepotidacin 1500 mg Fed12.848
Cohort 4: Gepotidacin 1500 mg Fasted12.540

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Cohort 4: Percentage of the Given Dose of Drug Excreted in Urine (fe%) of Gepotidacin Following Two 3000 mg Doses-Fed State

Urine samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. fe% was calculated as: (Ae total divided by Dose) multiplied by 100 %. (NCT04493931)
Timeframe: Pre-dose, 0-2 Hours, 2-4 Hours, 4-6 Hours, 6-8 Hours, 8-12 Hours, 12-14 Hours, 14-16 Hours, 16-18 Hours, 18-20 Hours, 20-24 Hours, 24-36 Hours, 36-48 Hours, 48-60 Hours post-dose in Treatment Period 3

InterventionPercent dose excreted (Geometric Mean)
Cohort 4: Gepotidacin 3000 mg Fed22.24

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Cohort 4: Percentage of the Given Dose of Drug Excreted in Urine (fe%) for Gepotidacin 1500 mg Under Fed Condition

Urine samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. fe% was calculated as: (Ae total divided by Dose) multiplied by 100%. (NCT04493931)
Timeframe: Pre-dose, 0-2 Hours, 2-4 Hours, 4-6 Hours, 6-8 Hours, 8-12 Hours, 12-24 Hours, 24-36 Hours, 36-48 Hours post-dose in each Treatment Periods 1 and 2

InterventionPercent dose excreted (Geometric Mean)
Cohort 4: Gepotidacin 1500 mg Fed19.57

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Cohort 4: Cmax of Gepotidacin in Plasma After the Second Dose of 3000 mg (Second Dose)-Fed State

Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. (NCT04493931)
Timeframe: Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3, 4, 6, 8, 12 Hours, 12 Hours 30 minutes, 13 Hours, 13 Hours 30 minutes, 14 Hours, 14 Hours 30 minutes, 15, 16, 18, 20, 24, 36, 48, 60 Hours post-dose in Treatment Period 3

InterventionMicrograms per milliliter (Geometric Mean)
Cohort 4: Gepotidacin 3000 mg Fed12.363

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Cohort 4: Cmax of Gepotidacin in Plasma After the First Dose of 3000 mg -Fed State

Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. (NCT04493931)
Timeframe: Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3, 4, 6, 8, 12 Hours, 12 Hours 30 minutes, 13 Hours, 13 Hours 30 minutes, 14 Hours, 14 Hours 30 minutes, 15, 16, 18, 20, 24, 36, 48, 60 Hours post-dose in Treatment Period 3

InterventionMicrograms per milliliter (Geometric Mean)
Cohort 4: Gepotidacin 3000 mg Fed11.204

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Cohort 4: Cmax of Gepotidacin Following Single Dose of 1500 mg in Plasma - Food Effect in Japanese Participants

Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. Analysis was performed using a linear mixed-effect model with treatment as a fixed effect and participant as a random effect. Geometric LS mean and 90 % CI of the geometric LS means have been presented. (NCT04493931)
Timeframe: Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hour, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours, 36 Hours, 48 Hours post-dose in each Treatment Periods 1 and 2

InterventionMicrograms per milliliter (Geometric Least Squares Mean)
Cohort 4: Gepotidacin 1500 mg Fed5.421
Cohort 4: Gepotidacin 1500 mg Fasted5.158

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Cohort 4: Cmax of Gepotidacin Following Single Dose of 1500 mg in Plasma

Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. (NCT04493931)
Timeframe: Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hour, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours, 36 Hours, 48 Hours post-dose in each Treatment Periods 1 and 2

InterventionMicrograms per milliliter (Geometric Mean)
Cohort 4: Gepotidacin 1500 mg Fed5.436
Cohort 4: Gepotidacin 1500 mg Fasted5.143

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Cohort 4: CLr of Gepotidacin Following Two 3000 mg Dose-Fed State

Urine samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. (NCT04493931)
Timeframe: Pre-dose, 0-2 Hours, 2-4 Hours, 4-6 Hours, 6-8 Hours, 8-12 Hours, 12-14 Hours, 14-16 Hours, 16-18 Hours, 18-20 Hours, 20-24 Hours, 24-36 Hours, 36-48 Hours, 48-60 Hours post-dose in Treatment Period 3

InterventionLiters per Hour (Geometric Mean)
Cohort 4: Gepotidacin 3000 mg Fed14.61

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Cohort 4: CLr of Gepotidacin Following Single Dose of 1500 mg Under Fed Condition

Urine samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. (NCT04493931)
Timeframe: Pre-dose, 0-2 Hours, 2-4 Hours, 4-6 Hours, 6-8 Hours, 8-12 Hours, 12-24 Hours, 24-36 Hours, 36-48 Hours post-dose in each Treatment Periods 1 and 2

InterventionLiters per Hour (Geometric Mean)
Cohort 4: Gepotidacin 1500 mg Fed13.42

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Cohort 4: CL/F of Gepotidacin Following Single Dose of 1500 mg in Plasma

Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. (NCT04493931)
Timeframe: Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hour, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours, 36 Hours, 48 Hours post-dose in each Treatment Periods 1 and 2

InterventionLiters per Hour (Geometric Mean)
Cohort 4: Gepotidacin 1500 mg Fed67.26
Cohort 4: Gepotidacin 1500 mg Fasted73.50

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Cohort 4: AUC(0-tau) of Gepotidacin in Urine Following Two 3000 mg Doses-Fed State

Urine samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. (NCT04493931)
Timeframe: Pre-dose, 0-2 Hours, 2-4 Hours, 4-6 Hours, 6-8 Hours, 8-12 Hours, 12-14 Hours, 14-16 Hours, 16-18 Hours, 18-20 Hours, 20-24 Hours, 24-36 Hours, 36-48 Hours, 48-60 Hours post-dose in Treatment Period 3

InterventionHours*micrograms per milliliter (Geometric Mean)
Cohort 4: Gepotidacin 3000 mg Fed4996.9

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Area Under the Plasma Concentration Versus Time Curve From Time 0 to the Last Quantifiable Concentration (AUC0-t) of Midazolam

AUC0-t was measured for midazolam alone on Day 1 and for midazolam administered with vonoprazan on Day 9. (NCT04545944)
Timeframe: Day 1 (midazolam alone): Pre-dose and 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, and 24 hours post-dose; Day 9 (midazolam and vonoprazan): Pre-dose and 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36 and 48 hours post-dose

InterventionNanogram Hours per Milliliter (ng•h/mL) (Mean)
Midazolam Alone24.2
Midazolam With Vonoprazan50.7

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Area Under the Plasma Concentration Versus Time Curve From Time 0 Extrapolated to Infinity (AUC0-inf) of Midazolam

