Page last updated: 2024-11-12

casopitant

Description Research Excerpts Clinical Trials Roles Classes Pathways Study Profile Bioassays Related Drugs Related Conditions Protein Interactions Research Growth Market Indicators

Cross-References

ID SourceID
PubMed CID9917021
CHEMBL ID1672054
CHEBI ID135967
SCHEMBL ID425342
MeSH IDM0525464

Synonyms (28)

Synonym
bdbm50336575
cis-(1''-acetyl-n-{(1r)-1-[3,5-bis(trifluoromethyl)phenyl]-ethyl}-2-(4-fluoro-2-methylphenyl)-n-methyl-4,4''-bipiperidine-1-carboxamide
gw-679769
zunrisa
casopitant
CHEBI:135967
gw679769
CHEMBL1672054 ,
414910-27-3
gw 679769
casopitant [inn]
3b03kpm27l ,
unii-3b03kpm27l
1-piperidinecarboxamide, 4-(4-acetyl-1-piperazinyl)-n-((1r)-1-(3,5-bis(trifluoromethyl)phenyl)ethyl)-2-(4-fluoro-2-methylphenyl)-n-methyl-, (2r,4s)-
852393-14-7
casopitant [mart.]
casopitant [who-dd]
(2r,4s)-4-(4-acetylpiperazin-1-yl)-n-[(1r)-1-[3,5-bis(trifluoromethyl)phenyl]ethyl]-2-(4-fluoro-2-methylphenyl)-n-methylpiperidine-1-carboxamide
rezonic (proposed trade name)
gtpl5758
zunrisa (proposed trade name)
SCHEMBL425342
NCGC00386657-01
Q5049003
DB06634
DTXSID40961762
xggtzckqrwxchw-wmtvxvaqsa-n
EN300-19880551

Research Excerpts

Overview

Casopitant mesylate is a novel, oral neurokinin-1 receptor antagonist. It has shown clinical efficacy in the prevention of chemotherapy-induced and postoperative-induced nausea and vomiting. Casopitant is a dose- and duration-dependent weak to moderate inhibitor of CYP3A.

ExcerptReferenceRelevance
"Casopitant is shown to be a substrate, an inhibitor, and an inducer of CYP3A4, and, because of this complex behavior, it was difficult to identify the primary mechanism by which it may give rise to drug-drug interactions (DDIs) of clinical relevance."( Casopitant: in vitro data and SimCyp simulation to predict in vivo metabolic interactions involving cytochrome P450 3A4.
Bonomo, F; Motta, P; Pagliarusco, S; Pellegatti, M; Pons, N, 2011
)
2.53
"Casopitant mesylate is a novel, oral neurokinin-1 receptor antagonist with demonstrated antiemetic efficacy. "( Randomized, double-blind, dose-ranging trial of the oral neurokinin-1 receptor antagonist casopitant mesylate for the prevention of cisplatin-induced nausea and vomiting.
Bandekar, RR; Dediu, M; Grunberg, SM; Ramlau, R; Roila, F; Rolski, J; Russo, MW, 2009
)
2.02
"Casopitant is a dose- and duration-dependent weak to moderate inhibitor of CYP3A."( Effect of single and repeat doses of casopitant on the pharmacokinetics of CYP450 3A4 substrates midazolam and nifedipine.
Adams, LM; Fernandes, SA; Fina, P; Fiore, M; Johnson, BM; Pagliarusco, S; Peroni, M; Zamuner, S, 2010
)
2.08
"Casopitant is a potent and selective NK-1 receptor antagonist that has shown clinical efficacy in the prevention of chemotherapy-induced and postoperative-induced nausea and vomiting."( The potential role for corticosterone in the induction of cleft palate in mice after treatment with a selective NK-1 receptor antagonist, casopitant (GW679769B).
Apostoli, AR; Clark, RL; Solomon, HM; Stanislaus, D; White, TE; Ziejewski, MK, 2012
)
2.02

Toxicity

ExcerptReferenceRelevance
" Adverse events occurred in 205 (77%) patients in the single-dose oral casopitant mesylate group and 203 (75%) patients in the 3-day intravenous and oral casopitant mesylate group compared with 194 (73%) of patients in the control group."( Efficacy and safety of casopitant mesylate, a neurokinin 1 (NK1)-receptor antagonist, in prevention of chemotherapy-induced nausea and vomiting in patients receiving cisplatin-based highly emetogenic chemotherapy: a randomised, double-blind, placebo-contr
Aziz, Z; Grunberg, SM; Guckert, M; Herrstedt, J; Lane, S; Rolski, J; Russo, MW; Strausz, J; Wissel, P; Wright, O, 2009
)
0.9
" All active doses seemed to be well tolerated; headache, dizziness, and constipation were the most frequently reported adverse events."( Phase II study to evaluate the safety and efficacy of the oral neurokinin-1 receptor antagonist casopitant (GW679769) administered with ondansetron for the prevention of postoperative and postdischarge nausea and vomiting in high-risk patients.
Blackburn, L; Chung, F; Johnson, B; Kutsogiannis, DJ; Lane, SR; Levin, J; Pergolizzi, JV; Singla, NK; Singla, SK, 2010
)
0.58

Pharmacokinetics

The largest changes in hydrodolasetron exposure after coadministration with casopitant were seen in CYP2D6 EMs. Venous blood samples were taken prior to and following oral dosing up to 24 h for a pharmacokinetic study.

ExcerptReferenceRelevance
" The additional pharmacodynamic benefit of the combination dose was not because of an alteration in the pharmacokinetics of either agent but is likely the result of the complementary mechanisms of pharmacologic action of the two drugs."( Pharmacokinetics and brain penetration of casopitant, a potent and selective neurokinin-1 receptor antagonist, in the ferret.
Bambal, R; Davis, CB; Gontarek, RR; Han, C; King, AG; Mencken, T; Minthorn, E; Rominger, D; Shu, A, 2008
)
0.61
" Log-transformed area under the curve (AUC) and Cmax were statistically analyzed by performing an analysis of variance."( Effect of casopitant, a novel NK-1 antagonist, on the pharmacokinetics of dolasetron and granisetron.
Adams, LM; Johnson, B; Kirby, LC; Lebowitz, P; Stoltz, R; Yue, L; Zhang, K, 2009
)
0.76
" Venous blood samples were taken prior to and following oral dosing up to 24 h for a pharmacokinetic study of casopitant concentration in plasma."( A pharmacokinetic PET study of NK₁ receptor occupancy.
Bani, M; Cunningham, VJ; Fernandes, SA; Gomeni, R; Gunn, RN; Rabiner, EA; Ratti, E; Zamuner, S, 2012
)
0.59

Compound-Compound Interactions

ExcerptReferenceRelevance
"This randomized, double-blind, dose-ranging, placebo-controlled, phase 2 trial evaluated the neurokinin-1 receptor antagonist casopitant mesylate in combination with ondansetron/dexamethasone (ond/dex) for the prevention of chemotherapy-induced nausea and vomiting (CINV) related to moderately emetogenic chemotherapy (MEC)."( Phase 2 trial results with the novel neurokinin-1 receptor antagonist casopitant in combination with ondansetron and dexamethasone for the prevention of chemotherapy-induced nausea and vomiting in cancer patients receiving moderately emetogenic chemothera
Albert, I; Arpornwirat, W; Bandekar, RR; Grunberg, SM; Hansen, VL; Levin, J, 2009
)
0.79

Bioavailability

ExcerptReferenceRelevance
"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

Dosage Studied

Casopitant was rapidly absorbed, with plasma and brain concentrations being approximately equal at 2 h postdose. Venous blood samples were taken prior to and following oral dosing up to 24 h for a pharmacokinetic study of casopitant concentration in plasma.

ExcerptRelevanceReference
" dosing to the ferret, casopitant was rapidly absorbed, with plasma and brain concentrations being approximately equal at 2 h postdose."( Pharmacokinetics and brain penetration of casopitant, a potent and selective neurokinin-1 receptor antagonist, in the ferret.
Bambal, R; Davis, CB; Gontarek, RR; Han, C; King, AG; Mencken, T; Minthorn, E; Rominger, D; Shu, A, 2008
)
0.92
" The distribution and metabolism of casopitant were studied in both species evaluating the accumulation of drug-related material (DRM) after repeat dosing and its potential relationship with pathological findings observed in myocardium."( Tissue distribution and characterization of drug-related material in rats and dogs after repeated oral administration of casopitant.
Bordini, E; Cufari, D; Ferrari, L; Martinucci, S; Miraglia, L; Pagliarusco, S; Pellegatti, M, 2011
)
0.85
" Venous blood samples were taken prior to and following oral dosing up to 24 h for a pharmacokinetic study of casopitant concentration in plasma."( A pharmacokinetic PET study of NK₁ receptor occupancy.
Bani, M; Cunningham, VJ; Fernandes, SA; Gomeni, R; Gunn, RN; Rabiner, EA; Ratti, E; Zamuner, S, 2012
)
0.59
[information is derived through text-mining from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Drug Classes (1)

ClassDescription
piperidines
[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 (10)

Potency Measurements

ProteinTaxonomyMeasurementAverage (µ)Min (ref.)Avg (ref.)Max (ref.)Bioassay(s)
cytochrome P450 family 3 subfamily A polypeptide 4Homo sapiens (human)Potency6.00810.01237.983543.2770AID1645841
GVesicular stomatitis virusPotency9.52210.01238.964839.8107AID1645842
cytochrome P450 2D6Homo sapiens (human)Potency26.83700.00108.379861.1304AID1645840
Interferon betaHomo sapiens (human)Potency9.52210.00339.158239.8107AID1645842
HLA class I histocompatibility antigen, B alpha chain Homo sapiens (human)Potency9.52210.01238.964839.8107AID1645842
Inositol hexakisphosphate kinase 1Homo sapiens (human)Potency9.52210.01238.964839.8107AID1645842
cytochrome P450 2C9, partialHomo sapiens (human)Potency9.52210.01238.964839.8107AID1645842
[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)
Substance-P receptorHomo sapiens (human)Ki0.00020.00000.79368.7470AID576859; AID577014
Sigma non-opioid intracellular receptor 1Homo sapiens (human)Ki2.98000.00000.490110.0000AID577016
[prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023]

Other Measurements

ProteinTaxonomyMeasurementAverageMin (ref.)Avg (ref.)Max (ref.)Bioassay(s)
Cytochrome P450 3A4Homo sapiens (human)Km10.10001.93005.90608.7000AID1216301
[prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023]

Biological Processes (107)

