Page last updated: 2024-12-04

clobazam

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Description

Clobazam is a benzodiazepine derivative that is used as an anticonvulsant medication. It is thought to work by increasing the effects of a neurotransmitter called GABA in the brain. GABA is an inhibitory neurotransmitter, which means that it helps to reduce the activity of nerve cells. This can help to reduce seizures and other symptoms of epilepsy. Clobazam is also used to treat anxiety, insomnia, and muscle spasms.

Clobazam is synthesized by reacting a compound called 7-chloro-1,3-dihydro-5-phenyl-2H-1,4-benzodiazepin-2-one with 1-amino-2-propanol. The resulting product is then treated with hydrochloric acid to form the hydrochloride salt.

Clobazam can have a number of side effects, including drowsiness, dizziness, and confusion. In some cases, it can also cause more serious side effects, such as liver damage or suicidal thoughts.

Clobazam is an important medication for the treatment of epilepsy, anxiety, and other conditions. It is often used in combination with other medications to achieve the desired therapeutic effect.

Clobazam is studied for its potential to treat a variety of conditions, including epilepsy, anxiety, insomnia, and muscle spasms. Researchers are also investigating its potential as a treatment for other conditions, such as Alzheimer's disease and Parkinson's disease.

Clobazam is a controlled substance in many countries. It is important to use this medication only as prescribed by a doctor.'

Clobazam: A benzodiazepine derivative that is a long-acting GABA-A RECEPTOR agonist. It is used as an antiepileptic in the treatment of SEIZURES, including seizures associated with LENNOX-GASTAUT SYNDROME. It is also used as an anxiolytic, for the short-term treatment of acute ANXIETY. [Medical Subject Headings (MeSH), National Library of Medicine, extracted Dec-2023]

clobazam : 7-Chloro-1H-1,5-benzodiazepine-2,4(3H,5H)-dione in which the hydrogen attached to the nitrogen at position 1 is substituted by a methyl group, whilst that attached to the other nitrogen is substituted by a phenyl group. It is used for the short-term management of acute anxiety and as an adjunct in the treatment of epilepsy in association with other antiepileptics. [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 CID2789
CHEMBL ID70418
CHEBI ID31413
SCHEMBL ID43038
MeSH IDM0059171

Synonyms (100)

Synonym
onfi
7-chloro-1-methyl-5-phenyl-1h-1,5-benzodiazepine-2,4(3h,5h)-dione
1-phenyl-5-methyl-8-chloro-1,2,4,5-tetrahydro-2,4-dioxo-3h-1, 5-benzodiazepine
7-chloro-1-methyl-5-phenyl-1,5-benzodiazepine-2,4-dione
1h-1,5-benzodiazepine-2,4(3h,5h)-dione, 7-chloro-1-methyl-5-phenyl-
7-chloro-1-methyl-5-phenyl-1h-1,5-benzodiazepine-2,4-(3h,5h)-dione
clobazam
lm 2717
lm-2717
urbanyl
h 4723
nsc336279
nsc-336279
h-4723
7-chloro-1-methyl-5-phenyl-1h-1,4(3h,5h)-dione
hr 376
wln: t67 gnv jvn ihj cg g1 kr
22316-47-8
7-chloro-1-methyl-5-phenyl-1h-1,4-(3h,5h)-dione
ru-4723
1h-1,4(3h,5h)-dione, 7-chloro-1-methyl-5-phenyl-
chlorepin
clorepin
1-phenyl-5-methyl-8-chloro-1,4,5-tetrahydro-2,4-dioxo-3h-1,5-benzodiazepine
frisium
1-phenyl-5-methyl-8-chloro-1,2,4,5-tetrahydro-2,4-diketo-3h-1,5-benzodiazepine
einecs 244-908-7
dea no. 2751
brn 0758410
clobazamum [inn-latin]
nsc 336279
ccris 7506
1-phenyl-5-methyl-8-chloro-1,2,4,5-tetrahydro-2,4-dioxo-3h-1,5-benzodiazepine
7-chloro-1-methyl-5-phenyl-1,5-dihydro-benzo[b][1,4]diazepine-2,4-dione
DB00349
onfi (tn)
mystan (tn)
clobazam (jan/usan/inn)
D01253
NCGC00168249-01
mystan
CHEMBL70418
urbadan
hr-376
colbazam
CHEBI:31413 ,
clobazamum
tox21_112608
dtxcid0026759
dtxsid2046759 ,
cas-22316-47-8
hsdb 8343
urbanil
clobazam [usan:inn:ban]
odipam
caastilium
noiafren
unii-2mro291b4u
2mro291b4u ,
5-24-08-00034 (beilstein handbook reference)
MLS003899217
smr000058811
clobazam [orange book]
clobazam [mi]
clobazam [who-dd]
clobazam [usan]
colbazam [vandf]
clobazam [jan]
sympazan
clobazam [mart.]
clobazam [vandf]
clobazam [ep monograph]
clobazam [inn]
7-chloro-1-methyl-5-phenyl-2,3,4,5-tetrahydro-1h-1,5-benzodiazepine-2,4-dione
gtpl7149
urbanol
SCHEMBL43038
1-phenyl 5-methyl 8-chloro 1,2,4,5-tetrahydro 2,4-dioxo 3h-1,5-benzodiazepine
1-phenyl 5-methyl 8-chloro 1,2,4,5-tetrahydo 2,4-dioxo 3h-1,5-benzodiazepine
clobazepam
AKOS025401921
sr-01000937603
SR-01000937603-2
CS-6756
HY-A0041
clobazam 0.1 mg/ml in methanol
clobazam 1.0 mg/ml in methanol
bdbm50247888
perizam
tapclob
Q412164
7-chloro-1-methyl-5-phenyl-1,5-benzodiazepine-2,4(3h)-dione
C-2991
clobazamum (inn-latin)
clobazam (ep monograph)
clobazam (mart.)
7-chloro-1-methyl-5-phenyl-1,5-dihydro-benzo(b)(1,4)diazepine-2,4-dione
n05ba09
clobazamum (latin)
clobazam, 1mg/ml in methanol

Research Excerpts

Overview

Clobazam is a 1,5-benzodiazepine that has been widely used as an anxiolytic and antiseizure drug (ASD) since it was first synthesized over 50 years ago. It is an effective agent to use as add-on AED in TRE, with 94% of patients showing a significant response within 6 months.

ExcerptReferenceRelevance
"Clobazam is a well-known benzodiazepine used as an anti-anxiety drug as well as an anti-epileptic, particularly for patients who are not responding to first-line treatments. "( Identification of novel signal of clobazam-associated drug reaction with eosinophilia and systemic symptoms syndrome: A disproportionality analysis.
Kumar, A; Sharma, A, 2022
)
2.44
"Clobazam is a 1,5-benzodiazepine that has been approved for use, in various parts of the world, as an add-on treatment for seizure disorders and as a treatment for anxiety. "( Gestational Exposure to Benzodiazepines, 3: Clobazam and Major Congenital Malformations.
Andrade, C, 2019
)
2.22
"Clobazam is an effective agent to use as add-on AED in TRE, with 94% of patients showing a significant response within 6 months. "( Efficacy of clobazam as add-on therapy in brain tumor-related epilepsy.
Bachman, E; Brahmbhatt, N; Bushara, O; Schuele, SU; Stupp, R; Templer, JW, 2021
)
2.44
"Clobazam (CLB) is an effective anticonvulsant used as an adjunctive treatment for several seizures and epilepsy syndromes. "( CLB add-on treatment in patients with epileptic encephalopathy: a single center experience with long-term follow-up.
Öztürk, G; Türkdoğan, D, 2022
)
2.16
"Clobazam (CLB) is a 1,5-benzodiazepine that has been widely used as an anxiolytic and antiseizure drug (ASD) since it was first synthesized over 50 years ago. "( A Comprehensive Overview of the Clinical Pharmacokinetics of Clobazam.
Larsen, F; Tolbert, D, 2019
)
2.2
"Clobazam is a commonly used long-acting benzodiazepine approved by the US Food and Drug Administration (FDA) to treat seizures associated with Lennox Gastaut syndrome. "( Safety and Efficacy of Supratherapeutic Doses of Clobazam.
Freedman, DA; Gedela, S; Glynn, P; Patel, AD; Salvator, A, 2019
)
2.21
"Clobazam (CLB) is a 1,5-benzodiazepine with antiepileptic properties. "( Effects of CYP2C19 and P450 oxidoreductase polymorphisms on the population pharmacokinetics of clobazam and N-desmethylclobazam in japanese patients with epilepsy.
Ishitsu, T; Kaneko, S; Nagata, R; Nakagawa, K; Nakashima, H; Nishimura, M; Ogusu, N; Saruwatari, J; Seo, T; Shimomasuda, M; Tanikawa, K; Tsuda, Y; Yasui-Furukori, N, 2014
)
2.06
"Clobazam is a well-tolerated antiepileptic drug with good response rates in pediatric patients with refractory epilepsy."( Clobazam: effect on frequency of seizures and safety profile in different subgroups of children with epilepsy.
Bergin, AM; Bolton, J; Bourgeois, B; Harini, C; Kadish, NE; Klehm, J; Libenson, M; Loddenkemper, T; Peters, J; Poduri, A; Rotenberg, A; Sánchez Fernández, I; Takeoka, M; Thome-Souza, S, 2014
)
3.29
"Clobazam is an oral 1,5-benzodiazepine used worldwide for the treatment of many types of epilepsies, although it is currently only approved for Lennox-Gastaut syndrome in the USA. "( Clobazam: A Safe, Efficacious, and Newly Rediscovered Therapeutic for Epilepsy.
Gauthier, AC; Mattson, RH, 2015
)
3.3
"Clobazam (CLB) is an antiepileptic drug that is metabolized to the major metabolite N-desmethylclobazam (N-CLB). "( Correlating blood and urinary concentrations of clobazam doses in Japanese children and adolescents with intractable epilepsy.
Ishida, T; Ishii, M; Iwasaki, T; Nonoda, Y; Toki, T, 2017
)
2.15
"Clobazam (CLB) is a well characterized antiepileptic drug (AED) that differs from other benzodiazepines by its basic chemical structure and pharmacodynamic properties. "( Effects of clobazam for treatment of refractory status epilepticus.
Gerner, ST; Geyer, A; Gollwitzer, S; Hamer, HM; Huttner, HB; Knappe, RU; Kuramatsu, JB; Madžar, D, 2016
)
2.27
"Clobazam was observed to be an effective broad-spectrum antiepileptic with 'mild' side effects in Indian children."( Clobazam in refractory childhood epilepsy.
Kalra, V; Mishra, D; Saha, NC; Seth, R, 2010
)
3.25
"Clobazam is a 1,5 benzodiazepine available in France since 1975, used in add-on with the other anticonvulsant drugs in the treatment of refractory epilepsies of child and adult and for the treatment of anxiety of adult. "( [Therapeutic drug monitoring of clobazam].
Bentué-Ferrer, D; Debruyne, D; Tribut, O; Verdier, MC,
)
1.86
"Clobazam is a benzodiazepine with anti-anxiety and anticonvulsant properties marketed in several countries. "( Blood concentrations of clobazam and norclobazam in a lethal case involving clobazam, meprobamate and clorazepate.
Charpenel-Durat, C; De Meo, P; De Saint Léger, MN; Duval, ML; Kuhlmann, E; Mauras, M; Navarette, C; Pok, PR, 2010
)
2.11
"Clobazam is a promising antiepileptic medication, given its effectiveness and relatively low rates of adverse effects."( Clobazam for patients with Lennox-Gastaut syndrome and epilepsy.
Ng, YT; Seif-Eddeine, H, 2012
)
2.54
"Clobazam is a 1,5-BZD, which exhibits less cognitive side effects than other benzodiazepines."( Antihyperalgesic effect of the GABA(A) ligand clobazam in a neuropathic pain model in mice: a pharmacokinetic-pharmacodynamic study.
Besson, M; Daali, Y; Dayer, P; Desmeules, J; Di Lio, A; Zeilhofer, HU, 2013
)
1.37
"Clobazam (CLB) is a 1,5-benzodiazepine, which is known to be effective for treating refractory partial epilepsy. "( Long-term use of clobazam in Lennox-Gastaut syndrome: experience in a single tertiary epilepsy center.
Choi, HW; Ko, TS; Lee, EH; Yum, MS,
)
1.91
"Clobazam is a benzodiazepine with known antiepileptic action; however, it is not considered first line therapy in the treatment of epilepsy. "( Clobazam as add-on therapy for temporal lobe epilepsy and hippocampal sclerosis.
Cendes, F; Ferreira, CM; Guerreiro, CA; Li, LM; Montenegro, MA, 2005
)
3.21
"Clobazam is a derivative of the benzodiazepines used as an anti-epileptics drug. "( Neuroembryopathic effect of clobazam in rat: a histological study.
Gupta, S; Pandey, SK, 2005
)
2.07
"Clobazam1 is a 1,5-benzodiazepine with antianxiety and anticonvulsant properties, advocated for the treatment of primary anxiety and that associated with organic or functional disorders. "( Clobazam: a review of its pharmacological properties and therapeutic use in anxiety.
Avery, GS; Brogden, RN; Heel, RC; Speight, TM, 1980
)
3.15
"Clobazam is a 1,5-benzodiazepine reported to have a wide spectrum of antiepileptic activity and is associated with less neurotoxicity than the 1,4-benzodiazepines, nitrazepam and clonazepam. "( Open study of clobazam in refractory epilepsy.
Farrell, K; Munn, R,
)
1.93
"Clobazam (CLB) is a structurally unique benzodiazepine (BZD) that has anticonvulsant activity in all types of refractory seizures. "( Clobazam in long-term epilepsy treatment: sustained responders versus those developing tolerance.
Boisvert, D; Guberman, AH; Singh, A, 1995
)
3.18
"Clobazam is a useful add-on medication for 65% of children with epilepsy."( Clobazam for intractable pediatric epilepsy.
Bodensteiner, JB; Goulden, KJ; Penney, S; Ronen, GM; Sheth, RD, 1995
)
2.46
"Clobazam is a 1,5-benzodiazepine effective in antiepileptic therapy of children and adults. "( Interactions of clobazam with conventional antiepileptics in children.
Cortez, M; Daneman, R; Hwang, P; Koren, G; Menzano, E; Sherwin, AL; Theis, JG, 1997
)
2.09
"Clobazam is a newer 1,5-benzodiazepine used for the treatment of epilepsy. "( Clobazam for the treatment of intractable childhood epilepsy.
Jan, MM; Shaabat, AO, 2000
)
3.19
"Clobazam is a well tolerated, safe, and very effective antiepileptic drug. "( Clobazam for the treatment of intractable childhood epilepsy.
Jan, MM; Shaabat, AO, 2000
)
3.19
"Clobazam (CLB) is a new antiepileptic drug that is the first 1,5-benzodiazepine (BZP) having nitrogen atoms in the 1 and 5 positions of the heterocyclic ring, whose chemical structure was designed to give it a different pharmacological profile from that of 1,4-BZPs. "( [A pharmacological profile of clobazam (Mystan), a new antiepileptic drug].
Nakajima, H, 2001
)
2.04
"Clobazam appears to be a safe and effective add-on antiepileptic for a wide variety of seizure types in intractable epilepsy."( Add-on trial of clobazam in intractable adult epilepsy with plasma level correlations.
Blaschuk, K; Couture, M; Guberman, A; Sherwin, A, 1990
)
1.35
"Clobazam is a new benzodiazepine recently introduced in Canada on an experimental basis. "( Clobazam for refractory childhood seizure disorders--a valuable supplementary drug.
Camfield, C; Camfield, P; Dooley, J; Munn, R, 1988
)
3.16

Effects

Clobazam (CLB) has an important antiepileptic effect and is less expensive than the new antiePileptic drugs (AEDs) It has not been considered as first-line drug in the treatment of epilepsy.