AUC0-inf was measured for midazolam alone on Day 1 and for midazolam administered with vonoprazan on Day 9. (NCT04545944)
Timeframe: Day 1 (midazolam alone): Pre-dose and 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, and 24 hours post-dose; Day 9 (midazolam and vonoprazan): Pre-dose and 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36 and 48 hours post-dose

InterventionNanogram Hours per Milliliter (ng•h/mL) (Mean)
Midazolam Alone25.5
Midazolam With Vonoprazan52.3

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Maximum Observed Plasma Concentration (Cmax) of Midazolam

Cmax was measured for midazolam alone on Day 1 and for midazolam administered with vonoprazan on Day 9. (NCT04545944)
Timeframe: Day 1 (midazolam alone): Pre-dose and 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, and 24 hours post-dose; Day 9 (midazolam and vonoprazan): Pre-dose and 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36 and 48 hours post-dose

InterventionNanograms per Milliliter (ng/mL) (Mean)
Midazolam Alone10.3
Midazolam With Vonoprazan20.3

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Area Under the Plasma Concentration-time Profile From Time 0 to Last Quantifiable Concentration (AUClast) of Rosuvastatin in Periods 1, 4 and 7

AUClast is area under the plasma concentration-time profile from time 0 to last quantifiable concentration. (NCT04621227)
Timeframe: At 0 (prior to rosuvastatin dose), 1, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 48, and 72 hours post rosuvastatin dose on Day 1 in Periods 1, 4, and 7

Interventionnanogram*hour per milliliter (ng*hr/mL) (Geometric Mean)
Rosuvastatin 10mg (Period 1)35.17
PF-06882961 120mg BID + Rosuvastatin 10mg (Period 4)72.15
PF-06882961 200mg BID + Rosuvastatin 10mg (Period 7)100.90

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Number of Participants With Categorical Scores on the Patient Health Questionnaire (PHQ-9)

"The PHQ-9 is a 9 item self-report scale for the assessment of depressive symptoms. The questions included little interest/pleasure in things, feeling down depressed or hopeless, trouble falling or staying asleep, feeling tired or little energy, poor appetite or overeating, feeling bad about yourself, trouble concentrating on things, moving slowly or fidgety/restless and thoughts you be better off dead. Each item was scored on scale of not at all, several days, more than half the days to nearly every day. Total score range: 0-27 (each item with scale from 0 [not at all] to 3 [nearly every day]. Higher score=greater severity)." (NCT04621227)
Timeframe: At BL (Period 1 Day 1), on Period 3 Days 1, 8, 15, and 22, Period 4 Day 1, Period 6 Days 1, 9, and 16, Period 8 Day 2, at Follow Up visit (Days 68-71) and Early Termination