Processvia Protein(s)Taxonomy
cell surface receptor signaling pathway via JAK-STATInterferon betaHomo sapiens (human)
response to exogenous dsRNAInterferon betaHomo sapiens (human)
B cell activation involved in immune responseInterferon betaHomo sapiens (human)
cell surface receptor signaling pathwayInterferon betaHomo sapiens (human)
cell surface receptor signaling pathway via JAK-STATInterferon betaHomo sapiens (human)
response to virusInterferon betaHomo sapiens (human)
positive regulation of autophagyInterferon betaHomo sapiens (human)
cytokine-mediated signaling pathwayInterferon betaHomo sapiens (human)
natural killer cell activationInterferon betaHomo sapiens (human)
positive regulation of peptidyl-serine phosphorylation of STAT proteinInterferon betaHomo sapiens (human)
cellular response to interferon-betaInterferon betaHomo sapiens (human)
B cell proliferationInterferon betaHomo sapiens (human)
negative regulation of viral genome replicationInterferon betaHomo sapiens (human)
innate immune responseInterferon betaHomo sapiens (human)
positive regulation of innate immune responseInterferon betaHomo sapiens (human)
regulation of MHC class I biosynthetic processInterferon betaHomo sapiens (human)
negative regulation of T cell differentiationInterferon betaHomo sapiens (human)
positive regulation of transcription by RNA polymerase IIInterferon betaHomo sapiens (human)
defense response to virusInterferon betaHomo sapiens (human)
type I interferon-mediated signaling pathwayInterferon betaHomo sapiens (human)
neuron cellular homeostasisInterferon betaHomo sapiens (human)
cellular response to exogenous dsRNAInterferon betaHomo sapiens (human)
cellular response to virusInterferon betaHomo sapiens (human)
negative regulation of Lewy body formationInterferon betaHomo sapiens (human)
negative regulation of T-helper 2 cell cytokine productionInterferon betaHomo sapiens (human)
positive regulation of apoptotic signaling pathwayInterferon betaHomo sapiens (human)
response to exogenous dsRNAInterferon betaHomo sapiens (human)
B cell differentiationInterferon betaHomo sapiens (human)
natural killer cell activation involved in immune responseInterferon betaHomo sapiens (human)
adaptive immune responseInterferon betaHomo sapiens (human)
T cell activation involved in immune responseInterferon betaHomo sapiens (human)
humoral immune responseInterferon betaHomo sapiens (human)
positive regulation of T cell mediated cytotoxicityHLA class I histocompatibility antigen, B alpha chain Homo sapiens (human)
adaptive immune responseHLA class I histocompatibility antigen, B alpha chain Homo sapiens (human)
antigen processing and presentation of endogenous peptide antigen via MHC class I via ER pathway, TAP-independentHLA class I histocompatibility antigen, B alpha chain Homo sapiens (human)
regulation of T cell anergyHLA class I histocompatibility antigen, B alpha chain Homo sapiens (human)
defense responseHLA class I histocompatibility antigen, B alpha chain Homo sapiens (human)
immune responseHLA class I histocompatibility antigen, B alpha chain Homo sapiens (human)
detection of bacteriumHLA class I histocompatibility antigen, B alpha chain Homo sapiens (human)
regulation of interleukin-12 productionHLA class I histocompatibility antigen, B alpha chain Homo sapiens (human)
regulation of interleukin-6 productionHLA class I histocompatibility antigen, B alpha chain Homo sapiens (human)
protection from natural killer cell mediated cytotoxicityHLA class I histocompatibility antigen, B alpha chain Homo sapiens (human)
innate immune responseHLA class I histocompatibility antigen, B alpha chain Homo sapiens (human)
regulation of dendritic cell differentiationHLA class I histocompatibility antigen, B alpha chain Homo sapiens (human)
antigen processing and presentation of endogenous peptide antigen via MHC class IbHLA class I histocompatibility antigen, B alpha chain Homo sapiens (human)
lipid hydroxylationCytochrome P450 3A4Homo sapiens (human)
lipid metabolic processCytochrome P450 3A4Homo sapiens (human)
steroid catabolic processCytochrome P450 3A4Homo sapiens (human)
xenobiotic metabolic processCytochrome P450 3A4Homo sapiens (human)
steroid metabolic processCytochrome P450 3A4Homo sapiens (human)
cholesterol metabolic processCytochrome P450 3A4Homo sapiens (human)
androgen metabolic processCytochrome P450 3A4Homo sapiens (human)
estrogen metabolic processCytochrome P450 3A4Homo sapiens (human)
alkaloid catabolic processCytochrome P450 3A4Homo sapiens (human)
monoterpenoid metabolic processCytochrome P450 3A4Homo sapiens (human)
calcitriol biosynthetic process from calciolCytochrome P450 3A4Homo sapiens (human)
xenobiotic catabolic processCytochrome P450 3A4Homo sapiens (human)
vitamin D metabolic processCytochrome P450 3A4Homo sapiens (human)
vitamin D catabolic processCytochrome P450 3A4Homo sapiens (human)
retinol metabolic processCytochrome P450 3A4Homo sapiens (human)
retinoic acid metabolic processCytochrome P450 3A4Homo sapiens (human)
long-chain fatty acid biosynthetic processCytochrome P450 3A4Homo sapiens (human)
aflatoxin metabolic processCytochrome P450 3A4Homo sapiens (human)
oxidative demethylationCytochrome P450 3A4Homo sapiens (human)
aggressive behaviorSubstance-P receptorHomo sapiens (human)
positive regulation of leukocyte migrationSubstance-P receptorHomo sapiens (human)
angiotensin-mediated drinking behaviorSubstance-P receptorHomo sapiens (human)
inflammatory responseSubstance-P receptorHomo sapiens (human)
phospholipase C-activating G protein-coupled receptor signaling pathwaySubstance-P receptorHomo sapiens (human)
positive regulation of cytosolic calcium ion concentrationSubstance-P receptorHomo sapiens (human)
tachykinin receptor signaling pathwaySubstance-P receptorHomo sapiens (human)
long-term memorySubstance-P receptorHomo sapiens (human)
associative learningSubstance-P receptorHomo sapiens (human)
detection of abiotic stimulusSubstance-P receptorHomo sapiens (human)
response to ozoneSubstance-P receptorHomo sapiens (human)
positive regulation of epithelial cell migrationSubstance-P receptorHomo sapiens (human)
response to auditory stimulusSubstance-P receptorHomo sapiens (human)
regulation of smooth muscle cell migrationSubstance-P receptorHomo sapiens (human)
positive regulation of synaptic transmission, cholinergicSubstance-P receptorHomo sapiens (human)
positive regulation of synaptic transmission, GABAergicSubstance-P receptorHomo sapiens (human)
response to estradiolSubstance-P receptorHomo sapiens (human)
response to progesteroneSubstance-P receptorHomo sapiens (human)
response to nicotineSubstance-P receptorHomo sapiens (human)
operant conditioningSubstance-P receptorHomo sapiens (human)
sperm ejaculationSubstance-P receptorHomo sapiens (human)
eating behaviorSubstance-P receptorHomo sapiens (human)
positive regulation of vascular permeabilitySubstance-P receptorHomo sapiens (human)
response to ethanolSubstance-P receptorHomo sapiens (human)
positive regulation of action potentialSubstance-P receptorHomo sapiens (human)
positive regulation of blood pressureSubstance-P receptorHomo sapiens (human)
positive regulation of ossificationSubstance-P receptorHomo sapiens (human)
positive regulation of vasoconstrictionSubstance-P receptorHomo sapiens (human)
positive regulation of hormone secretionSubstance-P receptorHomo sapiens (human)
behavioral response to painSubstance-P receptorHomo sapiens (human)
regulation of smooth muscle cell proliferationSubstance-P receptorHomo sapiens (human)
positive regulation of lymphocyte proliferationSubstance-P receptorHomo sapiens (human)
positive regulation of epithelial cell proliferationSubstance-P receptorHomo sapiens (human)
positive regulation of stress fiber assemblySubstance-P receptorHomo sapiens (human)
response to electrical stimulusSubstance-P receptorHomo sapiens (human)
smooth muscle contraction involved in micturitionSubstance-P receptorHomo sapiens (human)
positive regulation of uterine smooth muscle contractionSubstance-P receptorHomo sapiens (human)
positive regulation of flagellated sperm motilitySubstance-P receptorHomo sapiens (human)
inositol phosphate metabolic processInositol hexakisphosphate kinase 1Homo sapiens (human)
phosphatidylinositol phosphate biosynthetic processInositol hexakisphosphate kinase 1Homo sapiens (human)
negative regulation of cold-induced thermogenesisInositol hexakisphosphate kinase 1Homo sapiens (human)
inositol phosphate biosynthetic processInositol hexakisphosphate kinase 1Homo sapiens (human)
lipid transportSigma non-opioid intracellular receptor 1Homo sapiens (human)
nervous system developmentSigma non-opioid intracellular receptor 1Homo sapiens (human)
G protein-coupled opioid receptor signaling pathwaySigma non-opioid intracellular receptor 1Homo sapiens (human)
regulation of neuron apoptotic processSigma non-opioid intracellular receptor 1Homo sapiens (human)
protein homotrimerizationSigma non-opioid intracellular receptor 1Homo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Molecular Functions (43)

Processvia Protein(s)Taxonomy
cytokine activityInterferon betaHomo sapiens (human)
cytokine receptor bindingInterferon betaHomo sapiens (human)
type I interferon receptor bindingInterferon betaHomo sapiens (human)
protein bindingInterferon betaHomo sapiens (human)
chloramphenicol O-acetyltransferase activityInterferon betaHomo sapiens (human)
TAP bindingHLA class I histocompatibility antigen, B alpha chain Homo sapiens (human)
signaling receptor bindingHLA class I histocompatibility antigen, B alpha chain Homo sapiens (human)
protein bindingHLA class I histocompatibility antigen, B alpha chain Homo sapiens (human)
peptide antigen bindingHLA class I histocompatibility antigen, B alpha chain Homo sapiens (human)
TAP bindingHLA class I histocompatibility antigen, B alpha chain Homo sapiens (human)
protein-folding chaperone bindingHLA class I histocompatibility antigen, B alpha chain Homo sapiens (human)
monooxygenase activityCytochrome P450 3A4Homo sapiens (human)
steroid bindingCytochrome P450 3A4Homo sapiens (human)
iron ion bindingCytochrome P450 3A4Homo sapiens (human)
protein bindingCytochrome P450 3A4Homo sapiens (human)
steroid hydroxylase activityCytochrome P450 3A4Homo sapiens (human)
retinoic acid 4-hydroxylase activityCytochrome P450 3A4Homo sapiens (human)
oxidoreductase activityCytochrome P450 3A4Homo sapiens (human)
oxygen bindingCytochrome P450 3A4Homo sapiens (human)
enzyme bindingCytochrome P450 3A4Homo sapiens (human)
heme bindingCytochrome P450 3A4Homo sapiens (human)
vitamin D3 25-hydroxylase activityCytochrome P450 3A4Homo sapiens (human)
caffeine oxidase activityCytochrome P450 3A4Homo sapiens (human)
quinine 3-monooxygenase activityCytochrome P450 3A4Homo sapiens (human)
testosterone 6-beta-hydroxylase activityCytochrome P450 3A4Homo sapiens (human)
1-alpha,25-dihydroxyvitamin D3 23-hydroxylase activityCytochrome P450 3A4Homo sapiens (human)
anandamide 8,9 epoxidase activityCytochrome P450 3A4Homo sapiens (human)
anandamide 11,12 epoxidase activityCytochrome P450 3A4Homo sapiens (human)
anandamide 14,15 epoxidase activityCytochrome P450 3A4Homo sapiens (human)
aromatase activityCytochrome P450 3A4Homo sapiens (human)
vitamin D 24-hydroxylase activityCytochrome P450 3A4Homo sapiens (human)
estrogen 16-alpha-hydroxylase activityCytochrome P450 3A4Homo sapiens (human)
estrogen 2-hydroxylase activityCytochrome P450 3A4Homo sapiens (human)
1,8-cineole 2-exo-monooxygenase activityCytochrome P450 3A4Homo sapiens (human)
tachykinin receptor activitySubstance-P receptorHomo sapiens (human)
protein bindingSubstance-P receptorHomo sapiens (human)
substance P receptor activitySubstance-P receptorHomo sapiens (human)
inositol-1,3,4,5,6-pentakisphosphate kinase activityInositol hexakisphosphate kinase 1Homo sapiens (human)
inositol hexakisphosphate kinase activityInositol hexakisphosphate kinase 1Homo sapiens (human)
inositol heptakisphosphate kinase activityInositol hexakisphosphate kinase 1Homo sapiens (human)
inositol hexakisphosphate 5-kinase activityInositol hexakisphosphate kinase 1Homo sapiens (human)
protein bindingInositol hexakisphosphate kinase 1Homo sapiens (human)
ATP bindingInositol hexakisphosphate kinase 1Homo sapiens (human)
inositol hexakisphosphate 1-kinase activityInositol hexakisphosphate kinase 1Homo sapiens (human)
inositol hexakisphosphate 3-kinase activityInositol hexakisphosphate kinase 1Homo sapiens (human)
inositol 5-diphosphate pentakisphosphate 5-kinase activityInositol hexakisphosphate kinase 1Homo sapiens (human)
inositol diphosphate tetrakisphosphate kinase activityInositol hexakisphosphate kinase 1Homo sapiens (human)
G protein-coupled opioid receptor activitySigma non-opioid intracellular receptor 1Homo sapiens (human)
protein bindingSigma non-opioid intracellular receptor 1Homo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Ceullar Components (38)