Clobazam has been used in clinical practice as an adjunctive treatment for diverse seizure types and epilepsy syndromes. The drug is less expensive than the new antiepileptic drugs (AEDs), but still has not been considered as first-line drug in the treatment of epilepsy.

ExcerptReferenceRelevance
"Clobazam itself has a half-life of 18 hours, but that of the principal metabolite, N-desmethylclobazam, is about 50 hours."( Clobazam: a review of its pharmacological properties and therapeutic use in anxiety.
Avery, GS; Brogden, RN; Heel, RC; Speight, TM, 1980
)
2.43
"Clobazam (CLB) has an important antiepileptic effect and is less expensive than the new antiepileptic drugs (AEDs), but still has not been considered as first-line drug in the treatment of epilepsy. "( Efficacy of clobazam as add-on therapy in patients with refractory partial epilepsy.
Carvalho, MI; Cendes, F; Guerreiro, CA; Marques, LH; Montenegro, MA; Mory, SB; Noronha, AL, 2001
)
2.13
"Clobazam has been used in clinical practice as an adjunctive treatment for diverse seizure types and epilepsy syndromes. "( Clobazam: effect on frequency of seizures and safety profile in different subgroups of children with epilepsy.
Bergin, AM; Bolton, J; Bourgeois, B; Harini, C; Kadish, NE; Klehm, J; Libenson, M; Loddenkemper, T; Peters, J; Poduri, A; Rotenberg, A; Sánchez Fernández, I; Takeoka, M; Thome-Souza, S, 2014
)
3.29
"Clobazam has been reported to exhibit different in vivo adverse effects and addiction liability profile than the classic 1,4-benzodiazepines."( Functional characterization of the 1,5-benzodiazepine clobazam and its major active metabolite N-desmethylclobazam at human GABA(A) receptors expressed in Xenopus laevis oocytes.
Ebert, B; Hammer, H; Jensen, AA; Jensen, HS, 2015
)
1.39
"Clobazam has provided many benefits to epileptic patients."( Clobazam: A Safe, Efficacious, and Newly Rediscovered Therapeutic for Epilepsy.
Gauthier, AC; Mattson, RH, 2015
)
2.58
"Clobazam (CLB) has been used as an antiepileptic drug for several decades. "( Therapeutic Drug Monitoring of Clobazam and Its Metabolite-Impact of Age and Comedication on Pharmacokinetic Variability.
Baftiu, A; Burns, ML; Johannessen, SI; Landmark, CJ; Opdal, MS, 2016
)
2.16
"Clobazam has been used worldwide since the 1970s and is approved for adjunctive treatment of seizures associated with Lennox-Gastaut syndrome."( New antiepileptic drugs: focus on ezogabine, clobazam, and perampanel.
Gedzelman, ER; Karakis, I; Mauricio, EA; Rudzinski, LA; Shih, JJ; Vélez-Ruiz, NJ, 2016
)
1.42
"Clobazam (CLB) has proven efficacy against multiple seizure types. "( Efficacy of clobazam as add-on therapy for refractory epilepsy: experience at a US epilepsy center.
Arif, H; Hirsch, LJ; Montenegro, MA; Nahm, EA; Resor, SR,
)
1.95
"Clobazam has efficacy against a wide spectrum of seizure types and epilepsy etiologies."( Clobazam for the treatment of intractable epilepsy in children.
Bailey, L; Gilson, C; Hernandez, A; Kotecha, A; Malik, S; Perry, MS, 2013
)
2.55
"The clobazam C/D ratio has the potential to measure the contribution of CYP3A4 activity to the clearance of clobazam from the body."( Clobazam therapeutic drug monitoring: a comprehensive review of the literature with proposals to improve future studies.
de Leon, J; Diaz, FJ; Spina, E, 2013
)
2.31
"Clobazam has been used successfully in adults and children with partial epilepsy. "( Clobazam as add-on therapy in children with epileptic encephalopathy.
Guerreiro, CA; Guerreiro, MM; Montenegro, MA; Silva, RC, 2006
)
3.22
"Clobazam has demonstrated clinical benefit and has been administered safely in more than 50 European studies in which data were reported on greater than 3000 pediatric and adult patients with epilepsy, 300 of whom were diagnosed with LGS; therefore, its use is now being investigated in the U.S."( Clobazam.
Collins, SD; Ng, YT, 2007
)
2.5
"Clobazam itself has a half-life of 18 hours, but that of the principal metabolite, N-desmethylclobazam, is about 50 hours."( Clobazam: a review of its pharmacological properties and therapeutic use in anxiety.
Avery, GS; Brogden, RN; Heel, RC; Speight, TM, 1980
)
2.43
"Clobazam has nitrogen radicals in positions 1 and 5."( Antiepileptic effects of clobazam in children.
Abe, J; Futagi, Y; Kamio, M; Kato, M; Mimaki, T; Onoe, S; Shimizu, H; Sugita, T; Sumi, K; Tagawa, T; Yabuuchi, H; Yamatodani, A, 1982
)
1.29
"Clobazam (CLB) has an important antiepileptic effect and is less expensive than the new antiepileptic drugs (AEDs), but still has not been considered as first-line drug in the treatment of epilepsy. "( Efficacy of clobazam as add-on therapy in patients with refractory partial epilepsy.
Carvalho, MI; Cendes, F; Guerreiro, CA; Marques, LH; Montenegro, MA; Mory, SB; Noronha, AL, 2001
)
2.13

Actions

Clobazam did not produce either the objective, or the subjective impairment of performance and alertness found with lorazepam. The drug was chosen because of its relatively low sedative properties and CLN because it is used in neuropathic pain.

ExcerptReferenceRelevance
"Clobazam was chosen because of its relatively low sedative properties and CLN because of its use in neuropathic pain."( GABAergic modulation in central sensitization in humans: a randomized placebo-controlled pharmacokinetic-pharmacodynamic study comparing clobazam with clonazepam in healthy volunteers.
Besson, M; Curatolo, M; Daali, Y; Desmeules, J; Matthey, A; Poncet, A; Vuillemier, P; Zeilhofer, HU, 2015
)
1.34
"4 Clobazam did not produce either the objective, or the subjective impairment of performance and alertness found with lorazepam."( The effects of clobazam and lorazepam on aspects of psychomotor performance and car handling ability.
Gudgeon, AC; Hindmarch, I, 1980
)
1.17

Treatment

Clobazam offers a new treatment option for patients with refractory epilepsy. As an add-on treatment may reduce seizure frequency and may be most effective in partial onset seizures.

ExcerptReferenceRelevance
"Clobazam treatment was effective in reducing drop seizures regardless of aggression experience."( Clobazam and Aggression-Related Adverse Events in Pediatric Patients With Lennox-Gastaut Syndrome.
Drummond, R; Isojarvi, J; Lee, D; Paolicchi, JM; Ross, G, 2015
)
2.58
"Clobazam treatment tailored to the timing of patient's seizures may improve seizure control. "( Clobazam higher-evening differential dosing as an add-on therapy in refractory epilepsy.
Fernández, IS; Jackson, M; Kadish, NE; Klehm, J; Loddenkemper, T; Manganaro, S; Thome-Souza, S, 2016
)
3.32
"Clobazam offers a new treatment option for patients with refractory epilepsy. "( Clobazam for treatment of epilepsy.
Benbadis, SR; Giarratano, M; Standley, K, 2012
)
3.26
"Clobazam as an add-on treatment may reduce seizure frequency and may be most effective in partial onset seizures. "( Clobazam as an add-on in the management of refractory epilepsy.
Marson, AG; Michael, B, 2008
)
3.23

Toxicity

Clobazam was well tolerated, safe and more effective than phenytoin in the AED treatment of patients with SCG. Key outcomes were reduction in seizure frequency, differences in 50% responder rates, adverse events, and interactions with clobazem as co-therapy.

ExcerptReferenceRelevance
" They were followed over 6 months with the primary outcome measure being treatment failure (either discontinuation or modification of AEDs) due to either adverse effects or breakthrough seizures."( Safety and efficacy of clobazam versus phenytoin-sodium in the antiepileptic drug treatment of solitary cysticercus granulomas.
Chopra, SC; Kaushal, S; Rani, A; Singh, G, 2006
)
0.64
"2%) in the phenytoin-treated group who had adverse effects requiring treatment discontinuation."( Safety and efficacy of clobazam versus phenytoin-sodium in the antiepileptic drug treatment of solitary cysticercus granulomas.
Chopra, SC; Kaushal, S; Rani, A; Singh, G, 2006
)
0.64
"Clobazam was well tolerated, safe and more effective than phenytoin in the AED treatment of patients with SCG."( Safety and efficacy of clobazam versus phenytoin-sodium in the antiepileptic drug treatment of solitary cysticercus granulomas.
Chopra, SC; Kaushal, S; Rani, A; Singh, G, 2006
)
2.09
" The 4 most common adverse events were upper respiratory tract infection (18."( Long-term safety and efficacy of clobazam for Lennox-Gastaut syndrome: interim results of an open-label extension study.
Conry, J; Drummond, R; Isojarvi, J; Kernitsky, L; Lee, D; Mitchell, W; Ng, YT; Owen, R; Paolicchi, J, 2012
)
0.66
"3%) because adverse effects, 10 (37%) because of a lack of efficacy, and one (3."( Clobazam: effect on frequency of seizures and safety profile in different subgroups of children with epilepsy.
Bergin, AM; Bolton, J; Bourgeois, B; Harini, C; Kadish, NE; Klehm, J; Libenson, M; Loddenkemper, T; Peters, J; Poduri, A; Rotenberg, A; Sánchez Fernández, I; Takeoka, M; Thome-Souza, S, 2014
)
1.85
"To assess withdrawal-related adverse event (AE) rates following abrupt clobazam discontinuation in Phase I trials and gradual clobazam tapering (2-3 weeks) following discontinuation from III trials met the criteria for potential/III trials, we evaluated AE data from four multiple-dosage Phase I trials (duration: 8-34 days)."( Withdrawal-related adverse events from clinical trials of clobazam in Lennox-Gastaut syndrome.
Bekersky, I; Harris, SI; Isojarvi, J; Lee, D; Tolbert, D, 2014
)
0.88
" No differences in efficacy or adverse events were observed across age groups in OV-1012 and OV-1004."( Clobazam is equally safe and efficacious for seizures associated with Lennox-Gastaut syndrome across different age groups: Post hoc analyses of short- and long-term clinical trial results.
Buchhalter, J; Chung, S; Conry, J; Drummond, R; Isojarvi, J; Lee, D; Mitchell, WG; Ng, YT, 2015
)
1.86
" Twenty-two patients experienced stiripentol-related adverse events, with two having severe ones."( Long-term safety and efficacy of stiripentol for the treatment of Dravet syndrome: A multicenter, open-label study in Japan.
Inoue, Y; Ohtsuka, Y, 2015
)
0.42
"During adjunctive stiripentol use with clobazam and valproate, careful monitoring for adverse events such as somnolence and loss of appetite is recommended, and dose reduction may become needed for any of the antiepileptics."( Long-term safety and efficacy of stiripentol for the treatment of Dravet syndrome: A multicenter, open-label study in Japan.
Inoue, Y; Ohtsuka, Y, 2015
)
0.69
" Data from 194 patients were analyzed for a history of aggression/behavioral problems, occurrence of aggression-related adverse events, and by assessment of potential drug-related effects on four behavior domains of the Child Behavior Checklist."( Clobazam and Aggression-Related Adverse Events in Pediatric Patients With Lennox-Gastaut Syndrome.
Drummond, R; Isojarvi, J; Lee, D; Paolicchi, JM; Ross, G, 2015
)
1.86
"Twenty-nine aggression-related adverse events were reported for 27 (13."( Clobazam and Aggression-Related Adverse Events in Pediatric Patients With Lennox-Gastaut Syndrome.
Drummond, R; Isojarvi, J; Lee, D; Paolicchi, JM; Ross, G, 2015
)
1.86
" Treatment emergent adverse events (TEAEs) occurred for 80."( Evaluation of diazepam nasal spray in patients with epilepsy concomitantly using maintenance benzodiazepines: An interim subgroup analysis from a phase 3, long-term, open-label safety study.
Biton, V; Carrazana, E; Cascino, GD; Cook, DF; Desai, J; Dlugos, D; Hogan, RE; Liow, K; Miller, I; Rabinowicz, AL; Segal, EB; Sperling, MR; Tarquinio, D; Vazquez, B; Wheless, JW, 2021
)
0.62
" ≥50% reduction in drop seizure frequency from baseline and occurrence of treatment-emergent adverse events (TEAEs) were the primary efficacy and safety outcomes."( Short-term and long-term efficacy and safety of antiseizure medications in Lennox Gastaut syndrome: A network meta-analysis.
Ameen, R; Bansal, D; Devi, N; Madaan, P; Sahu, JK, 2022
)
0.72
" The mainstay of treatment is with multiple anti-seizure medications (ASMs); however, the ASMs themselves can be associated with psychobehavioural adverse events, and effects (negative or positive) on cognition and sleep."( Psychobehavioural and Cognitive Adverse Events of Anti-Seizure Medications for the Treatment of Developmental and Epileptic Encephalopathies.
Schubert-Bast, S; Strzelczyk, A, 2022
)
0.72
" The key outcomes were reduction in seizure frequency, differences in 50% responder rates, adverse events, and interactions with clobazam as co-therapy."( Clinical efficacy and safety of cannabidiol for pediatric refractory epilepsy indications: A systematic review and meta-analysis.
Aparasu, R; Estes, E; Reddy, DS; Talwar, A, 2023
)
1.12
"The aim of this study was to compare the safety profile of newer ASMs with older ASMs through an analysis of the US Food and Drug Administration Adverse Event Reporting System (FAERS) database, with a focus on suicidality."( Newer Antiseizure Medications and Suicidality: Analysis of the Food and Drug Administration Adverse Event Reporting System (FAERS) Database.
Doughty, BJ; Hurd, KL; Leppien, EE; McCall, KL; Piper, BJ; Strong, KN, 2023
)
0.91
" The results of this case control study of FDA adverse event reports spanning 10 years and 6309 cases of suicidality expand our understanding of the safety profile of newer ASMs."( Newer Antiseizure Medications and Suicidality: Analysis of the Food and Drug Administration Adverse Event Reporting System (FAERS) Database.
Doughty, BJ; Hurd, KL; Leppien, EE; McCall, KL; Piper, BJ; Strong, KN, 2023
)
0.91

Pharmacokinetics

This is the first simultaneous pharmacokinetic model for clobazam and N-CLB in epileptic children. Coadministration of ketoconazole (a CYP3A4 inhibitor) and clobzam increased clobZam's area under the concentration time curve from time zero extrapolated to infinity.

