Heart FailurePhase 1NCT03281122
A Study of BMS-986224 in Healthy Subjects and Heart Failure Patients With Reduced Ejection Fraction
A Phase 1 study testing BMS-986224 in people with Heart Failure, run by Bristol-Myers Squibb at 18 sites in 5 countries.
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 Read more about this study
- Who is it for?
- Ages 18 to 55 yearsHealthy volunteers can take part
- Conditions the study is for
- Heart Failure
- What is being tested?
- BMS-986224
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 199 participants
- Where
- 18 sitesin 5 countries
- Study dates
- 22 Sep 2017to 17 Apr 2019
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 55 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 9Show fewer
- 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
Trial locations and contacts
18 sites in 5 countries.
18 sites in 5 countries
Netherlands5 sites
Deventer Ziekenhuis
Deventer, 7416 SE
Universitair Medisch Centrum Groningen
Groningen, 9713 GZ
PRA Health Sciences - Groningen
Groningen, 9728 NZ
Spaarne Gasthuis - Haarlem-Zuid
Haarlem, 2035 RC
D & A Research and Genetics
Sneek, 8601 ZR
Spain5 sites
Hospital Universitario Ramon Y Cajal
Madrid, 28034
Hospital Universitario Fundacion Jimenez Diaz
Madrid, 28040
Complejo Hospitalario Universitario de Santiago
Santiago de Compostela, 15706
Hospital Clinico Universitario de Valencia
Valencia, 46010
Hospital Alvaro Cunqueiro
Vigo, 36312
United Kingdom4 sites
University Hospitals Birmingham NHS Foundation Trust
Birmingham, B15 2TH
NHS Tayside
Dundee, DD1 9SY
The University of Edinburgh
Edinburgh, EH16 4SB
Richmond Pharmacology
London
Czechia2 sites
Vseobecna Fakultni Nemocnice v Praze
Prague, 12808
Krajska zdravotni - Masarykova nemocnice v Usti nad Labem
Ústí nad Labem, 401 13
Poland2 sites
Samodzielny Publiczny Szpital Kliniczny Number 4 w Lublinie
Lublin, 20-954
4th Wojskowy Szpital Kliniczny z Poliklinika Samodzielny Publiczny Zaklad Opieki Zdrowotnej
Wroclaw, 50-981
About this study
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
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
- Conditions
- Heart Failure
- Being tested
- Placebo, BMS-986224
- Medical subject headings
- Heart Failure
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PlaceboDrug
Specified dose on specified days
BMS-986224Drug
Specified dose on specified days
| Study group | Role | What they receive |
|---|---|---|
| Arm A | Experimental | Specified dose on specified days Receives: Drug: Placebo; Drug: BMS-986224 |
| Arm B | Placebo comparator | Specified dose on specified days Receives: Drug: Placebo; Drug: BMS-986224 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Serious Adverse Events (SAEs)
Measured: Up to one month
Number of Adverse Events (AEs)
Measured: Up to one month
Number of deaths
Measured: Up to one month
Secondary outcomes (20)
Maximum observed plasma concentration (Cmax)
Measured: Up to one month
Time of maximum observed plasma concentration (Tmax)
Measured: Up to one month
Terminal elimination half-life (T-HALF)
Measured: Up to one month
Area under the plasma concentration-time curve from time zero to time of last quantifiable concentration [AUC(0-T)]
Measured: Up to one month
Area under the plasma concentration-time curve from time zero extrapoloated [AUC(INF)]
Measured: Up to one month
Area under the concentration-time curve in one dosing interval [AUC(TAU)]
Measured: Up to one month
Accumulation ratio: ratio of Cmax following last dose to Cmax following first dose (ARcmax)
Measured: Up to one month
Accumulation ratio: ratio of AUC(TAU) following last dose to AUC(TAU) following first dose (ARtau)
Measured: Up to one month
Terminal elimination rate constant (kel)
Measured: Up to one month
Apparent oral clearance, calculated as dose/AUC(INF) for single dose or dose/AUC(TAU) for multiple dose
Measured: Up to one month
Apparent volume of distribution at terminal phase (Vz/F)
Measured: Up to one month
Cumulative urinary excretion (of the unchanged drug) over one dosing interval [Ae(TAU)]
Measured: Up to one month
Cumulative urinary excretion (of the unchanged drug) [Aet]
Measured: Up to one month
Renal clearance (CLr)
Measured: Up to one month
Amount excreted unchanged (%) [UR%]
Measured: Up to one month
Ratio of Metabolite Cmax to Parent Cmax, corrected for molecular weight (MR_Cmax)
Measured: Up to one month
Ratio of Metabolite AUC(INF) to Parent AUC(INF), corrected for molecular weight
Measured: Up to one month
Ratio of Metabolite AUC(0-T) to Parent AUC(0-T), corrected for molecular weight [MR_AUC(0-T)]
Measured: Up to one month
Ratio of Metabolite AUC(TAU) to Parent AUC(TAU), corrected for molecular weight [MR_AUC(TAU)]
Measured: Up to one month
Drug-drug interaction (DDI) assessment
Measured: Up to one month
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Sep 2017
- Study start22 Sep 2017
- Primary completion17 Apr 2019
- Study completion17 Apr 2019
Why it stopped: Business objectives have changed
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Heart FailureStudies of the same condition, open and under way.
