Single and Multiple Ascending Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of BMS-986141 in Healthy Subjects
Phase 1
Completed
- Conditions
- Thrombosis
- Interventions
- Registration Number
- NCT02341638
- Lead Sponsor
- Bristol-Myers Squibb
- Brief Summary
The purpose of this study is to assess the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of a single and multiple oral doses of BMS-986141 in healthy subjects.
- Detailed Description
Maximum Age:
Part A SAD 65 years
Part B MAD 75 years
Part C MAD Japanese 75 years
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 148
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, drugs as specified in protocol
- Other protocol-defined exclusion criteria could apply
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Part D Panel 1: BMS-986141 and Aspirin BMS-986141 BMS-986141 and Aspirin by mouth as specified Part D Panel 1: Placebo matching BMS-986141 and Aspirin Aspirin BMS-986141 placebo and Aspirin by mouth as specified Part D Panel 1: Placebo matching BMS-986141 and Aspirin Placebo BMS-986141 placebo and Aspirin by mouth as specified Part B Panel 2: BMS-986141 or Placebo Placebo BMS-986141 or Placebo by mouth as specified Part C Panel 2: BMS-986141 or Placebo Placebo BMS-986141 or Placebo by mouth as specified Part A Panel 4: BMS-986141 or Placebo Placebo BMS-986141 or Placebo single dose by mouth as specified Part B Panel 1: BMS-986141 or Placebo Placebo BMS-986141 or Placebo by mouth as specified Part C Panel 3: BMS-986141 or Placebo Placebo BMS-986141 or Placebo by mouth as specified Part A Panel 2: BMS-986141 or Placebo Placebo BMS-986141 or Placebo single dose by mouth as specified Part A Panel 3: BMS-986141 or Placebo Placebo BMS-986141 or Placebo single dose by mouth as specified Part A Panel 6: BMS-986141 or Placebo Placebo BMS-986141 or Placebo single dose by mouth as specified Part A Panel 1: BMS-986141 or Placebo Placebo BMS-986141 or Placebo single dose by mouth as specified Part A Panel 5: BMS-986141 or Placebo Placebo BMS-986141 or Placebo single dose by mouth as specified Part B Panel 3: BMS-986141 or Placebo Placebo BMS-986141 or Placebo by mouth as specified Part C Panel 1: BMS-986141 or Placebo Placebo BMS-986141 or Placebo by mouth as specified Part B Panel 3: BMS-986141 or Placebo BMS-986141 BMS-986141 or Placebo by mouth as specified Part A Panel 4: BMS-986141 or Placebo BMS-986141 BMS-986141 or Placebo single dose by mouth as specified Part A Panel 5: BMS-986141 or Placebo BMS-986141 BMS-986141 or Placebo single dose by mouth as specified Part A Panel 6: BMS-986141 or Placebo BMS-986141 BMS-986141 or Placebo single dose by mouth as specified Part A Panel 8: BMS-986141 BMS-986141 Single dose by mouth as specified Part B Panel 1: BMS-986141 or Placebo BMS-986141 BMS-986141 or Placebo by mouth as specified Part D Panel 1: BMS-986141 and Aspirin Aspirin BMS-986141 and Aspirin by mouth as specified Part E Panel 1: BMS-986141 and Itraconazole BMS-986141 BMS-986141 and Itraconazole by mouth as specified Part E Panel 1: BMS-986141 and Itraconazole Itraconazole BMS-986141 and Itraconazole by mouth as specified Part A Panel 1: BMS-986141 or Placebo BMS-986141 BMS-986141 or Placebo single dose by mouth as specified Part A Panel 2: BMS-986141 or Placebo BMS-986141 BMS-986141 or Placebo single dose by mouth as specified Part A Panel 3: BMS-986141 or Placebo BMS-986141 BMS-986141 or Placebo single dose by mouth as specified Part A Panel 7: BMS-986141 BMS-986141 Single dose by mouth as specified Part B Panel 2: BMS-986141 or Placebo BMS-986141 BMS-986141 or Placebo by mouth as specified Part C Panel 1: BMS-986141 or Placebo BMS-986141 BMS-986141 or Placebo by mouth as specified Part C Panel 2: BMS-986141 or Placebo BMS-986141 BMS-986141 or Placebo by mouth as specified Part C Panel 3: BMS-986141 or Placebo BMS-986141 BMS-986141 or Placebo by mouth as specified
- Primary Outcome Measures
Name Time Method Safety measured by number of subjects who experience SAEs, deaths, AEs leading to discontinuation, and potential clinically significant changes in ECG parameters, vital signs, laboratory tests and physical examinations Up to 30 days post discontinuation of dosing or last participation in the study Serious adverse event (SAE)
Adverse event (AE)
