Heart FailurePhase 1NCT03891108
A Pharmacokinetics, Safety and Tolerability Study of Multiple Formulations of BMS-986231 in Healthy Participants
A Phase 1 study testing BMS-986231 Formulation A, BMS-986231 Formulation B and BMS-986231 Formulation C in people with Heart Failure, run by Bristol-Myers Squibb at 1 site in United States.
Trial summary
Main Objective of this study is to compare the single intravenous (IV) infusion pharmacokinetics (PK) of BMS-986231 and its metabolites (BMT-284730, BMT-279554, and CAR-000463) following of up to 2 test formulations of BMS-986231 relative to the reference formulation. Read more about this study
- Who is it for?
- Ages 18 to 40 yearsHealthy volunteers can take part
- Conditions the study is for
- Heart Failure
- What is being tested?
- BMS-986231 Formulation A, BMS-986231 Formulation B and BMS-986231 Formulation C
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 60 participants
- Where
- 1 siteUnited States
- Study dates
- 28 Feb 2019to 29 Jul 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 40 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Participants must be willing to participate in the study and sign the informed consent form (ICF).
- Participants must be willing and able to complete all study-specific procedures and visits.
- Healthy participant, as determined by no clinically significant deviation from normal in medical history, physical examination, ECGs, and clinical laboratory determinations in the opinion of the investigator.
- Body mass index of 18.0 to 32.0 kg/m2, inclusive, and body weight ≥ 45 kg and ≤ 110 kg, at screening.
- Heart rate > 45 bpm and < 95 bpm at screening or baseline (within 30 minutes prior to randomization).
- Systolic BP > 110 mmHg and < 140 mmHg at screening or baseline (within 30 minutes prior to randomization).
- Normal renal function at screening as evidenced by an estimated glomerular filtration rate > 80 mL/min/1.732 calculated with the Chronic Kidney Disease Epidemiology Collaboration formula.
- Males and females, ages 18 or local age of majority to 40 years, inclusive.
Who cannot join
- Any significant acute or chronic medical illness
- Diagnosis of fibromyalgia
- History of syncope, orthostatic instability, or recurrent dizziness
- History or family history of ocular disorders (eg, glaucoma)
- History of bleeding diathesis (unusual susceptibility to bleed [hemorrhage] mostly due to hypocoagulability)
- Personal history or strong family history of sudden cardiac death, myocardial infarction, or other heart disease considered to be clinically significant by the investigator
- Any major surgery within 4 weeks of study drug administration
- History of Gilbert's Syndrome
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Randomized, Open Label, Parallel Design, Single Continuous Intravenous Infusion Study of BMS-986231 to Assess the Pharmacokinetics, Safety and Tolerability of Multiple Formulations in Healthy Participants
Main Objective of this study is to compare the single intravenous (IV) infusion pharmacokinetics (PK) of BMS-986231 and its metabolites (BMT-284730, BMT-279554, and CAR-000463) following of up to 2 test formulations of BMS-986231 relative to the reference formulation.
Read the detailed description
Participants will be randomized 1:1:1:1 and dosed with either of the 4 treatments: A, B, C, or D; followed by review of safety and tolerability data during and after the infusion. The study will proceed with treatments A, and C unless one or more of these treatments shows poor tolerability; in which case the study may proceed with treatment B or D in the follow-up cohorts. Additional participants will be randomized equally to each of the treatments the study will proceed with.
- Conditions
- Heart Failure
- Being tested
- BMS-986231 Formulation A, BMS-986231 Formulation B, BMS-986231 Formulation C, BMS-986231 Formulation D
- Medical subject headings
- Heart Failure
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BMS-986231 Formulation ADrug
Participants will be administered BMS-986231 Formulation A as IV infusion for 48 hours.
BMS-986231 Formulation BDrug
Participants will be administered BMS-986231 Formulation B as IV infusion for 48 hours.
BMS-986231 Formulation CDrug
Participants will be administered BMS-986231 Formulation C as IV infusion for 48 hours.
BMS-986231 Formulation DDrug
Participants will be administered BMS-986231 Formulation D as IV infusion for 48 hours.
| Study group | Role | What they receive |
|---|---|---|
| Treatment A: BMS-986231 Formulation A | Active comparator | Participants will be administered Treatment A: BMS-986231 Formulation A as a 48-hour IV infusion on Day 1, followed by review of safety and tolerability data during and after the infusion. Receives: Drug: BMS-986231 Formulation A |
| Treatment B: BMS-986231 Formulation B | Experimental | Participants will be administered Treatment B: BMS-986231 Formulation B as a 48-hour IV infusion on Day 1, followed by review of safety and tolerability data during and after the infusion. Receives: Drug: BMS-986231 Formulation B |
| Treatment C: BMS-986231 Formulation C | Experimental | Participants will be administered Treatment C: BMS-986231 Formulation C as a 48-hour IV infusion on Day 1, followed by review of safety and tolerability data during and after the infusion. Receives: Drug: BMS-986231 Formulation C |
| Treatment D: BMS 986231 Formulation D | Experimental | Participants will be administered Treatment D: BMS 986231 Formulation D as a 48-hour IV infusion on Day 1, followed by review of safety and tolerability data during and after the infusion. Receives: Drug: BMS-986231 Formulation D |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum Plasma Concentration (Cmax) of BMS-986231 and its Metabolites (BMT-284730, BMT-279554, and CAR-000463)
Cmax is the maximum plasma concentration.
