A Study of BMS-986224 in Healthy Subjects and Heart Failure Patients With Reduced Ejection Fraction

Study Overview
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Brief Summary
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The purpose of this study is test the safety and tolerability of BMS-986224 and its effects on the body in healthy subjects and subjects with chronic heart failure with reduced ejection fraction

Official Title
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A Randomized, Double-Blinded, Placebo-Controlled, Single and Multiple Ascending Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of BMS-986224 in Healthy Subjects and Chronic Heart Failure Patients With Reduced Ejection Fraction

Conditions
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Heart Failure

Intervention / Treatment
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* Drug: Placebo
* Drug: BMS-986224


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: Healthy Subjects (Part A and B) Healthy subjects, as determined by no clinically significant deviations in medical history, physical examination, ECGs, vital signs, and clinical laboratory determinations Subjects must be willing and able to complete all study-specific procedures and visits Additional criterion for Japanese subjects in Groups BJ1 to BJ3: Subjects must be first generation Japanese (born in Japan and not living outside of Japan for > 10 years, and both parents are ethnically Japanese) Heart Failure Patients (Part C) Left ventricular EF <45% and >25%, as assessed by cardiac MRI within 3 months of first dose of study drug; or left ventricular EF <40% and >25% as assessed by echocardiogram at Screening or within 3 months of first dose of study drug; left ventricular EF Heart failure is considered to be stable at the discretion of the Investigator (i.e., no acute cardiovascular [CV] events or hospitalization (including emergency room visits) for CV causes within 3 months of first dose of study drug Regular sinus rhythm at Screening and no history of atrial fibrillation in the past 12 months Exclusion Criteria: Healthy Subjects (Part A and B) Major surgery within 4 weeks of (first) study treatment administration Inability to be venipunctured and/or tolerate venous access Subjects who have smoked or used smoking cessation or nicotine containing products (including, but not limited, to e-cigarettes, pipes, cigars, chewing tobacco, nicotine patches, nicotine lozenges, or nicotine gum, varenicline, bupropion) within 6 months of the first dose of study drug Heart Failure Patients (Part C) Current or recent (within 3 months of study treatment administration) gastrointestinal disease that could affect absorption Major surgery within 4 weeks of (first) study treatment administration Inability to be venipunctured and/or tolerate venous access Other protocol defined inclusion/exclusion criteria could 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: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm A<br>Specified dose on specified days | Drug: Placebo<br>* Specified dose on specified days<br>Drug: BMS-986224<br>* Specified dose on specified days<br>|
| Placebo Comparator: Arm B<br>Specified dose on specified days | Drug: Placebo<br>* Specified dose on specified days<br>Drug: BMS-986224<br>* Specified dose on specified days<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Serious Adverse Events (SAEs) |  | Up to one month | 
| Number of Adverse Events (AEs) |  | Up to one month | 
| Number of deaths |  | Up to one month | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum observed plasma concentration (Cmax) |  | Up to one month | 
| Time of maximum observed plasma concentration (Tmax) |  | Up to one month | 
| Terminal elimination half-life (T-HALF) |  | Up to one month | 
| Area under the plasma concentration-time curve from time zero to time of last quantifiable concentration [AUC(0-T)] |  | Up to one month | 
| Area under the plasma concentration-time curve from time zero extrapoloated [AUC(INF)] |  | Up to one month | 
| Area under the concentration-time curve in one dosing interval [AUC(TAU)] |  | Up to one month | 
| Accumulation ratio: ratio of Cmax following last dose to Cmax following first dose (ARcmax) |  | Up to one month | 
| Accumulation ratio: ratio of AUC(TAU) following last dose to AUC(TAU) following first dose (ARtau) |  | Up to one month | 
| Terminal elimination rate constant (kel) |  | Up to one month | 
| Apparent oral clearance, calculated as dose/AUC(INF) for single dose or dose/AUC(TAU) for multiple dose |  | Up to one month | 
| Apparent volume of distribution at terminal phase (Vz/F) |  | Up to one month | 
| Cumulative urinary excretion (of the unchanged drug) over one dosing interval [Ae(TAU)] |  | Up to one month | 
| Cumulative urinary excretion (of the unchanged drug) [Aet] |  | Up to one month | 
| Renal clearance (CLr) |  | Up to one month | 
| Amount excreted unchanged (%) [UR%] |  | Up to one month | 
| Ratio of Metabolite Cmax to Parent Cmax, corrected for molecular weight (MR_Cmax) |  | Up to one month | 
| Ratio of Metabolite AUC(INF) to Parent AUC(INF), corrected for molecular weight |  | Up to one month | 
| Ratio of Metabolite AUC(0-T) to Parent AUC(0-T), corrected for molecular weight [MR_AUC(0-T)] |  | Up to one month | 
| Ratio of Metabolite AUC(TAU) to Parent AUC(TAU), corrected for molecular weight [MR_AUC(TAU)] |  | Up to one month | 
| Drug-drug interaction (DDI) assessment |  | Up to one month |