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

Primary Purpose

Heart Failure

Status
Terminated
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
Placebo
BMS-986224
Sponsored by
Bristol-Myers Squibb
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional basic science trial for Heart Failure

Eligibility Criteria

18 Years - 55 Years (Adult)All SexesAccepts Healthy Volunteers

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

Sites / Locations

  • Vseobecna Fakultni Nemocnice v Praze
  • Krajska zdravotni - Masarykova nemocnice v Usti nad Labem
  • Deventer Ziekenhuis
  • Universitair Medisch Centrum Groningen
  • PRA Health Sciences - Groningen
  • Spaarne Gasthuis - Haarlem-Zuid
  • D & A Research and Genetics
  • Samodzielny Publiczny Szpital Kliniczny Number 4 w Lublinie
  • 4th Wojskowy Szpital Kliniczny z Poliklinika Samodzielny Publiczny Zaklad Opieki Zdrowotnej
  • Hospital Universitario Ramon Y Cajal
  • Hospital Universitario Fundacion Jimenez Diaz
  • Complejo Hospitalario Universitario de Santiago
  • Hospital Clinico Universitario de Valencia
  • Hospital Alvaro Cunqueiro
  • University Hospitals Birmingham NHS Foundation Trust
  • NHS Tayside
  • The University of Edinburgh
  • Richmond Pharmacology

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Arm A

Arm B

Arm Description

Specified dose on specified days

Specified dose on specified days

Outcomes

Primary Outcome Measures

Number of Serious Adverse Events (SAEs)
Number of Adverse Events (AEs)
Number of deaths

Secondary Outcome Measures

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

Full Information

First Posted
September 11, 2017
Last Updated
February 24, 2021
Sponsor
Bristol-Myers Squibb
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1. Study Identification

Unique Protocol Identification Number
NCT03281122
Brief Title
A Study of BMS-986224 in Healthy Subjects and Heart Failure Patients With Reduced Ejection Fraction
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
Study Type
Interventional

2. Study Status

Record Verification Date
February 2021
Overall Recruitment Status
Terminated
Why Stopped
Business objectives have changed
Study Start Date
September 22, 2017 (Actual)
Primary Completion Date
April 17, 2019 (Actual)
Study Completion Date
April 17, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Bristol-Myers Squibb

4. Oversight

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
Data Monitoring Committee
No

5. Study Description

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Heart Failure

7. Study Design

Primary Purpose
Basic Science
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
199 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Arm A
Arm Type
Experimental
Arm Description
Specified dose on specified days
Arm Title
Arm B
Arm Type
Placebo Comparator
Arm Description
Specified dose on specified days
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Specified dose on specified days
Intervention Type
Drug
Intervention Name(s)
BMS-986224
Intervention Description
Specified dose on specified days
Primary Outcome Measure Information:
Title
Number of Serious Adverse Events (SAEs)
Time Frame
Up to one month
Title
Number of Adverse Events (AEs)
Time Frame
Up to one month
Title
Number of deaths
Time Frame
Up to one month
Secondary Outcome Measure Information:
Title
Maximum observed plasma concentration (Cmax)
Time Frame
Up to one month
Title
Time of maximum observed plasma concentration (Tmax)
Time Frame
Up to one month
Title
Terminal elimination half-life (T-HALF)
Time Frame
Up to one month
Title
Area under the plasma concentration-time curve from time zero to time of last quantifiable concentration [AUC(0-T)]
Time Frame
Up to one month
Title
Area under the plasma concentration-time curve from time zero extrapoloated [AUC(INF)]
Time Frame
Up to one month
Title
Area under the concentration-time curve in one dosing interval [AUC(TAU)]
Time Frame
Up to one month
Title
Accumulation ratio: ratio of Cmax following last dose to Cmax following first dose (ARcmax)
Time Frame
Up to one month
Title
Accumulation ratio: ratio of AUC(TAU) following last dose to AUC(TAU) following first dose (ARtau)
Time Frame
Up to one month
Title
Terminal elimination rate constant (kel)
Time Frame
Up to one month
Title
Apparent oral clearance, calculated as dose/AUC(INF) for single dose or dose/AUC(TAU) for multiple dose
Time Frame
Up to one month
Title
Apparent volume of distribution at terminal phase (Vz/F)
Time Frame
Up to one month
Title
Cumulative urinary excretion (of the unchanged drug) over one dosing interval [Ae(TAU)]
Time Frame
Up to one month
Title
Cumulative urinary excretion (of the unchanged drug) [Aet]
Time Frame
Up to one month
Title
Renal clearance (CLr)
Time Frame
Up to one month
Title
Amount excreted unchanged (%) [UR%]
Time Frame
Up to one month
Title
Ratio of Metabolite Cmax to Parent Cmax, corrected for molecular weight (MR_Cmax)
Time Frame
Up to one month
Title
Ratio of Metabolite AUC(INF) to Parent AUC(INF), corrected for molecular weight
Time Frame
Up to one month
Title
Ratio of Metabolite AUC(0-T) to Parent AUC(0-T), corrected for molecular weight [MR_AUC(0-T)]
Time Frame
Up to one month
Title
Ratio of Metabolite AUC(TAU) to Parent AUC(TAU), corrected for molecular weight [MR_AUC(TAU)]
Time Frame
Up to one month
Title
Drug-drug interaction (DDI) assessment
Time Frame
Up to one month

