Multiple Ascending Dose Study to Evaluate the Safety, Tolerability and Pharmacokinetics of BMS-986120 in Healthy Subjects and the Effects of Co-Administration of Midazolam and BMS-986120
Phase 1
Completed
- Conditions
- Healthy Adult Volunteers
- Interventions
- Registration Number
- NCT02208882
- Lead Sponsor
- Bristol-Myers Squibb
- Brief Summary
The purpose of this study is to assess the safety, tolerability and effect on Midazolam pharmacokinetics of multiple oral doses of BMS-986120 in healthy subjects.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 24
Inclusion Criteria
- Healthy male and female subjects as determined by no clinically significant deviation from normal in medical history, physical examination, ECGs, and clinical laboratory determinations
- Body Mass Index (BMI) of 18 to 32 kg/m2, inclusive. BMI=Weight (kg)/[Height(m)]2
- Women who are not of childbearing potential (i.e., who are postmenopausal or surgically sterile) and men, ages 18 to 75, inclusive
Exclusion Criteria
-
Concurrent, or use within 2-weeks of study drug administration, of marketed or investigational, non-steroidal anti-inflammatory compounds (NSAIDS), aspirin or other antiplatelet agents, oral or parenteral anticoagulants
-
Subjects at screening or prior to first dose with the following abnormal laboratory values upon repeat testing are excluded:
- i) Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >upper limit of normal (ULN)
- ii) Total bilirubin >ULN, thyroid-stimulating hormone (TSH) >1.5 x ULN with T4 within normal limits (Subjects with mild unconjugated hyperbilirubinemia due to Gilbert's syndrome are excluded)
- iii) CK >3 x ULN (unless exercise related and CK-MB within normal limits)
- iv) Activated partial thromboplastin (aPTT) or Prothrombin Time (PT)/International Normalized Ratio (INR) >ULN
- v) Blood urea nitrogen (BUN) or creatinine (Cr) >ULN
-
Hemoglobin or hematocrit or platelet count <lower limit of normal (LLN)
-
Bleeding time exceeding 8 minutes at pre-dose on Day -1
-
Subjects with micro- or macro-hematuria and/or fecal occult blood detected during screening, baseline or documented during other recent medical assessment, unless deemed not clinically significant by the Investigator and Medical Monitor
-
Any significant acute or chronic medical illness
-
Current or recent (within 3 months of study drug administration) gastrointestinal disease
-
Any major surgery within 12 weeks of study drug administration
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Panel 3: BMS-986120 or Placebo + Midazolam BMS-986120 BMS-986120 or Placebo (multiple dose) + Midazolam (single dose) by mouth as specified Panel 1: BMS-986120 or Placebo Placebo BMS-986120 or Placebo multiple dose by mouth as specified Panel 4: BMS-986120 or Placebo Placebo BMS-986120 or Placebo multiple dose by mouth as specified Panel 2: BMS-986120 or Placebo BMS-986120 BMS-986120 or Placebo multiple dose by mouth as specified Panel 2: BMS-986120 or Placebo Placebo BMS-986120 or Placebo multiple dose by mouth as specified Panel 3: BMS-986120 or Placebo + Midazolam Placebo BMS-986120 or Placebo (multiple dose) + Midazolam (single dose) by mouth as specified Panel 1: BMS-986120 or Placebo BMS-986120 BMS-986120 or Placebo multiple dose by mouth as specified Panel 4: BMS-986120 or Placebo BMS-986120 BMS-986120 or Placebo multiple dose by mouth as specified Panel 3: BMS-986120 or Placebo + Midazolam Midazolam BMS-986120 or Placebo (multiple dose) + Midazolam (single dose) by mouth as specified
- Primary Outcome Measures
Name Time Method Safety and tolerability measured by number of subjects experience serious adverse events, deaths, adverse events leading to discontinuation, and potential clinically significant changes in electrocardiogram (ECG) parameters Up to 168 days Safety and tolerability measured by percent of subjects experience serious adverse events, deaths, adverse events leading to discontinuation, and potential clinically significant changes in electrocardiogram (ECG) parameters Up to 168 days
- Secondary Outcome Measures
Name Time Method Area under the concentration-time curve from time zero to 24h [AUC(TAU)] of BMS-986120 and BMT-141464 Part A (Days 1-8), Part B/C (Days 1-19), & Part D (Days 1-22) Apparent total body clearance (CLT/F) of BMS-986120, Midazolam, and 1'hydroxymidazolam Part A (Days 1-8), Part B/C (Days 1-19), & Part D (Days 1-22) AUC accumulation index (AI_AUC) of BMS-986120 and BMT-141464 Part A (Days 1-8), Part B/C (Days 1-19), & Part D (Days 1-22) Half-life (T-HALF) of BMS-986120 and BMT-141464 Part A (Days 1-8), Part B/C (Days 1-19), & Part D (Days 1-22) Ratio of metabolite Cmax to parent Cmax, corrected for molecular weight (MR_Cmax) of BMT-141464 Part A (Days 1-8), Part B/C (Days 1-19), & Part D (Days 1-22) Ratio of metabolite AUC(TAU) to parent AUC(TAU), corrected for molecular weight [MR_AUC(TAU)] of BMT-141464 Part A (Days 1-8), Part B/C (Days 1-19), & Part D (Days 1-22) Area under the concentration-time curve from time zero to the time of the last quantifiable concentration [AUC(0-T)] of Midazolam and 1'hydroxymidazolam Part A (Days 1-8), Part B/C (Days 1-19), & Part D (Days 1-22) Area under the concentration-time curve from time zero extrapolated to infinite time [AUC(INF)] of Midazolam and 1'hydroxymidazolam Part A (Days 1-8), Part B/C (Days 1-19), & Part D (Days 1-22) Concentration at the end of the dosing Interval (Ctau) of BMS-986120 and BMT-141464 Part A (Days 1-8), Part B/C (Days 1-19), & Part D (Days 1-22) Ratio of metabolite AUC(INF) to parent AUC(INF), corrected for molecular weight [MR_AUC(INF)] of 1'hydroxymidazolam Part A (Days 1-8), Part B/C (Days 1-19), & Part D (Days 1-22) Maximum observed plasma concentration (Cmax) of BMS-986120, BMT-141464, Midazolam, and 1'hydroxymidazolam Part A (Days 1-8), Part B/C (Days 1-19), & Part D (Days 1-22) Time of maximum observed plasma concentration (Tmax) of BMS-986120, BMT-141464, Midazolam, and 1'hydroxymidazolam Part A (Days 1-8), Part B/C (Days 1-19), & Part D (Days 1-22) Effective elimination half-life that explains the degree of AUC accumulation observed (T-HALFeff_AUC) of BMS-986120 Part A (Days 1-8), Part B/C (Days 1-19), & Part D (Days 1-22) Change from baseline in protease-activated receptor-4 - agonist peptide (PAR4-AP) induced platelet aggregation of BMS-986120 Part A (Days 1-3) & Part B/C (Days 1-19)
Trial Locations
- Locations (1)
Ppd Development, Lp
🇺🇸Austin, Texas, United States
Ppd Development, Lp🇺🇸Austin, Texas, United States