Single and Multiple Ascending Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of BMS-986141 in Healthy Subjects

Study Overview
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Brief Summary
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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
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Maximum Age: Part A SAD 65 years Part B MAD 75 years Part C MAD Japanese 75 years

Official Title
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Randomized, Double-Blinded, Placebo-Controlled Single and Multiple Ascending Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of BMS-986141 in Healthy Subjects

Conditions
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Thrombosis

Intervention / Treatment
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* Drug: BMS-986141
* Drug: Placebo
* Drug: Aspirin
* Drug: Itraconazole


Participation Criteria
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Eligibility Criteria
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For more information regarding BMS clinical trial participation, please visit www.BMSStudyConnect.com 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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part A Panel 1: BMS-986141 or Placebo<br>BMS-986141 or Placebo single dose by mouth as specified | Drug: BMS-986141<br> <br> Drug: Placebo<br> <br> |
| Experimental: Part A Panel 2: BMS-986141 or Placebo<br>BMS-986141 or Placebo single dose by mouth as specified | Drug: BMS-986141<br> <br> Drug: Placebo<br> <br> |
| Experimental: Part A Panel 3: BMS-986141 or Placebo<br>BMS-986141 or Placebo single dose by mouth as specified | Drug: BMS-986141<br> <br> Drug: Placebo<br> <br> |
| Experimental: Part A Panel 4: BMS-986141 or Placebo<br>BMS-986141 or Placebo single dose by mouth as specified | Drug: BMS-986141<br> <br> Drug: Placebo<br> <br> |
| Experimental: Part A Panel 5: BMS-986141 or Placebo<br>BMS-986141 or Placebo single dose by mouth as specified | Drug: BMS-986141<br> <br> Drug: Placebo<br> <br> |
| Experimental: Part A Panel 6: BMS-986141 or Placebo<br>BMS-986141 or Placebo single dose by mouth as specified | Drug: BMS-986141<br> <br> Drug: Placebo<br> <br> |
| Experimental: Part A Panel 7: BMS-986141<br>Single dose by mouth as specified | Drug: BMS-986141<br> <br> |
| Experimental: Part A Panel 8: BMS-986141<br>Single dose by mouth as specified | Drug: BMS-986141<br> <br> |
| Experimental: Part B Panel 1: BMS-986141 or Placebo<br>BMS-986141 or Placebo by mouth as specified | Drug: BMS-986141<br> <br> Drug: Placebo<br> <br> |
| Experimental: Part B Panel 2: BMS-986141 or Placebo<br>BMS-986141 or Placebo by mouth as specified | Drug: BMS-986141<br> <br> Drug: Placebo<br> <br> |
| Experimental: Part B Panel 3: BMS-986141 or Placebo<br>BMS-986141 or Placebo by mouth as specified | Drug: BMS-986141<br> <br> Drug: Placebo<br> <br> |
| Experimental: Part C Panel 1: BMS-986141 or Placebo<br>BMS-986141 or Placebo by mouth as specified | Drug: BMS-986141<br> <br> Drug: Placebo<br> <br> |
| Experimental: Part C Panel 2: BMS-986141 or Placebo<br>BMS-986141 or Placebo by mouth as specified | Drug: BMS-986141<br> <br> Drug: Placebo<br> <br> |
| Experimental: Part C Panel 3: BMS-986141 or Placebo<br>BMS-986141 or Placebo by mouth as specified | Drug: BMS-986141<br> <br> Drug: Placebo<br> <br> |
| Experimental: Part D Panel 1: BMS-986141 and Aspirin<br>BMS-986141 and Aspirin by mouth as specified | Drug: BMS-986141<br> <br> Drug: Aspirin<br> <br> |
| Placebo Comparator: Part D Panel 1: Placebo matching BMS-986141 and Aspirin<br>BMS-986141 placebo and Aspirin by mouth as specified | Drug: Placebo<br> <br> Drug: Aspirin<br> <br> |
| Experimental: Part E Panel 1: BMS-986141 and Itraconazole<br>BMS-986141 and Itraconazole by mouth as specified | Drug: BMS-986141<br> <br> Drug: Itraconazole<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | Serious adverse event (SAE) Adverse event (AE) Electrocardiogram (ECG) | 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 |  | 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 | 
| 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 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| 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 | 
| Half-life (T-HALF) of BMS-986141, BMT-162853, BMT-162856, and BMT-181551 |  | Up to Day 14 | 
| 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 | 
| 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 | 
| 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_Cmax of BMT-162853, BMT-162856, and BMT-181551 | Ratio of metabolite Cmax to parent Cmax, corrected for molecular weight (MR_Cmax) | Up to Day 14 | 
| MR_AUC(INF) of BMT-162853, BMT-162856, and BMT-181551 | Ratio of metabolite AUC(INF) to parent AUC(INF), corrected for molecular weight [MR_AUC(INF)] | Up to Day 14 | 
| MR_AUC(0-T) of BMT-162853, BMT-162856, and BMT-181551 | Ratio of metabolite AUC(0-T) to parent AUC(0-T), corrected for molecular weight [MR_AUC(0-T)] | Up to Day 14 | 
| MR_AUC(TAU) of BMT-162853, BMT-162856, and BMT-181551 | Ratio of metabolite AUC(TAU) to parent AUC(TAU), corrected for molecular weight [MR_AUC(TAU)] | Up to Day 14 | 
| Safety of multiple doses of BMS-986141 and aspirin in healthy subjects | 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 | 
| Tolerability of multiple doses of BMS-986141 and aspirin in healthy subjects | 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 | 
| Safety of BMS-986141 and itraconazole in healthy subjects | 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 | 
| Tolerability of BMS-986141 and itraconazole in healthy subjects | 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 |