A Study to Assess Administration of an Oral Anti-thrombotic With Antiplatelet Therapy in Healthy Subjects

Study Overview
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Brief Summary
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This study will investigate the safety and interaction of BMS-986177 in healthy volunteers, when administered with Aspirin and/or Clopidogrel

Official Title
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A Randomized, Cross-over Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of BMS-986177 (an Oral Antithrombotic) With Single and Dual Antiplatelet Therapy (Aspirin and Clopidogrel) in Healthy Participants

Conditions
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Healthy Volunteers

Intervention / Treatment
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* Drug: BMS-986177
* Other: Placebo (for BMS-986177)
* Drug: Clopidogrel
* Drug: Aspirin


Participation Criteria
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Eligibility Criteria
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For more information regarding Bristol-Myers Squibb Clinical Trial participation, please visit www.BMSStudyConnect.com Inclusion Criteria: Must have a Body Mass Index (BMI) of 18.0 to 32.0 kg/m2, inclusive. Must have a normal renal function at screening as evidenced by an estimated glomerular filtration rate (GFR) of > 80 mL/min/1.73 m2 calculated with the Chronic Kidney Disease Epidemiology Collaboration formula and the absence of protein in the urine For Parts 1 and 2: • Must be a clopidogrel responder (eg, a decrease in platelet aggregation of at least 30% after a single 600-mg dose of clopidogrel compared with baseline). Exclusion Criteria: Any significant acute or chronic medical illness, including tinnitus or any other condition listed as a contraindication in the aspirin package insert. History of dizziness and/or recurrent headaches (i.e. daily headaches lasting for 1 week's duration in the last month prior to study treatment administration). History of head injury in the last 2 years, including participants with base skull fractures, intracranial tumor, or aneurysm. History of gastroesophageal reflux disease, dyspepsia (indigestion), protracted nausea, or chronic diarrhea (defined as 3 or 4 loose stools per day that last for ≥ 4 weeks) within the past 6 months. Other protocol-defined inclusion/exclusion criteria apply.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 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: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BMS-986177 + Aspirin + Clopidogrel (Part 1)<br>BMS-986177 200 mg capsule twice daily (days 1-5) + Aspirin 325 mg tablet once daily (days 1-5) + Clopidogrel 300 mg tablet once daily (day 1) then 75 mg tablet once daily (days 2-5) | Drug: BMS-986177<br>* BMS-986177 capsule<br>Drug: Clopidogrel<br>* Clopidogrel tablet<br>Drug: Aspirin<br>* Aspirin tablet<br>|
| Experimental: BMS-986177 (Part 1)<br>BMS-986177 200 mg capsule twice daily (days 1-5) | Drug: BMS-986177<br>* BMS-986177 capsule<br>|
| Placebo Comparator: BMS-986177 placebo + Aspirin + Clopidogrel (Part 1)<br>BMS-986177 placebo match capsule twice daily (days 1-5) + Aspirin 325 mg tablet once daily (days 1-5) + Clopidogrel 300 mg once daily (day 1) then 75 mg tablet once daily (days 2-5) | Other: Placebo (for BMS-986177)<br>* BMS-986177 placebo match capsule<br>Drug: Clopidogrel<br>* Clopidogrel tablet<br>Drug: Aspirin<br>* Aspirin tablet<br>|
| Experimental: BMS-986177 (Part 2)<br>BMS-986177 200 mg capsule twice daily (days 1-5) | Drug: BMS-986177<br>* BMS-986177 capsule<br>|
| Placebo Comparator: BMS-986177 placebo + Clopidogrel (Part 2)<br>BMS-986177 placebo match capsule twice daily (days 1-5) + Clopidogrel 300 mg tablet once daily (day 1) then 75 mg tablet once daily (days 2-5) | Other: Placebo (for BMS-986177)<br>* BMS-986177 placebo match capsule<br>Drug: Clopidogrel<br>* Clopidogrel tablet<br>|
| Experimental: BMS-986177 + Clopidogrel (Part 2)<br>BMS-986177 200 mg capsule twice daily (days 1-5) + Clopidogrel 300 mg tablet once daily (day 1) then 75 mg tablet once daily (days 2-5) | Drug: BMS-986177<br>* BMS-986177 capsule<br>Drug: Clopidogrel<br>* Clopidogrel tablet<br>|
| Experimental: BMS-986177 (Part 3)<br>BMS-986177 200 mg capsule twice daily (days 1-5) | Drug: BMS-986177<br>* BMS-986177 capsule<br>|
| Placebo Comparator: BMS-986177 placebo + Aspirin (Part 3)<br>BMS-986177 placebo match capsule twice daily (days 1-5) + Aspirin 325 mg tablet once daily (days 1-5) | Other: Placebo (for BMS-986177)<br>* BMS-986177 placebo match capsule<br>Drug: Aspirin<br>* Aspirin tablet<br>|
| Experimental: BMS-986177 + Aspirin (Part 3)<br>BMS-986177 200 mg capsule twice daily (days 1-5) + Aspirin 325 mg tablet once daily (days 1-5) | Drug: BMS-986177<br>* BMS-986177 capsule<br>Drug: Aspirin<br>* Aspirin tablet<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Adverse Events (AEs) |  | Up to Day 33 | 
| Incidence of Serious Adverse Events (SAEs) |  | Up to Day 95 | 
| Incidence of Adverse Events (AEs) leading to discontinuation |  | Up to Day 33 | 
| Number of participants with vital sign abnormalities |  | Up to Day 33 | 
| Number of participants with 12-lead electrocardiogram (ECG) abnormalities |  | Up to Day 33 | 
| Number of participants with clinical laboratory abnormalities |  | Up to Day 33 | 
| Number of participants with physical examination abnormalities |  | Up to Day 33 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum observed plasma concentration (Cmax) | Cmax of BMS-986177, acetylsalicylic acid, salicylic acid, clopidogrel and clopidogrel metabolite | Up to Day 33 | 
| Area under the plasma concentration time curve in one dosing interval [AUC(TAU)] | AUC(TAU) of BMS-986177, acetylsalicylic acid, salicylic acid, clopidogrel and clopidogrel metabolite | Up to Day 33 | 
| Time of maximum observed concentration (Tmax) | Tmax of BMS-986177, acetylsalicylic acid, salicylic acid, clopidogrel and clopidogrel metabolite | Up to Day 33 | 
| Terminal plasma half-life (T-HALF) | T-Half of BMS-986177, acetylsalicylic acid, salicylic acid, clopidogrel and clopidogrel metabolite | Up to Day 33 | 
| Trough observed plasma concentration (Ctrough) | Ctrough of BMS-986177, acetylsalicylic acid, salicylic acid, clopidogrel and clopidogrel metabolite | Up to Day 26 | 
| Apparent total body clearance (CLT/F) | CLT/F of BMS-986177, aspirin, clopidogrel | Up to Day 33 | 
| Volume of distribution (Vz/F) | Vz/F of BMS-986177, aspirin, clopidogrel | Up to Day 33 |