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

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

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

Study Overview

• Status: Completed
• Conditions: Healthy Volunteers
• Intervention / Treatment: Drug: BMS-986177; Drug: Clopidogrel; Drug: Aspirin; Other: Placebo (for BMS-986177)

• Study Type: Interventional
• Enrollment (Actual): 113
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Texas
    • Austin, Texas, United States, 78744
      • PPD Development, LP

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

9

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: BMS-986177 + Aspirin + Clopidogrel (Part 1); 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; BMS-986177 capsule; Drug: Clopidogrel; Clopidogrel tablet; Drug: Aspirin; Aspirin tablet
Experimental: BMS-986177 (Part 1); BMS-986177 200 mg capsule twice daily (days 1-5)	Drug: BMS-986177; BMS-986177 capsule
Placebo Comparator: BMS-986177 placebo + Aspirin + Clopidogrel (Part 1); 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)	Drug: Clopidogrel; Clopidogrel tablet; Drug: Aspirin; Aspirin tablet; Other: Placebo (for BMS-986177); BMS-986177 placebo match capsule
Experimental: BMS-986177 (Part 2); BMS-986177 200 mg capsule twice daily (days 1-5)	Drug: BMS-986177; BMS-986177 capsule
Placebo Comparator: BMS-986177 placebo + Clopidogrel (Part 2); 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)	Drug: Clopidogrel; Clopidogrel tablet; Other: Placebo (for BMS-986177); BMS-986177 placebo match capsule
Experimental: BMS-986177 + Clopidogrel (Part 2); 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; BMS-986177 capsule; Drug: Clopidogrel; Clopidogrel tablet
Experimental: BMS-986177 (Part 3); BMS-986177 200 mg capsule twice daily (days 1-5)	Drug: BMS-986177; BMS-986177 capsule
Placebo Comparator: BMS-986177 placebo + Aspirin (Part 3); BMS-986177 placebo match capsule twice daily (days 1-5) + Aspirin 325 mg tablet once daily (days 1-5)	Drug: Aspirin; Aspirin tablet; Other: Placebo (for BMS-986177); BMS-986177 placebo match capsule
Experimental: BMS-986177 + Aspirin (Part 3); BMS-986177 200 mg capsule twice daily (days 1-5) + Aspirin 325 mg tablet once daily (days 1-5)	Drug: BMS-986177; BMS-986177 capsule; Drug: Aspirin; Aspirin tablet

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: Bristol-Myers Squibb

Publications and helpful links

Helpful Links

• BMS Clinical Trial Information
• BMS Clinical Trial Patient Recruiting
• Investigator Inquiry Form
• FDA Safety Alerts and Recalls

Study record dates

Study Major Dates

• Study Start (Actual): October 4, 2018
• Primary Completion (Actual): February 19, 2019
• Study Completion (Actual): February 19, 2019

Study Registration Dates

• First Submitted: October 4, 2018
• First Submitted That Met QC Criteria: October 4, 2018
• First Posted (Actual): October 9, 2018

Study Record Updates

• Last Update Posted (Actual): September 29, 2021
• Last Update Submitted That Met QC Criteria: September 24, 2021
• Last Verified: September 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Fibrinolytic Agents; Fibrin Modulating Agents; Platelet Aggregation Inhibitors; Cyclooxygenase Inhibitors; Antipyretics; Purinergic P2Y Receptor Antagonists; Purinergic P2 Receptor Antagonists; Purinergic Antagonists; Purinergic Agents; Aspirin; Clopidogrel
• Other Study ID Numbers: CV010-034

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No