Healthy Adult Volunteers
Conditions
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.
Interventions
Sponsors
Bristol-Myers Squibb
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
Yes
Inclusion criteria
For more information regarding BMS clinical trial participation, please visit www.BMSStudyConnect.com Inclusion Criteria: 1. Healthy male and female subjects as determined by no clinically significant deviation from normal in medical history, physical examination, ECGs, and clinical laboratory determinations 2. Body Mass Index (BMI) of 18 to 32 kg/m2, inclusive. BMI=Weight (kg)/\[Height(m)\]2 3. Women who are not of childbearing potential (i.e., who are postmenopausal or surgically sterile) and men, ages 18 to 75, inclusive
Exclusion criteria
1. 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 2. 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 3. Hemoglobin or hematocrit or platelet count \<lower limit of normal (LLN) 4. Bleeding time exceeding 8 minutes at pre-dose on Day -1 5. 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 6. Any significant acute or chronic medical illness 7. Current or recent (within 3 months of study drug administration) gastrointestinal disease 8. Any major surgery within 12 weeks of study drug administration
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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
| Measure | Time frame |
|---|---|
| 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) |
| 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) |
| 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) |
| 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) |
| 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) |
| 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) |
| 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) |
| 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) |
| 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) |
| 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) |
| 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) |
| 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) |
Countries
United States
Outcome results
None listed