InterventionParticipants (Count of Participants)
BL Little Interest/Pleasure in Things72022069BL Feeling Down Depressed or Hopeless72022069BL Trouble Falling or Staying Asleep72022069BL Feeling Tired or Little Energy72022069BL Poor Appetite or Overeating72022069BL Feeling Bad About Yourself72022069BL Trouble Concentrating on Things72022069BL Moving Slowly or Fidgety/Restless72022069BL Thoughts You Be Better Off Dead72022069Period 3 Day 1/PF-06882961 titration up to 120mg BID Little Interest/Pleasure in Things72022069Period 3 Day 1 / PF-06882961 titration up to 120mg BID Feeling Down Depressed or Hopeless72022069Period 3 Day 1 / PF-06882961 titration up to 120mg BID Trouble Falling or Staying Asleep72022069Period 3 Day 1 / PF-06882961 titration up to 120mg BID Feeling Tired or Little Energy72022069Period 3 Day 1 / PF-06882961 titration up to 120mg BID Poor Appetite or Overeating72022069Period 3 Day 1 / PF-06882961 titration up to 120mg BID Feeling Bad About Yourself72022069Period 3 Day 1 / PF-06882961 titration up to 120mg BID Trouble Concentrating on Things72022069Period 3 Day 1 / PF-06882961 titration up to 120mg BID Moving Slowly or Fidgety/Restless72022069Period 3 Day 1 / PF-06882961 titration up to 120mg BID Thoughts You Be Better Off Dead72022069Period 3 Day 8 / PF-06882961 titration up to 120mg BID Little Interest/Pleasure in Things72022069Period 3 Day 8 / PF-06882961 titration up to 120mg BID Feeling Down Depressed or Hopeless72022069Period 3 Day 8 / PF-06882961 titration up to 120mg BID Trouble Falling or Staying Asleep72022069Period 3 Day 8 / PF-06882961 titration up to 120mg BID Feeling Tired or Little Energy72022069Period 3 Day 8 / PF-06882961 titration up to 120mg BID Poor Appetite or Overeating72022069Period 3 Day 8 / PF-06882961 titration up to 120mg BID Feeling Bad About Yourself72022069Period 3 Day 8 / PF-06882961 titration up to 120mg BID Trouble Concentrating on Things72022069Period 3 Day 8 / PF-06882961 titration up to 120mg BID Moving Slowly or Fidgety/Restless72022069Period 3 Day 8 / PF-06882961 titration up to 120mg BID Thoughts You Be Better Off Dead72022069Period 3 Day 15 / PF-06882961 titration up to 120mg BID Little Interest/Pleasure in Things72022069Period 3 Day 15 / PF-06882961 titration up to 120mg BID Feeling Down Depressed or Hopeless72022069Period 3 Day 15 / PF-06882961 titration up to 120mg BID Trouble Falling or Staying Asleep72022069Period 3 Day 15 / PF-06882961 titration up to 120mg BID Feeling Tired or Little Energy72022069Period 3 Day 15 / PF-06882961 titration up to 120mg BID Poor Appetite or Overeating72022069Period 3 Day 15 / PF-06882961 titration up to 120mg BID Feeling Bad About Yourself72022069Period 3 Day 15 / PF-06882961 titration up to 120mg BID Trouble Concentrating on Things72022069Period 3 Day 15 / PF-06882961 titration up to 120mg BID Moving Slowly or Fidgety/Restless72022069Period 3 Day 15 / PF-06882961 titration up to 120mg BID Thoughts You Be Better Off Dead72022069Period 3 Day 22 / PF-06882961 titration up to 120mg BID Little Interest/Pleasure in Things72022069Period 3 Day 22 / PF-06882961 titration up to 120mg BID Feeling Down Depressed or Hopeless72022069Period 3 Day 22 / PF-06882961 titration up to 120mg BID Trouble Falling or Staying Asleep72022069Period 3 Day 22 / PF-06882961 titration up to 120mg BID Feeling Tired or Little Energy72022069Period 3 Day 22 / PF-06882961 titration up to 120mg BID Poor Appetite or Overeating72022069Period 3 Day 22 / PF-06882961 titration up to 120mg BID Feeling Bad About Yourself72022069Period 3 Day 22 / PF-06882961 titration up to 120mg BID Trouble Concentrating on Things72022069Period 3 Day 22 / PF-06882961 titration up to 120mg BID Moving Slowly or Fidgety/Restless72022069Period 3 Day 22 / PF-06882961 titration up to 120mg BID Thoughts You Be Better Off Dead72022069Period 4 Day 1 / PF-06882961 120mg BID + rosuvastatin 10mg Little Interest/Pleasure in Things72022069Period 4 Day 1 / PF-06882961 120mg BID + rosuvastatin 10mg Feeling Down Depressed or Hopeless72022069Period 4 Day 1 / PF-06882961 120mg BID + rosuvastatin 10mg Trouble Falling or Staying Asleep72022069Period 4 Day 1 / PF-06882961 120mg BID + rosuvastatin 10mg Feeling Tired or Little Energy72022069Period 4 Day 1 / PF-06882961 120mg BID + rosuvastatin 10mg Poor Appetite or Overeating72022069Period 4 Day 1 / PF-06882961 120mg BID + rosuvastatin 10mg Feeling Bad About Yourself72022069Period 4 Day 1 / PF-06882961 120mg BID + rosuvastatin 10mg Trouble Concentrating on Things72022069Period 4 Day 1 / PF-06882961 120mg BID + rosuvastatin 10mg Moving Slowly or Fidgety/Restless72022069Period 4 Day 1 / PF-06882961 120mg BID + rosuvastatin 10mg Thoughts You Be Better Off Dead72022069Period 6 Day 1 / PF-06882961 titration up to 200mg BID Little Interest/Pleasure in Things72022069Period 6 Day 1 / PF-06882961 titration up to 200mg BID Feeling Down Depressed or Hopeless72022069Period 6 Day 1 / PF-06882961 titration up to 200mg BID Trouble Falling or Staying Asleep72022069Period 6 Day 1 / PF-06882961 titration up to 200mg BID Feeling Tired or Little Energy72022069Period 6 Day 1 / PF-06882961 titration up to 200mg BID Poor Appetite or Overeating72022069Period 6 Day 1 / PF-06882961 titration up to 200mg BID Feeling Bad About Yourself72022069Period 6 Day 1 / PF-06882961 titration up to 200mg BID Trouble Concentrating on Things72022069Period 6 Day 1 / PF-06882961 titration up to 200mg BID Moving Slowly or Fidgety/Restless72022069Period 6 Day 1 / PF-06882961 titration up to 200mg BID Thoughts You Be Better Off Dead72022069Period 6 Day 9 / PF-06882961 titration up to 200mg BID Little Interest/Pleasure in Things72022069Period 6 Day 9 / PF-06882961 titration up to 200mg BID Feeling Down Depressed or Hopeless72022069Period 6 Day 9 / PF-06882961 titration up to 200mg BID Trouble Falling or Staying Asleep72022069Period 6 Day 9 / PF-06882961 titration up to 200mg BID Feeling Tired or Little Energy72022069Period 6 Day 9 / PF-06882961 titration up to 200mg BID Poor Appetite or Overeating72022069Period 6 Day 9 / PF-06882961 titration up to 200mg BID Feeling Bad About Yourself72022069Period 6 Day 9 / PF-06882961 titration up to 200mg BID Trouble Concentrating on Things72022069Period 6 Day 9 / PF-06882961 titration up to 200mg BID Moving Slowly or Fidgety/Restless72022069Period 6 Day 9 / PF-06882961 titration up to 200mg BID Thoughts You Be Better Off Dead72022069Period 6 Day 16 / PF-06882961 titration up to 200mg BID Little Interest/Pleasure in Things72022069Period 6 Day 16 / PF-06882961 titration up to 200mg BID Feeling Down Depressed or Hopeless72022069Period 6 Day 16 / PF-06882961 titration up to 200mg BID Trouble Falling or Staying Asleep72022069Period 6 Day 16 / PF-06882961 titration up to 200mg BID Feeling Tired or Little Energy72022069Period 6 Day 16 / PF-06882961 titration up to 200mg BID Poor Appetite or Overeating72022069Period 6 Day 16 / PF-06882961 titration up to 200mg BID Feeling Bad About Yourself72022069Period 6 Day 16 / PF-06882961 titration up to 200mg BID Trouble Concentrating on Things72022069Period 6 Day 16 / PF-06882961 titration up to 200mg BID Moving Slowly or Fidgety/Restless72022069Period 6 Day 16 / PF-06882961 titration up to 200mg BID Thoughts You Be Better Off Dead72022069Period 8 Day 2 / PF-06882961 200mg BID + midazolam 2mg Little Interest/Pleasure in Things72022069Period 8 Day 2 / PF-06882961 200mg BID + midazolam 2mg Feeling Down Depressed or Hopeless72022069Period 8 Day 2 / PF-06882961 200mg BID + midazolam 2mg Trouble Falling or Staying Asleep72022069Period 8 Day 2 / PF-06882961 200mg BID + midazolam 2mg Feeling Tired or Little Energy72022069Period 8 Day 2 / PF-06882961 200mg BID + midazolam 2mg Poor Appetite or Overeating72022069Period 8 Day 2 / PF-06882961 200mg BID + midazolam 2mg Feeling Bad About Yourself72022069Period 8 Day 2 / PF-06882961 200mg BID + midazolam 2mg Trouble Concentrating on Things72022069Period 8 Day 2 / PF-06882961 200mg BID + midazolam 2mg Moving Slowly or Fidgety/Restless72022069Period 8 Day 2 / PF-06882961 200mg BID + midazolam 2mg Thoughts You Be Better Off Dead72022069Follow Up Little Interest/Pleasure in Things72022069Follow Up Feeling Down Depressed or Hopeless72022069Follow Up Trouble Falling or Staying Asleep72022069Follow Up Feeling Tired or Little Energy72022069Follow Up Poor Appetite or Overeating72022069Follow Up Feeling Bad About Yourself72022069Follow Up Trouble Concentrating on Things72022069Follow Up Moving Slowly or Fidgety/Restless72022069Follow Up Thoughts You Be Better Off Dead72022069ET Little Interest/Pleasure in Things72022069ET Feeling Down Depressed or Hopeless72022069ET Trouble Falling or Staying Asleep72022069ET Feeling Tired or Little Energy72022069ET Poor Appetite or Overeating72022069ET Feeling Bad About Yourself72022069ET Trouble Concentrating on Things72022069ET Moving Slowly or Fidgety/Restless72022069ET Thoughts You Be Better Off Dead72022069
Not At AllSeveral DaysMore Than Half The DaysNearly Every Day
All Participants16
All Participants11
All Participants3
All Participants13
All Participants2
All Participants12
All Participants1
All Participants14
All Participants0
All Participants15

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Number of Participants With Vital Signs Data Meeting the Pre-defined Categorical Summarization Criteria