Measured: Day 1 to Day 5
Average Concentration Over a Dosing Interval (Css-av) of BMS-986231 and its Metabolites (BMT-284730, BMT-279554, and CAR-000463)
Css-av is defined as the average concentration over a dosing interval.
Measured: Day 1 to Day 5
Area Under the Plasma Concentration-Time Curve From Time 0 (Dosing) Extrapolated to Infinity (AUC(INF)) of BMS-986231 and its Metabolites (BMT-284730, BMT-279554, and CAR-000463)
AUC(INF) is defined as area under the plasma concentration-time curve from time 0 (dosing) extrapolated to infinity.
Measured: Day 1 to Day 5
Area Under the Concentration-Time Curve From Time 0 (Dosing) to the Time of the Last Quantifiable Concentration Observed (AUC(0-T)) of BMS-986231 and its Metabolites (BMT-284730, BMT-279554, and CAR-000463)
AUC(0-T) is defined as area under the concentration-time curve from time 0 (dosing) to the time of the last quantifiable concentration observed (T).
Measured: Day 1 to Day 5
Terminal Elimination Phase Half-Life (T-HALF) of BMS-986231 and its Metabolites (BMT-284730, BMT-279554, and CAR-000463)
T-HALF is terminal elimination phase half-life.
Measured: Day 1 to Day 5
Time to Reach Cmax in Plasma (Tmax) of BMS-986231 and its Metabolites (BMT-284730, BMT-279554, and CAR-000463)
Tmax is defined as time to reach Cmax in plasma.
Measured: Day 1 to Day 5
Metabolite to Parent Molar Ratio of AUC(INF) (MRAUC[INF]) and Metabolite to Parent Molar Ratio of Css-av (MRCssav) of Metabolites of BMS-986231 (BMT-284730, BMT-279554, and CAR-000463)
MRAUC(INF) is determined using AUC(INF) for metabolite / AUC(INF) for BMS-986231. MRCss-av is determined using Css-av for metabolite / Css-av for BMS-986231.
Measured: Day 1 to Day 5
Total Systemic Clearance (CLT) of BMS-986231
CLT is total systemic clearance.
Measured: Day 1 to Day 5
Apparent Volume of Distribution During the Terminal Phase (Vz) of BMS-986231
Vz is apparent volume of distribution during the terminal phase.
Measured: Day 1 to Day 5
Volume of Distribution at Steady State (Vss) of BMS-986231
Vss is volume of distribution at steady state.
Measured: Day 1 to Day 5
Secondary outcomes (6)
Number of Participants with Adverse Events (AEs)
An AE is defined as any new untoward medical occurrence or worsening of a preexisting medical condition in a clinical investigation participant administered study drug and that does not necessarily have a causal relationship with this treatment.
Measured: Day 1 up to Day 13
Number of Participants with Serious AEs (SAEs)
A SAE is any untoward medical occurrence that at any dose: results in death, is life-threatening, requires inpatient hospitalisation or prolongation of existing hospitalisation, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, or is an important medical event (defined as a medical event(s) that may not be immediately life threatening or result in death or hospitalization but, based upon appropriate medical and scientific judgment, may jeopardize the participant or may require intervention).
Measured: From signature of informed consent up to 30 days post last treatment
Number of Participants With Significant Changes in Clinical Laboratory Values
Serology (includes hepatitis C antibody, hepatitis B surface antigen, and human immunodeficiency virus [HIV]-1 and -2 antibody), Hematology and Serum Chemistry (includes C-reactive protein and fibrinogen), Follicle-Stimulating Hormone (FSH) on blood samples, and urinalysis will be performed as part of clinical lab tests.
Measured: Day 1 up to Day 13
Number of Participants with Significant Changes in Vital Signs
Vital signs include body temperature, respiratory rate, and semi-supine blood pressure, and heart rate.
Measured: Day 1 up to Day 13
Number of Participants with Significant Changes in Electrocardiograms (ECGs)
A reflex 12-lead ECG will be conducted to confirm any significant changes in ECGs.