Processvia Protein(s)Taxonomy
extracellular spaceInterferon betaHomo sapiens (human)
extracellular regionInterferon betaHomo sapiens (human)
Golgi membraneHLA class I histocompatibility antigen, B alpha chain Homo sapiens (human)
endoplasmic reticulumHLA class I histocompatibility antigen, B alpha chain Homo sapiens (human)
Golgi apparatusHLA class I histocompatibility antigen, B alpha chain Homo sapiens (human)
plasma membraneHLA class I histocompatibility antigen, B alpha chain Homo sapiens (human)
cell surfaceHLA class I histocompatibility antigen, B alpha chain Homo sapiens (human)
ER to Golgi transport vesicle membraneHLA class I histocompatibility antigen, B alpha chain Homo sapiens (human)
membraneHLA class I histocompatibility antigen, B alpha chain Homo sapiens (human)
secretory granule membraneHLA class I histocompatibility antigen, B alpha chain Homo sapiens (human)
phagocytic vesicle membraneHLA class I histocompatibility antigen, B alpha chain Homo sapiens (human)
early endosome membraneHLA class I histocompatibility antigen, B alpha chain Homo sapiens (human)
recycling endosome membraneHLA class I histocompatibility antigen, B alpha chain Homo sapiens (human)
extracellular exosomeHLA class I histocompatibility antigen, B alpha chain Homo sapiens (human)
lumenal side of endoplasmic reticulum membraneHLA class I histocompatibility antigen, B alpha chain Homo sapiens (human)
MHC class I protein complexHLA class I histocompatibility antigen, B alpha chain Homo sapiens (human)
extracellular spaceHLA class I histocompatibility antigen, B alpha chain Homo sapiens (human)
external side of plasma membraneHLA class I histocompatibility antigen, B alpha chain Homo sapiens (human)
cytoplasmCytochrome P450 3A4Homo sapiens (human)
endoplasmic reticulum membraneCytochrome P450 3A4Homo sapiens (human)
intracellular membrane-bounded organelleCytochrome P450 3A4Homo sapiens (human)
plasma membraneSubstance-P receptorHomo sapiens (human)
cell surfaceSubstance-P receptorHomo sapiens (human)
dendriteSubstance-P receptorHomo sapiens (human)
sperm flagellumSubstance-P receptorHomo sapiens (human)
cell bodySubstance-P receptorHomo sapiens (human)
sperm headSubstance-P receptorHomo sapiens (human)
sperm midpieceSubstance-P receptorHomo sapiens (human)
plasma membraneSubstance-P receptorHomo sapiens (human)
sperm midpieceSubstance-P receptorHomo sapiens (human)
fibrillar centerInositol hexakisphosphate kinase 1Homo sapiens (human)
nucleoplasmInositol hexakisphosphate kinase 1Homo sapiens (human)
cytosolInositol hexakisphosphate kinase 1Homo sapiens (human)
nucleusInositol hexakisphosphate kinase 1Homo sapiens (human)
cytoplasmInositol hexakisphosphate kinase 1Homo sapiens (human)
nuclear envelopeSigma non-opioid intracellular receptor 1Homo sapiens (human)
nuclear inner membraneSigma non-opioid intracellular receptor 1Homo sapiens (human)
nuclear outer membraneSigma non-opioid intracellular receptor 1Homo sapiens (human)
endoplasmic reticulumSigma non-opioid intracellular receptor 1Homo sapiens (human)
endoplasmic reticulum membraneSigma non-opioid intracellular receptor 1Homo sapiens (human)
lipid dropletSigma non-opioid intracellular receptor 1Homo sapiens (human)
cytosolSigma non-opioid intracellular receptor 1Homo sapiens (human)
postsynaptic densitySigma non-opioid intracellular receptor 1Homo sapiens (human)
membraneSigma non-opioid intracellular receptor 1Homo sapiens (human)
growth coneSigma non-opioid intracellular receptor 1Homo sapiens (human)
cytoplasmic vesicleSigma non-opioid intracellular receptor 1Homo sapiens (human)
anchoring junctionSigma non-opioid intracellular receptor 1Homo sapiens (human)
postsynaptic density membraneSigma non-opioid intracellular receptor 1Homo sapiens (human)
endoplasmic reticulumSigma non-opioid intracellular receptor 1Homo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Bioassays (89)