Single, supine vital signs assessments included systolic blood pressure (BP), diastolic BP and pulse rate. Abnormality in vital signs included: pulse rate <40 beats per minute (bpm) or >120bpm; supine diastolic BP <50 millimeter of mercury (mmHg), increase and decrease in change from BL of >=20mmHg; supine systolic blood pressure <90mmHg, increase and decrease in change from BL of >=30mmHg. (NCT04621227)
Timeframe: From BL (Day 1, the last pre-dose measurement in Period 1) to Follow Up visit (Days 68-71) (approximately up to 71 days)

,,,,,,,
InterventionParticipants (Count of Participants)
Pulse rate value <40bpmPulse rate value >120bpmSupine diastolic BP value <50mmHgSupine diastolic BP change >=20mmHg increaseSupine diastolic BP change >=20mmHg decreaseSupine systolic BP value <90mmHgSupine systolic BP change >=30mmHg increaseSupine systolic BP change >=30mmHg decrease
Midazolam 2mg (Period 2)00000000
PF-06882961 120mg BID + Midazolam 2mg (Period 5)00003002
PF-06882961 120mg BID + Rosuvastatin 10mg (Period 4)00000100
PF-06882961 200mg BID + Midazolam 2mg (Period 8)00101000
PF-06882961 200mg BID + Rosuvastatin 10mg (Period 7)01001002
PF-06882961 Titration up to 120mg BID (Period 3)00001002
PF-06882961 Titration up to 200mg BID (Period 6)00003103
Rosuvastatin 10mg (Period 1)00000000

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Number of Participants With Treatment-emergent Adverse Events (TEAEs)

An adverse event (AE) was any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. A serious adverse event (SAE) was defined as any untoward medical occurrence that, at any dose: resulted in death; was life-threatening; required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent disability/incapacity; was a congenital anomaly/birth defect; or other serious situations such as important medical events. TEAEs were events between first dose of study drug and up to follow-up visit that were absent before treatment or that worsened after treatment. AEs presented below were TEAEs. The investigator was required to use clinical judgment to assess the potential relationship between investigational product and each AE, to define an treatment-related AE. (NCT04621227)
Timeframe: From first dose of study drug (Day 1) to telephone Follow Up (Days 89-96) (approximately up to 96 days)

,,,,,,,
InterventionParticipants (Count of Participants)
All-causality TEAEsTreatment-related TEAEs
Midazolam 2mg (Period 2)20
PF-06882961 120mg BID + Midazolam 2mg (Period 5)55
PF-06882961 120mg BID + Rosuvastatin 10mg (Period 4)65
PF-06882961 200mg BID + Midazolam 2mg (Period 8)87
PF-06882961 200mg BID + Rosuvastatin 10mg (Period 7)73
PF-06882961 Titration up to 120mg BID (Period 3)1311
PF-06882961 Titration up to 200mg BID (Period 6)1110
Rosuvastatin 10mg (Period 1)00

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Number of Participants With Positive Response on the Columbia Suicide Severity Rating Scale (C-SSRS)

"The C-SSRS was an interview-based rating scale to systematically assess suicidal ideation and suicidal behavior. C-SSRS assessed whether participant experienced any of the following 1: completed suicide, 2: suicide attempt (response of yes on actual attempt), 3: preparatory acts towards imminent suicidal behavior (yes on aborted attempt, interrupted attempt, preparatory acts/behavior), 4: suicidal ideation (yes on wish to be dead, non-specific active suicidal thoughts), 7: self-injurious behavior, no suicidal intent (yes on has participant engaged in non-suicidal self-injurious behavior). In this outcome, number of participants with positive response (response of yes) to suicidal behavior, ideation, or any self-injurious behavior were reported." (NCT04621227)
Timeframe: At BL (Period 1 Day 1), on Period 3 Days 1, 8, 15, and 22, Period 4 Day 1, Period 6 Days 1, 9, and 16, Period 8 Day 2, at Follow Up visit (Days 68-71) and Early Termination

InterventionParticipants (Count of Participants)
BLBL (Past 12 months)Period 3 Day 1 / PF-06882961 titration up to 120mg BID (Since last visit)Period 3 Day 8 / PF-06882961 titration up to 120mg BID (Since last visit)Period 3 Day 15 / PF-06882961 titration up to 120mg BID (Since last visit)Period 3 Day 22 / PF-06882961 titration up to 120mg BID (Since last visit)Period 4 Day 1 / PF-06882961 120mg BID + rosuvastatin 10mg (Since last visit)Period 6 Day 1 / PF-06882961 titration up to 200mg BID (Since last visit)Period 6 Day 9 / PF-06882961 titration up to 200mg BID (Since last visit)Period 6 Day 16 / PF-06882961 titration up to 200mg BID (Since last visit)Period 8 Day 2 / PF-06882961 200mg BID + midazolam 2mg (Since last visit)Follow Up (Since last visit)Early Termination (ET) (Since last visit)
All Participants0000000000000

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Number of Participants With Electrocardiogram (ECG) Data Meeting the Pre-defined Categorical Summarization Criteria

ECG assessments included pulse rate (PR), QT, QTcF intervals and QRS complex. ECG abnormalities criteria included: PR interval value >= 300msec, or BL >200msec and >=25% increase from BL, or BL <=200msec and >=50% increase from BL; QRS interval value >= 140msec, or percent change from BL >=50%; QTcF value >400 and <=480msec, or >480 and <=500 msec, or >500msec, or change from BL>30 and <=60msec, or change from BL >60msec. (NCT04621227)
Timeframe: From BL (Day 1, the last pre-dose measurement in Period 1) to Follow Up visit (Days 68-71) (approximately up to 71 days)

,,,,,,,
InterventionParticipants (Count of Participants)
PR interval value>=300 msecPR interval %change >=25/50% (BL >200 msec and >=25% increase or BL <=200 msec and >=50% increase)QRS interval value>=140 msecQRS interval %change >=50%QTcF value >450 and <=480 msecQTcF value >480 and <=500 msecQTcF value >500 msecQTcF change >30 and <=60 msecQTcF change >60 msec
Midazolam 2mg (Period 2)000010000
PF-06882961 120mg BID + Midazolam 2mg (Period 5)110000000
PF-06882961 120mg BID + Rosuvastatin 10mg (Period 4)110000000
PF-06882961 200mg BID + Midazolam 2mg (Period 8)000000000
PF-06882961 200mg BID + Rosuvastatin 10mg (Period 7)010000000
PF-06882961 Titration up to 120mg BID (Period 3)000020000
PF-06882961 Titration up to 200mg BID (Period 6)000010000
Rosuvastatin 10mg (Period 1)000000000

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Change From Baseline in Body Weight

