Clinical trial NCT01766050: Study to Evaluate Effect of Belatacept on Pharmacokinetics of Inje Cocktail in Healthy Volunteers
Official title: An Open-label, Single-sequence Study of the Effect of Belatacept on the Pharmacokinetics of Caffeine, Losartan, Omeprazole, Dextromethorphan, and Midazolam Administered as "Inje Cocktail" in Healthy Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Transplant Rejection
Lead sponsor: Bristol-Myers Squibb
Sponsor class: INDUSTRY
First posted: 2013-01-11
Enrollment: 45
Sex: ALL
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: BASIC_SCIENCE

Brief summary: The purpose of this study is to determine the effects of belatacept on the pharmacokinetics of caffeine, losartan, omeprazole, dextromethorphan and midazolam


Eligibility criteria: Inclusion Criteria:

* BMI 18 to 30 kg/m2
* Men and women ages 18 to 45

Exclusion Criteria:

* Active tuberculosis
* Any recent infection requiring antibiotic treatment within 4 weeks of dosing
* Positive urine screen for drugs of abuse

Primary outcomes:
measure: Adjusted Geometric Mean Maximum Drug Concentration (Cmax) of Midazolam With and Without the Coadministration of Belatacept - Pharmacokinetic (PK) Evaluable Population
timeFrame: Pre-dose to 24 hours after dose of the Inje Cocktail on Days 1, 4, 7 and 11
measure: Adjusted Geometric Mean Area Under the Concentration Time Curve (AUC) From Zero to Last Concentration (0-T) and AUC Extrapolated to Infinity (INF) of Midazolam With and Without the Coadministration of Belatacept - Pharmacokinetic (PK) Evaluable Population
timeFrame: Pre-dose to 24 hours after dose of the Inje Cocktail on Days 1, 4, 7and 11
measure: Adjusted Geometric Mean Cmax of Losartan With and Without the Coadministration of Belatacept - PK Evaluable Population
timeFrame: Pre-dose to 24 hours after dose of the Inje Cocktail on Days 1, 4, 7 and 11
measure: Adjusted Geometric Mean AUC (0-T) and AUC (INF) of Losartan With and Without the Coadministration of Belatacept - Pharmacokinetic (PK) Evaluable Population
timeFrame: Pre-dose to 24 hours after dose of the Inje Cocktail on Days 1, 4, 7 and 11
measure: Adjusted Geometric Mean Cmax of Omeprazole With and Without the Coadministration of Belatacept - Pharmacokinetic (PK) Evaluable Population
timeFrame: Pre-dose to 24 hours after dose of the Inje Cocktail on Days 1, 4, 7 and 11
measure: Adjusted Geometric Mean AUC (0-T) and AUC (INF) of Omeprazole With and Without the Coadministration of Belatacept - Pharmacokinetic (PK) Evaluable Population
timeFrame: Pre-dose to 24 hours after dose of the Inje Cocktail on Days 1, 4, 7 and 11
measure: Adjusted Geometric Mean Cmax of Dextromethorphan With and Without the Coadministration of Belatacept - PK Evaluable Population
timeFrame: Pre-dose to 24 hours after dose of the Inje Cocktail on Days 1, 4, 7 and 11
measure: Adjusted Geometric Mean AUC (0-T) and AUC (INF) of Dextromethorphan With and Without the Coadministration of Belatacept - PK Evaluable Population
timeFrame: Pre-dose to 24 hours after dose of the Inje Cocktail on Days 1, 4, 7 and 11
measure: Adjusted Geometric Mean Cmax of Caffeine With and Without the Coadministration of Belatacept - PK Evaluable Population
timeFrame: Pre-dose to 24 hours after dose of the Inje Cocktail on Days 1, 4, 7 and 11
measure: Adjusted Geometric Mean AUC (0-T) and AUC (INF) of Caffeine With and Without the Coadministration of Belatacept - PK Evaluable Population
timeFrame: Pre-dose to 24 hours after dose of the Inje Cocktail on Days 1, 4, 7 and 11
Secondary outcomes:
measure: Time of Maximum Observed Plasma Concentration (Tmax) of the Inje Cocktail Components (Midazolam, Losartan, Omeprazole, Dextromethorphan, and Caffeine) With and Without Coadministration of Belatacept - PK Evaluable Population
timeFrame: Pre-dose to 24 hours after dose of the Inje Cocktail on Days 1, 4, 7 and 11
measure: Plasma Half-Life (T-HALF) of the Inje Cocktail Components (Midazolam, Losartan, Omeprazole, Dextromethorphan, and Caffeine) With and Without Coadministration of Belatacept - PK Evaluable Population
timeFrame: Pre-dose to 24 hours after dose of the Inje Cocktail on Days 1, 4, 7 and 11
measure: Apparent Total Body Clearance (CLT/F) of the Inje Cocktail Components (Midazolam, Losartan, Omeprazole, Dextromethorphan and Caffeine) With and Without Coadministration of Belatacept - PK Evaluable Population
timeFrame: Pre-dose to 24 hours after dose of the Inje Cocktail on Days 1, 4, 7 and 11
measure: Cmax of Inje Cocktail Metabolites (1'-Hydroxy-Midazolam, E-3174, 5-Hydroxyomeprazole, Dextrorphan, and Paraxanthine) With and Without Coadministration of Belatacept - PK Evaluable Population
timeFrame: Pre-dose to 24 hours after dose of the Inje Cocktail on Days 1, 4, 7 and 11
measure: AUC(0-T) of Inje Cocktail Component Metabolites (1'-Hydroxy-Midazolam, E-3174, 5-Hydroxyomeprazole, Dextrorphan, and Paraxanthine) With and Without Coadministration of Belatacept - PK Evaluable Population
timeFrame: Pre-dose to 24 hours after dose of the Inje Cocktail on Days 1, 4, 7 and 11
measure: AUC(INF) of Inje Cocktail Component Metabolites (1'-Hydroxy-Midazolam, E-3174, 5-Hydroxyomeprazole, Dextrorphan, and Paraxanthine) With and Without Coadministration of Belatacept - PK Evaluable Population
timeFrame: Pre-dose to 24 hours after dose of the Inje Cocktail on Days 1, 4, 7 and 11
measure: Tmax of Inje Cocktail Component Metabolites (1'-Hydroxy-Midazolam, E-3174, 5-Hydroxyomeprazole, Dextrorphan, and Paraxanthine) With and Without the Coadministration of Belatacept - PK Evaluable Population
timeFrame: Pre-dose to 24 hours after dose of the Inje Cocktail on Days 1, 4, 7 and 11
measure: T-HALF of Inje Cocktail Component Metabolites (1'-Hydroxy-Midazolam, E-3174, 5-Hydroxyomeprazole, Dextrorphan, and Paraxanthine) With and Without the Coadministration of Belatacept - PK Evaluable Population
timeFrame: Pre-dose to 24 hours after dose of the Inje Cocktail on Days 1, 4, 7 and 11
measure: Ratio of Paraxanthine AUC(0-T) to Caffeine AUC(0-T) and Paraxanthine AUC (INF) to Caffeine AUC (INF), Corrected for Molecular Weight [MR_AUC(0-T) and MR_AUC (INF)] With and Without Coadministration of Belatacept - PK Evaluable Population
timeFrame: Pre-dose to 24 hours after dose of the Inje Cocktail on Days 1, 4, 7 and 11
measure: Ratio of Paraxanthine (Cmax) to Caffeine (Cmax), Corrected for Molecular Weight (MR_Cmax) With and Without Coadministration of Belatacept - PK Evaluable Population
timeFrame: Pre-dose to 24 hours after dose of the Inje Cocktail on Days 1, 4, 7 and 11
measure: Ratio of E-3174 AUC(0-T) to Losartan AUC(0-T) and E3174 AUC (INF) to Losartan AUC (INF) Corrected for Molecular Weight [MR_AUC(0-T), MR_AUC(INF)] With and Without Coadministration of Belatacept - PK Evaluable Population
timeFrame: Pre-dose to 24 hours after dose of the Inje Cocktail on Days 1, 4, 7 and 11
measure: Ratio of E-3174 (Cmax) to Losartan (Cmax), Corrected for Molecular Weight (MR_Cmax) With and Without Coadministration of Belatacept - PK Evaluable Population