ExcerptReferenceRelevance
" The pharmacodynamic effects of buspirone and clobazam were compared in two volunteer studies."( Pharmacodynamic effects of buspirone and clobazam.
Alford, C; Bhatti, JZ; Curran, S; Hindmarch, I; McKay, G, 1991
)
0.81
" Steady-state pharmacokinetic data are described from four healthy male volunteers and eight epileptic patients taking NDMC."( Pharmacokinetics of N-desmethylclobazam in healthy volunteers and patients with epilepsy.
Feely, MP; Haigh, JR; Peaker, S; Pullar, T, 1987
)
0.56
" 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
"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
"The pharmacokinetic interaction between clobazam and cimetidine was studied in 9 healthy male volunteers in an open-labelled study."( Pharmacokinetic aspects of the interaction between clobazam and cimetidine.
Grigoleit, HG; Hajdú, P; Hundt, HK; Koeppen, D; Malerczyk, V; Meyer, BH; Müller, FO; Witte, PU, 1983
)
0.79
" Among all subjects, pharmacokinetic variables for clobazam determined in a previous single-dose study were highly consistent with the multiple-dose pharmacokinetic profile."( Reduced single-dose clearance of clobazam in elderly men predicts increased multiple-dose accumulation.
Divoll, M; Greenblatt, DJ; Ho, I; Puri, SK; Shader, RI; Zinny, MA,
)
0.66
"The pharmacokinetic effect of a single oral in dose of 20 mg clobazam was studied in 15 patients with liver disease and in 6 healthy volunteers."( Pharmacokinetics of a single oral dose of clobazam in patients with liver disease.
Antoni, M; Botta-Frindlund, D; Bun, H; Cano, JP; Durand, A; Gauthier, A; Monjanel-Mouterde, S, 1994
)
0.79
"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
)
0.87
" The blood and brain kinetics of clobazam were linear over the range of doses tested with a short half-life of the parent compound and a ready penetration of the blood-brain barrier."( Antihyperalgesic effect of the GABA(A) ligand clobazam in a neuropathic pain model in mice: a pharmacokinetic-pharmacodynamic study.
Besson, M; Daali, Y; Dayer, P; Desmeules, J; Di Lio, A; Zeilhofer, HU, 2013
)
0.93
" The aim of this study was to evaluate the impact of the CYP2C19 and POR genotypes on the pharmacokinetic parameters of CLB and N-CLB."( Effects of CYP2C19 and P450 oxidoreductase polymorphisms on the population pharmacokinetics of clobazam and N-desmethylclobazam in japanese patients with epilepsy.
Ishitsu, T; Kaneko, S; Nagata, R; Nakagawa, K; Nakashima, H; Nishimura, M; Ogusu, N; Saruwatari, J; Seo, T; Shimomasuda, M; Tanikawa, K; Tsuda, Y; Yasui-Furukori, N, 2014
)
0.62
"To develop a physiologically based pharmacokinetic model in adults and children for clobazam, its active metabolite norclobazam and stiripentol and to account for significant clinical interaction that has been reported when clobazam and stiripentol are co-administered."( A physiologically based pharmacokinetic model for clobazam and stiripentol in adults and children.
Aarons, L; Ogungbenro, K, 2015
)
0.89
"Thirty-five children with epilepsy were included in a prospective population pharmacokinetic study (using NONMEM(®) software)."( Pharmacokinetics of clobazam and N-desmethylclobazam in children with dravet syndrome receiving concomitant stiripentol and valproic Acid.
Chhun, S; Chiron, C; Dulac, O; Jullien, V; Pons, G; Rey, E; Tod, M, 2015
)
0.74
"This is the first simultaneous pharmacokinetic model for clobazam and N-CLB in epileptic children."( Pharmacokinetics of clobazam and N-desmethylclobazam in children with dravet syndrome receiving concomitant stiripentol and valproic Acid.
Chhun, S; Chiron, C; Dulac, O; Jullien, V; Pons, G; Rey, E; Tod, M, 2015
)
0.99
"A metabolic mechanism-based characterization of antiepileptic drug-drug interactions (DDIs) with clobazam in patients with Lennox-Gastaut syndrome (LGS) was performed using a population pharmacokinetic (PPK) approach."( Drug-metabolism mechanism: Knowledge-based population pharmacokinetic approach for characterizing clobazam drug-drug interactions.
Bekersky, I; Chu, HM; Ette, EI; Tolbert, D, 2016
)
0.87
" There is still insufficient data regarding its pharmacokinetic variability in clinical practice."( Therapeutic Drug Monitoring of Clobazam and Its Metabolite-Impact of Age and Comedication on Pharmacokinetic Variability.
Baftiu, A; Burns, ML; Johannessen, SI; Landmark, CJ; Opdal, MS, 2016
)
0.72
"The pharmacokinetic variability of CLB and its metabolite NCLB in clinical practice is extensive, and is influenced by drug-drug interactions, age, and pharmacogenetics."( Therapeutic Drug Monitoring of Clobazam and Its Metabolite-Impact of Age and Comedication on Pharmacokinetic Variability.
Baftiu, A; Burns, ML; Johannessen, SI; Landmark, CJ; Opdal, MS, 2016
)
0.72
" The half-life of CLB after a single oral dose ranges from 36 to 42 hours; the half-life of N-desmethylclobazam ranges from 59 to 74 hours."( A Comprehensive Overview of the Clinical Pharmacokinetics of Clobazam.
Larsen, F; Tolbert, D, 2019
)
0.97
" Pharmacokinetic sampling for clobazam and N-desmethylclobazam was carried out until 21 days postdose with a 28-day washout."( Pharmacokinetics of clobazam oral soluble film.
Buan, CV; Heller, AH; Jung, C; Schobel, AM; Wargacki, S; Wyatt, DJ, 2018
)
1.09
" However, the intrinsic anticonvulsant activity of CBD has been questioned due to a pharmacokinetic interaction between CBD and a first-line medication, clobazam."( Coadministered cannabidiol and clobazam: Preclinical evidence for both pharmacodynamic and pharmacokinetic interactions.
Abelev, SV; Absalom, NL; Anderson, LL; Arnold, JC; Chebib, M; Doohan, PT; Low, IK; Martin, LJ; McGregor, IS, 2019
)
1
"Our study highlights the involvement of both pharmacodynamic and pharmacokinetic interactions between CBD and clobazam that may contribute to its efficacy in Dravet syndrome."( Coadministered cannabidiol and clobazam: Preclinical evidence for both pharmacodynamic and pharmacokinetic interactions.
Abelev, SV; Absalom, NL; Anderson, LL; Arnold, JC; Chebib, M; Doohan, PT; Low, IK; Martin, LJ; McGregor, IS, 2019
)
1.01
" The aim was to use long-term TDM to investigate pharmacokinetic variability of ASMs in these patients."( Pharmacokinetic Variability During Long-Term Therapeutic Drug Monitoring of Valproate, Clobazam, and Levetiracetam in Patients With Dravet Syndrome.
Bjørnvold, M; Burns, ML; Heger, K; Johannessen Landmark, C; Johannessen, SI; Lund, C; Sætre, E, 2020
)
0.78
" Pharmacokinetic variability of the total number of measurements of valproate (n = 417), clobazam and N-desmethylclobazam (n = 328), and levetiracetam (n = 238) was determined."( Pharmacokinetic Variability During Long-Term Therapeutic Drug Monitoring of Valproate, Clobazam, and Levetiracetam in Patients With Dravet Syndrome.
Bjørnvold, M; Burns, ML; Heger, K; Johannessen Landmark, C; Johannessen, SI; Lund, C; Sætre, E, 2020
)
1
" Pharmacokinetic variability and interactions can thus be identified and adjusted to facilitate decision making to achieve the optimal treatment outcome."( Pharmacokinetic Variability During Long-Term Therapeutic Drug Monitoring of Valproate, Clobazam, and Levetiracetam in Patients With Dravet Syndrome.
Bjørnvold, M; Burns, ML; Heger, K; Johannessen Landmark, C; Johannessen, SI; Lund, C; Sætre, E, 2020
)
0.78
" The most important pharmacokinetic parameters of the chosen 29 AEDs, mechanism of action and clinical application, as well as their biotransformation, are presented."( Pharmacokinetic Drug-Drug Interactions among Antiepileptic Drugs, Including CBD, Drugs Used to Treat COVID-19 and Nutrients.
Główka, AK; Główka, FK; Karaźniewicz-Łada, M; Mikulska, AA, 2021
)
0.62
" VPA showed a relatively short half-life in both mice and rats, which correlated with a sharp decline in efficacy."( Evaluating the efficacy of prototype antiseizure drugs using a preclinical pharmacokinetic approach.
Johnson, K; Mensah, JA; Metcalf, CS; Reilly, CA; Rower, JE; Wilcox, KS, 2022
)
0.72
"Report insights into the pharmacokinetic and pharmacodynamic interaction between cenobamate (CNB) and clobazam (CLB), derived from data in patients enrolled at our center in a global multicenter open-label safety study of CNB."( The cenobamate-clobazam interaction- evidence of synergy in addition to pharmacokinetic interaction.
Abou-Khalil, B; Osborn, M, 2023
)
1.48
" To support the use of cenobamate monotherapy, this pharmacokinetic (PK)-based simulation analysis evaluated the predicted PK exposure of cenobamate when used as monotherapy versus adjunctive therapy."( Pharmacokinetics of cenobamate as monotherapy compared with adjunctive therapy.
Ferrari, L; Kamin, M; Rosenfeld, WE; Vashi, V, 2023
)
0.91
"A population pharmacokinetic (PopPK) model of cenobamate was developed using pooled human data from eight phase 1 studies in healthy subjects or special populations, and three phase 2 and 3 studies in patients with focal seizures (N = 960)."( Pharmacokinetics of cenobamate as monotherapy compared with adjunctive therapy.
Ferrari, L; Kamin, M; Rosenfeld, WE; Vashi, V, 2023
)
0.91

Compound-Compound Interactions

The open-label, fixed-sequence, drug-drug interaction, healthy volunteer trial investigated the impact of cannabidiol on steady-state pharmacokinetics of clobazam, stiripentol, and valproate. When pantoprazole is used in combination with clobzam, dose reduction should be considered, or significance of PPIs is seen to avoid adverse effects.

ExcerptReferenceRelevance
"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
)
0.89
"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
)
0.64
"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
)
0.64
"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
)
0.86
" 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
)
0.86
"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
)
0.87
" Because CLB and CBD are both metabolized in the cytochrome P450 (CYP) pathway, we predicted a drug-drug interaction, which we evaluate in this article."( Drug-drug interaction between clobazam and cannabidiol in children with refractory epilepsy.
Bruno, PL; Geffrey, AL; Pollack, SF; Thiele, EA, 2015
)
0.71
"A metabolic mechanism-based characterization of antiepileptic drug-drug interactions (DDIs) with clobazam in patients with Lennox-Gastaut syndrome (LGS) was performed using a population pharmacokinetic (PPK) approach."( Drug-metabolism mechanism: Knowledge-based population pharmacokinetic approach for characterizing clobazam drug-drug interactions.
Bekersky, I; Chu, HM; Ette, EI; Tolbert, D, 2016
)
0.87
"Pharmacokinetic variability of CLB in pediatric patients is extensive, and it is influenced by drug-drug interactions and age."( Impact of Drug Interactions on Clobazam and N-Desmethylclobazam Concentrations in Pediatric Patients With Epilepsy.
Phelps, SJ; Russell, GR; Shelton, CM; Wheless, JW, 2018
)
0.77
"Phase I, open-label, randomized, single-dose, 3-period crossover study assessing pharmacokinetics (PK) and safety of ZX008, a liquid oral formulation of fenfluramine (FFA) under development for adjunctive treatment of Dravet syndrome and Lennox-Gastaut syndrome, administered with and without a combined antiepileptic drug (AED) regimen of stiripentol (STP), valproate (VPA), and clobazam (CLB) (STP regimen)."( A phase I, randomized, open-label, single-dose, 3-period crossover study to evaluate the drug-drug interaction between ZX008 (fenfluramine HCl oral solution) and a regimen of stiripentol, clobazam, and valproate in healthy subjects
.
Boyd, B; Farfel, GM; Galer, BS; Gammaitoni, A; Smith, S, 2019
)
0.87
" This open-label, fixed-sequence, drug-drug interaction, healthy volunteer trial investigated the impact of cannabidiol on steady-state pharmacokinetics of clobazam (and N-desmethylclobazam), stiripentol, and valproate; the reciprocal effect of clobazam, stiripentol, and valproate on cannabidiol and its major metabolites (7-hydroxy-cannabidiol [7-OH-CBD] and 7-carboxy-cannabidiol [7-COOH-CBD]); and cannabidiol safety and tolerability when coadministered with each antiepileptic drug."( A Phase 1, Open-Label, Pharmacokinetic Trial to Investigate Possible Drug-Drug Interactions Between Clobazam, Stiripentol, or Valproate and Cannabidiol in Healthy Subjects.
Blakey, G; Crockett, J; Morrison, G; Sommerville, K, 2019
)
0.93
" In the secondary analyses, participants were divided into groups depending on whether they were taking at least 1/4 of the other AEDs shown to interact with CBD (iAED)."( Drug-drug interactions with cannabidiol (CBD) appear to have no effect on treatment response in an open-label Expanded Access Program.
Ampah, SB; Bebin, EM; Cutter, GR; Gaston, TE; Grayson, LP; Liu, Y; Szaflarski, JP, 2019
)
0.51
" When pantoprazole is used in combination with clobazam, dose reduction of clobazam should be considered, or significance of PPIs is seen to avoid adverse effects."( Clinical Impact of Co-medication of Levetiracetam and Clobazam with Proton Pump Inhibitors: A Drug Interaction Study.
Baddam, R; Gone, V; Pasupuleti, B; Prasad, OP; Venisetty, RK, 2020
)
1.06
" It is important to consider the possibility of drug-drug interactions (DDIs)."( Clinical implications of trials investigating drug-drug interactions between cannabidiol and enzyme inducers or inhibitors or common antiseizure drugs.
Critchley, D; Gidal, B; Morrison, G; Patsalos, PN; Szaflarski, JP; VanLandingham, K, 2020
)
0.56
" The purpose of this review is to present data from the last few years on drug-drug interactions among of AEDs, as well as AEDs with other drugs, nutrients and food."( Pharmacokinetic Drug-Drug Interactions among Antiepileptic Drugs, Including CBD, Drugs Used to Treat COVID-19 and Nutrients.
Główka, AK; Główka, FK; Karaźniewicz-Łada, M; Mikulska, AA, 2021
)
0.62
"The aim of this study was to assess potential drug-drug interactions between highly purified cannabidiol (CBD) and anti-seizure medications (ASMs)."( Final analysis of potential drug-drug interactions between highly purified cannabidiol and anti-seizure medications in an open-label expanded access program.
Bebin, EM; Cutter, GR; Gaston, TE; Grayson, L; Szaflarski, JP, 2023
)
0.91

Bioavailability

The study looked at the bioavailability of clobazam following ingestion of 10, 20 and 40 mg doses. Data from 153 patients with LGS in study OV-1012 (NCT00518713) and 18 healthy participants in bioavailability study Ov-1017 were pooled.

