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

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

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.

Study Overview

• Status: Completed
• Conditions: Thrombosis
• Intervention / Treatment: Drug: Placebo; Drug: Aspirin; Drug: Itraconazole; Drug: BMS-986141

Detailed Description

Maximum Age:

Part A SAD 65 years

Part B MAD 75 years

Part C MAD Japanese 75 years

• Study Type: Interventional
• Enrollment (Actual): 148
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Cypress, California, United States, 90630
      • West Coast Clinical Trials, Llc
  • Texas
    • Austin, Texas, United States, 78744
      • PPD Development, LP

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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, drugs as specified in protocol
2. Other protocol-defined exclusion criteria could apply

Study Plan

How is the study designed?

Design Details

• Primary Purpose: BASIC_SCIENCE
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

17

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Bristol-Myers Squibb

Publications and helpful links

Helpful Links

• BMS clinical trial educational resource

Study record dates

Study Major Dates

• Study Start: September 1, 2014
• Primary Completion (ACTUAL): September 1, 2015
• Study Completion (ACTUAL): September 1, 2015

Study Registration Dates

• First Submitted: January 14, 2015
• First Submitted That Met QC Criteria: January 14, 2015
• First Posted (ESTIMATE): January 19, 2015

Study Record Updates

• Last Update Posted (ACTUAL): March 31, 2017
• Last Update Submitted That Met QC Criteria: March 29, 2017
• Last Verified: September 1, 2015

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Embolism and Thrombosis; Thrombosis; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; 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; Hormones, Hormone Substitutes, and Hormone Antagonists; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; Hormone Antagonists; Antifungal Agents; Steroid Synthesis Inhibitors; 14-alpha Demethylase Inhibitors; Aspirin; Itraconazole
• Other Study ID Numbers: CV006-003