Electrocardiogram (ECG)Tolerability measured by number of subjects who experience SAEs, deaths, AEs leading to discontinuation, and potential clinically significant changes in ECG parameters, vital signs, laboratory tests and physical examinations Up to 30 days post discontinuation of dosing or last participation in the study Tolerability measured by percent of subjects who experience SAEs, deaths, AEs leading to discontinuation, and potential clinically significant changes in ECG parameters, vital signs, laboratory tests and physical examinations Up to 30 days post discontinuation of dosing or last participation in the study Safety measured by percent of subjects who experience SAEs, deaths, AEs leading to discontinuation, and potential clinically significant changes in ECG parameters, vital signs, laboratory tests and physical examinations Up to 30 days post discontinuation of dosing or last participation in the study
- Secondary Outcome Measures
Name Time Method Area under the concentration-time curve from time zero extrapolated to infinite time [AUC(INF)] of BMS-986141, BMT-162853, BMT-162856, and BMT-181551 Up to Day 14 Area under the plasma concentration-time curve from time zero to time of last quantifiable concentration [AUC(0-T)] of BMS-986141, BMT-162853, BMT-162856, and BMT-181551 Up to Day 14 Concentration at 24 hours (C24) of BMS-986141, BMT-162853, BMT-162856, and BMT-181551 Up to Day 14 MR_Cmax of BMT-162853, BMT-162856, and BMT-181551 Up to Day 14 Ratio of metabolite Cmax to parent Cmax, corrected for molecular weight (MR_Cmax)
MR_AUC(INF) of BMT-162853, BMT-162856, and BMT-181551 Up to Day 14 Ratio of metabolite AUC(INF) to parent AUC(INF), corrected for molecular weight \[MR_AUC(INF)\]
AUC accumulation index (AI_AUC) of BMS-986141, BMT-162853, BMT-162856, and BMT-181551; ratio of AUC(TAU) at steady-state to AUC(TAU) after the first dose Up to Day 14 Safety of multiple doses of BMS-986141 and aspirin in healthy subjects Up to 30 days post discontinuation of dosing or last participation in the study Safety measured by number of subjects who experience SAEs, deaths, AEs leading to discontinuation, and potential clinically significant changes in ECG parameters, vital signs, laboratory tests and physical examinations.
Area under the concentration-time curve in one dosing interval [AUC(TAU)] of BMS-986141, BMT-162853, BMT-162856, and BMT-181551 Up to Day 14 MR_AUC(0-T) of BMT-162853, BMT-162856, and BMT-181551 Up to Day 14 Ratio of metabolite AUC(0-T) to parent AUC(0-T), corrected for molecular weight \[MR_AUC(0-T)\]
Half-life (T-HALF) of BMS-986141, BMT-162853, BMT-162856, and BMT-181551 Up to Day 14 Effective elimination half-life that explains the degree of AUC accumulation observed (T-HALFeff_AUC) of BMS-986141, BMT-162853, BMT-162856, and BMT-181551 Up to Day 14 MR_AUC(TAU) of BMT-162853, BMT-162856, and BMT-181551 Up to Day 14 Ratio of metabolite AUC(TAU) to parent AUC(TAU), corrected for molecular weight \[MR_AUC(TAU)\]
Tolerability of BMS-986141 and itraconazole in healthy subjects Up to 30 days post discontinuation of dosing or last participation in the study Tolerability measured by number of subjects who experience SAEs, deaths, AEs leading to discontinuation, and potential clinically significant changes in ECG parameters, vital signs, laboratory tests and physical examinations
Maximum observed plasma concentration (Cmax) of BMS-986141, BMT-162853, BMT-162856, and BMT-181551 Up to Day 14 Time of maximum observed plasma concentration (Tmax) of BMS-986141, BMT-162853, BMT-162856, and BMT-181551 Up to Day 14 Safety of BMS-986141 and itraconazole in healthy subjects Up to 30 days post discontinuation of dosing or last participation in the study Safety measured by number of subjects who experience SAEs, deaths, AEs leading to discontinuation, and potential clinically significant changes in ECG parameters, vital signs, laboratory tests and physical examinations
Tolerability of multiple doses of BMS-986141 and aspirin in healthy subjects Up to 30 days post discontinuation of dosing or last participation in the study Tolerability measured by number of subjects who experience SAEs, deaths, AEs leading to discontinuation, and potential clinically significant changes in ECG parameters, vital signs, laboratory tests and physical examinations
Trial Locations
- Locations (2)
West Coast Clinical Trials, Llc
🇺🇸Cypress, California, United States
Ppd Development, Lp
🇺🇸Austin, Texas, United States