Changes from Baseline in body weight of the participants were measured. (NCT04621227)
Timeframe: At BL (Period 1 Day 1), on Period 3 Days 1, 8, 15 and 22, Period 4 Day 1, Period 6 Days 1 and 9, Period 7 Day 1, Period 8 Day 2, and at Follow Up visit (Days 68-71)

Interventionkilogram (kg) (Mean)
Period 3 Day 1 / PF-06882961 titration up to 120 mg BIDPeriod 3 Day 8 / PF-06882961 titration up to 120 mg BIDPeriod 3 Day 15 / PF-06882961 titration up to 120 mg BIDPeriod 3 Day 22 / PF-06882961 titration up to 120 mg BIDPeriod 4 Day 1 / PF-06882961 120 mg BID + rosuvastatin 10 mgPeriod 6 Day 1 / PF-06882961 titration up to 200 mg BIDPeriod 6 Day 9 / PF-06882961 titration up to 200 mg BIDPeriod 7 Day 1 / PF-06882961 200 mg BID + rosuvastatin 10 mgPeriod 8 Day 2 / PF-06882961 200 mg BID + midazolam 2 mgFollow up
All Participants-1.5-1.9-3.3-4.3-5.2-6.1-7.5-9.1-9.9-5.7

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Number of Participants With Laboratory Abnormalities (Without Regard to Baseline [BL] Abnormality)

Safety laboratory assessments included clinical chemistry, hematology, urinalysis, and other tests. Abnormality was determined at the investigator's discretion. (NCT04621227)
Timeframe: From BL (Day 1, the last pre-dose measurement in Period 1) to Follow Up visit (Days 68-71) (approximately up to 71 days)

InterventionParticipants (Count of Participants)
Rosuvastatin 10mg (Period 1)0
Midazolam 2mg (Period 2)3
PF-06882961 Titration up to 120mg BID (Period 3)5
PF-06882961 120mg BID + Rosuvastatin 10mg (Period 4)2
PF-06882961 120mg BID + Midazolam 2mg (Period 5)3
PF-06882961 Titration up to 200mg BID (Period 6)5
PF-06882961 200mg BID + Rosuvastatin 10mg (Period 7)0
PF-06882961 200mg BID + Midazolam 2mg (Period 8)9

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AUClast of Midazolam in Periods 2, 5 and 8

AUClast is area under the plasma concentration-time profile from time 0 to last quantifiable concentration. (NCT04621227)
Timeframe: At 0 (prior to midazolam dose), 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, and 24 hours post midazolam dose on Day 1 in Periods 2, 5, and 8

Interventionnanogram*hour per milliliter (ng*hr/mL) (Geometric Mean)
Midazolam 2mg (Period 2)39.24
PF-06882961 120mg BID + Midazolam 2mg (Period 5)19.98
PF-06882961 200mg BID + Midazolam 2mg (Period 8)20.21

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Area Under the Concentration-time Curve of Midazolam in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-infinity, Midazolam)

Area under the concentration-time curve of midazolam in plasma over the time interval from 0 extrapolated to infinity (AUC0-infinity, midazolam) is reported. (NCT04679948)
Timeframe: Within 2 hours (h) predose for period 1, within 15 minutes predose for period 2 and 0.5 h, 1 h, 1.5 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h, 24 h after midazolam administration in both periods.

Interventionhours * nanomole/Liter (h*nmol/L) (Geometric Least Squares Mean)
Midazolam (Reference (R))56.81
BI 730357 + Midazolam (Test (T))72.07

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Area Under the Concentration-time Curve of Omeprazole in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-infinity, Omeprazole)

Area under the concentration-time curve of omeprazole in plasma over the time interval from 0 extrapolated to infinity (AUC0-infinity, omeprazole) is reported. (NCT04679948)
Timeframe: Within 2 hours (h) predose for period 1, within 15 minutes predose for period 2 and 0.5 h, 1 h, 1.5 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h, 24 h after omeprazole administration in both periods.

Interventionhours * nanomole/Liter (h*nmol/L) (Geometric Least Squares Mean)
Omeprazole (Reference (R))933.62
BI 730357 + Omeprazole (Test (T))931.22

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Area Under the Concentration-time Curve of S-warfarin in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-infinity, S-warfarin)

Warfarin sodium is a racemic mixture of the R-and S-enantiomers. Area under the concentration-time curve of S-warfarin in plasma over the time interval from 0 extrapolated to infinity (AUC0-infinity,S-warfain) is reported. (NCT04679948)
Timeframe: Within 2 hours (h) predose for period 1, within 15 minutes predose for period 2 and 0.5 h, 1 h, 1.5 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h, 24 h, 48 h, 71 h, 95 h, 119 h, 143 h after warfarin administration in both periods.

Interventionhours * nanomole/Liter (h*nmol/L) (Geometric Least Squares Mean)
Warfarin (Reference (R))55770.25
BI 730357 + Warfarin (Test (T))61559.60

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Area Under the Concentration-time Curve of Caffeine in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-infinity, Caffeine)

Area under the concentration-time curve of caffeine in plasma over the time interval from 0 extrapolated to infinity (AUC0-infinity, caffeine) is reported. (NCT04679948)
Timeframe: Within 2 hours (h) predose for period 1, within 15 minutes predose for period 2 and 0.5 h, 1 h, 1.5 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h, 24 h, 48 h after caffeine administration in both periods.

Interventionhours *nanomole/Liter (h*nmol/L) (Geometric Least Squares Mean)
Caffeine (Reference (R))84569.29
BI 730357 + Caffeine (Test (T))94764.64

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Maximum Measured Concentration of Omeprazole in Plasma (Cmax, Omeprazole)

Maximum measured concentration of omeprazole in plasma (Cmax, omeprazole) is reported. (NCT04679948)
Timeframe: Within 2 hours (h) predose for period 1, within 15 minutes predose for period 2 and 0.5 h, 1 h, 1.5 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h, 24 h after omeprazole administration in both periods.

Interventionnanomole/Liter (nmol/L) (Geometric Least Squares Mean)
Omeprazole (Reference (R))504.07
BI 730357 + Omeprazole (Test (T))359.50

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Maximum Measured Concentration of the Caffeine in Plasma (Cmax, Caffeine)

Maximum measured concentration of the caffeine in plasma (Cmax, caffeine) is reported. (NCT04679948)
Timeframe: Within 2 hours (h) predose for period 1, within 15 minutes predose for period 2 and 0.5 h, 1 h, 1.5 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h, 24 h, 48 h after caffeine administration in both periods.

Interventionnanomole/Liter (nmol/L) (Geometric Least Squares Mean)
Caffeine (Reference (R))11973.25
BI 730357 + Caffeine (Test (T))11583.25

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Maximum Measured Concentration of Midazolam in Plasma (Cmax, Midazolam)

Maximum measured concentration of midazolam in plasma (Cmax, midazolam) is reported. (NCT04679948)
Timeframe: Within 2 hours (h) predose for period 1, within 15 minutes predose for period 2 and 0.5 h, 1 h, 1.5 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h, 24 h after midazolam administration in both periods.

