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

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

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

Study Overview

• Status: Terminated
• Conditions: Heart Failure
• Intervention / Treatment: Drug: Placebo; Drug: BMS-986224

• Study Type: Interventional
• Enrollment (Actual): 199
• Phase: Phase 1

Contacts and Locations

Study Locations

• Czechia
  • Praha 2, Czechia, 12808
    • Vseobecna fakultni nemocnice v Praze
  • Usti nad Labem, Czechia, 401 13
    • Krajska zdravotni - Masarykova nemocnice v Usti nad Labem
• Netherlands
  • Deventer, Netherlands, 7416 SE
    • Deventer Ziekenhuis
  • Groningen, Netherlands, 9713 GZ
    • Universitair Medisch Centrum Groningen
  • Groningen, Netherlands, 9728 NZ
    • PRA Health Sciences - Groningen
  • Haarlem, Netherlands, 2035 RC
    • Spaarne Gasthuis - Haarlem-Zuid
  • Sneek, Netherlands, 8601 ZR
    • D & A Research and Genetics
• Poland
  • Lublin, Poland, 20-954
    • Samodzielny Publiczny Szpital Kliniczny Number 4 w Lublinie
  • Wroclaw, Poland, 50-981
    • 4th Wojskowy Szpital Kliniczny z Poliklinika Samodzielny Publiczny Zaklad Opieki Zdrowotnej
• Spain
  • Madrid, Spain, 28034
    • Hospital Universitario Ramón y Cajal
  • Madrid, Spain, 28040
    • Hospital Universitario Fundacion Jimenez Diaz
  • Santiago de Compostela, Spain, 15706
    • Complejo Hospitalario Universitario de Santiago
  • Valencia, Spain, 46010
    • Hospital Clinico Universitario de Valencia
  • Vigo, Spain, 36312
    • Hospital Álvaro Cunqueiro
• United Kingdom
  • Birmingham, United Kingdom, B15 2TH
    • University Hospitals Birmingham NHS Foundation Trust
  • Dundee, United Kingdom, DD1 9SY
    • NHS Tayside
  • Edinburgh, United Kingdom, EH16 4SB
    • The University of Edinburgh
  • London, United Kingdom
    • Richmond Pharmacology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm A; Specified dose on specified days	Drug: Placebo; Specified dose on specified days; Drug: BMS-986224; Specified dose on specified days
Placebo Comparator: Arm B; Specified dose on specified days	Drug: Placebo; Specified dose on specified days; Drug: BMS-986224; Specified dose on specified days

What is the study measuring?

Primary Outcome Measures

Outcome 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 Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: Bristol-Myers Squibb

Publications and helpful links

Helpful Links

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

Study record dates

Study Major Dates

• Study Start (Actual): September 22, 2017
• Primary Completion (Actual): April 17, 2019
• Study Completion (Actual): April 17, 2019

Study Registration Dates

• First Submitted: September 11, 2017
• First Submitted That Met QC Criteria: September 11, 2017
• First Posted (Actual): September 13, 2017

Study Record Updates

• Last Update Posted (Actual): February 25, 2021
• Last Update Submitted That Met QC Criteria: February 24, 2021
• Last Verified: February 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Heart Failure
• Other Study ID Numbers: CV016-007

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes