Study to Evaluate Effect of Belatacept on Pharmacokinetics of Inje Cocktail in Healthy Volunteers

Condition(s) targeted: Transplant Rejection

Intervention: Caffeine (Drug); Losartan (Drug); Omeprazole (Drug); Dextromethorphan (Drug); Midazolam (Drug); Belatacept (Biological)

Phase: Phase 4

Status: Completed

Sponsored by: Bristol-Myers Squibb

Official(s) and/or principal investigator(s):
Bristol-Myers Squibb, Study Director, Affiliation: Bristol-Myers Squibb

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

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 design: Endpoint Classification: Pharmacokinetics Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Basic Science

Primary outcome:

Adjusted Geometric Mean Maximum Drug Concentration (Cmax) of Midazolam With and Without the Coadministration of Belatacept - Pharmacokinetic (PK) Evaluable Population

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

Adjusted Geometric Mean Cmax of Losartan With and Without the Coadministration of Belatacept - PK Evaluable Population

Adjusted Geometric Mean AUC (0-T) and AUC (INF) of Losartan With and Without the Coadministration of Belatacept - Pharmacokinetic (PK) Evaluable Population

Adjusted Geometric Mean Cmax of Omeprazole With and Without the Coadministration of Belatacept - Pharmacokinetic (PK) Evaluable Population

Adjusted Geometric Mean AUC (0-T) and AUC (INF) of Omeprazole With and Without the Coadministration of Belatacept - Pharmacokinetic (PK) Evaluable Population

Adjusted Geometric Mean Cmax of Dextromethorphan With and Without the Coadministration of Belatacept - PK Evaluable Population

Adjusted Geometric Mean AUC (0-T) and AUC (INF) of Dextromethorphan With and Without the Coadministration of Belatacept - PK Evaluable Population

Adjusted Geometric Mean Cmax of Caffeine With and Without the Coadministration of Belatacept - PK Evaluable Population

Adjusted Geometric Mean AUC (0-T) and AUC (INF) of Caffeine With and Without the Coadministration of Belatacept - PK Evaluable Population

Secondary outcome:

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

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

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

Cmax of Inje Cocktail Metabolites (1'-Hydroxy-Midazolam, E-3174, 5-Hydroxyomeprazole, Dextrorphan, and Paraxanthine) With and Without Coadministration of Belatacept - PK Evaluable Population

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

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

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

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

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

Ratio of Paraxanthine (Cmax) to Caffeine (Cmax), Corrected for Molecular Weight (MR_Cmax) With and Without Coadministration of Belatacept - PK Evaluable Population

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

Ratio of E-3174 (Cmax) to Losartan (Cmax), Corrected for Molecular Weight (MR_Cmax) With and Without Coadministration of Belatacept - PK Evaluable Population

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

Ratio of 5-Hydroxyomeprazole (Cmax) to Omeprazole (Cmax), Corrected for Molecular Weight (MR_Cmax) With and Without Coadministration of Belatacept - PK Evaluable Population

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

Ratio of 5-Dextrorphan (Cmax) to Dextromethorphan (Cmax), Corrected for Molecular Weight (MR_Cmax) With and Without Coadministration of Belatacept - PK Evaluable Population

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

Ratio of 1'-Hydroxy-Midazolam (Cmax) to Midazolam (Cmax), Corrected for Molecular Weight (MR_Cmax) With and Without Coadministration of Belatacept - PK Evaluable Population

Number of Participants With Adverse Events (AEs), Serious AEs (SAEs), Deaths, and AEs Leading to Discontinuation - All Treated Participants

Number of Participants With Marked Serum Chemistry Laboratory Abnormalities - All Treated Participants

Number of Participants With Marked Hematology and Urinalysis Laboratory Abnormalities - All Treated Participants

Number of Participants With Out-of-Range Electrocardiogram Intervals - All Treated Participants

Mean Change From Baseline in Sitting Systolic and Diastolic Blood Pressure - All Treated Participants

Mean Change From Baseline in Sitting Heart Rate - All Treated Participants

Mean Change From Baseline in Systolic and Diastolic Blood Pressure at Study Discharge (Day 46±2 Days)

Mean Change From Baseline in Heart Rate at Study Discharge (Day 46±2 Days)

Minimum age: 18 Years. Maximum age: 45 Years. Gender(s): Both.

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

Healthcare Discoveries, Llc D/B/A Icon Development Solutions, San Antonio, Texas 78209, United States

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Starting date: January 2013
Last updated: May 27, 2014