Heart Failure
Conditions
Brief summary
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
Interventions
DRUGPlacebo
Specified dose on specified days
DRUGBMS-986224
Specified dose on specified days
Sponsors
Bristol-Myers Squibb
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
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/
Design outcomes
Primary
| Measure | 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
| Measure | Time frame |
|---|---|
| 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 |
| 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 |
| 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 |
| Apparent volume of distribution at terminal phase (Vz/F) | 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 |
| 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 |
| Area under the plasma concentration-time curve from time zero to time of last quantifiable concentration [AUC(0-T)] | 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 |
Countries
Czechia, Netherlands, Poland, Spain, United Kingdom
Outcome results
None listed