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.
AID1347159Primary screen GU Rhodamine qHTS for Zika virus inhibitors: Unlinked NS2B-NS3 protease assay2020Proceedings of the National Academy of Sciences of the United States of America, 12-08, Volume: 117, Issue:49
Therapeutic candidates for the Zika virus identified by a high-throughput screen for Zika protease inhibitors.
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.
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.
AID1347160Primary screen NINDS Rhodamine qHTS for Zika virus inhibitors2020Proceedings of the National Academy of Sciences of the United States of America, 12-08, Volume: 117, Issue:49
Therapeutic candidates for the Zika virus identified by a high-throughput screen for Zika protease inhibitors.
AID1216338Metabolism dependent inhibition of CYP3A4 in human liver microsomes pretreated with compound for 20 mins in presence of midazolam substrate and NADPH by HPLC-MS/MS method relative to untreated control2011Drug metabolism and disposition: the biological fate of chemicals, Mar, Volume: 39, Issue:3
Casopitant: in vitro data and SimCyp simulation to predict in vivo metabolic interactions involving cytochrome P450 3A4.
AID577033Oral bioavailability in rat at 1 mg/kg2011Journal of medicinal chemistry, Feb-24, Volume: 54, Issue:4
Discovery and biological characterization of (2R,4S)-1'-acetyl-N-{(1R)-1-[3,5-bis(trifluoromethyl)phenyl]ethyl}-2-(4-fluoro-2-methylphenyl)-N-methyl-4,4'-bipiperidine-1-carboxamide as a new potent and selective neurokinin 1 (NK1) receptor antagonist clini
AID779999Plasma clearance in rat at 0.5 mg/kg, iv and 1 mg/kg, po2013Bioorganic & medicinal chemistry, Nov-01, Volume: 21, Issue:21
Identification, biological characterization and pharmacophoric analysis of a new potent and selective NK1 receptor antagonist clinical candidate.
AID577023Toxicity in Mongolian gerbil assessed as abnormal behavior at 0.3 to 1 mg/kg, po2011Journal of medicinal chemistry, Feb-24, Volume: 54, Issue:4
Discovery and biological characterization of (2R,4S)-1'-acetyl-N-{(1R)-1-[3,5-bis(trifluoromethyl)phenyl]ethyl}-2-(4-fluoro-2-methylphenyl)-N-methyl-4,4'-bipiperidine-1-carboxamide as a new potent and selective neurokinin 1 (NK1) receptor antagonist clini
AID577044Half life in marmoset at 1 mg/kg, iv2011Journal of medicinal chemistry, Feb-24, Volume: 54, Issue:4
Discovery and biological characterization of (2R,4S)-1'-acetyl-N-{(1R)-1-[3,5-bis(trifluoromethyl)phenyl]ethyl}-2-(4-fluoro-2-methylphenyl)-N-methyl-4,4'-bipiperidine-1-carboxamide as a new potent and selective neurokinin 1 (NK1) receptor antagonist clini
AID577029Oral bioavailability in mouse at 2 mg/kg2011Journal of medicinal chemistry, Feb-24, Volume: 54, Issue:4
Discovery and biological characterization of (2R,4S)-1'-acetyl-N-{(1R)-1-[3,5-bis(trifluoromethyl)phenyl]ethyl}-2-(4-fluoro-2-methylphenyl)-N-methyl-4,4'-bipiperidine-1-carboxamide as a new potent and selective neurokinin 1 (NK1) receptor antagonist clini
AID779992Oral bioavailability in dog at 1 mg/kg2013Bioorganic & medicinal chemistry, Nov-01, Volume: 21, Issue:21
Identification, biological characterization and pharmacophoric analysis of a new potent and selective NK1 receptor antagonist clinical candidate.
AID1216318Tmax in healthy human at 150 mg, po administered as single dose2011Drug metabolism and disposition: the biological fate of chemicals, Mar, Volume: 39, Issue:3
Casopitant: in vitro data and SimCyp simulation to predict in vivo metabolic interactions involving cytochrome P450 3A4.
AID577025Toxicity in Mongolian gerbil assessed as locomotor activity at 1 mg/kg, po2011Journal of medicinal chemistry, Feb-24, Volume: 54, Issue:4
Discovery and biological characterization of (2R,4S)-1'-acetyl-N-{(1R)-1-[3,5-bis(trifluoromethyl)phenyl]ethyl}-2-(4-fluoro-2-methylphenyl)-N-methyl-4,4'-bipiperidine-1-carboxamide as a new potent and selective neurokinin 1 (NK1) receptor antagonist clini
AID1216315AUC (0 to t) in healthy human at 150 mg, po administered as single dose on day 8 and cotreated with rifampin at 600 mg, po qd on day 1 to 92011Drug metabolism and disposition: the biological fate of chemicals, Mar, Volume: 39, Issue:3
Casopitant: in vitro data and SimCyp simulation to predict in vivo metabolic interactions involving cytochrome P450 3A4.
AID577036Half life in dog at 0.5 mg/kg, iv2011Journal of medicinal chemistry, Feb-24, Volume: 54, Issue:4
Discovery and biological characterization of (2R,4S)-1'-acetyl-N-{(1R)-1-[3,5-bis(trifluoromethyl)phenyl]ethyl}-2-(4-fluoro-2-methylphenyl)-N-methyl-4,4'-bipiperidine-1-carboxamide as a new potent and selective neurokinin 1 (NK1) receptor antagonist clini
AID1216332Ratio of drug level in blood to plasma in human2011Drug metabolism and disposition: the biological fate of chemicals, Mar, Volume: 39, Issue:3
Casopitant: in vitro data and SimCyp simulation to predict in vivo metabolic interactions involving cytochrome P450 3A4.
AID1216321Half life in healthy human at 150 mg, po administered as single dose on day 8 and cotreated with rifampin at 600 mg, po qd on day 1 to 92011Drug metabolism and disposition: the biological fate of chemicals, Mar, Volume: 39, Issue:3
Casopitant: in vitro data and SimCyp simulation to predict in vivo metabolic interactions involving cytochrome P450 3A4.
AID577045Bioavailability in marmoset at 1 mg/kg, iv2011Journal of medicinal chemistry, Feb-24, Volume: 54, Issue:4
Discovery and biological characterization of (2R,4S)-1'-acetyl-N-{(1R)-1-[3,5-bis(trifluoromethyl)phenyl]ethyl}-2-(4-fluoro-2-methylphenyl)-N-methyl-4,4'-bipiperidine-1-carboxamide as a new potent and selective neurokinin 1 (NK1) receptor antagonist clini
AID1216344Unbound fraction in human gut2011Drug metabolism and disposition: the biological fate of chemicals, Mar, Volume: 39, Issue:3
Casopitant: in vitro data and SimCyp simulation to predict in vivo metabolic interactions involving cytochrome P450 3A4.
AID1216340Metabolism dependent inactivation of CYP3A4 in human liver microsomes pretreated with compound in presence of midazolam substrate and NADPH by HPLC-MS/MS method relative to untreated control2011Drug metabolism and disposition: the biological fate of chemicals, Mar, Volume: 39, Issue:3
Casopitant: in vitro data and SimCyp simulation to predict in vivo metabolic interactions involving cytochrome P450 3A4.
AID1216351Cmax in healthy human assessed as fold change at 100 mg, po in presence of 400 mg ketoconazole2011Drug metabolism and disposition: the biological fate of chemicals, Mar, Volume: 39, Issue:3
Casopitant: in vitro data and SimCyp simulation to predict in vivo metabolic interactions involving cytochrome P450 3A4.
AID577043Volume of distribution at steady state in marmoset at 1 mg/kg, iv2011Journal of medicinal chemistry, Feb-24, Volume: 54, Issue:4
Discovery and biological characterization of (2R,4S)-1'-acetyl-N-{(1R)-1-[3,5-bis(trifluoromethyl)phenyl]ethyl}-2-(4-fluoro-2-methylphenyl)-N-methyl-4,4'-bipiperidine-1-carboxamide as a new potent and selective neurokinin 1 (NK1) receptor antagonist clini
AID1216308Tmax in healthy human at 100 mg, po administered as single dose on day 4 and cotreated with ketoconazole at 400 mg, po qd on day 1 to 72011Drug metabolism and disposition: the biological fate of chemicals, Mar, Volume: 39, Issue:3
Casopitant: in vitro data and SimCyp simulation to predict in vivo metabolic interactions involving cytochrome P450 3A4.
AID577026Plasma clearance in mouse at 2 mg/kg, po2011Journal of medicinal chemistry, Feb-24, Volume: 54, Issue:4
Discovery and biological characterization of (2R,4S)-1'-acetyl-N-{(1R)-1-[3,5-bis(trifluoromethyl)phenyl]ethyl}-2-(4-fluoro-2-methylphenyl)-N-methyl-4,4'-bipiperidine-1-carboxamide as a new potent and selective neurokinin 1 (NK1) receptor antagonist clini
AID577015Displacement of [3H]GR205171 from human NK1 receptor in cortex homogenate at 0.5 nM by liquid scintillation counting2011Journal of medicinal chemistry, Feb-24, Volume: 54, Issue:4
Discovery and biological characterization of (2R,4S)-1'-acetyl-N-{(1R)-1-[3,5-bis(trifluoromethyl)phenyl]ethyl}-2-(4-fluoro-2-methylphenyl)-N-methyl-4,4'-bipiperidine-1-carboxamide as a new potent and selective neurokinin 1 (NK1) receptor antagonist clini
AID1216343Volume of distribution at steady state in human2011Drug metabolism and disposition: the biological fate of chemicals, Mar, Volume: 39, Issue:3
Casopitant: in vitro data and SimCyp simulation to predict in vivo metabolic interactions involving cytochrome P450 3A4.
AID577022Antidepressant activity against po dosed Mongolian gerbil assessed as increase in social interaction time2011Journal of medicinal chemistry, Feb-24, Volume: 54, Issue:4
Discovery and biological characterization of (2R,4S)-1'-acetyl-N-{(1R)-1-[3,5-bis(trifluoromethyl)phenyl]ethyl}-2-(4-fluoro-2-methylphenyl)-N-methyl-4,4'-bipiperidine-1-carboxamide as a new potent and selective neurokinin 1 (NK1) receptor antagonist clini
AID1216333Unbound fraction in human plasma2011Drug metabolism and disposition: the biological fate of chemicals, Mar, Volume: 39, Issue:3
Casopitant: in vitro data and SimCyp simulation to predict in vivo metabolic interactions involving cytochrome P450 3A4.
AID577012Inhibition of GR73632-induced foot tapping in orally dosed Mongolian gerbil after 8 hrs2011Journal of medicinal chemistry, Feb-24, Volume: 54, Issue:4
Discovery and biological characterization of (2R,4S)-1'-acetyl-N-{(1R)-1-[3,5-bis(trifluoromethyl)phenyl]ethyl}-2-(4-fluoro-2-methylphenyl)-N-methyl-4,4'-bipiperidine-1-carboxamide as a new potent and selective neurokinin 1 (NK1) receptor antagonist clini
AID1216334Fraction drug absorption in human2011Drug metabolism and disposition: the biological fate of chemicals, Mar, Volume: 39, Issue:3
Casopitant: in vitro data and SimCyp simulation to predict in vivo metabolic interactions involving cytochrome P450 3A4.
AID1216316Cmax in healthy human at 150 mg, po administered as single dose2011Drug metabolism and disposition: the biological fate of chemicals, Mar, Volume: 39, Issue:3
Casopitant: in vitro data and SimCyp simulation to predict in vivo metabolic interactions involving cytochrome P450 3A4.
AID779997Volume of distribution at steady state in rat at 0.5 mg/kg, iv and 1 mg/kg, po2013Bioorganic & medicinal chemistry, Nov-01, Volume: 21, Issue:21
Identification, biological characterization and pharmacophoric analysis of a new potent and selective NK1 receptor antagonist clinical candidate.
AID1216305Cmax in healthy human at 100 mg, po administered as single dose2011Drug metabolism and disposition: the biological fate of chemicals, Mar, Volume: 39, Issue:3
Casopitant: in vitro data and SimCyp simulation to predict in vivo metabolic interactions involving cytochrome P450 3A4.
AID1216307Tmax in healthy human at 100 mg, po administered as single dose2011Drug metabolism and disposition: the biological fate of chemicals, Mar, Volume: 39, Issue:3
Casopitant: in vitro data and SimCyp simulation to predict in vivo metabolic interactions involving cytochrome P450 3A4.
AID779996Volume of distribution at steady state in dog at 0.5 mg/kg, iv and 1 mg/kg, po2013Bioorganic & medicinal chemistry, Nov-01, Volume: 21, Issue:21
Identification, biological characterization and pharmacophoric analysis of a new potent and selective NK1 receptor antagonist clinical candidate.
AID577042Plasma clearance in marmoset at 1 mg/kg, iv2011Journal of medicinal chemistry, Feb-24, Volume: 54, Issue:4
Discovery and biological characterization of (2R,4S)-1'-acetyl-N-{(1R)-1-[3,5-bis(trifluoromethyl)phenyl]ethyl}-2-(4-fluoro-2-methylphenyl)-N-methyl-4,4'-bipiperidine-1-carboxamide as a new potent and selective neurokinin 1 (NK1) receptor antagonist clini
AID577027Volume of distribution at steady state in mouse at 2 mg/kg, po2011Journal of medicinal chemistry, Feb-24, Volume: 54, Issue:4
Discovery and biological characterization of (2R,4S)-1'-acetyl-N-{(1R)-1-[3,5-bis(trifluoromethyl)phenyl]ethyl}-2-(4-fluoro-2-methylphenyl)-N-methyl-4,4'-bipiperidine-1-carboxamide as a new potent and selective neurokinin 1 (NK1) receptor antagonist clini
AID779995Half life in rat at 0.5 mg/kg, iv and 1 mg/kg, po2013Bioorganic & medicinal chemistry, Nov-01, Volume: 21, Issue:21
Identification, biological characterization and pharmacophoric analysis of a new potent and selective NK1 receptor antagonist clinical candidate.
AID577009Inhibition of GR73632-induced foot tapping in orally dosed Mongolian gerbil after 1 hr2011Journal of medicinal chemistry, Feb-24, Volume: 54, Issue:4
Discovery and biological characterization of (2R,4S)-1'-acetyl-N-{(1R)-1-[3,5-bis(trifluoromethyl)phenyl]ethyl}-2-(4-fluoro-2-methylphenyl)-N-methyl-4,4'-bipiperidine-1-carboxamide as a new potent and selective neurokinin 1 (NK1) receptor antagonist clini
AID1216306Cmax in healthy human at 100 mg, po administered as single dose on day 4 and cotreated with ketoconazole at 400 mg, po qd on day 1 to 72011Drug metabolism and disposition: the biological fate of chemicals, Mar, Volume: 39, Issue:3
Casopitant: in vitro data and SimCyp simulation to predict in vivo metabolic interactions involving cytochrome P450 3A4.
AID577019Binding affinity to calcium channel L type benzodiazepine binding site2011Journal of medicinal chemistry, Feb-24, Volume: 54, Issue:4
Discovery and biological characterization of (2R,4S)-1'-acetyl-N-{(1R)-1-[3,5-bis(trifluoromethyl)phenyl]ethyl}-2-(4-fluoro-2-methylphenyl)-N-methyl-4,4'-bipiperidine-1-carboxamide as a new potent and selective neurokinin 1 (NK1) receptor antagonist clini
AID1216341Drug metabolism in human liver microsomes assessed as CYP3A4-mediated GSK525060 formation at 5 to 20 uM up to 30 mins by HPLC-MS/MS method2011Drug metabolism and disposition: the biological fate of chemicals, Mar, Volume: 39, Issue:3
Casopitant: in vitro data and SimCyp simulation to predict in vivo metabolic interactions involving cytochrome P450 3A4.
AID1216320Half life in healthy human at 150 mg, po administered as single dose2011Drug metabolism and disposition: the biological fate of chemicals, Mar, Volume: 39, Issue:3
Casopitant: in vitro data and SimCyp simulation to predict in vivo metabolic interactions involving cytochrome P450 3A4.
AID577037Bioavailability in dog at 0.5 mg/kg, iv2011Journal of medicinal chemistry, Feb-24, Volume: 54, Issue:4
Discovery and biological characterization of (2R,4S)-1'-acetyl-N-{(1R)-1-[3,5-bis(trifluoromethyl)phenyl]ethyl}-2-(4-fluoro-2-methylphenyl)-N-methyl-4,4'-bipiperidine-1-carboxamide as a new potent and selective neurokinin 1 (NK1) receptor antagonist clini
AID577016Binding affinity to sigma 1 receptor2011Journal of medicinal chemistry, Feb-24, Volume: 54, Issue:4
Discovery and biological characterization of (2R,4S)-1'-acetyl-N-{(1R)-1-[3,5-bis(trifluoromethyl)phenyl]ethyl}-2-(4-fluoro-2-methylphenyl)-N-methyl-4,4'-bipiperidine-1-carboxamide as a new potent and selective neurokinin 1 (NK1) receptor antagonist clini