Interventionnanomole/Liter (nmol/L) (Geometric Least Squares Mean)
Midazolam (Reference (R))19.09
BI 730357 + Midazolam (Test (T))24.87

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Maximum Measured Concentration of the S-warfarin in Plasma (Cmax, S-warfarin)

Warfarin sodium is a racemic mixture of the R-and S-enantiomers. Maximum measured concentration of the S-warfarin in plasma (Cmax) is reported. (NCT04679948)
Timeframe: Within 2 hours (h) predose for period 1, within 15 minutes predose for period 2 and 0.5 h, 1 h, 1.5 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h, 24 h, 48 h, 71 h, 95 h, 119 h, 143 h after warfarin administration in both periods.

Interventionnanomole/Liter (nmol/L) (Geometric Least Squares Mean)
Warfarin (Reference (R))1622.94
BI 730357 + Warfarin (Test (T))1760.38

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Apparent Clearance (CL/F) of Midazolam When Administered Alone, With PF-07321332/Ritonavir, and With Ritonavir

CL/F for midazolam following single dose administration with and without PF-07321332/ritonavir or ritonavir was calculated by Dose/AUCinf. (NCT05032950)
Timeframe: Midazolam: Day 1 Predose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36 hours postdose; Midazolam+PF-07321332/ritonavir: Day 5 predose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36, 48 and 72 hours postdose

InterventionLitre/hour (Geometric Mean)
Midazolam 2 mg76.57
PF-07321332 300 mg/Ritonavir 100 mg + Midazolam 2 mg5.500
Ritonavir 100mg+ Midazolam 2mg4.776

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Apparent Volume of Distribution (Vz/F) of Midazolam When Administered Alone, With PF-07321332/Ritonavir, and With Ritonavir

Vz/F for midazolam following single dose administration with and without PF-07321332/ritonavir or ritonavir was calculated by Dose/(AUCinf • kel). (NCT05032950)
Timeframe: Midazolam: Day 1 Predose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36 hours postdose; Midazolam+PF-07321332/ritonavir: Day 5 predose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36, 48 and 72 hours postdose

InterventionLitre (Geometric Mean)
Midazolam 2 mg488.6
PF-07321332 300 mg/Ritonavir 100 mg + Midazolam 2 mg79.84
Ritonavir 100mg+ Midazolam 2mg76.43

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Area Under the Plasma Concentration-time Profile From Time 0 Extrapolated to Infinity Time (AUCinf) of Midazolam When Administered Alone and With PF-07321332/Ritonavir

AUCinf for midazolam following single dose administration with and without PF-07321332/ritonavir was calculated by AUClast + (Clast/kel), where Clast was the predicted plasma concentration at the last quantifiable time point estimated from the log-linear regression analysis. Natural log-transformed AUCinf for Midazolam were analyzed using a mixed effect model with sequence, period and treatment as fixed effects and participant within sequence as a random effect. The ratios (PF-07321332/ritonavir + midazolam [test]/midazolam [reference] and 90% CIs) were expressed as percentages. (NCT05032950)
Timeframe: Midazolam: Day 1 Predose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36 hours postdose; Midazolam+PF-07321332/ritonavir: Day 5 predose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36, 48 and 72 hours postdose

Interventionng*hr/mL (Geometric Mean)
Midazolam 2 mg26.13
PF-07321332 300 mg/Ritonavir 100 mg + Midazolam 2 mg363.9

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Area Under the Plasma Concentration-time Profile From Time 0 to the Time of the Last Quantifiable Concentration (Clast) (AUClast) of Midazolam When Administered Alone and With PF-07321332/Ritonavir

AUClast for midazolam following single dose administration with and without PF-07321332/ritonavir was calculated by Linear/Log trapezoidal method. Natural log-transformed AUClast for Midazolam were analyzed using a mixed effect model with sequence, period and treatment as fixed effects and participant within sequence as a random effect. The ratios (PF-07321332/ritonavir + midazolam [test]/midazolam [reference] and 90% CIs) were expressed as percentages. (NCT05032950)
Timeframe: Midazolam: Day 1 Predose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36 hours postdose; Midazolam+PF-07321332/ritonavir: Day 5 predose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36, 48 and 72 hours postdose

Interventionng*hr/mL (Geometric Mean)
Midazolam 2 mg25.02
PF-07321332 300 mg/Ritonavir 100 mg + Midazolam 2 mg353.8

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AUCinf of Midazolam When Administered Alone and With Ritonavir

AUCinf for midazolam following single dose administration with and without ritonavir was calculated by AUClast + (Clast/kel), where Clast was the predicted plasma concentration at the last quantifiable time point estimated from the log-linear regression analysis. Natural log-transformed AUCinf for Midazolam were analyzed using a mixed effect model with sequence, period and treatment as fixed effects and participant within sequence as a random effect. The ratios (ritonavir + midazolam [test]/midazolam [reference] and 90% CIs) were expressed as percentages. (NCT05032950)
Timeframe: Midazolam: Day 1 Predose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36 hours postdose; Midazolam/ritonavir: Day 5 predose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36, 48 and 72 hours postdose

Interventionng*hr/mL (Geometric Mean)
Midazolam 2 mg26.13
Ritonavir 100 mg + Midazolam 2 mg418.6

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AUClast of Midazolam When Administered Alone and With Ritonavir

AUClast for midazolam following single dose administration with and without ritonavir was calculated by Linear/Log trapezoidal method. Natural log-transformed AUClast for Midazolam were analyzed using a mixed effect model with sequence, period and treatment as fixed effects and participant within sequence as a random effect. The ratios (ritonavir + midazolam [test]/midazolam [reference] and 90% CIs) were expressed as percentages. (NCT05032950)
Timeframe: Midazolam: Day 1 Predose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36 hours postdose; Midazolam/ritonavir: Day 5 pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36, 48 and 72 hours post-dose

Interventionng*hr/mL (Geometric Mean)
Midazolam 2 mg25.02
Ritonavir 100 mg + Midazolam 2 mg408.8

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Cmax of Midazolam When Administered Alone and With Ritonavir

Cmax for midazolam following single dose administration with and without ritonavir was observed directly form data. Natural log-transformed Cmax for Midazolam were analyzed using a mixed effect model with sequence, period and treatment as fixed effects and participant within sequence as a random effect. The ratios (ritonavir + midazolam [test]/midazolam [reference] and 90% CIs) were expressed as percentages. (NCT05032950)
Timeframe: Midazolam: Day 1 Predose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36 hours postdose; Midazolam/ritonavir: Day 5 predose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36, 48 and 72 hours postdose

Interventionng/mL (Geometric Mean)
Midazolam 2 mg9.812
Ritonavir 100 mg + Midazolam 2 mg38.03

