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

Heart Failure Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03281122
• Other study ID #: CV016-007
• Status: Terminated
• Phase: Phase 1
• Start date: September 22, 2017
• Est. completion date: April 17, 2019

Study information

• Verified date: February 2021
• Source: Bristol-Myers Squibb
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 199
• Est. completion date: April 17, 2019
• Est. primary completion date: April 17, 2019
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 55 Years

Eligibility

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

Related Conditions & MeSH terms

• Heart Failure

Intervention

Drug:
• Placebo
Specified dose on specified days
• BMS-986224
Specified dose on specified days

Locations

Country	Name	City	State
Czechia	Vseobecna Fakultni Nemocnice v Praze	Praha 2
Czechia	Krajska zdravotni - Masarykova nemocnice v Usti nad Labem	Usti nad Labem
Netherlands	Deventer Ziekenhuis	Deventer
Netherlands	PRA Health Sciences - Groningen	Groningen
Netherlands	Universitair Medisch Centrum Groningen	Groningen
Netherlands	Spaarne Gasthuis - Haarlem-Zuid	Haarlem
Netherlands	D & A Research and Genetics	Sneek
Poland	Samodzielny Publiczny Szpital Kliniczny Number 4 w Lublinie	Lublin
Poland	4th Wojskowy Szpital Kliniczny z Poliklinika Samodzielny Publiczny Zaklad Opieki Zdrowotnej	Wroclaw
Spain	Hospital Universitario Fundacion Jimenez Diaz	Madrid
Spain	Hospital Universitario Ramon Y Cajal	Madrid
Spain	Complejo Hospitalario Universitario de Santiago	Santiago de Compostela
Spain	Hospital Clinico Universitario de Valencia	Valencia
Spain	Hospital Alvaro Cunqueiro	Vigo
United Kingdom	University Hospitals Birmingham NHS Foundation Trust	Birmingham
United Kingdom	NHS Tayside	Dundee
United Kingdom	The University of Edinburgh	Edinburgh
United Kingdom	Richmond Pharmacology	London

Sponsors (1)

Lead Sponsor	Collaborator
Bristol-Myers Squibb

Countries where clinical trial is conducted

Czechia,  Netherlands,  Poland,  Spain,  United Kingdom, 

Outcome

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

External Links

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