AID1216336Inhibition of CYP3A4 in human liver microsomes using midazolam substrate by HPLC-MS/MS method2011Drug metabolism and disposition: the biological fate of chemicals, Mar, Volume: 39, Issue:3
Casopitant: in vitro data and SimCyp simulation to predict in vivo metabolic interactions involving cytochrome P450 3A4.
AID1216354AUC in healthy human assessed as fold change at 150 mg, po in presence of 600 mg rifampin2011Drug metabolism and disposition: the biological fate of chemicals, Mar, Volume: 39, Issue:3
Casopitant: in vitro data and SimCyp simulation to predict in vivo metabolic interactions involving cytochrome P450 3A4.
AID1216301Drug metabolism assessed as human recombinant CYP3A4-mediated GSK525060 formation after 30 mins by HPLC-MS/MS method2011Drug metabolism and disposition: the biological fate of chemicals, Mar, Volume: 39, Issue:3
Casopitant: in vitro data and SimCyp simulation to predict in vivo metabolic interactions involving cytochrome P450 3A4.
AID577028Half life in mouse at 2 mg/kg, po2011Journal of medicinal chemistry, Feb-24, Volume: 54, Issue:4
Discovery and biological characterization of (2R,4S)-1'-acetyl-N-{(1R)-1-[3,5-bis(trifluoromethyl)phenyl]ethyl}-2-(4-fluoro-2-methylphenyl)-N-methyl-4,4'-bipiperidine-1-carboxamide as a new potent and selective neurokinin 1 (NK1) receptor antagonist clini
AID1216352AUC in healthy human assessed as fold change at 100 mg, po in presence of 400 mg ketoconazole2011Drug metabolism and disposition: the biological fate of chemicals, Mar, Volume: 39, Issue:3
Casopitant: in vitro data and SimCyp simulation to predict in vivo metabolic interactions involving cytochrome P450 3A4.
AID576859Displacement of [3H]SP from human NK1 receptor expressed in CHO cells by liquid scintillation counting2011Journal of medicinal chemistry, Feb-24, Volume: 54, Issue:4
Discovery and biological characterization of (2R,4S)-1'-acetyl-N-{(1R)-1-[3,5-bis(trifluoromethyl)phenyl]ethyl}-2-(4-fluoro-2-methylphenyl)-N-methyl-4,4'-bipiperidine-1-carboxamide as a new potent and selective neurokinin 1 (NK1) receptor antagonist clini
AID577041Bioavailability in cynomolgus monkey at 1 mg/kg, iv2011Journal of medicinal chemistry, Feb-24, Volume: 54, Issue:4
Discovery and biological characterization of (2R,4S)-1'-acetyl-N-{(1R)-1-[3,5-bis(trifluoromethyl)phenyl]ethyl}-2-(4-fluoro-2-methylphenyl)-N-methyl-4,4'-bipiperidine-1-carboxamide as a new potent and selective neurokinin 1 (NK1) receptor antagonist clini
AID779998Plasma clearance in dog at 0.5 mg/kg, iv and 1 mg/kg, po2013Bioorganic & medicinal chemistry, Nov-01, Volume: 21, Issue:21
Identification, biological characterization and pharmacophoric analysis of a new potent and selective NK1 receptor antagonist clinical candidate.
AID1216299Drug metabolism assessed as human recombinant CYP3A4-mediated GSK525060 formation at 10 uM after 30 mins by HPLC-MS/MS method2011Drug metabolism and disposition: the biological fate of chemicals, Mar, Volume: 39, Issue:3
Casopitant: in vitro data and SimCyp simulation to predict in vivo metabolic interactions involving cytochrome P450 3A4.
AID577017Binding affinity to sodium channel site 22011Journal of medicinal chemistry, Feb-24, Volume: 54, Issue:4
Discovery and biological characterization of (2R,4S)-1'-acetyl-N-{(1R)-1-[3,5-bis(trifluoromethyl)phenyl]ethyl}-2-(4-fluoro-2-methylphenyl)-N-methyl-4,4'-bipiperidine-1-carboxamide as a new potent and selective neurokinin 1 (NK1) receptor antagonist clini
AID1216304AUC (0 to t) in healthy human at 100 mg, po administered as single dose2011Drug metabolism and disposition: the biological fate of chemicals, Mar, Volume: 39, Issue:3
Casopitant: in vitro data and SimCyp simulation to predict in vivo metabolic interactions involving cytochrome P450 3A4.
AID577038Plasma clearance in cynomolgus monkey at 1 mg/kg, iv2011Journal of medicinal chemistry, Feb-24, Volume: 54, Issue:4
Discovery and biological characterization of (2R,4S)-1'-acetyl-N-{(1R)-1-[3,5-bis(trifluoromethyl)phenyl]ethyl}-2-(4-fluoro-2-methylphenyl)-N-methyl-4,4'-bipiperidine-1-carboxamide as a new potent and selective neurokinin 1 (NK1) receptor antagonist clini
AID1216319Tmax in healthy human at 150 mg, po administered as single dose on day 8 and cotreated with rifampin at 600 mg, po qd on day 1 to 92011Drug metabolism and disposition: the biological fate of chemicals, Mar, Volume: 39, Issue:3
Casopitant: in vitro data and SimCyp simulation to predict in vivo metabolic interactions involving cytochrome P450 3A4.
AID577034Plasma clearance in dog at 0.5 mg/kg, iv2011Journal of medicinal chemistry, Feb-24, Volume: 54, Issue:4
Discovery and biological characterization of (2R,4S)-1'-acetyl-N-{(1R)-1-[3,5-bis(trifluoromethyl)phenyl]ethyl}-2-(4-fluoro-2-methylphenyl)-N-methyl-4,4'-bipiperidine-1-carboxamide as a new potent and selective neurokinin 1 (NK1) receptor antagonist clini
AID577014Displacement of [3H]GR205171 from human NK1 receptor in cortex homogenate by liquid scintillation counting2011Journal of medicinal chemistry, Feb-24, Volume: 54, Issue:4
Discovery and biological characterization of (2R,4S)-1'-acetyl-N-{(1R)-1-[3,5-bis(trifluoromethyl)phenyl]ethyl}-2-(4-fluoro-2-methylphenyl)-N-methyl-4,4'-bipiperidine-1-carboxamide as a new potent and selective neurokinin 1 (NK1) receptor antagonist clini
AID1216337Inhibition of CYP3A4 in human liver microsomes using nifedipine substrate by HPLC-MS/MS method2011Drug metabolism and disposition: the biological fate of chemicals, Mar, Volume: 39, Issue:3
Casopitant: in vitro data and SimCyp simulation to predict in vivo metabolic interactions involving cytochrome P450 3A4.
AID1216317Cmax in healthy human at 150 mg, po administered as single dose on day 8 and cotreated with rifampin at 600 mg, po qd on day 1 to 92011Drug metabolism and disposition: the biological fate of chemicals, Mar, Volume: 39, Issue:3
Casopitant: in vitro data and SimCyp simulation to predict in vivo metabolic interactions involving cytochrome P450 3A4.
AID1216331Dissociation constant, pKa of the compound2011Drug metabolism and disposition: the biological fate of chemicals, Mar, Volume: 39, Issue:3
Casopitant: in vitro data and SimCyp simulation to predict in vivo metabolic interactions involving cytochrome P450 3A4.
AID1216346Fraction of drug metabolized assessed as human CYP3A4-mediated drug metabolism2011Drug metabolism and disposition: the biological fate of chemicals, Mar, Volume: 39, Issue:3
Casopitant: in vitro data and SimCyp simulation to predict in vivo metabolic interactions involving cytochrome P450 3A4.
AID577021Antidepressant activity against Mongolian gerbil assessed as increase in social interaction time at 0.3 to 1 mg/kg, po2011Journal of medicinal chemistry, Feb-24, Volume: 54, Issue:4
Discovery and biological characterization of (2R,4S)-1'-acetyl-N-{(1R)-1-[3,5-bis(trifluoromethyl)phenyl]ethyl}-2-(4-fluoro-2-methylphenyl)-N-methyl-4,4'-bipiperidine-1-carboxamide as a new potent and selective neurokinin 1 (NK1) receptor antagonist clini
AID779993Oral bioavailability in rat at 1 mg/kg2013Bioorganic & medicinal chemistry, Nov-01, Volume: 21, Issue:21
Identification, biological characterization and pharmacophoric analysis of a new potent and selective NK1 receptor antagonist clinical candidate.
AID577018Binding affinity to calcium channel L type dihydropyridine binding site2011Journal of medicinal chemistry, Feb-24, Volume: 54, Issue:4
Discovery and biological characterization of (2R,4S)-1'-acetyl-N-{(1R)-1-[3,5-bis(trifluoromethyl)phenyl]ethyl}-2-(4-fluoro-2-methylphenyl)-N-methyl-4,4'-bipiperidine-1-carboxamide as a new potent and selective neurokinin 1 (NK1) receptor antagonist clini
AID1216314AUC (0 to t) in healthy human at 150 mg, po administered as single dose2011Drug metabolism and disposition: the biological fate of chemicals, Mar, Volume: 39, Issue:3
Casopitant: in vitro data and SimCyp simulation to predict in vivo metabolic interactions involving cytochrome P450 3A4.
AID577030Plasma clearance in rat at 1 mg/kg, iv and po2011Journal of medicinal chemistry, Feb-24, Volume: 54, Issue:4
Discovery and biological characterization of (2R,4S)-1'-acetyl-N-{(1R)-1-[3,5-bis(trifluoromethyl)phenyl]ethyl}-2-(4-fluoro-2-methylphenyl)-N-methyl-4,4'-bipiperidine-1-carboxamide as a new potent and selective neurokinin 1 (NK1) receptor antagonist clini
AID1216345Intrinsic clearance in human liver microsomes assessed per mg protein2011Drug metabolism and disposition: the biological fate of chemicals, Mar, Volume: 39, Issue:3
Casopitant: in vitro data and SimCyp simulation to predict in vivo metabolic interactions involving cytochrome P450 3A4.
AID577013Inhibition of GR73632-induced foot tapping in orally dosed Mongolian gerbil after 24 hrs2011Journal of medicinal chemistry, Feb-24, Volume: 54, Issue:4
Discovery and biological characterization of (2R,4S)-1'-acetyl-N-{(1R)-1-[3,5-bis(trifluoromethyl)phenyl]ethyl}-2-(4-fluoro-2-methylphenyl)-N-methyl-4,4'-bipiperidine-1-carboxamide as a new potent and selective neurokinin 1 (NK1) receptor antagonist clini
AID577024Antidepressant activity against po dosed Mongolian gerbil assessed as increase in social interaction time at 1 mg/kg, po (Rbv = 19+/-1.2seconds)2011Journal of medicinal chemistry, Feb-24, Volume: 54, Issue:4
Discovery and biological characterization of (2R,4S)-1'-acetyl-N-{(1R)-1-[3,5-bis(trifluoromethyl)phenyl]ethyl}-2-(4-fluoro-2-methylphenyl)-N-methyl-4,4'-bipiperidine-1-carboxamide as a new potent and selective neurokinin 1 (NK1) receptor antagonist clini
AID1216302Drug metabolism assessed as human recombinant CYP3A4-mediated GSK525060 formation per pmol of protein after 30 mins by HPLC-MS/MS method2011Drug metabolism and disposition: the biological fate of chemicals, Mar, Volume: 39, Issue:3
Casopitant: in vitro data and SimCyp simulation to predict in vivo metabolic interactions involving cytochrome P450 3A4.
AID577035Volume of distribution at steady state in dog at 0.5 mg/kg, iv2011Journal of medicinal chemistry, Feb-24, Volume: 54, Issue:4
Discovery and biological characterization of (2R,4S)-1'-acetyl-N-{(1R)-1-[3,5-bis(trifluoromethyl)phenyl]ethyl}-2-(4-fluoro-2-methylphenyl)-N-methyl-4,4'-bipiperidine-1-carboxamide as a new potent and selective neurokinin 1 (NK1) receptor antagonist clini
AID1216297Drug metabolism in human liver microsomes assessed as CYP3A4-mediated GSK525060 formation after 30 mins by HPLC-MS/MS method2011Drug metabolism and disposition: the biological fate of chemicals, Mar, Volume: 39, Issue:3
Casopitant: in vitro data and SimCyp simulation to predict in vivo metabolic interactions involving cytochrome P450 3A4.
AID1216330Lipophilicity, log P of the compound2011Drug metabolism and disposition: the biological fate of chemicals, Mar, Volume: 39, Issue:3
Casopitant: in vitro data and SimCyp simulation to predict in vivo metabolic interactions involving cytochrome P450 3A4.
AID577011Inhibition of GR73632-induced foot tapping in sc dosed Mongolian gerbil after 1 hr2011Journal of medicinal chemistry, Feb-24, Volume: 54, Issue:4
Discovery and biological characterization of (2R,4S)-1'-acetyl-N-{(1R)-1-[3,5-bis(trifluoromethyl)phenyl]ethyl}-2-(4-fluoro-2-methylphenyl)-N-methyl-4,4'-bipiperidine-1-carboxamide as a new potent and selective neurokinin 1 (NK1) receptor antagonist clini
AID1216298Drug metabolism in human liver microsomes assessed as CYP3A4-mediated GSK525060 formation per pmol of protein after 30 mins by HPLC-MS/MS method2011Drug metabolism and disposition: the biological fate of chemicals, Mar, Volume: 39, Issue:3
Casopitant: in vitro data and SimCyp simulation to predict in vivo metabolic interactions involving cytochrome P450 3A4.
AID779994Half life in dog at 0.5 mg/kg, iv and 1 mg/kg, po2013Bioorganic & medicinal chemistry, Nov-01, Volume: 21, Issue:21
Identification, biological characterization and pharmacophoric analysis of a new potent and selective NK1 receptor antagonist clinical candidate.
AID577031Volume of distribution at steady state in rat at 1 mg/kg, iv and po2011Journal of medicinal chemistry, Feb-24, Volume: 54, Issue:4
Discovery and biological characterization of (2R,4S)-1'-acetyl-N-{(1R)-1-[3,5-bis(trifluoromethyl)phenyl]ethyl}-2-(4-fluoro-2-methylphenyl)-N-methyl-4,4'-bipiperidine-1-carboxamide as a new potent and selective neurokinin 1 (NK1) receptor antagonist clini
AID577039Volume of distribution at steady state in cynomolgus monkey at 1 mg/kg, iv2011Journal of medicinal chemistry, Feb-24, Volume: 54, Issue:4
Discovery and biological characterization of (2R,4S)-1'-acetyl-N-{(1R)-1-[3,5-bis(trifluoromethyl)phenyl]ethyl}-2-(4-fluoro-2-methylphenyl)-N-methyl-4,4'-bipiperidine-1-carboxamide as a new potent and selective neurokinin 1 (NK1) receptor antagonist clini
AID1216353Cmax in healthy human assessed as fold change at 150 mg, po in presence of 600 mg rifampin2011Drug metabolism and disposition: the biological fate of chemicals, Mar, Volume: 39, Issue:3
Casopitant: in vitro data and SimCyp simulation to predict in vivo metabolic interactions involving cytochrome P450 3A4.
AID577040Half life in dog at cynomolgus monkey at 1 mg/kg, iv2011Journal of medicinal chemistry, Feb-24, Volume: 54, Issue:4
Discovery and biological characterization of (2R,4S)-1'-acetyl-N-{(1R)-1-[3,5-bis(trifluoromethyl)phenyl]ethyl}-2-(4-fluoro-2-methylphenyl)-N-methyl-4,4'-bipiperidine-1-carboxamide as a new potent and selective neurokinin 1 (NK1) receptor antagonist clini
AID1216303AUC (0 to t) in healthy human at 100 mg, po administered as single dose on day 4 and cotreated with ketoconazole at 400 mg, po qd on day 1 to 72011Drug metabolism and disposition: the biological fate of chemicals, Mar, Volume: 39, Issue:3
Casopitant: in vitro data and SimCyp simulation to predict in vivo metabolic interactions involving cytochrome P450 3A4.
AID577032Half life in rat at 1 mg/kg, iv and po2011Journal of medicinal chemistry, Feb-24, Volume: 54, Issue:4
Discovery and biological characterization of (2R,4S)-1'-acetyl-N-{(1R)-1-[3,5-bis(trifluoromethyl)phenyl]ethyl}-2-(4-fluoro-2-methylphenyl)-N-methyl-4,4'-bipiperidine-1-carboxamide as a new potent and selective neurokinin 1 (NK1) receptor antagonist clini
AID1216339Metabolism dependent inhibition of CYP3A4 in human liver microsomes pretreated with compound for 20 mins in presence of nifedipine substrate and NADPH by HPLC-MS/MS method relative to untreated control2011Drug metabolism and disposition: the biological fate of chemicals, Mar, Volume: 39, Issue:3
Casopitant: in vitro data and SimCyp simulation to predict in vivo metabolic interactions involving cytochrome P450 3A4.
AID1346346Human NK1 receptor (Tachykinin receptors)2010Expert opinion on therapeutic patents, Aug, Volume: 20, Issue:8
Neurokinin-1 receptor antagonists: a comprehensive patent survey.
AID1346346Human NK1 receptor (Tachykinin receptors)2013Journal of receptor and signal transduction research, Dec, Volume: 33, Issue:6
Why receptor reserve matters for neurokinin1 (NK1) receptor antagonists.
[information is prepared from bioassay data collected from National Library of Medicine (NLM), extracted Dec-2023]

Research

Studies (43)

TimeframeStudies, This Drug (%)All Drugs %
pre-19900 (0.00)18.7374
1990's0 (0.00)18.2507
2000's12 (27.91)29.6817
2010's29 (67.44)24.3611
2020's2 (4.65)2.80
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Market Indicators

Research Demand Index: 26.18

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 moderate demand-to-supply ratio for research on this compound.

MetricThis Compound (vs All)
Research Demand Index26.18 (24.57)
Research Supply Index4.11 (2.92)
Research Growth Index4.50 (4.65)
Search Engine Demand Index31.58 (26.88)
Search Engine Supply Index2.00 (0.95)

This Compound (26.18)

All Compounds (24.57)

Study Types

Publication TypeThis drug (%)All Drugs (%)
Trials17 (39.53%)5.53%
Reviews7 (16.28%)6.00%
Case Studies0 (0.00%)4.05%
Observational0 (0.00%)0.25%
Other19 (44.19%)84.16%
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Clinical Trials (30)

Trial Overview

TrialPhaseEnrollmentStudy TypeStart DateStatus
A Randomized, Double-Blind, Placebo-Controlled, Crossover Study to Evaluate the Effects of GW679769 (30mg and 90mg) on Sleep Continuity, PSG Sleep Recordings, Subjective Sleep Assessment, and Daytime Cognitive Function in Subjects With Primary Insomnia [NCT00650871]Phase 248 participants (Actual)Interventional2004-07-30Completed
A Study of Single Dose Intravenous Casopitant in Combination With Ondansetron and Dexamethasone for the Prevention of Oxaliplatin Induced Nausea and Vomiting. [NCT00601172]Phase 3710 participants (Actual)Interventional2008-03-10Completed
A Study of Single Dose Intravenous Casopitant in Combination With Ondansetron and Dexamethasone for the Prevention of Cisplatin-Induced Nausea and Vomiting [NCT00891761]Phase 30 participants (Actual)Interventional2009-09-30Withdrawn(stopped due to This study has been cancelled prior to enrollment.)
See Detailed Description [NCT00169572]Phase 2492 participants Interventional2005-02-28Completed
A Randomized, Double-blind, Placebo-controlled, Cross-over Study to Evaluate the Effects of GW679769 on Polysomnographic Sleep Recordings, Subjective Sleep Assessment, and Daytime Cognitive Function in Elderly and Non-elderly Subjects With Primary Insomni [NCT00280436]Phase 2122 participants (Actual)Interventional2006-01-31Completed
An Open-Label, Phase I Study to Assess the Pharmacokinetic Interaction Between Repeat Doses of Oral Casopitant and Intravenous and Oral Doses of Dexamethasone and Intravenous and Oral Doses of Ondansetron When Administered in Healthy Adult Subjects [NCT00437229]Phase 137 participants (Actual)Interventional2007-02-19Completed
An Open-Label, Two Period, Fixed Sequence Study of Healthy Subjects to Assess the Effect of Repeat Oral Dosing of [Rifampin] on the Pharmacokinetics of a Single Oral Dose of [GW679769] [NCT00405080]Phase 112 participants (Actual)Interventional2006-11-11Completed
A Phase III, Multicenter, Randomized, Double-Blind, Active Controlled, Parallel Group Study of the Safety and Efficacy of the Intravenous and Oral Formulations of the Neurokinin-1 Receptor Antagonist Casopitant (GW679769) in Combination With Ondansetron a [NCT00366834]Phase 31,840 participants (Actual)Interventional2006-07-31Completed
A Phase I, Randomized, Double-Blind Study to Assess the Effects of Repeat Oral Dosing of Ketoconazole on the Pharmacokinetics of Repeat Oral Dosing of Casopitant in Healthy Subjects [NCT00460707]Phase 185 participants (Actual)Interventional2007-04-16Completed
An Open-Label, Three-Part, Two Period, Single Sequence Study to Assess the Pharmacokinetic Interaction Between Repeat Doses of Oral Casopitant and Repeat Oral Doses of Dolasetron, Granisetron or Rosiglitazone When Co-Administered in Healthy Adult Subjects [NCT00511823]Phase 116 participants (Actual)Interventional2007-07-23Completed
An Exploratory Study to Investigate the Effects of the NK1 Antagonist GW679769, 60 mg Once Daily for 4 Days, on Gastric Accommodation, Gastric Emptying and Gastric Distension-induced Perception and Discomfort in Adult Male and Female Patients With Functio [NCT00358410]Phase 213 participants (Actual)Interventional2006-01-31Completed
A Phase II Multicenter, Randomized, Double-blind, Placebo-controlled, Dose-ranging, Parallel Group Study of the Safety and Efficacy of the Oral NeuroKinin-1 Receptor Antagonist, GW679769 in Combination With Ondansetron Hydrochloride and Dexamethasone for [NCT00104403]Phase 2722 participants (Actual)Interventional2004-12-31Completed
An Outpatient, Randomised, Double-blind, Placebo Controlled, Parallel Group Exploratory Study to Evaluate Safety, Tolerability and Efficacy of GW679769 in Patients With Fibromyalgia Syndrome Comorbid With Depression. [NCT00264628]8 participants (Actual)Observational2005-10-31Completed
A Randomized, Double-Blind, Parallel-Group, Placebo-Controlled, Fixed-Dose Study Evaluating the Efficacy and Safety of GW679769 in Subjects With Major Depressive Disorder. [NCT00102492]Phase 2356 participants (Actual)Interventional2004-10-31Completed
A Multicenter, Randomised, Double-blind, Placebo-controlled, Parallel Group, Phase II Study to Evaluate the Safety and Efficacy of Oral Dosing With GW679769 (50 mg or 150 mg) for Three Consecutive Days When Administered With a Single Intravenous Dose of O [NCT00274690]Phase 2435 participants (Actual)Interventional2005-02-28Completed
A 28 Day, Polysomnographic and Subjective Assessment of GW679769 for the Treatment of Primary Insomnia: A Randomized, Double-blind, Parallel-Group, Placebo-Controlled Trial. [NCT00280423]Phase 2342 participants (Actual)Interventional2006-01-31Completed
A Phase III, Multicenter, Randomized, Double-blind, Parallel Group Study to Evaluate the Safety and Efficacy of 50mg Oral Dosing With the Neurokinin-1 Receptor Antagonist GW679769 for the Prevention of Postoperative Nausea and Vomiting in Female Subjects [NCT00326248]Phase 3482 participants (Actual)Interventional2006-03-31Completed
A Phase III Multicenter, Randomized, Double-Blind, Active-Controlled, Parallel Group Study of the Efficacy and Safety of the Intravenous and Oral Formulations of the Neurokinin-1 Receptor Antagonist, Casopitant, Administered in Combination With ZOFRAN and [NCT00431236]Phase 3810 participants (Actual)Interventional2006-11-06Completed
A Phase I, Open-Label, Randomized, Two Period Crossover Study to Investigate the Effects of GW679769 on the Pharmacokinetics of Docetaxel in Subjects With Cancer [NCT00440128]Phase 112 participants (Actual)Interventional2007-05-04Completed
An Open-label Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Steady-State Warfarin When Co-administered With Repeat Doses of Casopitant [GW679769] in Healthy Adult Subjects. [NCT00404274]Phase 197 participants (Actual)Interventional2006-11-01Completed
An Open-label, Two Period, Fixed Sequence Study of Healthy Subjects to Assess the Effect of Repeat Oral Dosing of Ketoconazole on the Pharmacokinetics of a Single Oral Dose of [GW679769] [NCT00404378]Phase 115 participants (Actual)Interventional2006-10-20Completed
An Open Label, Repeat Dose, Randomized, Two Period Crossover Study to Investigate the Potential Pharmacokinetic Interactions Between Oral GW679769 and Intravenous Cyclophosphamide in Cancer Patients [NCT00334646]Phase 125 participants (Actual)Interventional2005-08-10Terminated(stopped due to compound terminated)
A Randomised, Double-Blind, Double-Dummy, Parallel-Group, Placebo-Controlled, Forced Dose Titration Study Evaluating the Efficacy and Safety of GW679769 and Paroxetine in Subjects With Major Depressive Disorder (MDD) [NCT00413023]Phase 2348 participants (Actual)Interventional2005-06-30Completed
NK1 Receptor Antagonist vs Placebo in the Treatment of Overactive Bladder Symptoms [NCT00321477]Phase 2160 participants (Anticipated)Interventional2005-12-31Completed
See Detailed Description [NCT00332319]Phase 21 participants (Actual)Interventional2006-01-31Terminated
A Phase III Multicenter, Randomized, Double-blind, Parallel Group Study to Evaluate the Safety and Efficacy of the 30 mg Intravenous Formulation of the Neurokinin-1 Receptor Antagonist GW679769 for Prevention of Postoperative Nausea and Vomiting in Female [NCT00334152]Phase 3515 participants (Actual)Interventional2006-03-31Completed
A Randomized, Double-blind, Placebo-controlled, Crossover Study to Evaluate the Effects of Morning Administration of GW679769 (10mg and 30 mg) on Polysomnograph Sleep Recordings, Subjective Sleep Assessment, Daytime Cognition and Psychomotor Function in S [NCT00354809]Phase 268 participants (Actual)Interventional2006-05-31Completed
An Open-Label, Non-Randomized, Pharmacokinetic and Safety Study of Multiple Oral Doses of GW679769 in Subjects With Hepatic Impairment [NCT00359177]Phase 124 participants (Actual)Interventional2005-12-01Completed
A Double-Blind, Randomized, Placebo-Controlled, Double-Dummy, Parallel Group, fMRI Study Comparing BOLD Activation Patterns Before and After 12 Weeks of Treatment With Placebo, Comparator and GW679769 in Subjects With Social Anxiety Disorder (SAD). [NCT00332046]Phase 157 participants Interventional2006-01-31Completed
An Open-Label, Non-Randomized, Pharmacokinetic and Safety Study of Multiple Oral Doses of GW679769 in Subjects With Renal Impairment [NCT00358813]Phase 118 participants (Actual)Interventional2006-09-08Completed
[information is prepared from clinicaltrials.gov, extracted Sep-2024]

Trial Outcomes

TrialOutcome
NCT00601172 (25) [back to overview]Percentage of Participants Who Achieved a Complete Response in the Acute Phase of Cycle 1
NCT00601172 (25) [back to overview]Percentage of Participants Who Achieved a Complete Response in the Delayed Phase of Cycle 1
NCT00601172 (25) [back to overview]Percentage of Participants Who Achieved a Complete Response in the Overall Phase (0-120 Hours) Following Initiation of the First Cycle of an Oxaliplatin Based Moderately Emetogenic Chemotherapy (MEC) Regimen
NCT00601172 (25) [back to overview]Percentage of Participants Who Achieved a Complete Response in the Overall Phase of Cycle 2
NCT00601172 (25) [back to overview]Single-dose Pharmacokinetic Parameters: Clearance (CL) for Casopitant
NCT00601172 (25) [back to overview]Single-dose Pharmacokinetic Parameters: Volume of Distribution (Vdss) for Casopitant
NCT00601172 (25) [back to overview]Time to First Anti-emetic Rescue Medication
NCT00601172 (25) [back to overview]Time to First Emetic Event
NCT00601172 (25) [back to overview]Evaluation of Vital Signs: Mean Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP)
NCT00601172 (25) [back to overview]Evaluation of Vital Signs: Mean Heart Rate
NCT00601172 (25) [back to overview]Maximum Nausea Score, Assessed by a Visual Analogue Scale (VAS)
NCT00601172 (25) [back to overview]Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAE)
NCT00601172 (25) [back to overview]Number of Participants With Clinical Chemistry Toxicity Grade Shifts From Baseline to Toxicity Grade 3 and 4
NCT00601172 (25) [back to overview]Number of Participants With Hematology Toxicity Grade Shifts From Baseline to Toxicity Grade 3 and 4
NCT00601172 (25) [back to overview]Percentage of Participants Who Achieved Complete Protection Defined as Complete Responders With no Significant Nausea
NCT00601172 (25) [back to overview]Percentage of Participants Who Achieved Total Control, Defined as Complete Responders Who Had no Nausea
NCT00601172 (25) [back to overview]Percentage of Participants Who Received Rescue Medication
NCT00601172 (25) [back to overview]Percentage of Participants Who Reported Nausea, Defined as a Maximum Score of >= 5 mm on the VAS
NCT00601172 (25) [back to overview]Percentage of Participants Who Reported Significant Nausea, Defined as a Maximum Score >= 25 mm on the VAS
NCT00601172 (25) [back to overview]Percentage of Participants Who Vomited and/or Retched
NCT00601172 (25) [back to overview]Percentage of Participants Whose Daily Life Activities Were Impacted in the Overall Phase of Cycle 1, Assessed by Functional Living Index-Emesis (FLIE) Questionnaire
NCT00601172 (25) [back to overview]Single-dose Pharmacokinetic (PK) Parameters: Area Under the Curve (AUC) 0 to Infinity (0-∞), AUC 0 to t (0-t) and AUC 0 to 24 Hours (0-24) for Casopitant; AUC (0-t) and AUC (0-24) for Metabolites GSK525060, GSK517142 and GSK631832
NCT00601172 (25) [back to overview]Single-dose Pharmacokinetic Parameters: Maximum Observed Drug Concentration (Cmax) for Casopitant and Metabolites GSK525060, GSK517142 and GSK631832
NCT00601172 (25) [back to overview]Single-dose Pharmacokinetic Parameters: Time to Maximum Observed Drug Concentration (Tmax) and Observed Elimination Half-life (t1/2) for Casopitant and Metabolites GSK525060, GSK517142 and GSK631832
NCT00601172 (25) [back to overview]Severity of Nausea in the Overall, Acute, and Delayed Phases of Cycle 1 Assessed by a Categorical Scale