ExcerptReferenceRelevance
" This would suggest that cimetidine either increases the bioavailability of clobazam or reduces that of NDMC."( The effect of cimetidine on the single dose pharmacokinetics of oral clobazam and N-desmethylclobazam.
Edwards, D; Feely, MP; Haigh, JR; Peaker, S; Pullar, T, 1987
)
0.74
"It is evident that substantial intersubject and intrasubject varition in the bioavailability of clobazam exists following ingestion of 10, 20 and 40 mg doses in these 12 volunteers."( Plasma levels of clobazam after 10-, 20-, and 40-mg tablet doses in healthy subjects.
Brown, WJ; Honigberg, IL; Kotzan, JA; Needham, TE; Stewart, JT; Vallner, JJ, 1980
)
0.82
" Peak plasma levels were significantly lower when the drug was taken with or after meals suggesting that the rate of absorption was reduced by food."( No effect of food intake on clobazam absorption.
Brachet-Liermain, A; Cenraud, B; Guyot, M; Levy, RH; Loiseau, P; Moreland, TA; Morselli, PL, 1983
)
0.56
"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
" To characterize potential DDIs with clobazam, pharmacokinetic (PK) data from 153 patients with LGS in study OV-1012 (NCT00518713) and 18 healthy participants in bioavailability study OV-1017 were pooled."( Drug-metabolism mechanism: Knowledge-based population pharmacokinetic approach for characterizing clobazam drug-drug interactions.
Bekersky, I; Chu, HM; Ette, EI; Tolbert, D, 2016
)
0.92
"The ATP-binding cassette transporter P-glycoprotein (P-gp) is known to limit both brain penetration and oral bioavailability of many chemotherapy drugs."( A High-Throughput Screen of a Library of Therapeutics Identifies Cytotoxic Substrates of P-glycoprotein.
Ambudkar, SV; Brimacombe, KR; Chen, L; Gottesman, MM; Guha, R; Hall, MD; Klumpp-Thomas, C; Lee, OW; Lee, TD; Lusvarghi, S; Robey, RW; Shen, M; Tebase, BG, 2019
)
0.51
" Cannabidiol is rapidly absorbed and its  bioavailability increases when administered with high fat meals."( Clinical pharmacology of cannabidiol in refractory epilepsy.
Cáceres-Guido, P; Maldonado, C; Riva, N; Schaiquevich, P; Vázquez, M, 2020
)
0.56

Dosage Studied

Clobazam oral soluble film (COSF) is a novel dosage form under development for the adjunctive treatment of seizures associated with Lennox-Gastaut syndrome.

ExcerptRelevanceReference
" These results indicate improved reaction time and memory performance with repeated dosing of clobazam in contrast to buspirone."( Pharmacodynamic effects of buspirone and clobazam.
Alford, C; Bhatti, JZ; Curran, S; Hindmarch, I; McKay, G, 1991
)
0.77
" Plasma levels of the active metabolite N-desmethylclobazam were linearly related to dosage and appeared to correlate with both therapeutic and toxic responses."( Add-on trial of clobazam in intractable adult epilepsy with plasma level correlations.
Blaschuk, K; Couture, M; Guberman, A; Sherwin, A, 1990
)
0.88
" Fully kindled rats were dosed three times daily for 2 or 4 weeks."( Tolerance to anticonvulsant effects of diazepam, clonazepam, and clobazam in amygdala-kindled rats.
Chiu, TH; Rosenberg, HC; Tietz, EI,
)
0.37
" The anticonvulsant and motor impairment effects of clobazam and 2 1,4-benzodiazepine, diazepam and clonazepam, were compared by dose-response analysis in amygdala-kindled rats and on 3 tests of motor function: gross motor impairment, a vertical screen test, and muscle tone."( A comparison of the anticonvulsant effects of 1,4- and 1,5-benzodiazepines in the amygdala-kindled rat and their effects on motor function.
Chiu, TH; Rosenberg, HC; Tietz, EI,
)
0.38
"The effect of 1,5-benzodiazepine clobazam was assessed in a double-blind add-on trial in 20 patients with chronic complex partial seizures uncontrolled by maximally tolerable daily dosage of standard antiepileptic drug therapy."( Clobazam for refractory focal epilepsy. A controlled trial.
Roeder-Wanner, U; Rohde, M; Schmidt, D; Wolf, P, 1986
)
2
" It was speculated that the relatively high daily dosage of diazepam may have been contributed to these results."( Clobazam and diazepam in anxiety.
Brown, AS; Cohen, D; Harris, H; Hurowitz, A; Lindenbaum, EJ; Rickels, K; Ross, HA; Weinstock, R; Wiseman, K; Zal, M, 1981
)
1.71
" In view of the changes in the overall severity of the symptoms, in "persistent anxiety" and "anxiety crises", in "sleep disorders", the global clinical impression and the tolerance, it is concluded that clobazam is a useful drug in the treatment of anxiety, and that single or divided daily dosage schedules produce similar results."( Clobazam: single or divided doses?
Arnau, C; Costa Molinari, JM; Piña, C; Vallvé, C, 1982
)
1.89
" The anxiolytic action, the tolerability, the degree of satisfaction and the dosage of clobazam were evaluated by means of a modified "Rating Scale for Anxiety" by Hamilton and self-evaluation scales."( [Use of clobazam 20 mg in general practice].
De Nayer, AR; Delire, M,
)
0.79
" 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 rate and extent of accumulation of clobazam and its major metabolite, desmethylclobazam, during multiple dosage with clobazam were evaluated in 4 similarly sized groups of young male, young female, elderly male, and elderly female volunteers."( Reduced single-dose clearance of clobazam in elderly men predicts increased multiple-dose accumulation.
Divoll, M; Greenblatt, DJ; Ho, I; Puri, SK; Shader, RI; Zinny, MA,
)
0.68
" Serum concentrations of clobazam increased with dosage and age, and decreased with phenobarbital cotherapy."( Interactions of clobazam with conventional antiepileptics in children.
Cortez, M; Daneman, R; Hwang, P; Koren, G; Menzano, E; Sherwin, AL; Theis, JG, 1997
)
0.95
" The disorder occurred with a short latency after initiation of therapy and at a relatively low dosage of CLB."( Aggression in children treated with clobazam for epilepsy.
Goulden, KJ; Ronen, GM; Sheth, RD, 1994
)
0.56
"Three patients aged 16, 19, and 65 years with a 13- to 36-year history of partial epilepsy were receiving a therapeutic dosage of carbamazepine or phenobarbital plus either clobazam (CLB) or valproate (VPA)."( Negative myoclonic status due to antiepileptic drug tapering: report of three cases.
Aguglia, U; Gambardella, A; Oliveri, RL; Quattrone, A; Russo, C; Zappia, M, 1997
)
0.49
" Both CBZ and CBZ-epoxide (CBZ-E) blood levels were elevated, and the symptoms resolved quickly when CBZ dosage was reduced and CLB discontinued."( Carbamazepine intoxication with negative myoclonus after the addition of clobazam.
Genton, P; Mesdjian, E; Nguyen, VH, 1998
)
0.53
" They could be so severe in patients over 12 years of age that the stiripentol dosage could not be increased to 50 mg kg-1 j-1."( [Long-term efficacy and tolerance of stiripentaol in severe myoclonic epilepsy of infancy (Dravet's syndrome)].
Chiron, C; Dellatolas, G; Dulac, O; Pons, G; Rey, E; Thanh, TN; Vincent, J, 2002
)
0.31
" Dosage of clobazam ranged from 5 to 60 mg/day (mean=22."( Clobazam as add-on therapy for temporal lobe epilepsy and hippocampal sclerosis.
Cendes, F; Ferreira, CM; Guerreiro, CA; Li, LM; Montenegro, MA, 2005
)
2.16
" Clobazam dosage ranged from 5 to 60 mg/day (mean = 37."( Clobazam as add-on therapy in children with epileptic encephalopathy.
Guerreiro, CA; Guerreiro, MM; Montenegro, MA; Silva, RC, 2006
)
2.69
" Clobazam mean dosage was 23."( Effectiveness of clobazam as add-on therapy in children with refractory focal epilepsy.
da Silveira, MR; Franzon, RC; Guerreiro, CA; Guerreiro, MM; Montenegro, MA, 2006
)
1.58
"The aim of this study was to characterize the anticonvulsant effects of stiripentol (STP) in combination with clobazam [CLB], and valproate [VPA]) in the mouse maximal electroshock (MES)-induced seizure model using the type I isobolographic analysis for parallel and non-parallel dose-response relationship curves (DRRCs)."( Interactions of stiripentol with clobazam and valproate in the mouse maximal electroshock-induced seizure model.
Czuczwar, SJ; Luszczki, JJ; Patsalos, PN; Ratnaraj, N; Trojnar, MK, 2010
)
0.85
" However, because of the kinetic interactions, a dosage of clobazam and norclobazam can be useful in certain cases."( [Therapeutic drug monitoring of clobazam].
Bentué-Ferrer, D; Debruyne, D; Tribut, O; Verdier, MC,
)
0.66
" Cyp2b1, Cyp3a1, Cyp3a2, and Ugt2b2 mRNA levels in the liver were upregulated as compared to the control group throughout the dosing period."( Toxicological approach for elucidation of clobazam-induced hepatomegaly in male rats.
Funabashi, H; Horie, H; Inada, H; Kimura, J; Matsumoto, I; Miyawaki, I; Seki, T, 2011
)
0.63
" 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
)
0.64
" Mean PGB dosage was 279 mg/day."( Effect of pregabalin add-on treatment on seizure control, quality of life, and anxiety in patients with brain tumour-related epilepsy: a pilot study.
Carapella, CM; Dinapoli, L; Fabi, A; Maschio, M; Pace, A; Pompili, A; Sperati, F; Vidiri, A, 2012
)
0.38
"The anticonvulsant interaction profile between 1-MeTHIQ and CLB in the mouse MES model was determined using an isobolographic analysis for parallel dose-response relationship curves."( Additive interactions between 1-methyl-1,2,3,4-tetrahydroisoquinoline and clobazam in the mouse maximal electroshock-induced tonic seizure model--an isobolographic analysis for parallel dose-response relationship curves.
Andres-Mach, M; Haratym-Maj, A; Luszczki, JJ; Zagaja, M, 2014
)
0.63
" The applicability of the proposed method was evaluated in commercial dosage forms analysis."( A stability indicating HPLC method for the determination of clobazam and its basic degradation product characterization.
Ahmadkhaniha, R; Amini, M; Farahani, AD; Souri, E, 2014
)
0.64
"5 mg/day) and dosage increased until N-CLB serum concentration reaches 1100 ng/mL or until the desired effect is acquired, a recommendation that is particularly important for PMs."( Effect of CYP2C19 polymorphisms on the clinical outcome of low-dose clobazam therapy in Japanese patients with epilepsy.
Hashi, S; Ikeda, A; Kinoshita, M; Masuda, S; Matsubara, K; Matsumoto, R; Shibata, M; Takahashi, R; Yano, I, 2015
)
0.65
"From these cases, we observe that a rough estimate of final clobazam dosage for each mg of clonazepam under substitution is likely to be at least 10-fold, probably closer to 15-fold for many patients, and as high as 20-fold for a few."( Clinical considerations in transitioning patients with epilepsy from clonazepam to clobazam: a case series.
Chung, S; Kuzniecky, R; Perry, MS; Sankar, R; Sinha, S, 2014
)
0.87
" Dosage is between 5 mg and 40 mg a day, depending on patient weight, efficacy, and tolerability."( Clobazam: A Safe, Efficacious, and Newly Rediscovered Therapeutic for Epilepsy.
Gauthier, AC; Mattson, RH, 2015
)
1.86
" Because the formation of N-CLB is elimination-rate limited and the total apparent clearance of clobazam is unaffected by hepatic impairment, the PPK model suggests that patients with LGS and hepatic impairment may not require clobazam dosage modification."( An integrative population pharmacokinetics approach to the characterization of the effect of hepatic impairment on clobazam pharmacokinetics.
Bekersky, I; Chu, HM; Ette, EI; Tolbert, D, 2016
)
0.86
" Because concomitant use of AEDs that are either CYP450 inhibitors or inducers with clobazam in the treatment of LGS patients had negligible to no effect on clobazam PK in this study, dosage adjustments may not be required for clobazam in the presence of the AEDs investigated here."( Drug-metabolism mechanism: Knowledge-based population pharmacokinetic approach for characterizing clobazam drug-drug interactions.
Bekersky, I; Chu, HM; Ette, EI; Tolbert, D, 2016
)
0.88
"Post hoc analyses indicate that the overall rate of aggression with clobazam treatment was low and dosage dependent."( Clobazam and Aggression-Related Adverse Events in Pediatric Patients With Lennox-Gastaut Syndrome.
Drummond, R; Isojarvi, J; Lee, D; Paolicchi, JM; Ross, G, 2015
)
2.1
" The median CLB dosage did not change from baseline to last follow-up, while median CZP dosage increased 25% in adults and 50% in children."( Clobazam and clonazepam use in epilepsy: Results from a UK database incident user cohort study.
Brodie, MJ; Chung, S; François, C; Guiraud-Diawara, A; Isojarvi, J; Quelen, C; Shen, V; Verpillat, P; Wade, A, 2016
)
1.88
" The median CLB dosage used by both adults and children remained stable over the 16-year study period, while the median CZP dosage increased in both adults and children."( Clobazam and clonazepam use in epilepsy: Results from a UK database incident user cohort study.
Brodie, MJ; Chung, S; François, C; Guiraud-Diawara, A; Isojarvi, J; Quelen, C; Shen, V; Verpillat, P; Wade, A, 2016
)
1.88
"Differential dosing with higher evening dosing was started based on a high proportion of seizures (>80%) at nighttime (6p."( Clobazam higher-evening differential dosing as an add-on therapy in refractory epilepsy.
Fernández, IS; Jackson, M; Kadish, NE; Klehm, J; Loddenkemper, T; Manganaro, S; Thome-Souza, S, 2016
)
1.88
"Twenty-seven patients were treated with clobazam differential dosing as an add-on therapy."( Clobazam higher-evening differential dosing as an add-on therapy in refractory epilepsy.
Fernández, IS; Jackson, M; Kadish, NE; Klehm, J; Loddenkemper, T; Manganaro, S; Thome-Souza, S, 2016
)
2.14
" Chronotherapy tailored to the patients' seizure susceptibility patterns may improve care in epilepsy patients as differential dosing may allow for higher overall treatment doses at times of greatest seizure susceptibility without increased side effects at other times."( Clobazam higher-evening differential dosing as an add-on therapy in refractory epilepsy.
Fernández, IS; Jackson, M; Kadish, NE; Klehm, J; Loddenkemper, T; Manganaro, S; Thome-Souza, S, 2016
)
1.88
" In the absence of clinical trial data on optimization of AED dosage in patients with LGS, dose titration is guided by personal experience, anecdotal evidence, and specific patient factors (age, comorbid conditions and medications, seizure types, etc."( Optimizing clobazam treatment in patients with Lennox-Gastaut syndrome.
Chung, S; Gidal, BE; Isojarvi, J; Wechsler, RT, 2018
)
0.87
"Clobazam oral soluble film (COSF) is a novel dosage form under development for the adjunctive treatment of seizures associated with Lennox-Gastaut syndrome."( Pharmacokinetics of clobazam oral soluble film.
Buan, CV; Heller, AH; Jung, C; Schobel, AM; Wargacki, S; Wyatt, DJ, 2018
)
2.25
"COSF is a novel clobazam dosage form that is bioequivalent to CTAB."( Pharmacokinetics of clobazam oral soluble film.
Buan, CV; Heller, AH; Jung, C; Schobel, AM; Wargacki, S; Wyatt, DJ, 2018
)
1.15
" We review the use of short burst Clobazam dosing on discharge from the Epilepsy monitoring unit (EMU) to determine if this might reduce rates of representation with seizures."( Short burst Clobazam dosing at discharge from VEEG evaluation reduces re-presentation with seizures.
Dionisio, S; Gillinder, L; Scarborough, L, 2019
)
1.17
" Further prospective studies on clobazam for infantile spasms, focusing on specific good response groups, dosing protocols, and long-term outcome are needed."( Clobazam as an adjunctive treatment for infantile spasms.
Chang, MJ; Hahn, J; Kang, HC; Kim, HD; Kim, SH; Lee, H; Lee, JS, 2019
)
2.24
" The FDA approved maximum dosage of clobazam is 1 mg/kg/d or a total of 40 mg a day."( Safety and Efficacy of Supratherapeutic Doses of Clobazam.
Freedman, DA; Gedela, S; Glynn, P; Patel, AD; Salvator, A, 2019
)
1.04
" Primary outcomes were drug number, dosage changes, and seizure outcome."( Need of Immediate Drug Reduction after Epilepsy Surgery - A Prospective Observational Study.
Bajaj, J; Chandra, SP; Doddamani, R; Girishan, S; Ramanujam, B; Tripathi, M,
)
0.13
" Dosage was reduced in 23/38 (60."( Need of Immediate Drug Reduction after Epilepsy Surgery - A Prospective Observational Study.
Bajaj, J; Chandra, SP; Doddamani, R; Girishan, S; Ramanujam, B; Tripathi, M,
)
0.13
"To describe the use of a population pharmacokinetic (PopPK) model incorporating weight and ontogeny to identify effective clobazam (CLB) dosing for use in a clinical trial in pediatric patients with Dravet syndrome."( Pharmacometrics of clobazam in pediatrics: Prediction of effective clobazam doses for Dravet syndrome.
Chu, HM; Ette, EI; Tolbert, D, 2019
)
1.05
" Dosage adjustments based on renal function in the package information are effective in controlling the trough and peak concentrations in similar ranges."( [Clinical Pharmacometrics for Rational Drug Treatment].
Yano, I, 2019
)
0.51
" This practical guide provides an overview of these main ASMs including their indications/contraindications, mechanism of action, efficacy, safety and tolerability profile, dosage requirements, and laboratory and clinical parameters to be evaluated."( A Practical Guide to the Treatment of Dravet Syndrome with Anti-Seizure Medication.
Schubert-Bast, S; Strzelczyk, A, 2022
)
0.72
" Other factors, including dosage and clobazam co-therapy, were significantly associated with a greater effect on seizure control and side effects of CBD."( Clinical efficacy and safety of cannabidiol for pediatric refractory epilepsy indications: A systematic review and meta-analysis.
Aparasu, R; Estes, E; Reddy, DS; Talwar, A, 2023
)
1.18
[information is derived through text-mining from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Roles (3)