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
55 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility 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/exclusion criteria could apply
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Bristol-Myers Squibb
Organizational Affiliation
Bristol-Myers Squibb
Official's Role
Study Director
Facility Information:
Facility Name
Vseobecna Fakultni Nemocnice v Praze
City
Praha 2
ZIP/Postal Code
12808
Country
Czechia
Facility Name
Krajska zdravotni - Masarykova nemocnice v Usti nad Labem
City
Usti nad Labem
ZIP/Postal Code
401 13
Country
Czechia
Facility Name
Deventer Ziekenhuis
City
Deventer
ZIP/Postal Code
7416 SE
Country
Netherlands
Facility Name
Universitair Medisch Centrum Groningen
City
Groningen
ZIP/Postal Code
9713 GZ
Country
Netherlands
Facility Name
PRA Health Sciences - Groningen
City
Groningen
ZIP/Postal Code
9728 NZ
Country
Netherlands
Facility Name
Spaarne Gasthuis - Haarlem-Zuid
City
Haarlem
ZIP/Postal Code
2035 RC
Country
Netherlands
Facility Name
D & A Research and Genetics
City
Sneek
ZIP/Postal Code
8601 ZR
Country
Netherlands
Facility Name
Samodzielny Publiczny Szpital Kliniczny Number 4 w Lublinie
City
Lublin
ZIP/Postal Code
20-954
Country
Poland
Facility Name
4th Wojskowy Szpital Kliniczny z Poliklinika Samodzielny Publiczny Zaklad Opieki Zdrowotnej
City
Wroclaw
ZIP/Postal Code
50-981
Country
Poland
Facility Name
Hospital Universitario Ramon Y Cajal
City
Madrid
ZIP/Postal Code
28034
Country
Spain
Facility Name
Hospital Universitario Fundacion Jimenez Diaz
City
Madrid
ZIP/Postal Code
28040
Country
Spain
Facility Name
Complejo Hospitalario Universitario de Santiago
City
Santiago de Compostela
ZIP/Postal Code
15706
Country
Spain
Facility Name
Hospital Clinico Universitario de Valencia
City
Valencia
ZIP/Postal Code
46010
Country
Spain
Facility Name
Hospital Alvaro Cunqueiro
City
Vigo
ZIP/Postal Code
36312
Country
Spain
Facility Name
University Hospitals Birmingham NHS Foundation Trust
City
Birmingham
ZIP/Postal Code
B15 2TH
Country
United Kingdom
Facility Name
NHS Tayside
City
Dundee
ZIP/Postal Code
DD1 9SY
Country
United Kingdom
Facility Name
The University of Edinburgh
City
Edinburgh
ZIP/Postal Code
EH16 4SB
Country
United Kingdom
Facility Name
Richmond Pharmacology
City
London
Country
United Kingdom

12. IPD Sharing Statement

Links:
URL
https://www.bms.com/researchers-and-partners/clinical-trials-and-research.html
Description
BMS Clinical Trial Information
URL
https://www.bmsstudyconnect.com/s/US/English/USenHome
Description
BMS Clinical Trial Patient Recruiting
URL
https://www.fda.gov/Safety/MedWatch/SafetyInformation/default.htm
Description
FDA Safety Alerts and Recalls

Learn more about this trial

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

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