Percentage of Participants Who Achieved a Complete Response in the Acute Phase of Cycle 1

Complete response was defined as no vomiting, no retching and no use of anti-emetic rescue medication. Participants who vomited or retched or received rescue medication in the acute phase (0- 24 hours) following administration of oxaliplatin were also considered as complete response failures in the subsequent delayed (24-120 hour) time period, irrespective of actual response in the delayed phase. However, participants who vomited or retched or received rescue medication in the delayed (24-120 hours) phase were not considered as failures in the acute (0-24 hours) phase. Percentage of participants who achieved a complete response in the acute phase of Cycle 1 are presented. (NCT00601172)
Timeframe: 0 to 24 hours in the first cycle of chemotherapy

InterventionPercentage of participants (Number)
Placebo96
Casopitant 90 mg97

[back to top]

Percentage of Participants Who Achieved a Complete Response in the Delayed Phase of Cycle 1

Complete response was defined as no vomiting, no retching and no use of anti-emetic rescue medication. Participants who vomited or retched or received rescue medication in the acute phase (0- 24 hours) following administration of oxaliplatin were also considered as complete response failures in the subsequent delayed (24-120 hour) time period, irrespective of actual response in the delayed phase. However, participants who vomited or retched or received rescue medication in the delayed (24-120 hours) phase were not considered as failures in the acute (0-24 hours) phase. Percentage of participants who achieved a complete response in the delayed phase of Cycle 1 are presented. (NCT00601172)
Timeframe: 24 to 120 hours (delayed phase) in the first cycle of chemotherapy

InterventionPercentage of participants (Number)
Placebo85
Casopitant 90 mg86

[back to top]

Percentage of Participants Who Achieved a Complete Response in the Overall Phase (0-120 Hours) Following Initiation of the First Cycle of an Oxaliplatin Based Moderately Emetogenic Chemotherapy (MEC) Regimen

Complete response was defined as no vomiting, no retching and no use of anti-emetic rescue medication. Participants who vomited or retched or received rescue medication in the acute phase (0- 24 hours) following administration of oxaliplatin were also considered as complete response failures in the subsequent delayed (24-120 hour) time period, irrespective of actual response in the delayed phase. However, participants who vomited or retched or received rescue medication in the delayed (24-120 hours) phase were not considered as failures in the acute (0-24 hours) phase. The overall phase began at the start of the administration of the oxaliplatin infusion. Percentage of participants who achieved a complete response in the overall phase (0-120 hours) are presented. (NCT00601172)
Timeframe: 0 to 120 hours in the first cycle of chemotherapy

InterventionPercentage of participants (Number)
Placebo85
Casopitant 90 mg86

[back to top]

Percentage of Participants Who Achieved a Complete Response in the Overall Phase of Cycle 2

Complete response was defined as no vomiting, no retching and no use of anti-emetic rescue medication. Participants who vomited or retched or received rescue medication in the acute phase (0- 24 hours) following administration of oxaliplatin were also considered as complete response failures in the subsequent delayed (24-120 hour) time period, irrespective of actual response in the delayed phase. However, participants who vomited or retched or received rescue medication in the delayed (24-120 hours) phase were not considered as failures in the acute (0-24 hours) phase. The overall phase began at the start of the administration of the oxaliplatin infusion. Percentage of participants who achieved a complete response in the overall phase of Cycle 2 are presented. (NCT00601172)
Timeframe: 0 to 120 hours in the second cycle of chemotherapy

InterventionPercentage of participants (Number)
Placebo84
Casopitant 90 mg90

[back to top]

Single-dose Pharmacokinetic Parameters: Clearance (CL) for Casopitant

Blood samples were obtained during Cycle 1 at the following times relative to the investigational product administration: pre-dose, end of infusion, 0.5, 1, 3, 5, 8, 12, 16, and 24 hours after the end of infusion. A final PK sample was collected between 30 and 48 hours after the investigational product infusion had completed. The actual time each sample was collected was captured to the nearest minute in the eCRF. Following unblinding, only those participants who had been randomized to receive casopitant were included in the PK analyses. CL for casopitant is presented. (NCT00601172)
Timeframe: Pre-dose, end of infusion and 0.5, 1, 3, 5, 8, 12, 16, 24 hours after the end of infusion

InterventionLiter/hour (Geometric Mean)
Casopitant 90 mg10.457

[back to top]

Single-dose Pharmacokinetic Parameters: Volume of Distribution (Vdss) for Casopitant

Blood samples were obtained during Cycle 1 at the following times relative to the investigational product administration: pre-dose, end of infusion, 0.5, 1, 3, 5, 8, 12, 16, and 24 hours after the end of infusion. A final PK sample was collected between 30 and 48 hours after the investigational product infusion had completed. The actual time each sample was collected was captured to the nearest minute in the eCRF. Following unblinding, only those participants who had been randomized to receive casopitant were included in the PK analyses. Vdss for casopitant is presented. (NCT00601172)
Timeframe: Pre-dose, end of infusion and 0.5, 1, 3, 5, 8, 12, 16, 24 hours after the end of infusion

InterventionLiter (Geometric Mean)
Casopitant 90 mg126.776

[back to top]

Time to First Anti-emetic Rescue Medication

Time to first rescue medication was defined as the length of time from initiation of oxaliplatin till the first reported use of a rescue medication. Participants withdrawing prematurely during the 120 hour assessment period without having received a rescue medication were assumed to have done so and the time of rescue medication was set to 0 hours. The first quartile for time to use of anti-emetic rescue medication was evaluated when 25th percentile of participants of MITT population reported use of anti-emetic rescue medication. Similarly, median and 75th percentile of participants of MITT population was planned to be reported. If, less than 25th percentile of participants reported use of anti-emetic rescue medication at the end of the 120 hour time period, then the observation was censored for the purpose of this analysis and in such case the data was planned to be reported as not evaluable (NA). (NCT00601172)
Timeframe: 0 to 120 hours in the first cycle of chemotherapy

InterventionHours (Median)
PlaceboNA
Casopitant 90 mgNA

[back to top]

Time to First Emetic Event

Time to first emetic event was defined as the length of time from initiation of oxaliplatin until the time of first emetic event. Participants withdrawing prematurely from the study without having experienced an emetic event were assumed to have done so and the time of emetic event was set to 0 hours. The first quartile for time to emetic event was evaluated when 25th percentile of participants of MITT population reported emetic event. Similarly, median and 75th percentile of participants of MITT population was planned to be reported. If, less than 25th percentile of participants reported emetic event at the end of the 120 hour time period, then the observation was censored for the purpose of this analysis and in such case the data was planned to be reported as not evaluable (NA). (NCT00601172)
Timeframe: 0 to 120 hours in the first cycle of chemotherapy

InterventionHours (Median)
PlaceboNA
Casopitant 90 mgNA

[back to top]

Evaluation of Vital Signs: Mean Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP)

Vital signs assessment included DBP and SBP. SBP and DBP were recorded at Screening, on Day 1 of each cycle immediately before start of the investigational product infusion, at the completion of the infusion, and immediately after the end of the oxaliplatin infusion, then again at each end of cycle visit. Mean SBP and DBP are presented. (NCT00601172)
Timeframe: Up to End of Cycle for 6 cycles, an average of 24 days per cycle

,
InterventionMillimeters of mercury (mmHg) (Mean)
DBP: Cycle 1, post-oxaliplatinDBP: Cycle 1, End of cycleDBP: Cycle 2, post-oxaliplatinDBP: Cycle 2, End of cycleDBP: Cycle 3, post-oxaliplatinDBP: Cycle 3, End of cycleDBP: Cycle 4, post-oxaliplatinDBP: Cycle 4, End of cycleDBP: Cycle 5, post-oxaliplatinDBP: Cycle 5, End of cycleDBP: Cycle 6, post-oxaliplatinDBP: Cycle 6, End of cycleSBP: Cycle 1, post-oxaliplatinSBP: Cycle 1, End of cycleSBP: Cycle 2, post-oxaliplatinSBP: Cycle 2, End of cycleSBP: Cycle 3, post-oxaliplatinSBP: Cycle 3, End of cycleSBP: Cycle 4, post-oxaliplatinSBP: Cycle 4, End of cycleSBP: Cycle 5, post-oxaliplatinSBP: Cycle 5, End of cycleSBP: Cycle 6, post-oxaliplatinSBP: Cycle 6, End of cycle
Casopitant 90 mg76.576.576.877.176.677.276.976.477.777.777.677.5126.8126.7129.3127.8128.7127.7129.0128.3129.7128.8131.5129.1
Placebo77.276.977.776.878.077.378.276.877.477.177.977.9130.6128.7130.1128.9131.0128.8131.8128.0131.3128.6132.2129.7

[back to top]

Evaluation of Vital Signs: Mean Heart Rate

Vital sign included heart rate which was recorded at Screening, on Day 1 of each cycle immediately before start of the investigational product infusion, at the completion of the infusion, and immediately after the end of the oxaliplatin infusion, then again at each end of cycle visit. Mean heart rate is presented. (NCT00601172)
Timeframe: Up to End of Cycle for 6 cycles, an average of 24 days per cycle

,
InterventionBeats/minute (Mean)
Cycle 1, post-oxaliplatinCycle 1, End of cycleCycle 2, post-oxaliplatinCycle 2, End of cycleCycle 3, post-oxaliplatinCycle 3, End of cycleCycle 4, post-oxaliplatinCycle 4, End of cycleCycle 5, post-oxaliplatinCycle 5, End of cycleCycle 6, post-oxaliplatinCycle 6, End of cycle
Casopitant 90 mg73.775.373.774.772.275.472.274.772.975.073.475.6
Placebo73.175.173.074.873.274.972.675.072.874.773.574.7

[back to top]

Maximum Nausea Score, Assessed by a Visual Analogue Scale (VAS)

VAS was used to assess severity of nausea. The participants rated the severity of nausea by marking a line on a 100 millimeter (mm) (0 to 100 mm) long scale. A line placed on the extreme left, that is 0 mm indicated no nausea and extreme right that is 100 mm indicated nausea as bad as it can be. This scale has no subscales. The participant perception of their symptoms was measured using the VAS. (NCT00601172)
Timeframe: 0 to 24 hours, 24 to 120 hours and 0 to 120 hours in the first cycle of chemotherapy

,
InterventionScores on a Scale (Mean)
0-120 hours0-24 hours24-120 hours
Casopitant 90 mg16.05.315.3
Placebo13.54.313.0

[back to top]

Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAE)

An AE is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. A SAE is defined as any untoward medical occurrence that, at any dose, results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability or incapacity, is a congenital anomaly or birth defect. Any SAEs assessed as related to study participation (e.g. study treatment, protocol-mandated procedures, invasive tests, or change in existing therapy) or related to a GSK product was recorded from the time a participant consents to participate in the study up to and including any follow-up contact. (NCT00601172)
Timeframe: Up to 35 days

,
InterventionParticipants (Count of Participants)
AESAE
Casopitant 90 mg17126
Placebo17623

[back to top]

Number of Participants With Clinical Chemistry Toxicity Grade Shifts From Baseline to Toxicity Grade 3 and 4

Grade shifts from Baseline were assessed as shift from any Grade to Grade 3 or Grade 4 in any cycle. Toxicities were graded according to the NCI-CTCAE, version 3.0. Grade refers to the severity of the toxicity. The NCI-CTCAE displays Grades 1 through 5 with unique clinical descriptions of severity for each toxicity based on the following general guideline: Grade 1: Mild AE, Grade 2: Moderate AE, Grade 3: Severe AE, Grade 4: Life-threatening or disabling AE and Grade 5: Death related to AE. It was assessed on Baseline (Day 1), during Day 6-10 and end of cycle. Clinical chemistry parameters assessed were alanine amino transferase (ALT), aspartate amino transferase (AST), chloride, glucose, potassium, sodium and total bilirubin. Data has been presented for the number of participants with chemistry toxicity grade shifts from Baseline to toxicity grade 3 and 4 for all cycles in a consolidated format. (NCT00601172)
Timeframe: Up to Day 24

,
InterventionParticipants (Count of Participants)
ALT: All cycles, Grade 0 to 3ALT: All cycles, Grade 2 to 3AST: All cycles, Grade 0 to 3High chloride: All cycles, Grade 1 to 3Low chloride: All cycles, Grade 0 to 3Hyperglycemia: Al cycles, Grade 0 to 3Hyperglycemia: All cycles, Grade 1 to 3Hyperglycemia: All cycles, Grade 2 to 3Hyperglycemia: All cycles, Grade 3 to 3Hypoglycemia: All cycles, Grade 0 to 4Hyperkalemia: All cycles, Grade 2 to 3Hyperkalemia: All cycles, Grade 4 to 3Hyperkalemia: All cycles, Grade 0 to 3Hyperkalemia: All cycles, Grade 0 to 4Hypokalemia: All cycles, Grade 0 to 3Hyponatremia: All cycles, Grade 1 to 3Total Bilirubin: All cycles, Grade 0 to 3Total Bilirubin: All cycles, Grade 0 to 4
Casopitant 90 mg201013253100228810
Placebo110201193111006611