- More trials run by Bristol-Myers SquibbThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 199 participants (actual)
Sponsor and investigators
- Lead sponsor
- Bristol-Myers Squibb
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Bristol-Myers Squibb, Study director, Bristol-Myers Squibb
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03281122
- Sponsor's protocol ID
- CV016-007
- Status last verified
- Feb 2021
- First submitted
- 11 Sep 2017
- Last updated
- 25 Feb 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 25 Feb 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT03281122
- Acronym / sponsor ID
- CV016-007
- Conditions
- Heart Failure
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Business objectives have changed
- Enrolment
- 199 participants (actual)
- Lead sponsor
- Bristol-Myers SquibbIndustry (pharma, biotech, devices)
- Study start
- 22 Sep 2017 (actual)
- Primary completion
- 17 Apr 2019 (actual)
- Study completion
- 17 Apr 2019 (actual)
- First posted
- 13 Sep 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Arm A | Experimental | Drug: Placebo, Drug: BMS-986224Specified dose on specified days |
| Arm B | Placebo comparator | Drug: Placebo, Drug: BMS-986224Specified dose on specified days |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (8 listed)
- 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)
Key exclusion criteria (9 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PlaceboSpecified dose on specified days | Drug | Arm A, Arm B |
| BMS-986224Specified dose on specified days | Drug | Arm A, Arm B |
Primary outcome
Number of Serious Adverse Events (SAEs)
Time frame: Up to one month
Number of Adverse Events (AEs)
Time frame: Up to one month
Number of deaths
Time frame: Up to one month
20 secondary outcomes
Maximum observed plasma concentration (Cmax)
Time frame: Up to one month
Time of maximum observed plasma concentration (Tmax)
Time frame: Up to one month
Terminal elimination half-life (T-HALF)
Time frame: Up to one month
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
Area under the plasma concentration-time curve from time zero extrapoloated [AUC(INF)]
Time frame: Up to one month
Area under the concentration-time curve in one dosing interval [AUC(TAU)]
Time frame: Up to one month
Accumulation ratio: ratio of Cmax following last dose to Cmax following first dose (ARcmax)
Time frame: Up to one month
Accumulation ratio: ratio of AUC(TAU) following last dose to AUC(TAU) following first dose (ARtau)
Time frame: Up to one month
Terminal elimination rate constant (kel)
Time frame: Up to one month
Apparent oral clearance, calculated as dose/AUC(INF) for single dose or dose/AUC(TAU) for multiple dose
Time frame: Up to one month
Apparent volume of distribution at terminal phase (Vz/F)
Time frame: Up to one month
Cumulative urinary excretion (of the unchanged drug) over one dosing interval [Ae(TAU)]
Time frame: Up to one month
Cumulative urinary excretion (of the unchanged drug) [Aet]
Time frame: Up to one month
Renal clearance (CLr)
Time frame: Up to one month
Amount excreted unchanged (%) [UR%]
Time frame: Up to one month
Ratio of Metabolite Cmax to Parent Cmax, corrected for molecular weight (MR_Cmax)
Time frame: Up to one month
Ratio of Metabolite AUC(INF) to Parent AUC(INF), corrected for molecular weight
Time frame: Up to one month
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
Ratio of Metabolite AUC(TAU) to Parent AUC(TAU), corrected for molecular weight [MR_AUC(TAU)]
Time frame: Up to one month
Drug-drug interaction (DDI) assessment
Time frame: Up to one month
Results and safety
The study was stopped early (reason given: Business objectives have changed). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Feb 2021.
- BMS Clinical Trial InformationLink provided by the sponsor.
- BMS Clinical Trial Patient RecruitingLink provided by the sponsor.
- FDA Safety Alerts and RecallsLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Bristol-Myers Squibb study director
Bristol-Myers Squibb
18 sites in 5 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing BMS-986224 in people with Heart Failure, run by Bristol-Myers Squibb at 18 sites in 5 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 25 Feb 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 18 sites in Netherlands, Spain, United Kingdom, Czechia, Poland. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Business objectives have changed). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Serious Adverse Events (SAEs) (time frame: Up to one month). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Feb 2021.