Phase 4
Completed N=22
Study to Evaluate Effect of Belatacept on Pharmacokinetics of Inje Cocktail in Healthy Volunteers
Transplant Rejection
Source: ClinicalTrials.gov NCT01766050 ↗
Enrolled (actual)
22
Serious AEs
0.0%
Results posted
Jun 2014
Primary outcomePrimary: Adjusted Geometric Mean Maximum Drug Concentration (Cmax) of Midazolam With and Without the Coadministration of Belatacept - Pharmacokinetic (PK) Evaluable Population — 24.376; 24.152; 22.211; 24.220 ng/mL
Summary
The purpose of this study is to determine the effects of belatacept on the pharmacokinetics of caffeine, losartan, omeprazole, dextromethorphan and midazolam
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Adjusted Geometric Mean Maximum Drug Concentration (Cmax) of Midazolam With and Without the Coadministration of Belatacept - Pharmacokinetic (PK) Evaluable Population |
24.376; 24.152; 22.211; 24.220 | — |
| PRIMARY 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 |
65.548; 68.833; 63.303; 67.717; 67.743; 71.039 | — |
| PRIMARY Adjusted Geometric Mean Cmax of Losartan With and Without the Coadministration of Belatacept - PK Evaluable Population |
119.789; 118.663; 127.184; 126.461 | — |
| PRIMARY Adjusted Geometric Mean AUC (0-T) and AUC (INF) of Losartan With and Without the Coadministration of Belatacept - Pharmacokinetic (PK) Evaluable Population |
332.191; 336.531; 337.487; 332.400; 338.033; 341.644 | — |
| PRIMARY Adjusted Geometric Mean Cmax of Omeprazole With and Without the Coadministration of Belatacept - Pharmacokinetic (PK) Evaluable Population |
583.047; 734.776; 753.126; 686.929 | — |
| PRIMARY Adjusted Geometric Mean AUC (0-T) and AUC (INF) of Omeprazole With and Without the Coadministration of Belatacept - Pharmacokinetic (PK) Evaluable Population |
1361.024; 1577.017; 1671.173; 1653.491; 1368.593; 1632.455 | — |
| PRIMARY Adjusted Geometric Mean Cmax of Dextromethorphan With and Without the Coadministration of Belatacept - PK Evaluable Population |
0.927; 0.800; 0.855; 0.794 | — |
| PRIMARY Adjusted Geometric Mean AUC (0-T) and AUC (INF) of Dextromethorphan With and Without the Coadministration of Belatacept - PK Evaluable Population |
6.176; 5.651; 6.195; 5.949; 6.220; 5.455 | — |
| PRIMARY Adjusted Geometric Mean Cmax of Caffeine With and Without the Coadministration of Belatacept - PK Evaluable Population |
4696.505; 4450.019; 4332.326; 4479.687 | — |
| PRIMARY Adjusted Geometric Mean AUC (0-T) and AUC (INF) of Caffeine With and Without the Coadministration of Belatacept - PK Evaluable Population |
37394.5; 35200.3; 36853.4; 38407.0; 40084.1; 37647.8 | — |
| SECONDARY 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 |
0.50; 0.50; 0.50; 1.0; 1.52; 2.00 | — |
| SECONDARY 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 |
4.01; 4.43; 4.27; 4.05; 2.96; 2.56 | — |
| SECONDARY 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 |
73.8; 71.3; 77.3; 71.4; 148; 146 | — |
| SECONDARY Cmax of Inje Cocktail Metabolites (1'-Hydroxy-Midazolam, E-3174, 5-Hydroxyomeprazole, Dextrorphan, and Paraxanthine) With and Without Coadministration of Belatacept - PK Evaluable Population |
11.1; 11.9; 11.4; 12.3; 262; 276 | — |
| SECONDARY 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 |
28.9; 31.8; 32.5; 33.6; 1995; 1999 | — |
| SECONDARY 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 |
30.5; 33.8; 32.9; 35.1; 2103; 2060 | — |
| SECONDARY 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 |
1.00; 1.00; 1.00; 1.00; 4.00; 4.00 | — |
| SECONDARY 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 |
5.29; 6.35; 5.61; 5.31; 4.86; 4.57 | — |
| SECONDARY 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 |
0.627; 0.677; 0.635; 0.603; 0.827; 0.827 | — |
| SECONDARY Ratio of Paraxanthine (Cmax) to Caffeine (Cmax), Corrected for Molecular Weight (MR_Cmax) With and Without Coadministration of Belatacept - PK Evaluable Population |
0.303; 0.337; 0.333; 0.323 | — |
| SECONDARY 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 |
5.81; 5.75; 5.99; 6.17; 6.02; 5.99 | — |
| SECONDARY Ratio of E-3174 (Cmax) to Losartan (Cmax), Corrected for Molecular Weight (MR_Cmax) With and Without Coadministration of Belatacept - PK Evaluable Population |
2.31; 2.24; 2.26; 2.26 | — |
| SECONDARY 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 |
0.700; 0.609; 0.551; 0.610; 0.705; 0.558 | — |
| SECONDARY Ratio of 5-Hydroxyomeprazole (Cmax) to Omeprazole (Cmax), Corrected for Molecular Weight (MR_Cmax) With and Without Coadministration of Belatacept - PK Evaluable Population |
0.548; 0.471; 0.424; 0.478 | — |
| SECONDARY 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 |
201; 200; 177; 193; 173; 177 | — |
| SECONDARY Ratio of 5-Dextrorphan (Cmax) to Dextromethorphan (Cmax), Corrected for Molecular Weight (MR_Cmax) With and Without Coadministration of Belatacept - PK Evaluable Population |
280; 303; 275; 303 | — |
| SECONDARY 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 |
0.421; 0.447; 0.495; 0.472; 0.428; 0.460 | — |
| SECONDARY Ratio of 1'-Hydroxy-Midazolam (Cmax) to Midazolam (Cmax), Corrected for Molecular Weight (MR_Cmax) With and Without Coadministration of Belatacept - PK Evaluable Population |
0.432; 0.476; 0.497; 0.490 | — |
| SECONDARY Number of Participants With Adverse Events (AEs), Serious AEs (SAEs), Deaths, and AEs Leading to Discontinuation - All Treated Participants |
4; 2; 1; 1; 5; 0 | — |
| SECONDARY Number of Participants With Marked Serum Chemistry Laboratory Abnormalities - All Treated Participants |
1; 1; 1; 1; 1; 2 | — |
| SECONDARY Number of Participants With Marked Hematology and Urinalysis Laboratory Abnormalities - All Treated Participants |
1; 4; 2; 1; 1 | — |
| SECONDARY Number of Participants With Out-of-Range Electrocardiogram Intervals - All Treated Participants |
0; 0 | — |
| SECONDARY Mean Change From Baseline in Sitting Systolic and Diastolic Blood Pressure - All Treated Participants |
-0.6; 0.1; -4.9; -4.7; 0.2; 2.0 | — |
| SECONDARY Mean Change From Baseline in Sitting Heart Rate - All Treated Participants |
-3.3; -4.2; -1.8; -1.6; -3.5; 0.2 | — |
| SECONDARY Mean Change From Baseline in Systolic and Diastolic Blood Pressure at Study Discharge (Day 46±2 Days) |
-5.9; -5.7 | — |
| SECONDARY Mean Change From Baseline in Heart Rate at Study Discharge (Day 46±2 Days) |
1.0 | — |
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
Data sourced from ClinicalTrials.gov (NCT01766050). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.