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Number of Participants With Hematology Toxicity Grade Shifts From Baseline to Toxicity Grade 3 and 4

Grade shifts from Baseline were assessed as shift from any Grade to Grade 3 or Grade 4 in any cycle. Toxicities were graded according to the National Cancer Institute common toxicity criteria for adverse events (NCI-CTCAE), version 3.0. Grade refers to the severity of the toxicity. The NCI-CTCAE displays Grades 1 through 5 with unique clinical descriptions of severity for each toxicity based on the following general guideline: Grade 1: Mild AE, Grade 2: Moderate AE, Grade 3: Severe AE, Grade 4: Life-threatening or disabling AE and Grade 5: Death related to AE. It was assessed on Baseline (Day 1), during Day 6-10 and end of cycle. Hematology parameters assessed were hematocrit, hemoglobin, platelet count, total neutrophils and white blood cell count. Data has been presented for the number of participants with hematology toxicity grade shifts from Baseline to toxicity grade 3 and 4 for all cycles in a consolidated format. (NCT00601172)
Timeframe: Baseline (Day 1) to Day 24

,
InterventionParticipants (Count of Participants)
Hematocrit: All cycles, Grade 2 to Grade 3Hemoglobin: All cycles, Grade 1 to Grade 3Hemoglobin: All cycles, Grade 2 to Grade 3Hemoglobin: All cycles, Grade 3 to Grade 3Platelet count: All cycles, Grade 0 to 3Total Neutrophils: All cycles, Grade 0 to 3Total Neutrophils: All cycles, Grade 1 to 3Total Neutrophils: All cycles, Grade 2 to 3White Blood Cell count: All cycles, Grade 0 to 3White Blood Cell count: All cycles, Grade 1 to 3White Blood Cell count: All cycles, Grade 2 to 3
Casopitant 90 mg101213710512
Placebo0230124011001

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Percentage of Participants Who Achieved Complete Protection Defined as Complete Responders With no Significant Nausea

Complete protection was defined as no vomiting/retching, no use of rescue medication and no significant nausea. Percentage of participants who achieved complete protection or complete responders with no significant nausea are presented. (NCT00601172)
Timeframe: 0 to 24 hours, 24 to 120 hours and 0 to 120 hours in the first cycle of chemotherapy

,
InterventionPercentage of participants (Number)
0-120 hours0-24 hours24-120 hours
Casopitant 90 mg749374
Placebo759375

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Percentage of Participants Who Achieved Total Control, Defined as Complete Responders Who Had no Nausea

Total control was defined as no vomiting/retching, no use of rescue medication and no nausea. Percentage of participants who achieved total control or complete responders with no nausea are presented. (NCT00601172)
Timeframe: 0 to 24 hours, 24 to 120 hours and 0 to 120 hours in the first cycle of chemotherapy

,
InterventionPercentage of participants (Number)
0-120 hours0-24 hours24-120 hours
Casopitant 90 mg548354
Placebo618861

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Percentage of Participants Who Received Rescue Medication

Anti-emetic rescue medication was defined as medication that was administered specifically for the treatment of nausea and/or emesis during Days 1-6 of each cycle. The choice of rescue anti-emetic medication was left to the discretion of the investigator. Participants who required antiemetic rescue medication(s) during the 120-hour assessment period were considered treatment failures for that cycle. Percentage of participants who received rescue medication are presented. (NCT00601172)
Timeframe: 0 to 24 hours, 24 to 120 hours and 0 to 120 hours in the first cycle of chemotherapy

,
InterventionPercentage of participants (Number)
0-120 hours0-24 hours24-120 hours
Casopitant 90 mg818
Placebo929

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Percentage of Participants Who Reported Nausea, Defined as a Maximum Score of >= 5 mm on the VAS

VAS was used to assess severity of nausea. The participants rated the severity of nausea by marking a line on a 100 mm (0 to 100 mm) long scale. A line placed on the extreme left, that is 0 mm indicated no nausea and extreme right that is 100 mm indicated nausea as bad as it can be. This scale has no subscales. The participant perception of their symptoms was measured using the VAS. Percentage of participants who reported nausea, defined as a maximum score of >= 5 mm on the VAS are presented. (NCT00601172)
Timeframe: 0 to 24 hours, 24 to 120 hours and 0 to 120 hours in the first cycle of chemotherapy

,
InterventionPercentage of participants (Number)
0-120 hours0-24 hours24-120 hours
Casopitant 90 mg451545
Placebo371237

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Percentage of Participants Who Reported Significant Nausea, Defined as a Maximum Score >= 25 mm on the VAS

VAS was used to assess severity of nausea. The participants rated the severity of nausea by marking a line on a 100 mm (0 to 100 mm) long scale. A line placed on the extreme left, that is 0 mm indicated no nausea and extreme right that is 100 mm indicated nausea as bad as it can be. This scale has no subscales. The participant perception of their symptoms was measured using the VAS. Percentage of participants who reported significant nausea, defined as a maximum score >= 25 mm on the VAS are presented. (NCT00601172)
Timeframe: 0 to 24 hours, 24 to 120 hours and 0 to 120 hours in the first cycle of chemotherapy

,
InterventionPercentage of participants (Number)
0-120 hours0-24 hours24-120 hours
Casopitant 90 mg21521
Placebo19419

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Percentage of Participants Who Vomited and/or Retched

Vomiting was defined as the forceful expulsion of gastrointestinal contents through the mouth or nose. Retching was defined as the labored, spasmodic, rhythmic contraction of the respiratory and abdominal muscles in an attempt to vomit, that is not productive of gastrointestinal contents (also known as dry heaves). If a participant took rescue medication but there was no evidence of vomiting or retching, then the participant was considered as not having vomited. Percentage of participants who vomited and/or retched during the first 120 hours of the first cycle of chemotherapy are presented. (NCT00601172)
Timeframe: 0 to 24 hours, 24 to 120 hours and 0 to 120 hours in the first cycle of chemotherapy

,
InterventionPercentage of participants (Number)
0-120 hours0-24 hours24-120 hours
Casopitant 90 mg10210
Placebo11311

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Percentage of Participants Whose Daily Life Activities Were Impacted in the Overall Phase of Cycle 1, Assessed by Functional Living Index-Emesis (FLIE) Questionnaire

FLIE questionnaire specifically addresses the impact of nausea and vomiting on daily activities (physical, social and emotional function, ability to enjoy meals). It consists of 18 items with questions divided into two domains: Nausea (questions 1-9) and Vomiting (questions 10-18). Each item is scored on a VAS with 7 hatch marks. The scale is anchored at 1 (Not at all) and 7 (A great deal). For questions 1,2,4,5,7,8-10,12-14,16 and 17 the final score was calculated by subtracting the initial score from 100 for questions 3,6,11,15 and 18 the final score was the one provided in the dataset. The score for the nausea domain: ([sum of nausea item scores] ÷ [Number of items answered] x 9) and for vomiting domain: ([sum of vomiting item scores] ÷ [Number of items answered] x 9). The total score was the sum of the nausea and vomiting domain scores. Higher scores indicate less impairment on daily life as a result of nausea or vomiting. (NCT00601172)
Timeframe: 0 to 120 hours in the first cycle of chemotherapy

,
InterventionPercentage of participants (Number)
Nausea impactVomiting impact
Casopitant 90 mg23.711.5
Placebo21.312.5

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Single-dose Pharmacokinetic (PK) Parameters: Area Under the Curve (AUC) 0 to Infinity (0-∞), AUC 0 to t (0-t) and AUC 0 to 24 Hours (0-24) for Casopitant; AUC (0-t) and AUC (0-24) for Metabolites GSK525060, GSK517142 and GSK631832

Blood samples were obtained during Cycle 1 at the following times relative to the investigational product administration: pre-dose, end of infusion, 0.5, 1, 3, 5, 8, 12, 16, and 24 hours after the end of infusion. A final PK sample was collected between 30 and 48 hours after the investigational product infusion had completed. The actual time each sample was collected was captured to the nearest minute in the electronic case report form (eCRF). Following unblinding, only those participants who had been randomized to receive casopitant were included in the PK analyses. AUC(0-∞), AUC(0-t), AUC(0-24) for casopitant and metabolites GSK525060, GSK517142 and GSK631832 are presented. (NCT00601172)
Timeframe: Pre-dose, end of infusion and 0.5, 1, 3, 5, 8, 12, 16, 24 hours after the end of infusion

InterventionHour*nanogram/milliliter (hr*ng/mL) (Geometric Mean)
Casopitant: AUC(0-24)Casopitant: AUC(0-inf)Casopitant: AUC(0-t)GSK525060: AUC(0-24)GSK525060: AUC(0-t)GSK517142: AUC(0-24)GSK517142: AUC(0-t)GSK631832: AUC(0-24)GSK631832: AUC(0-t)
Casopitant 90 mg6913.6268607.0497688.5622247.2902796.73449.96440.997165.550231.018

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Single-dose Pharmacokinetic Parameters: Maximum Observed Drug Concentration (Cmax) for Casopitant and Metabolites GSK525060, GSK517142 and GSK631832

Blood samples were obtained during Cycle 1 at the following times relative to the investigational product administration: pre-dose, end of infusion, 0.5, 1, 3, 5, 8, 12, 16, and 24 hours after the end of infusion. A final PK sample was collected between 30 and 48 hours after the investigational product infusion had completed. The actual time each sample was collected was captured to the nearest minute in the electronic case report form (eCRF). Following unblinding, only those participants who had been randomized to receive casopitant were included in the PK analyses. (Cmax) for casopitant and metabolites GSK525060, GSK517142 and GSK631832 are presented. (NCT00601172)
Timeframe: Pre-dose, end of infusion and 0.5, 1, 3, 5, 8, 12, 16, 24 hours after the end of infusion

InterventionNanogram/milliliter (ng/mL) (Geometric Mean)
CasopitantGSK525060GSK517142GSK631832
Casopitant 90 mg2078.776143.0383.4269.853

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Single-dose Pharmacokinetic Parameters: Time to Maximum Observed Drug Concentration (Tmax) and Observed Elimination Half-life (t1/2) for Casopitant and Metabolites GSK525060, GSK517142 and GSK631832

Blood samples were obtained during Cycle 1 at the following times relative to the investigational product administration: pre-dose, end of infusion, 0.5, 1, 3, 5, 8, 12, 16, and 24 hours after the end of infusion. A final PK sample was collected between 30 and 48 hours after the investigational product infusion had completed. The actual time each sample was collected was captured to the nearest minute in the eCRF. Following unblinding, only those participants who had been randomized to receive casopitant were included in the PK analyses. Tmax and t1/2 for casopitant and metabolites GSK525060, GSK517142 and GSK631832 are presented. (NCT00601172)
Timeframe: Pre-dose, end of infusion and 0.5, 1, 3, 5, 8, 12, 16, 24 hours after the end of infusion

InterventionHour (Median)
Casopitant: TmaxCasopitant: t1/2GSK525060: TmaxGSK517142: TmaxGSK631832: Tmax
Casopitant 90 mg0.52012.3473.5801.5005.500

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Severity of Nausea in the Overall, Acute, and Delayed Phases of Cycle 1 Assessed by a Categorical Scale

Participants were asked to rate the level of nausea he/she experienced over the previous (24 hours for a period of 120 hours following the administration of MEC), by placing a vertical mark on a VAS. The severity of nausea and was calculated by using a 0 - 100 VAS where 0 = No Nausea and 100 = Nausea as bad as it can be. The categorical scale assessed the participants severity of his/her nausea using the following: mild: Queasiness/upset stomach that is manageable and minimally (if at all) affects daily activities, moderate: increased queasiness, sometimes with the feeling of having to vomit/throw up (but not vomiting), that has significant negative effect on the daily activities (for example, being unable to work, eat and drink, prepare food, care for children or others) and severe: feeling sick and vomiting or feeling like you are going to vomit, and unable to perform most daily activities. Higher scores indicated worst outcome. (NCT00601172)
Timeframe: 0 to 24 hours, 24 to 120 hours and 0 to 120 hours in the first cycle of chemotherapy

InterventionParticipants (Count of Participants)
0-120 hours723799890-120 hours723799900-24 hours723799890-24 hours7237999024-120 hours7237999024-120 hours72379989
MildModerateSevereNone
Placebo218
Placebo73
Casopitant 90 mg97
Placebo49
Casopitant 90 mg54
Placebo12
Casopitant 90 mg12
Placebo313
Casopitant 90 mg299
Placebo23
Casopitant 90 mg40
Placebo13
Casopitant 90 mg15
Placebo3
Casopitant 90 mg1
Casopitant 90 mg192

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