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Maximum Plasma Concentration (Cmax) of Midazolam When Administered Alone and With PF-07321332/Ritonavir

Cmax for midazolam following single dose administration with and without PF-07321332/ritonavir was observed directly from data. Natural log-transformed Cmax for Midazolam were analyzed using a mixed effect model with sequence, period and treatment as fixed effects and participant within sequence as a random effect. The ratios (PF-07321332/ritonavir + midazolam [test]/midazolam [reference] and 90% CIs) were expressed as percentages. (NCT05032950)
Timeframe: Midazolam: Day 1 Predose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36 hours postdose; Midazolam+PF-07321332/ritonavir: Day 5 predose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36, 48 and 72 hours postdose

Interventionng/mL (Geometric Mean)
Midazolam 2 mg9.812
PF-07321332 300 mg/Ritonavir 100 mg + Midazolam 2 mg36.18

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Number of Participants With Vital Signs Abnormalities

Baseline was the last predose recording in each study period. Only post baseline values are included in this analysis (NCT05032950)
Timeframe: Baseline up to Day 28

InterventionParticipants (Count of Participants)
Midazolam 2 mg0
PF-07321332 300 mg/Ritonavir 100 mg + Midazolam 2 mg1
Ritonavir 100 mg + Midazolam 2 mg0

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Terminal Half-life (t1/2) of Midazolam When Administered Alone, With PF-07321332/Ritonavir, and With Ritonavir

t½ for midazolam following single dose administration with and without PF-07321332/ritonavir or ritonavir was calculated by Loge(2)/kel, where kel was the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve. Only those data points judged to describe the terminal log-linear. (NCT05032950)
Timeframe: Midazolam: Day 1 Predose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36 hours postdose; Midazolam+PF-07321332/ritonavir: Day 5 predose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36, 48 and 72 hours postdose

InterventionHour (Mean)
Midazolam 2 mg4.988
PF-07321332 300 mg/Ritonavir 100 mg + Midazolam 2 mg10.47
Ritonavir 100 mg + Midazolam 2 mg11.54

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Time for Cmax (Tmax) of Midazolam When Administered Alone, With PF-07321332/Ritonavir, and With Ritonavir

Tmax for midazolam following single dose administration with and without PF-07321332/ritonavir or ritonavir was calculated by observed directly from data as time of first occurrence. (NCT05032950)
Timeframe: Midazolam: Day 1 Predose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36 hours postdose; Midazolam+PF-07321332/ritonavir: Day 5 predose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36, 48 and 72 hours postdose

InterventionHour (Median)
Midazolam 2 mg1.00
PF-07321332 300 mg/Ritonavir 100 mg + Midazolam 2 mg1.00
Ritonavir 100mg+ Midazolam 2mg1.02

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Number of Participants With Electrocardiogram (ECG) Abnormalities

Baseline and changes from baseline in PR, QT, QRS, heart rate and QTcF were summarized by treatment and time postdose. Baseline was defined as the average of the triplicate predose recordings in each study period. ECG endpoints and changes from baseline (QTcF, PR, QRS), over all measurements taken postdose, were also summarized descriptively by treatment using categories as defined in the Criteria for Safety Values of Potential Clinical Concern appendix of the protocol and for QTc values corresponding to ICH E14 thresholds, which are: QTcF (msec): 450500; QTcF (msec) increase from baseline: 3060 (NCT05032950)
Timeframe: Baseline up to Day 28

,,
InterventionParticipants (Count of Participants)
PR INTERVAL, AGGREGATE (MSEC) - Value≥300PR INTERVAL, AGGREGATE (MSEC) - %Change≥25/50%QRS DURATION, AGGREGATE (MSEC) - Value≥140QRS DURATION, AGGREGATE (MSEC) - %Change≥50%QTCF INTERVAL, AGGREGATE (MSEC) - 450QTCF INTERVAL, AGGREGATE (MSEC) - 480QTCF INTERVAL, AGGREGATE (MSEC) - Value>500QTCF INTERVAL, AGGREGATE (MSEC) - 30QTCF INTERVAL, AGGREGATE (MSEC) - Change>60
Midazolam 2 mg000000000
PF-07321332 300 mg/Ritonavir 100 mg + Midazolam 2 mg000000000
Ritonavir 100 mg + Midazolam 2 mg000000000

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Number of Participants With Laboratory Abnormalities

The haematological, clinical chemistry (serum) and urinalysis safety tests were assessed against the criteria specified in the sponsor reporting standards to determine if there were any clinically significant laboratory abnormalities. The assessment took into account whether each participant's baseline test result was within or outside the laboratory reference range for the particular laboratory parameter. Baseline was defined as the last planned predose measurement taken in each study period. (NCT05032950)
Timeframe: Baseline up to Day 28

,,
InterventionParticipants (Count of Participants)
HEMATOLOGY - Lymphocytes/Leukocytes (%) >1.2x ULNHEMATOLOGY - Neutrophils (10^3/mm^3) <0.8x LLNHEMATOLOGY - Neutrophils/Leukocytes (%) <0.8x LLNHEMATOLOGY - Eosinophils/Leukocytes (%) >1.2x ULNHEMATOLOGY - Monocytes/Leukocytes (%) >1.2x ULNHEMATOLOGY - Prothrombin Time (sec) >1.1x ULNCLINICAL CHEMISTRY - Thyrotropin (uIU/mL) <0.8x LLNCLINICAL CHEMISTRY - Fibrinogen (mg/dL) >1.25x BaselineURINALYSIS - URINE Hemoglobin (Scalar) ≥1
Midazolam 2 mg000010112
PF-07321332 300 mg/Ritonavir 100 mg + Midazolam 2 mg001110111
Ritonavir 100 mg + Midazolam 2 mg111121103

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Number of Participants With Treatment-emergent Adverse Events (TEAEs)

An adverse event was considered a TEAE if the event started during the effective duration of treatment. All events that start on or after the first dosing day and time/ start time, if collected, but before the last dose plus the lag time (28 days) were flagged as TEAEs. The algorithm did consider any events that started prior to the first dose date. Any events occurring following start of treatment or increasing in severity were counted as treatment emergent. Events that occur in a non-treatment period (for example, Washout or Follow-up) were counted as treatment emergent and attributed to the previous treatment taken. (NCT05032950)
Timeframe: Baseline up to Day 28

,,
InterventionParticipants (Count of Participants)
Participants with adverse events (All Causalities)Participants with adverse events (Treatment related)Participants with serious adverse eventsParticipants with severe adverse events
Midazolam 2 mg4400
PF-07321332 300 mg/Ritonavir 100 mg + Midazolam 2 mg9900
Ritonavir 100 mg + Midazolam 2 mg7700

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Area Under the Plasma Concentration-time Curve Over the Dosing Interval τ (8 Hours) (AUC0-τ) of Cefiderocol

This outcome measure presents the pharmacokinetics of cefiderocol when coadministered with midazolam. AUC0-τ was calculated by the linear up/log down trapezoidal method and is reported as micrograms times hours/milliliter (μg*hrs/mL). (NCT05395104)
Timeframe: Day 15

Interventionμg*hrs/mL (Geometric Mean)
Cefiderocol Plus Midazolam355.4

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Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUC0-last) of Midazolam

This outcome measure presents the effects of repeated doses of cefiderocol on the pharmacokinetics of midazolam. AUC0-last was calculated using the linear up/log down trapezoidal method and is reported as nanograms times hours/milliliter (ng*hrs/mL). Day -1 is defined as Baseline. (NCT05395104)
Timeframe: 0 (predose) up to 24 hours postdose on Day -1 (Midazolam alone at Baseline) and Day 15

Interventionng*hrs/mL (Geometric Mean)
Midazolam AloneMidazolam + Cefiderocol
Cefiderocol Plus Midazolam66.1377.37

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Maximum Observed Plasma Concentration (Cmax) of Midazolam

This outcome measure presents the effects of repeated doses of cefiderocol on the pharmacokinetics of midazolam. Cmax is reported as nanograms/milliliter (ng/mL). Day -1 is defined as Baseline. (NCT05395104)
Timeframe: 0 (predose) up to 24 hours postdose on Day -1 (Midazolam alone at Baseline) and Day 15

Interventionng/mL (Geometric Mean)
Midazolam AloneMidazolam + Cefiderocol
Cefiderocol Plus Midazolam25.328.8

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Terminal Elimination Half-life (t1/2,z) of Midazolam

This outcome measure presents the effects of repeated doses of cefiderocol on the pharmacokinetics of midazolam. t1/2,z was calculated as: (ln2)/λz on Days -1 and 15. Day -1 is defined as Baseline. (NCT05395104)
Timeframe: 0 (predose) up to 24 hours postdose on Day -1 (Midazolam alone at Baseline) and Day 15

Interventionhrs (Geometric Mean)
Midazolam AloneMidazolam + Cefiderocol
Cefiderocol Plus Midazolam5.396.10

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Terminal Elimination Rate Constant (λz) of Midazolam

This outcome measure presents the effects of repeated doses of cefiderocol on the pharmacokinetics of midazolam. λz is the magnitude of the slope of the linear regression of the log concentration versus time profile during the terminal phase on Days -1 and 15 and is reported as 1/hours (1/h). Day -1 is defined as Baseline. (NCT05395104)
Timeframe: 0 (predose) up to 24 hours postdose on Day -1 (Midazolam alone at Baseline) and Day 15

Intervention1/hrs (Geometric Mean)
Midazolam AloneMidazolam + Cefiderocol
Cefiderocol Plus Midazolam0.12870.1135

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Time to Maximum Plasma Concentration (Tmax) of Midazolam

This outcome measure presents the effects of repeated doses of cefiderocol on the pharmacokinetics of midazolam. Tmax is reported in hours (hrs). Day -1 is defined as Baseline. (NCT05395104)
Timeframe: 0 (predose) up to 24 hours postdose on Day -1 (Midazolam alone at Baseline) and Day 15

Interventionhrs (Median)
Midazolam AloneMidazolam + Cefiderocol
Cefiderocol Plus Midazolam0.510.51

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Area Under the Concentration-time Curve Extrapolated From Time 0 to Infinity (AUC0-inf) of Midazolam

This outcome measure presents the effects of repeated doses of cefiderocol on the pharmacokinetics of midazolam. AUC0-inf was calculated as: AUC0-last + [Clast/λz], where Clast is the last measured concentration and λz is the plasma terminal elimination rate constant on Days -1 and 15. Day -1 is defined as Baseline. (NCT05395104)
Timeframe: 0 (predose) up to 24 hours postdose on Day -1 (Midazolam alone at Baseline) and Day 15

Interventionng*hrs/mL (Geometric Mean)
Midazolam AloneMidazolam + Cefiderocol
Cefiderocol Plus Midazolam68.6981.07

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Apparent Volume of Distribution (Vz/F) of Midazolam

This outcome measure presents the effects of repeated doses of cefiderocol on the pharmacokinetics of midazolam. Vz/F was calculated as: Dose/AUC0-inf/λz on Days -1 and 15 and is reported as liters. Day -1 is defined as Baseline. (NCT05395104)
Timeframe: 0 (predose) up to 24 hours postdose on Day -1 (Midazolam alone at Baseline) and Day 15

Interventionliters (Geometric Mean)
Midazolam AloneMidazolam + Cefiderocol
Cefiderocol Plus Midazolam538543

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Apparent Total Clearance (CL/F) of Midazolam

This outcome measure presents the effects of repeated doses of cefiderocol on the pharmacokinetics of midazolam. CL/F was calculated as: Dose/AUC0-inf on Days -1 and 15 and is reported as liters/hr. Day -1 is defined as Baseline. (NCT05395104)
Timeframe: 0 (predose) up to 24 hours postdose on Day -1 (Midazolam alone at Baseline) and Day 15

Interventionliters/hr (Geometric Mean)
Midazolam AloneMidazolam + Cefiderocol
Cefiderocol Plus Midazolam69.361.7

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Tmax of Cefiderocol

This outcome measure presents the pharmacokinetics of cefiderocol when coadministered with midazolam. (NCT05395104)
Timeframe: Day 15

Interventionhrs (Median)
Cefiderocol Plus Midazolam2.92

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Cmax of Cefiderocol

This outcome measure presents the pharmacokinetics of cefiderocol when coadministered with midazolam. Cmax is reported as micrograms/milliliter (μg/mL). (NCT05395104)
Timeframe: Day 15

Interventionμg/mL (Geometric Mean)
Cefiderocol Plus Midazolam80.5

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CL of Cefiderocol

This outcome measure presents the PK of cefiderocol when coadministered with midazolam. CL was calculated as: Dose/AUC0-τ on Day 15. (NCT05395104)
Timeframe: Day 15

Interventionliter/hr (Geometric Mean)
Cefiderocol Plus Midazolam5.63

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Mean Residence Time (MRT) of Midazolam

This outcome measure presents the effects of repeated doses of cefiderocol on the pharmacokinetics of midazolam. MRT was calculated as: AUMC0-inf/AUC0-inf, and AUMC0-inf is the area under the first moment curve extrapolated to infinity on Days -1 and 15. Day -1 is defined as Baseline. (NCT05395104)
Timeframe: 0 (predose) up to 24 hours postdose on Day -1 (Midazolam alone at Baseline) and Day 15

Interventionhrs (Geometric Mean)
Midazolam AloneMidazolam + Cefiderocol
Cefiderocol Plus Midazolam4.865.51

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