RoleDescription
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.
GABA modulatorA substance that does not act as agonist or antagonist but does affect the gamma-aminobutyric acid receptor-ionophore complex. GABA-A receptors appear to have at least three allosteric sites at which modulators act: a site at which benzodiazepines act by increasing the opening frequency of gamma-aminobutyric acid-activated chloride channels; a site at which barbiturates act to prolong the duration of channel opening; and a site at which some steroids may act.
[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 (2)

ClassDescription
1,4-benzodiazepinone
organochlorine compoundAn organochlorine compound is a compound containing at least one carbon-chlorine bond.
[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 (7)

Potency Measurements

ProteinTaxonomyMeasurementAverage (µ)Min (ref.)Avg (ref.)Max (ref.)Bioassay(s)
pregnane X nuclear receptorHomo sapiens (human)Potency28.18380.005428.02631,258.9301AID1346985
cytochrome P450, family 19, subfamily A, polypeptide 1, isoform CRA_aHomo sapiens (human)Potency11.88320.001723.839378.1014AID743083
nuclear receptor subfamily 1, group I, member 2Rattus norvegicus (Norway rat)Potency39.81070.10009.191631.6228AID1346983
[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)
ATP-binding cassette sub-family C member 3Homo sapiens (human)IC50 (µMol)133.00000.63154.45319.3000AID1473740
Multidrug resistance-associated protein 4Homo sapiens (human)IC50 (µMol)133.00000.20005.677410.0000AID1473741
Bile salt export pumpHomo sapiens (human)IC50 (µMol)133.00000.11007.190310.0000AID1473738
Canalicular multispecific organic anion transporter 1Homo sapiens (human)IC50 (µMol)133.00002.41006.343310.0000AID1473739
[prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023]

Biological Processes (41)

Processvia Protein(s)Taxonomy
xenobiotic metabolic processATP-binding cassette sub-family C member 3Homo sapiens (human)
xenobiotic transmembrane transportATP-binding cassette sub-family C member 3Homo sapiens (human)
bile acid and bile salt transportATP-binding cassette sub-family C member 3Homo sapiens (human)
glucuronoside transportATP-binding cassette sub-family C member 3Homo sapiens (human)
xenobiotic transportATP-binding cassette sub-family C member 3Homo sapiens (human)
transmembrane transportATP-binding cassette sub-family C member 3Homo sapiens (human)
leukotriene transportATP-binding cassette sub-family C member 3Homo sapiens (human)
monoatomic anion transmembrane transportATP-binding cassette sub-family C member 3Homo sapiens (human)
transport across blood-brain barrierATP-binding cassette sub-family C member 3Homo sapiens (human)
prostaglandin secretionMultidrug resistance-associated protein 4Homo sapiens (human)
cilium assemblyMultidrug resistance-associated protein 4Homo sapiens (human)
platelet degranulationMultidrug resistance-associated protein 4Homo sapiens (human)
xenobiotic metabolic processMultidrug resistance-associated protein 4Homo sapiens (human)
xenobiotic transmembrane transportMultidrug resistance-associated protein 4Homo sapiens (human)
bile acid and bile salt transportMultidrug resistance-associated protein 4Homo sapiens (human)
prostaglandin transportMultidrug resistance-associated protein 4Homo sapiens (human)
urate transportMultidrug resistance-associated protein 4Homo sapiens (human)
glutathione transmembrane transportMultidrug resistance-associated protein 4Homo sapiens (human)
transmembrane transportMultidrug resistance-associated protein 4Homo sapiens (human)
cAMP transportMultidrug resistance-associated protein 4Homo sapiens (human)
leukotriene transportMultidrug resistance-associated protein 4Homo sapiens (human)
monoatomic anion transmembrane transportMultidrug resistance-associated protein 4Homo sapiens (human)
export across plasma membraneMultidrug resistance-associated protein 4Homo sapiens (human)
transport across blood-brain barrierMultidrug resistance-associated protein 4Homo sapiens (human)
guanine nucleotide transmembrane transportMultidrug resistance-associated protein 4Homo 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)
xenobiotic metabolic processCanalicular multispecific organic anion transporter 1Homo sapiens (human)
xenobiotic transmembrane transportCanalicular multispecific organic anion transporter 1Homo sapiens (human)
negative regulation of gene expressionCanalicular multispecific organic anion transporter 1Homo sapiens (human)
bile acid and bile salt transportCanalicular multispecific organic anion transporter 1Homo sapiens (human)
bilirubin transportCanalicular multispecific organic anion transporter 1Homo sapiens (human)
heme catabolic processCanalicular multispecific organic anion transporter 1Homo sapiens (human)
xenobiotic export from cellCanalicular multispecific organic anion transporter 1Homo sapiens (human)
transmembrane transportCanalicular multispecific organic anion transporter 1Homo sapiens (human)
transepithelial transportCanalicular multispecific organic anion transporter 1Homo sapiens (human)
leukotriene transportCanalicular multispecific organic anion transporter 1Homo sapiens (human)
monoatomic anion transmembrane transportCanalicular multispecific organic anion transporter 1Homo sapiens (human)
transport across blood-brain barrierCanalicular multispecific organic anion transporter 1Homo sapiens (human)
xenobiotic transport across blood-brain barrierCanalicular multispecific organic anion transporter 1Homo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Molecular Functions (24)

Processvia Protein(s)Taxonomy
ATP bindingATP-binding cassette sub-family C member 3Homo sapiens (human)
ABC-type xenobiotic transporter activityATP-binding cassette sub-family C member 3Homo sapiens (human)
glucuronoside transmembrane transporter activityATP-binding cassette sub-family C member 3Homo sapiens (human)
ABC-type glutathione S-conjugate transporter activityATP-binding cassette sub-family C member 3Homo sapiens (human)
ABC-type bile acid transporter activityATP-binding cassette sub-family C member 3Homo sapiens (human)
ATP hydrolysis activityATP-binding cassette sub-family C member 3Homo sapiens (human)
ATPase-coupled transmembrane transporter activityATP-binding cassette sub-family C member 3Homo sapiens (human)
xenobiotic transmembrane transporter activityATP-binding cassette sub-family C member 3Homo sapiens (human)
ATPase-coupled inorganic anion transmembrane transporter activityATP-binding cassette sub-family C member 3Homo sapiens (human)
icosanoid transmembrane transporter activityATP-binding cassette sub-family C member 3Homo sapiens (human)
ABC-type transporter activityATP-binding cassette sub-family C member 3Homo sapiens (human)
guanine nucleotide transmembrane transporter activityMultidrug resistance-associated protein 4Homo sapiens (human)
protein bindingMultidrug resistance-associated protein 4Homo sapiens (human)
ATP bindingMultidrug resistance-associated protein 4Homo sapiens (human)
ABC-type xenobiotic transporter activityMultidrug resistance-associated protein 4Homo sapiens (human)
prostaglandin transmembrane transporter activityMultidrug resistance-associated protein 4Homo sapiens (human)
urate transmembrane transporter activityMultidrug resistance-associated protein 4Homo sapiens (human)
purine nucleotide transmembrane transporter activityMultidrug resistance-associated protein 4Homo sapiens (human)
ABC-type glutathione S-conjugate transporter activityMultidrug resistance-associated protein 4Homo sapiens (human)
ABC-type bile acid transporter activityMultidrug resistance-associated protein 4Homo sapiens (human)
efflux transmembrane transporter activityMultidrug resistance-associated protein 4Homo sapiens (human)
15-hydroxyprostaglandin dehydrogenase (NAD+) activityMultidrug resistance-associated protein 4Homo sapiens (human)
ATP hydrolysis activityMultidrug resistance-associated protein 4Homo sapiens (human)
glutathione transmembrane transporter activityMultidrug resistance-associated protein 4Homo sapiens (human)
ATPase-coupled transmembrane transporter activityMultidrug resistance-associated protein 4Homo sapiens (human)
xenobiotic transmembrane transporter activityMultidrug resistance-associated protein 4Homo sapiens (human)
ATPase-coupled inorganic anion transmembrane transporter activityMultidrug resistance-associated protein 4Homo sapiens (human)
ABC-type transporter activityMultidrug resistance-associated protein 4Homo 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 bindingCanalicular multispecific organic anion transporter 1Homo sapiens (human)
ATP bindingCanalicular multispecific organic anion transporter 1Homo sapiens (human)
organic anion transmembrane transporter activityCanalicular multispecific organic anion transporter 1Homo sapiens (human)
ABC-type xenobiotic transporter activityCanalicular multispecific organic anion transporter 1Homo sapiens (human)
bilirubin transmembrane transporter activityCanalicular multispecific organic anion transporter 1Homo sapiens (human)
ABC-type glutathione S-conjugate transporter activityCanalicular multispecific organic anion transporter 1Homo sapiens (human)
ATP hydrolysis activityCanalicular multispecific organic anion transporter 1Homo sapiens (human)
ATPase-coupled transmembrane transporter activityCanalicular multispecific organic anion transporter 1Homo sapiens (human)
xenobiotic transmembrane transporter activityCanalicular multispecific organic anion transporter 1Homo sapiens (human)
ATPase-coupled inorganic anion transmembrane transporter activityCanalicular multispecific organic anion transporter 1Homo sapiens (human)
ABC-type transporter activityCanalicular multispecific organic anion transporter 1Homo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Ceullar Components (17)

Processvia Protein(s)Taxonomy
plasma membraneATP-binding cassette sub-family C member 3Homo sapiens (human)
basal plasma membraneATP-binding cassette sub-family C member 3Homo sapiens (human)
basolateral plasma membraneATP-binding cassette sub-family C member 3Homo sapiens (human)
membraneATP-binding cassette sub-family C member 3Homo sapiens (human)
nucleolusMultidrug resistance-associated protein 4Homo sapiens (human)
Golgi apparatusMultidrug resistance-associated protein 4Homo sapiens (human)
plasma membraneMultidrug resistance-associated protein 4Homo sapiens (human)
membraneMultidrug resistance-associated protein 4Homo sapiens (human)
basolateral plasma membraneMultidrug resistance-associated protein 4Homo sapiens (human)
apical plasma membraneMultidrug resistance-associated protein 4Homo sapiens (human)
platelet dense granule membraneMultidrug resistance-associated protein 4Homo sapiens (human)
external side of apical plasma membraneMultidrug resistance-associated protein 4Homo sapiens (human)
plasma membraneMultidrug resistance-associated protein 4Homo 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)
plasma membraneCanalicular multispecific organic anion transporter 1Homo sapiens (human)
cell surfaceCanalicular multispecific organic anion transporter 1Homo sapiens (human)
apical plasma membraneCanalicular multispecific organic anion transporter 1Homo sapiens (human)
intercellular canaliculusCanalicular multispecific organic anion transporter 1Homo sapiens (human)
apical plasma membraneCanalicular multispecific organic anion transporter 1Homo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Bioassays (53)

Assay IDTitleYearJournalArticle
AID1296008Cytotoxic Profiling of Annotated Libraries Using Quantitative High-Throughput Screening2020SLAS discovery : advancing life sciences R & D, 01, Volume: 25, Issue:1
Cytotoxic Profiling of Annotated and Diverse Chemical Libraries Using Quantitative High-Throughput Screening.
AID1346987P-glycoprotein substrates identified in KB-8-5-11 adenocarcinoma cell line, qHTS therapeutic library screen2019Molecular pharmacology, 11, Volume: 96, Issue:5
A High-Throughput Screen of a Library of Therapeutics Identifies Cytotoxic Substrates of P-glycoprotein.
AID1346986P-glycoprotein substrates identified in KB-3-1 adenocarcinoma cell line, qHTS therapeutic library screen2019Molecular pharmacology, 11, Volume: 96, Issue:5
A High-Throughput Screen of a Library of Therapeutics Identifies Cytotoxic Substrates of P-glycoprotein.
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.
AID256135Effect on GABA level in rat whole brain concentration after 2 hr post-treatment at a dose of 100 mg/Kg when given i.p.; Control 48.42005Journal of medicinal chemistry, Oct-06, Volume: 48, Issue:20
Discovery of N-(2,6-dimethylphenyl)-substituted semicarbazones as anticonvulsants: hybrid pharmacophore-based design.
AID113273Antiaggressive anxiolytic activity in the electroshock-induced fighting test in mice (po); Range (1.03-4.7;)1990Journal of medicinal chemistry, Nov, Volume: 33, Issue:11
Chemistry and pharmacology of the non-benzodiazepine anxiolytic enciprazine and related compounds.
AID489300Increase in GABA level in Wistar rat midbrain assessed per mg of tissue at 30 mg/kg, ip after 2 hrs2010Bioorganic & medicinal chemistry letters, Jul-15, Volume: 20, Issue:14
Novel semicarbazones based 2,5-disubstituted-1,3,4-oxadiazoles: one more step towards establishing four binding site pharmacophoric model hypothesis for anticonvulsant activity.
AID1079941Liver damage due to vascular disease: peliosis hepatitis, hepatic veno-occlusive disease, Budd-Chiari syndrome. Value is number of references indexed. [column 'VASC' in source]
AID1079931Moderate liver toxicity, defined via clinical-chemistry results: ALT or AST serum activity 6 times the normal upper limit (N) or alkaline phosphatase serum activity of 1.7 N. Value is number of references indexed. [column 'BIOL' in source]
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.
AID113677Effect on hexobarbital induced sleep was determined in hexobarbital potentiation test; Range (9.6-17.1)1990Journal of medicinal chemistry, Nov, Volume: 33, Issue:11
Chemistry and pharmacology of the non-benzodiazepine anxiolytic enciprazine and related compounds.
AID1079937Severe hepatitis, defined as possibly life-threatening liver failure or through clinical observations. Value is number of references indexed. [column 'MASS' in source]
AID227701Anticonvulsant activity; NC denotes that compound is not classified2003Bioorganic & medicinal chemistry letters, Aug-18, Volume: 13, Issue:16
Topological virtual screening: a way to find new anticonvulsant drugs from chemical diversity.
AID29363Dissociation constant (pKa)2000Journal of medicinal chemistry, Jun-29, Volume: 43, Issue:13
QSAR model for drug human oral bioavailability.
AID235587Ratio of ED50 (hexobarbital) to that of ED50 (fighting)1990Journal of medicinal chemistry, Nov, Volume: 33, Issue:11
Chemistry and pharmacology of the non-benzodiazepine anxiolytic enciprazine and related compounds.
AID235588Ratio of ED50 (rotarod) to that of ED50 (fighting)1990Journal of medicinal chemistry, Nov, Volume: 33, Issue:11
Chemistry and pharmacology of the non-benzodiazepine anxiolytic enciprazine and related compounds.
AID1079940Granulomatous liver disease, proven histopathologically. Value is number of references indexed. [column 'GRAN' in source]
AID727834Antiepileptic activity in Wistar rat assessed as GABA level in medulla oblangata per 100 mg at 30 mg/kg ip after 2 hrs (Rvb = 31.86 +/- 4.65 ug)2013Bioorganic & medicinal chemistry letters, Feb-01, Volume: 23, Issue:3
Novel limonene and citral based 2,5-disubstituted-1,3,4-oxadiazoles: a natural product coupled approach to semicarbazones for antiepileptic activity.
AID489304Increase in GABA level in Wistar rat cerebellum assessed per mg of tissue at 30 mg/kg, ip after 2 hrs2010Bioorganic & medicinal chemistry letters, Jul-15, Volume: 20, Issue:14
Novel semicarbazones based 2,5-disubstituted-1,3,4-oxadiazoles: one more step towards establishing four binding site pharmacophoric model hypothesis for anticonvulsant activity.
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.
AID114461Ataxic activity in mice by rotarod test; Range (2.2-6.4)1990Journal of medicinal chemistry, Nov, Volume: 33, Issue:11
Chemistry and pharmacology of the non-benzodiazepine anxiolytic enciprazine and related compounds.
AID1079936Choleostatic liver toxicity, either proven histopathologically or where the ratio of maximal ALT or AST activity above normal to that of Alkaline Phosphatase is < 2 (see ACUTE). Value is number of references indexed. [column 'CHOLE' in source]
AID1079946Presence of at least one case with successful reintroduction. [column 'REINT' in source]
AID1143187Increase in GABA level in Wistar rat whole brain at 30 mg/kg, po after 2 hrs measured per 100 mg of tissue (Rvb = 46.8 +/- 6.03 ug)2014European journal of medicinal chemistry, Jun-10, Volume: 80Anticonvulsant evaluation of clubbed indole-1,2,4-triazine derivatives: a synthetic approach.
AID1079933Acute liver toxicity defined via clinical observations and clear clinical-chemistry results: serum ALT or AST activity > 6 N or serum alkaline phosphatases activity > 1.7 N. This category includes cytolytic, choleostatic and mixed liver toxicity. Value is
AID1079935Cytolytic liver toxicity, either proven histopathologically or where the ratio of maximal ALT or AST activity above normal to that of Alkaline Phosphatase is > 5 (see ACUTE). Value is number of references indexed. [column 'CYTOL' in source]
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.
AID1079949Proposed mechanism(s) of liver damage. [column 'MEC' in source]
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.
AID1079948Times to onset, minimal and maximal, observed in the indexed observations. [column 'DELAI' in source]
AID1079942Steatosis, proven histopathologically. Value is number of references indexed. [column 'STEAT' in source]
AID1065309Anticonvulsant activity in Wistar rat assessed as inhibition of GABA-induced seizures measuring minimum GABA level per 100 mg whole brain required for 50 % inhibition at 30 mg/kg, po for 7 days (Rvb = 51.5 +/- 2.60 ug/100 mg brain)2013European journal of medicinal chemistry, Sep, Volume: 67Design, synthesis and anticonvulsant evaluation of N-(benzo[d]thiazol-2-ylcarbamoyl)-2-methyl-4-oxoquinazoline-3(4H)-carbothioamide derivatives: a hybrid pharmacophore approach.
AID1079934Highest frequency of acute liver toxicity observed during clinical trials, expressed as a percentage. [column '% AIGUE' in source]
AID727832Antiepileptic activity in Wistar rat assessed as GABA level in cerebellum per 100 mg at 30 mg/kg ip after 2 hrs (Rvb = 23.48+/- 2.48 ug)2013Bioorganic & medicinal chemistry letters, Feb-01, Volume: 23, Issue:3
Novel limonene and citral based 2,5-disubstituted-1,3,4-oxadiazoles: a natural product coupled approach to semicarbazones for antiepileptic activity.
AID28681Partition coefficient (logD6.5)2000Journal of medicinal chemistry, Jun-29, Volume: 43, Issue:13
QSAR model for drug human oral bioavailability.
AID29811Oral bioavailability in human2000Journal of medicinal chemistry, Jun-29, Volume: 43, Issue:13
QSAR model for drug human oral bioavailability.
AID489302Increase in GABA level in Wistar rat medulla oblangata assessed per mg of tissue at 30 mg/kg, ip after 2 hrs2010Bioorganic & medicinal chemistry letters, Jul-15, Volume: 20, Issue:14
Novel semicarbazones based 2,5-disubstituted-1,3,4-oxadiazoles: one more step towards establishing four binding site pharmacophoric model hypothesis for anticonvulsant activity.
AID27167Delta logD (logD6.5 - logD7.4)2000Journal of medicinal chemistry, Jun-29, Volume: 43, Issue:13
QSAR model for drug human oral bioavailability.
AID1065310Anticonvulsant activity in Wistar rat assessed as inhibition of GABA-induced seizures measuring minimum GABA level per 100 mg whole brain required for 50 % inhibition at 30 mg/kg, ip as single dose measured after 2 hrs (Rvb = 46.4 +/- 5.50 ug/100 mg brain2013European journal of medicinal chemistry, Sep, Volume: 67Design, synthesis and anticonvulsant evaluation of N-(benzo[d]thiazol-2-ylcarbamoyl)-2-methyl-4-oxoquinazoline-3(4H)-carbothioamide derivatives: a hybrid pharmacophore approach.
AID727836Antiepileptic activity in Wistar rat assessed as GABA level in midbrain per 100 mg at 30 mg/kg ip after 2 hrs (Rvb = 35.42 +/- 2.14 ug)2013Bioorganic & medicinal chemistry letters, Feb-01, Volume: 23, Issue:3
Novel limonene and citral based 2,5-disubstituted-1,3,4-oxadiazoles: a natural product coupled approach to semicarbazones for antiepileptic activity.
AID256146Effect on GABA level in rat whole brain concentration after 7 days post-treatment at a dose of 30 mg/Kg when given orally; Control 50.52005Journal of medicinal chemistry, Oct-06, Volume: 48, Issue:20
Discovery of N-(2,6-dimethylphenyl)-substituted semicarbazones as anticonvulsants: hybrid pharmacophore-based design.
AID1079938Chronic liver disease either proven histopathologically, or through a chonic elevation of serum amino-transferase activity after 6 months. Value is number of references indexed. [column 'CHRON' in source]
AID1079939Cirrhosis, proven histopathologically. Value is number of references indexed. [column 'CIRRH' in source]
AID135326BBB penetration classification2000Journal of medicinal chemistry, Jun-01, Volume: 43, Issue:11
Predicting blood-brain barrier permeation from three-dimensional molecular structure.
AID1079943Malignant tumor, proven histopathologically. Value is number of references indexed. [column 'T.MAL' in source]
AID1079944Benign tumor, proven histopathologically. Value is number of references indexed. [column 'T.BEN' in source]
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.
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.
AID1143184Increase in GABA level in Wistar rat whole brain at 30 mg/kg, po for 7 days measured at 4 hrs after last drug dose per 100 mg of tissue (Rvb = 49.2 +/- 3.01 ug)2014European journal of medicinal chemistry, Jun-10, Volume: 80Anticonvulsant evaluation of clubbed indole-1,2,4-triazine derivatives: a synthetic approach.
AID1079932Highest frequency of moderate liver toxicity observed during clinical trials, expressed as a percentage. [column '% BIOL' in source]
AID1079947Comments (NB not yet translated). [column 'COMMENTAIRES' in source]
AID1079945Animal toxicity known. [column 'TOXIC' in source]
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.
[information is prepared from bioassay data collected from National Library of Medicine (NLM), extracted Dec-2023]

Research

Studies (520)

TimeframeStudies, This Drug (%)All Drugs %
pre-1990132 (25.38)18.7374
1990's84 (16.15)18.2507
2000's73 (14.04)29.6817
2010's160 (30.77)24.3611
2020's71 (13.65)2.80
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Market Indicators

Research Demand Index: 101.19

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 Index101.19 (24.57)
Research Supply Index6.51 (2.92)
Research Growth Index4.82 (4.65)
Search Engine Demand Index184.73 (26.88)
Search Engine Supply Index2.00 (0.95)

This Compound (101.19)

All Compounds (24.57)

Study Types

Publication TypeThis drug (%)All Drugs (%)
Trials110 (19.50%)5.53%
Reviews65 (11.52%)6.00%
Case Studies86 (15.25%)4.05%
Observational3 (0.53%)0.25%
Other300 (53.19%)84.16%
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Clinical Trials (21)

Trial Overview

TrialPhaseEnrollmentStudy TypeStart DateStatus
[NCT01291316]Phase 1/Phase 225 participants (Actual)Interventional2010-04-30Completed
Linking Altered Central Pain Processing and Genetic Polymorphism to Drug Efficacy in Chronic Low Back Pain [NCT01179828]Phase 3150 participants (Actual)Interventional2010-07-31Completed
A Phase III, Randomized, Open Label, Single Center, Study on the Effects of Treatment of Epilepsia Partialis Continua With Clobazam Compared to Treatment With or in Addition to Lorazepam and/or Clonazepam [NCT02134366]Phase 37 participants (Actual)Interventional2014-07-31Terminated(stopped due to Recruitment Issues - Lack of target population)
Electrical Status Epilepticus in Sleep: Response of Neuropsychological Deficits and Epileptiform Activity to Clobazam Treatment [NCT02127918]17 participants (Actual)Observational [Patient Registry]2012-07-31Completed
Multi-site, Prospective, Randomised, Double-blind, Placebo-controlled, Parallel-group, Interventional Study to Evaluate the Efficacy, Safety, and Tolerability of Clobazam as Adjunctive Therapy in Paediatric Patients Aged ≥1 to ≤16 Years With Dravet Syndro [NCT02174094]Phase 30 participants (Actual)Interventional2015-03-31Withdrawn(stopped due to The study was terminated due to recruitment challenges)
Modulation of the Brain Excitatory/Inhibitory (E/I) Balance Through Neuronal Systems in Autism Spectrum Disorder (ASD) [NCT03678129]50 participants (Anticipated)Interventional2018-12-07Recruiting
Pharmacokinetics, Pharmacodynamics, and Safety Profile of Understudied Drugs [NCT04278404]5,000 participants (Anticipated)Observational2020-03-05Recruiting
A Randomised Controlled Trial of the Ketogenic Diet in the Treatment of Epilepsy in Children Under the Age of Two Years [NCT02205931]Phase 4160 participants (Anticipated)Interventional2015-01-31Recruiting
The Efficacy and Safety of First-Line Anti-Epileptic Drugs (AEDs) as Substitution Therapy in Children Who Are Resistant to Second-Line AEDs [NCT05697614]Phase 4100 participants (Anticipated)Interventional2023-03-01Recruiting
Effects of Gaba-a-Agonists on Pain Mechanisms: An Experimental Study in Healthy Volunteers [NCT01011036]Phase 317 participants (Actual)Interventional2009-12-31Completed
Safety and Efficacy of Clobazam in Subjects With Lennox-Gastaut Syndrome [NCT00162981]Phase 268 participants (Actual)Interventional2005-10-31Completed
Evaluation of Onfi Conversion Therapy Replacing Clonazepam in Patients With Medically Refractory Epilepsy: Efficacy, Tolerability, Dosing Equivalence, and Retention Rate [NCT01932502]Phase 421 participants (Anticipated)Interventional2013-02-28Active, not recruiting
Safety and Effectiveness of Open-Label Clobazam in Subjects With Lennox-Gastaut Syndrome [NCT01160770]Phase 3267 participants (Actual)Interventional2005-12-31Completed
Prospective Open Label Evaluation of Clobazam Adjunctive Treatment of Adults With Refractory Focal Epilepsy: A Pilot Study [NCT02726919]Phase 420 participants (Anticipated)Interventional2015-02-28Recruiting
Double-Blind, Placebo-Controlled, Efficacy and Safety Study of Clobazam in Patients With Lennox-Gastaut Syndrome [NCT00518713]Phase 3238 participants (Actual)Interventional2007-08-31Completed
Use of Clobazam in Treating Anxiety Comorbid With Pediatric Epilepsy [NCT03371836]Phase 420 participants (Actual)Interventional2017-10-01Completed
A Phase 2, Double-blind, Randomized, Placebo-controlled Study to Investigate Possible Drug-drug Interactions Between Clobazam and Cannabidiol (GWP42003-P) [NCT02565108]Phase 220 participants (Actual)Interventional2016-01-20Completed
A Phase 2, Double-blind, Randomized, Placebo-controlled Study to Investigate Possible Drug-drug Interactions Between Clobazam and Cannabidiol (GWP42003-P) [NCT02564952]Phase 218 participants (Actual)Interventional2016-03-11Completed
Multi-site, Prospective, Open-label, Long-term, Flexible Dose, Interventional Study to Evaluate the Safety and Tolerability of Clobazam as Adjunctive Therapy in Paediatric Patients Aged ≥1 to ≤16 Years With Dravet Syndrome [NCT02187809]Phase 33 participants (Actual)Interventional2015-03-31Terminated(stopped due to The study was terminated due to recruitment challenges)
Pharmacovigilance in Gerontopsychiatric Patients [NCT02374567]Phase 3407 participants (Actual)Interventional2015-01-31Terminated
Population Pharmacokinetics of Antiepileptic in Pediatrics [NCT03196466]1,000 participants (Anticipated)Observational2017-06-19Recruiting
[information is prepared from clinicaltrials.gov, extracted Sep-2024]