timeFrame: Pre-dose to 24 hours after dose of the Inje Cocktail on Days 1, 4, 7 and 11
measure: Ratio of 5-Hydroxyomeprazole AUC(0-T) to Omeprazole AUC(0-T) and 5-Hydroxyomeprazole AUC(INF) to Omeprazole AUC(INF) , Corrected for Molecular Weight [MR_AUC(0-T), MR_AUC(INF)] With and Without Coadministration of Belatacept - PK Evaluable Population
timeFrame: Pre-dose to 24 hours after dose of the Inje Cocktail on Days 1, 4, 7 and 11
measure: Ratio of 5-Hydroxyomeprazole (Cmax) to Omeprazole (Cmax), Corrected for Molecular Weight (MR_Cmax) With and Without Coadministration of Belatacept - PK Evaluable Population
timeFrame: Pre-dose to 24 hours after dose of the Inje Cocktail on Days 1, 4, 7 and 11
measure: Ratio of 5-Dextrorphan AUC(0-T) to Dextromethorphan AUC(0-T) and 5-Dextrorphan AUC(INF) to Dextromethorphan AUC(INF), Corrected for Molecular Weight [MR_AUC(0-T), MR_AUC (INF)] With and Without Coadministration of Belatacept - PK Evaluable Population
timeFrame: Pre-dose to 24 hours after dose of the Inje Cocktail on Days 1, 4, 7 and 11
measure: Ratio of 5-Dextrorphan (Cmax) to Dextromethorphan (Cmax), Corrected for Molecular Weight (MR_Cmax) With and Without Coadministration of Belatacept - PK Evaluable Population
timeFrame: Pre-dose to 24 hours after dose of the Inje Cocktail on Days 1, 4, 7 and 11
measure: Ratio of 1'-Hydroxy-Midazolam AUC(0-T) to Midazolam AUC(0-T) and 1'-Hydroxy-Midazolam AUC(INF) to Midazolam AUC(INF), Corrected for Molecular Weight [MR_AUC(0-T), MR_AUC (INF)] With and Without Coadministration of Belatacept - PK Evaluable Population
timeFrame: Pre-dose to 24 hours after dose of the Inje Cocktail on Days 1, 4, 7 and 11
measure: Ratio of 1'-Hydroxy-Midazolam (Cmax) to Midazolam (Cmax), Corrected for Molecular Weight (MR_Cmax) With and Without Coadministration of Belatacept - PK Evaluable Population
timeFrame: Pre-dose to 24 hours after dose of the Inje Cocktail on Days 1, 4, 7 and 11
measure: Number of Participants With Adverse Events (AEs), Serious AEs (SAEs), Deaths, and AEs Leading to Discontinuation - All Treated Participants
timeFrame: Day 1 to Day of discharge (Day 46±2)
measure: Number of Participants With Marked Serum Chemistry Laboratory Abnormalities - All Treated Participants
timeFrame: Day -1 to Day 46 ±2 days or at early termination
measure: Number of Participants With Marked Hematology and Urinalysis Laboratory Abnormalities - All Treated Participants
timeFrame: Day -1 to Day 46 ±2 days or at early termination
measure: Number of Participants With Out-of-Range Electrocardiogram Intervals - All Treated Participants
timeFrame: Day 1 to Day 46 ±2 days or at early termination
measure: Mean Change From Baseline in Sitting Systolic and Diastolic Blood Pressure - All Treated Participants
timeFrame: Baseline and 0.5 and 2.0 hours Post Dose on Days 1, 4, 7, and 11
measure: Mean Change From Baseline in Sitting Heart Rate - All Treated Participants
timeFrame: Baseline and 0.5 and 2.0 hours Post Dose on Days 1, 4, 7, and 11
measure: Mean Change From Baseline in Systolic and Diastolic Blood Pressure at Study Discharge (Day 46±2 Days)
timeFrame: Baseline and Day 46 ±2 days
measure: Mean Change From Baseline in Heart Rate at Study Discharge (Day 46±2 Days)
timeFrame: Baseline and Day 46 ±2 days
Other outcomes:
Locations:
city: San Antonio
country: United States
facility: Healthcare Discoveries, Llc D/B/A Icon Development Solutions
state: Texas
Study officials:
affiliation: Bristol-Myers Squibb
name: Bristol-Myers Squibb
role: STUDY_DIRECTOR
References: