A Study of BMS-986224 in Healthy Subjects and Heart Failure Patients With Reduced Ejection Fraction
- Conditions
- Heart Failure
- Interventions
- Drug: PlaceboDrug: BMS-986224
- Registration Number
- NCT03281122
- Lead Sponsor
- Bristol-Myers Squibb
- 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
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 199
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
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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Arm A BMS-986224 Specified dose on specified days Arm B Placebo Specified dose on specified days Arm B BMS-986224 Specified dose on specified days Arm A Placebo Specified dose on specified days
- Primary Outcome Measures
Name Time Method Number of Adverse Events (AEs) Up to one month Number of Serious Adverse Events (SAEs) Up to one month Number of deaths Up to one month
- Secondary Outcome Measures
Name Time Method Terminal elimination half-life (T-HALF) Up to one month Ratio of Metabolite AUC(INF) to Parent AUC(INF), corrected for molecular weight Up to one month Maximum observed plasma concentration (Cmax) Up to one month Time of maximum observed plasma concentration (Tmax) Up to one month Accumulation ratio: ratio of AUC(TAU) following last dose to AUC(TAU) following first dose (ARtau) 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 Cumulative urinary excretion (of the unchanged drug) [Aet] Up to one month Ratio of Metabolite AUC(TAU) to Parent AUC(TAU), corrected for molecular weight [MR_AUC(TAU)] Up to one month Area under the plasma concentration-time curve from time zero extrapoloated [AUC(INF)] 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 Renal clearance (CLr) 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 Terminal elimination rate constant (kel) 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 Drug-drug interaction (DDI) assessment 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 Area under the plasma concentration-time curve from time zero to time of last quantifiable concentration [AUC(0-T)] Up to one month
Trial Locations
- Locations (18)
Vseobecna Fakultni Nemocnice v Praze
🇨🇿Praha 2, Czechia
Krajska zdravotni - Masarykova nemocnice v Usti nad Labem
🇨🇿Usti nad Labem, Czechia
Hospital Universitario Ramon Y Cajal
🇪🇸Madrid, Spain
4th Wojskowy Szpital Kliniczny z Poliklinika Samodzielny Publiczny Zaklad Opieki Zdrowotnej
🇵🇱Wroclaw, Poland
Hospital Universitario Fundacion Jimenez Diaz
🇪🇸Madrid, Spain
Complejo Hospitalario Universitario de Santiago
🇪🇸Santiago de Compostela, Spain
Hospital Clinico Universitario de Valencia
🇪🇸Valencia, Spain
University Hospitals Birmingham NHS Foundation Trust
🇬🇧Birmingham, United Kingdom
NHS Tayside
🇬🇧Dundee, United Kingdom
Richmond Pharmacology
🇬🇧London, United Kingdom
Spaarne Gasthuis - Haarlem-Zuid
🇳🇱Haarlem, Netherlands
Deventer Ziekenhuis
🇳🇱Deventer, Netherlands
Samodzielny Publiczny Szpital Kliniczny Number 4 w Lublinie
🇵🇱Lublin, Poland
The University of Edinburgh
🇬🇧Edinburgh, United Kingdom
PRA Health Sciences - Groningen
🇳🇱Groningen, Netherlands
D & A Research and Genetics
🇳🇱Sneek, Netherlands
Universitair Medisch Centrum Groningen
🇳🇱Groningen, Netherlands
Hospital Alvaro Cunqueiro
🇪🇸Vigo, Spain