Trial Outcomes

TrialOutcome
NCT00162981 (5) [back to overview]A Comparison of the High Dose Group to Low Dose Group of the Percent Reduction in Number of Drop Seizures.
NCT00162981 (5) [back to overview]Percent Reduction in Number of Drop Seizures.
NCT00162981 (5) [back to overview]Parent/Caregiver Global Evaluations of the Patient's Overall Change in Symptoms.
NCT00162981 (5) [back to overview]Parent/Caregiver Global Evaluations of the Patient's Overall Change in Symptoms.
NCT00162981 (5) [back to overview]Percent of Patients Considered Treatment Responders Defined as Those With a >= 25%, >= 50%, >= 75%, and 100% Reduction in Drop Seizures.
NCT00518713 (13) [back to overview]Parent/Caregiver Global Evaluations of the Patient's Overall Change in Symptoms.
NCT00518713 (13) [back to overview]Percent of Patients Considered Treatment Responders Defined as Those With a >=25%, >=50%, >=75%, 100% Reduction in Drop Seizures (12-week Maintenance Period).
NCT00518713 (13) [back to overview]Percent of Patients Considered Treatment Responders Defined as Those With a >=25%, >=50%, >=75%, 100% Reduction in Drop Seizures (First 4 Weeks of the 12-week Maintenance Period).
NCT00518713 (13) [back to overview]Percent of Patients Considered Treatment Responders Defined as Those With a >=25%, >=50%, >=75%, 100% Reduction in Drop Seizures (Last 4 Weeks of the 12-week Maintenance Period).
NCT00518713 (13) [back to overview]Percent of Patients Considered Treatment Responders Defined as Those With a >=25%, >=50%, >=75%, 100% Reduction in Drop Seizures (Middle 4 Weeks of the 12-week Maintenance Period).
NCT00518713 (13) [back to overview]Tolerance
NCT00518713 (13) [back to overview]Percent Reduction in Number of Drop Seizures (12-week Maintenance Period).
NCT00518713 (13) [back to overview]Percent Reduction in Number of Drop Seizures (First 4 Weeks of the 12-week Maintenance Period).
NCT00518713 (13) [back to overview]Percent Reduction in Number of Drop Seizures (Last 4 Weeks of the 12-week Maintenance Period).
NCT00518713 (13) [back to overview]Percent Reduction in Number of Drop Seizures (Middle 4 Weeks of the 12-week Maintenance Period).
NCT00518713 (13) [back to overview]Percent Reduction in the Number of Non-drop Seizures.
NCT00518713 (13) [back to overview]Percent Reduction of Total (Drop and Non-Drop) Seizures.
NCT00518713 (13) [back to overview]Investigator Global Evaluations of the Patient's Overall Change in Symptoms.
NCT01160770 (6) [back to overview]Median Percent Reduction in Average Weekly Rate of Drop Seizures Based on the 7-day Assessment
NCT01160770 (6) [back to overview]Median Percent Reduction in Average Weekly Rate of Drop Seizures Based on the Last 30-day Assessment
NCT01160770 (6) [back to overview]Investigator Global Evaluations of the Patient's Overall Change in Symptoms
NCT01160770 (6) [back to overview]Parent/Caregiver Global Evaluations of the Patient's Overall Change in Symptoms
NCT01160770 (6) [back to overview]Percent of Patients Considered Treatment Responders Defined as Those With a ≥25%, ≥50%, ≥75%, 100% Reduction in Drop Seizures Based on the 7-day Assessment
NCT01160770 (6) [back to overview]Percent of Patients Considered Treatment Responders Defined as Those With a ≥25%, ≥50%, ≥75%, 100% Reduction in Drop Seizures Based on the Last 30-day Assessment
NCT02187809 (2) [back to overview]Number of Participants With Adverse Events as a Measure of Safety and Tolerability
NCT02187809 (2) [back to overview]Number of Participants With Adverse Events of Special Interest as a Measure of Safety and Tolerability Based on Dose
NCT02564952 (1) [back to overview]Number Of Participants Who Experienced Severe OLE-Emergent AEs
NCT02565108 (6) [back to overview]Number Of Participants Who Experienced Severe Treatment-Emergent Adverse Events (TEAEs)
NCT02565108 (6) [back to overview]Pharmacokinetics (PK): Maximum Measured Plasma Concentration (Cmax) Of CLB And N-CLB With GWP42003-P Treatment, Days 1 And 33
NCT02565108 (6) [back to overview]PK: Area Under The Plasma Concentration-Time Curve Over A Dosing Interval, Where Tau Is The Dosing Interval (AUCtau) Of CLB And N-CLB With GWP42003-P Treatment, Days 1 And 33
NCT02565108 (6) [back to overview]PK: Geometric Mean Ratios Of CLB And N-CLB For AUCtau On Day 33 Compared With Day 1
NCT02565108 (6) [back to overview]PK: Geometric Mean Ratios Of CLB And N-CLB For Cmax On Day 33 Compared With Day 1
NCT02565108 (6) [back to overview]PK: Time To The Maximum Plasma Concentration (Tmax) Of CLB And N-CLB With GWP42003-P Treatment, Days 1 And 33
NCT03371836 (1) [back to overview]CGI-I

A Comparison of the High Dose Group to Low Dose Group of the Percent Reduction in Number of Drop Seizures.

Number of drop seizures (average per week) was obtained from seizure diaries. The average drop in seizures per week for patients who did not complete the maintenance period was calculated based on the time from the beginning of the maintenance period to date of withdrawal. (NCT00162981)
Timeframe: 4-week baseline period and the 4-week maintenance period

InterventionPercent Reduction (Median)
Clobazam Low Dose29
Clobazam High Dose93

[back to top]

Percent Reduction in Number of Drop Seizures.

Number of drop seizures (average per week) was obtained from seizure diaries. The average drop in seizures per week for patients who did not complete the maintenance period was calculated based on the time from the beginning of the maintenance period to date of withdrawal. (NCT00162981)
Timeframe: 4-week baseline period and 4-week maintenance period

InterventionPercent Reduction (Mean)
Clobazam Low Dose10.1
Clobazam High Dose85.2

[back to top]

Parent/Caregiver Global Evaluations of the Patient's Overall Change in Symptoms.

"The parent/caregiver was asked to rate the patient's overall change in symptoms and overall change in seizure activity and Quality of Life since the beginning of clobazam treatment by checking very much improved, much improved, minimally improved, no change, minimally worse, much worse, or very much worse." (NCT00162981)
Timeframe: Week 3

,
Interventionparticipants (Number)
Very Much ImprovedMuch ImprovedMinimally ImprovedNo ChangeMinimally WorseMuch WorseVery Much Worse
Clobazam High Dose151510100
Clobazam Low Dose7993010

[back to top]

Parent/Caregiver Global Evaluations of the Patient's Overall Change in Symptoms.

"The parent/caregiver was asked to rate the patient's overall change in symptoms and overall change in seizure activity and Quality of Life since the beginning of clobazam treatment by checking very much improved, much improved, minimally improved, no change, minimally worse, much worse, or very much worse." (NCT00162981)
Timeframe: Week 7

,
Interventionparticipants (Number)
Very Much ImprovedMuch ImprovedMinimally ImprovedNo ChangeMinimally WorseMuch WorseVery Much Worse
Clobazam High Dose161110100
Clobazam Low Dose66105100

[back to top]

Percent of Patients Considered Treatment Responders Defined as Those With a >= 25%, >= 50%, >= 75%, and 100% Reduction in Drop Seizures.

Number of drop seizures (average per week) was obtained from seizure diaries. The average drop in seizures per week for patients who did not complete the maintenance period was calculated based on the time from the beginning of the maintenance period to date of withdrawal. (NCT00162981)
Timeframe: 4-week baseline period and 4-week maintenance period

,
InterventionPercent of participants (Number)
≥ 25% reduction≥ 50% reduction≥ 75% reduction100% reduction
Clobazam High Dose3230238
Clobazam Low Dose181272

[back to top]

Parent/Caregiver Global Evaluations of the Patient's Overall Change in Symptoms.

"The parent/caregiver was asked to rate the patient's overall change in symptoms and overall change in seizure activity and Quality of Life since the beginning of clobazam treatment by checking very much improved, much improved, minimally improved, no change, minimally worse, much worse, or very much worse." (NCT00518713)
Timeframe: Week 15

,,,
Interventionparticipants (Number)
Very much improvedMuch improvedMinimally improvedNo changeMinimally worseMuch worseVery much worse
Clobazam High Dose1118114320
Clobazam Low Dose814208201
Clobazam Medium Dose1319147220
Placebo4101121630

[back to top]

Percent of Patients Considered Treatment Responders Defined as Those With a >=25%, >=50%, >=75%, 100% Reduction in Drop Seizures (12-week Maintenance Period).

Number of drop seizures (average per week) was obtained from seizure diaries. The average drop in seizures per week for patients who did not complete the maintenance period was calculated based on the time from the beginning of the maintenance period to date of withdrawal. (NCT00518713)
Timeframe: 4-week baseline period and the 12-week maintenance period

,,,
InterventionPercent of responders (Number)
≥ 25% reduction≥ 50% reduction≥ 75% reduction100% reduction
Clobazam High Dose41383112
Clobazam Low Dose3423154
Clobazam Medium Dose4634227
Placebo281862

[back to top]

Percent of Patients Considered Treatment Responders Defined as Those With a >=25%, >=50%, >=75%, 100% Reduction in Drop Seizures (First 4 Weeks of the 12-week Maintenance Period).

Number of drop seizures (average per week) was obtained from seizure diaries. The average drop in seizures per week for patients who did not complete the maintenance period was calculated based on the time from the beginning of the maintenance period to date of withdrawal. (NCT00518713)
Timeframe: 4-week baseline period and the first 4 weeks of the 12-week maintenance period

,,,
InterventionPercent of responders (Number)
≥ 25% reduction≥ 50% reduction≥ 75% reduction100% reduction
Clobazam High Dose89.877.663.330.6
Clobazam Low Dose71.747.235.813.2
Clobazam Medium Dose82.872.444.819.0
Placebo52.631.614.03.5

[back to top]

Percent of Patients Considered Treatment Responders Defined as Those With a >=25%, >=50%, >=75%, 100% Reduction in Drop Seizures (Last 4 Weeks of the 12-week Maintenance Period).

Number of drop seizures (average per week) was obtained from seizure diaries. The average drop in seizures per week for patients who did not complete the maintenance period was calculated based on the time from the beginning of the maintenance period to date of withdrawal. (NCT00518713)
Timeframe: 4-week baseline period and the last 4 weeks of the 12-week maintenance period

,,,
InterventionPercent Responders (Number)
≥ 25% reduction≥ 50% reduction≥ 75% reduction100% reduction
Clobazam High Dose71.467.357.120.4
Clobazam Low Dose66.045.328.313.2
Clobazam Medium Dose60.350.036.215.5
Placebo43.929.812.35.3

[back to top]

Percent of Patients Considered Treatment Responders Defined as Those With a >=25%, >=50%, >=75%, 100% Reduction in Drop Seizures (Middle 4 Weeks of the 12-week Maintenance Period).

Number of drop seizures (average per week) was obtained from seizure diaries. The average drop in seizures per week for patients who did not complete the maintenance period was calculated based on the time from the beginning of the maintenance period to date of withdrawal. (NCT00518713)
Timeframe: 4-week baseline period and the middle 4 weeks of the 12-week maintenance period

,,,
InterventionPercent Responders (Number)
≥ 25% reduction≥ 50% reduction≥ 75% reduction100% reduction
Clobazam High Dose75.571.459.226.5
Clobazam Low Dose64.243.428.39.4
Clobazam Medium Dose65.551.734.515.5
Placebo50.924.612.35.3

[back to top]

Tolerance

Study responders who have ≥50% reduction in their drop seizure rate during the first 4 or first 8 weeks of maintenance compared to the 4 week baseline period. (NCT00518713)
Timeframe: 4-week baseline period and first 4/first 8 weeks of the maintenance period

,,,
InterventionParticipants (Number)
≥ 50% reduction - first 4 weeks of maintenance≥ 50% reduction - first 8 weeks of maintenance
Clobazam High Dose3838
Clobazam Low Dose2523
Clobazam Medium Dose4238
Placebo1820

[back to top]

Percent Reduction in Number of Drop Seizures (12-week Maintenance Period).

Number of drop seizures (average per week) was obtained from seizure diaries. The average drop in seizures per week for patients who did not complete the maintenance period was calculated based on the time from the beginning of the maintenance period to date of withdrawal. (NCT00518713)
Timeframe: 4-week baseline period and 12-week maintenance period

InterventionPercent Reduction (Least Squares Mean)
Clobazam Low Dose41.2
Clobazam Medium Dose49.4
Clobazam High Dose68.3
Placebo12.1

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Percent Reduction in Number of Drop Seizures (First 4 Weeks of the 12-week Maintenance Period).

Number of drop seizures (average per week) was obtained from seizure diaries. The average drop in seizures per week for patients who did not complete the maintenance period was calculated based on the time from the beginning of the maintenance period to date of withdrawal. (NCT00518713)
Timeframe: 4-week baseline period and the first 4 weeks of the 12-week maintenance period

InterventionPercent reduction (Least Squares Mean)
Clobazam Low Dose47.8
Clobazam Medium Dose58.9
Clobazam High Dose71.0
Placebo18.6

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Percent Reduction in Number of Drop Seizures (Last 4 Weeks of the 12-week Maintenance Period).

Number of drop seizures (average per week) was obtained from seizure diaries. The average drop in seizures per week for patients who did not complete the maintenance period was calculated based on the time from the beginning of the maintenance period to date of withdrawal. (NCT00518713)
Timeframe: 4-week baseline period and the last 4 weeks of the 12-week maintenance period

InterventionPercent reduction (Least Squares Mean)
Clobazam Low Dose31.8
Clobazam Medium Dose56.0
Clobazam High Dose68.0
Placebo-0.1

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Percent Reduction in Number of Drop Seizures (Middle 4 Weeks of the 12-week Maintenance Period).

Number of drop seizures (average per week) was obtained from seizure diaries. The average drop in seizures per week for patients who did not complete the maintenance period was calculated based on the time from the beginning of the maintenance period to date of withdrawal. (NCT00518713)
Timeframe: 4-week baseline period and the middle 4 weeks of the 12-week maintenance period

InterventionPercent reduction (Least Squares Mean)
Clobazam Low Dose44.1
Clobazam Medium Dose38.8
Clobazam High Dose64.9
Placebo21.1

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Percent Reduction in the Number of Non-drop Seizures.

This outcome measure evaluated the percent reduction (average per week) in non-drop Seizures. Non-drop seizures were other seizures not meeting the drop seizure definition. Drop seizures were defined as a drop attack or spell (atonic, tonic or myoclonic) involving the entire body, trunk, or head that led to a fall, injury, slumping in chair, or head hitting surface or that could have led to a fall or injury, depending on the position of the patient at the time of the attack or spell. (NCT00518713)
Timeframe: 4-week baseline period and the 12-week maintenance period

InterventionPercent reduction (Least Squares Mean)
Clobazam Low Dose-53.3
Clobazam Medium Dose-3.3
Clobazam High Dose40.0
Placebo-76.3

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Percent Reduction of Total (Drop and Non-Drop) Seizures.

This outcome measure evaluated the percent reduction in average weekly rate in total (drop and non-drop) seizures. Drop seizures were defined as a drop attack or spell (atonic, tonic or myoclonic) involving the entire body, trunk, or head that led to a fall, injury, slumping in chair, or head hitting surface or that could have led to a fall or injury, depending on the position of the patient at the time of the attack or spell. Non-drop seizures were other seizures not meeting the drop seizure definition. (NCT00518713)
Timeframe: 4-week baseline period and 12-week maintenance period

InterventionPercent reduction (Least Squares Mean)
Clobazam Low Dose34.8
Clobazam Medium Dose45.3
Clobazam High Dose65.3
Placebo9.3

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Investigator Global Evaluations of the Patient's Overall Change in Symptoms.

"The physician was asked to rate the patient's overall change in symptoms and overall change in seizure activity and Quality of Life since the beginning of clobazam treatment by checking very much improved, much improved, minimally improved, no change, minimally worse, much worse, or very much worse." (NCT00518713)
Timeframe: Week 15

,,,
Interventionparticipants (Number)
Very much improvedMuch improvedMinimally improvedNo changeMinimally worseMuch worseVery much worse
Clobazam High Dose82386310
Clobazam Low Dose4201312210
Clobazam Medium Dose102799200
Placebo3101322610

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Median Percent Reduction in Average Weekly Rate of Drop Seizures Based on the 7-day Assessment

Number of drop seizures was obtained from seizure diaries (NCT01160770)
Timeframe: Baseline to month 36

Interventionpercentage of drop seizures (Median)
Clobazam92.3

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Median Percent Reduction in Average Weekly Rate of Drop Seizures Based on the Last 30-day Assessment

Number of drop seizures was obtained from seizure diaries (NCT01160770)
Timeframe: Baseline to month 36

Interventionpercentage of drop seizures (Median)
Clobazam92.7

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Investigator Global Evaluations of the Patient's Overall Change in Symptoms

"The physician was asked to rate the patient's overall change in symptoms since the beginning of clobazam treatment by checking very much improved, much improved, minimally improved, no change, minimally worse, much worse, or very much worse." (NCT01160770)
Timeframe: Baseline to month 36

Interventionpercentage of participants (Number)
VERY MUCH IMPROVEDMUCH IMPROVEDMINIMALLY IMPROVEDNO CHANGEMINIMALLY WORSEMUCH WORSEVERY MUCH WORSE
Clobazam35.045.314.62.20.71.50.7

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Parent/Caregiver Global Evaluations of the Patient's Overall Change in Symptoms

"The parent/caregiver was asked to rate the patient's overall change in symptoms since the beginning of clobazam treatment by checking very much improved, much improved, minimally improved, no change, minimally worse, much worse, or very much worse." (NCT01160770)
Timeframe: Baseline to month 36

Interventionpercentage of participants (Number)
VERY MUCH IMPROVEDMUCH IMPROVEDMINIMALLY IMPROVEDNO CHANGEMINIMALLY WORSEMUCH WORSEVERY MUCH WORSE
Clobazam45.335.011.73.61.52.90.0

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Percent of Patients Considered Treatment Responders Defined as Those With a ≥25%, ≥50%, ≥75%, 100% Reduction in Drop Seizures Based on the 7-day Assessment

Number of drop seizures obtained from seizure diaries (NCT01160770)
Timeframe: Baseline to month 36

Interventionpercentage of participants (Number)
Any reduction≥25% reduction≥50% reduction≥75% reduction100% reduction
Clobazam85.882.377.964.638.1

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Percent of Patients Considered Treatment Responders Defined as Those With a ≥25%, ≥50%, ≥75%, 100% Reduction in Drop Seizures Based on the Last 30-day Assessment

Number of drop seizures obtained from seizure diaries (NCT01160770)
Timeframe: Baseline to month 36

Interventionpercentage of participants (Number)
Any reduction≥25% reduction≥50% reduction≥75% reduction100% reduction
Clobazam86.083.579.364.531.4

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

(NCT02187809)
Timeframe: Up to Day 390

Interventionparticipants (Number)
Clobazam0

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Number of Participants With Adverse Events of Special Interest as a Measure of Safety and Tolerability Based on Dose

(NCT02187809)
Timeframe: Up to Day 390

Interventionparticipants (Number)
Clobazam0

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Number Of Participants Who Experienced Severe OLE-Emergent AEs

"An OLE-emergent AE was defined as an AE with an onset date after the first dose of IMP in the OLE phase of the study. The number of participants who experienced 1 or more severe OLE-emergent AEs after the first dose of IMP in the OLE phase of the study up to the Safety follow-up visit (28 [± 3] days following the last dose of IMP) is presented.~A summary of serious and all other non-serious AEs, regardless of causality, is located in the Reported Adverse Events module." (NCT02564952)
Timeframe: Postdose on Day 2 of Visit 4 up to Safety follow-up (28 [± 3] days following the last dose of IMP)

InterventionParticipants (Count of Participants)
GWP42003-P4

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Number Of Participants Who Experienced Severe Treatment-Emergent Adverse Events (TEAEs)

"A TEAE was defined as an adverse event with an onset date on or after the first dose of IMP. If an adverse event (AE) had a partial onset date and it was unclear from the partial date (or the stop date) whether the AE started prior to or following the first dose of IMP then the AE was considered a TEAE. The number of participants who experienced 1 or more severe TEAEs after screening up to Day 71.~A summary of serious and all other non-serious AEs regardless of causality is located in the Reported Adverse Events module." (NCT02565108)
Timeframe: Postdose on Day 2 up to Safety follow-up (Day 71)

InterventionParticipants (Count of Participants)
GWP42003-P 20 mg/kg/Day Dose1
Placebo0

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Pharmacokinetics (PK): Maximum Measured Plasma Concentration (Cmax) Of CLB And N-CLB With GWP42003-P Treatment, Days 1 And 33

"The Cmax of CLB and its primary metabolite N-desmethylclobazam (N-CLB) was measured on Day 1 (before beginning GWP42003-P treatment; participants were taking CLB only) and Day 33 (following 21 days of GWP42003-P or placebo maintenance; participants were taking CLB and GWP42003-P or CLB and placebo). PK samples were taken at time points relative to the morning dose of CLB, as follows: Predose, 15 minutes (min), 30 min, 1 hour (h), 1.5 h, 2 h, 4 h, 6 h, 12 h, and 24 h.~One participant in the placebo group was excluded from the PK set because placebo was administered on Day 1, after predose sampling. Six participants in the GWP42003-P group were excluded from the PK set because of GWP42003-P and/or CLB dose modification, discontinuation of IMP, discontinuation from trial, or administration of incorrect IMP dose." (NCT02565108)
Timeframe: Predose, 0.25, 0.5, 1, 1.5, 2, 4, 6, 12, and 24 h postdose on Days 1 and 33

,
Interventionng/mL (Geometric Mean)
Cmax: CLB Day 1Cmax: CLB Day 33Cmax: N-CLB Day 1Cmax: N-CLB Day 33Cmax: CLB Dose-normalized Day 1Cmax: CLB Dose-normalized Day 33Cmax: N-CLB Dose-normalized Day 1Cmax: N-CLB Dose-normalized Day 33
GWP42003-P 20 mg/kg/Day Dose3303292060457019.319.2121267
Placebo4404611130132022.023.156.666.1

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PK: Area Under The Plasma Concentration-Time Curve Over A Dosing Interval, Where Tau Is The Dosing Interval (AUCtau) Of CLB And N-CLB With GWP42003-P Treatment, Days 1 And 33

"The AUCtau of CLB and its primary metabolite N-CLB was measured on Day 1 (before first GWP42003-P dose; participants were taking CLB only) and Day 33 (following 21 days of GWP42003-P or placebo maintenance; participants were taking CLB and GWP42003-P or CLB and placebo). PK samples were taken at time points relative to the morning dose of CLB, as follows: Predose, 15 min, 30 min, 1 h, 1.5 h, 2 h, 4 h, 6 h, 12 h, and 24 h.~One participant in the placebo group was excluded from the PK set because placebo was administered on Day 1, after predose sampling. Six participants in the GWP42003-P group were excluded from the PK set because of GWP42003-P and/or CLB dose modification, discontinuation of IMP, discontinuation from trial, or administration of incorrect IMP dose." (NCT02565108)
Timeframe: Predose, 0.25, 0.5, 1, 1.5, 2, 4, 6, 12, and 24 h postdose on Days 1 and 33

,
Interventionh*ng/mL (Geometric Mean)
AUCtau: CLB Day 1AUCtau: CLB Day 33AUCtau: N-CLB Day 1AUCtau: N-CLB Day 33AUCtau: CLB Dose-normalized Day 1AUCtau: CLB Dose-normalized Day 33AUCtau: N-CLB Dose-normalized Day 1AUCtau: N-CLB Dose-normalized Day 33
GWP42003-P 20 mg/kg/Day Dose26902840183004840015716610702830
Placebo332033101140011500166165571573

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PK: Geometric Mean Ratios Of CLB And N-CLB For AUCtau On Day 33 Compared With Day 1

The Day 33 compared to Day 1 geometric mean ratios of CLB and N-CLB were calculated for AUCtau to look for evidence of drug-drug interactions between GWP42003-P/Placebo and CLB and between GWP42003-P/Placebo and N-CLB. A standard 90% CI approach for the between time point ratios of geometric means of AUCtau was carried out on a logarithmic scale using a linear mixed effect model. The no-effect boundary was set between 0.5 and 2.0, and if the 90% CI for the ratio of the geometric means of a PK variable fell within the interval [0.5, 2.0], a lack of meaningful effect was declared. Estimates were back transformed to provide summaries on the original scale. The model included a fixed effect term for PK assessment period. An unstructured covariance matrix was used. Kenward and Roger's method was used to calculate the denominator degrees of freedom for the fixed effects. (NCT02565108)
Timeframe: Predose, 0.25, 0.5, 1, 1.5, 2, 4, 6, 12, and 24 h postdose on Days 1 and 33

,
InterventionRatio (Number)
Geometric Mean Ratio of CLB, AUCtauGeometric Mean Ratio of N-CLB, AUCtau
GWP42003-P 20 mg/kg/Day Dose1.062.64
Placebo0.9961.00

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PK: Geometric Mean Ratios Of CLB And N-CLB For Cmax On Day 33 Compared With Day 1

The Day 33 compared to Day 1 geometric mean ratios of CLB and N-CLB were calculated for Cmax to look for evidence of drug-drug interactions between GWP42003-P/Placebo and CLB and between GWP42003-P/Placebo and N-CLB. A standard 90% confidence interval (CI) approach for the between time point ratios of geometric means of Cmax was carried out on a logarithmic scale using a linear mixed effect model. The no-effect boundary was set between 0.5 and 2.0, and if the 90% CI for the ratio of the geometric means of a PK variable fell within the interval [0.5, 2.0], a lack of meaningful effect was declared. Estimates were back transformed to provide summaries on the original scale. The model included a fixed effect term for PK assessment period. An unstructured covariance matrix was used. Kenward and Roger's method was used to calculate the denominator degrees of freedom for the fixed effects. (NCT02565108)
Timeframe: Predose, 0.25, 0.5, 1, 1.5, 2, 4, 6, 12, and 24 h postdose on Days 1 and 33

,
InterventionRatio (Number)
Geometric Mean Ratio of CLB, CmaxGeometric Mean Ratio of N-CLB, Cmax
GWP42003-P 20 mg/kg/Day Dose0.9972.22
Placebo1.051.17

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PK: Time To The Maximum Plasma Concentration (Tmax) Of CLB And N-CLB With GWP42003-P Treatment, Days 1 And 33

"The tmax of CLB and its primary metabolite N-CLB was measured on Day 1 (before beginning GWP42003-P treatment; participants were taking CLB only) and Day 33 (following 21 days of GWP42003-P or placebo maintenance; participants were taking CLB and GWP42003-P or CLB and placebo). PK samples were taken at time points relative to the morning dose of CLB, as follows: Predose, 15 min, 30 min, 1 h, 1.5 h, 2 h, 4 h, 6 h, 12 h, and 24 h.~One participant in the placebo group was excluded from the PK set because placebo was administered on Day 1, after predose sampling. Six participants in the GWP42003-P group were excluded from the PK set because of GWP42003-P and/or CLB dose modification, discontinuation of IMP, discontinuation from trial, or administration of incorrect IMP dose." (NCT02565108)
Timeframe: Predose, 0.25, 0.5, 1, 1.5, 2, 4, 6, 12, and 24 h postdose on Days 1 and 33

,
Interventionh (Median)
tmax: CLB Day 1tmax: CLB Day 33tmax: N-CLB Day 1tmax: N-CLB Day 33
GWP42003-P 20 mg/kg/Day Dose1.001.861.503.03
Placebo1.171.582.001.00

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CGI-I

Mean of Clinical Global Impression-Improvement from baseline. (1-7 point scale; lower score equals a better outcome; 1 is the maximum improvement, 7 is the minimum improvement) (NCT03371836)
Timeframe: 14-18 weeks

Interventionunits on a scale (Mean)
Clobazam2

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