Measured: Day 1 up to Day 13
Number of Participants with Significant Changes in Physical Examinations
The full physical examination will include general appearance, head, eyes, ears, nose, throat, neck, lungs, heart, abdomen, extremities, peripheral pulses, skin, and neurologic examination. Targeted physical exams will include general appearance, oral mucosa, heart, lungs, abdomen, and skin.
Measured: Day 1 up to Day 13
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Mar 2019
- Study start28 Feb 2019
- Primary completion29 Jul 2019
- Study completion29 Jul 2019
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
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 60 participants (actual)
Sponsor and investigators
- Lead sponsor
- Bristol-Myers Squibb
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03891108
- Sponsor's protocol ID
- CV013-038
- Status last verified
- Sep 2019
- First submitted
- 25 Mar 2019
- Last updated
- 1 Oct 2019
- 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 1 Oct 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Open Label, Parallel Design, Single Continuous Intravenous Infusion Study of BMS-986231 to Assess the Pharmacokinetics, Safety and Tolerability of Multiple Formulations in Healthy Participants
- ClinicalTrials.gov ID
- NCT03891108
- Acronym / sponsor ID
- CV013-038
- Conditions
- Heart Failure
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 60 participants (actual)
- Lead sponsor
- Bristol-Myers SquibbIndustry (pharma, biotech, devices)
- Study start
- 28 Feb 2019 (actual)
- Primary completion
- 29 Jul 2019 (actual)
- Study completion
- 29 Jul 2019 (actual)
- First posted
- 26 Mar 2019 (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.
Main Objective of this study is to compare the single intravenous (IV) infusion pharmacokinetics (PK) of BMS-986231 and its metabolites (BMT-284730, BMT-279554, and CAR-000463) following of up to 2 test formulations of BMS-986231 relative to the reference formulation.
Detailed description
Participants will be randomized 1:1:1:1 and dosed with either of the 4 treatments: A, B, C, or D; followed by review of safety and tolerability data during and after the infusion. The study will proceed with treatments A, and C unless one or more of these treatments shows poor tolerability; in which case the study may proceed with treatment B or D in the follow-up cohorts. Additional participants will be randomized equally to each of the treatments the study will proceed with.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Treatment A: BMS-986231 Formulation A | Active comparator | Drug: BMS-986231 Formulation AParticipants will be administered Treatment A: BMS-986231 Formulation A as a 48-hour IV infusion on Day 1, followed by review of safety and tolerability data during and after the infusion. |
| Treatment B: BMS-986231 Formulation B | Experimental | Drug: BMS-986231 Formulation BParticipants will be administered Treatment B: BMS-986231 Formulation B as a 48-hour IV infusion on Day 1, followed by review of safety and tolerability data during and after the infusion. |
| Treatment C: BMS-986231 Formulation C | Experimental | Drug: BMS-986231 Formulation CParticipants will be administered Treatment C: BMS-986231 Formulation C as a 48-hour IV infusion on Day 1, followed by review of safety and tolerability data during and after the infusion. |
| Treatment D: BMS 986231 Formulation D | Experimental | Drug: BMS-986231 Formulation DParticipants will be administered Treatment D: BMS 986231 Formulation D as a 48-hour IV infusion on Day 1, followed by review of safety and tolerability data during and after the infusion. |
Who may qualify
- Ages
- 18 to 40 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (8 listed)
- Participants must be willing to participate in the study and sign the informed consent form (ICF).
- Participants must be willing and able to complete all study-specific procedures and visits.
- Healthy participant, as determined by no clinically significant deviation from normal in medical history, physical examination, ECGs, and clinical laboratory determinations in the opinion of the investigator.
- Body mass index of 18.0 to 32.0 kg/m2, inclusive, and body weight ≥ 45 kg and ≤ 110 kg, at screening.
- Heart rate > 45 bpm and < 95 bpm at screening or baseline (within 30 minutes prior to randomization).
Key exclusion criteria (8 listed)
- Any significant acute or chronic medical illness
- Diagnosis of fibromyalgia
- History of syncope, orthostatic instability, or recurrent dizziness
- History or family history of ocular disorders (eg, glaucoma)
- History of bleeding diathesis (unusual susceptibility to bleed [hemorrhage] mostly due to hypocoagulability)
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 |
|---|---|---|
| BMS-986231 Formulation AParticipants will be administered BMS-986231 Formulation A as IV infusion for 48 hours. | Drug | Treatment A: BMS-986231 Formulation A |
| BMS-986231 Formulation BParticipants will be administered BMS-986231 Formulation B as IV infusion for 48 hours. | Drug | Treatment B: BMS-986231 Formulation B |
| BMS-986231 Formulation CParticipants will be administered BMS-986231 Formulation C as IV infusion for 48 hours. | Drug | Treatment C: BMS-986231 Formulation C |
| BMS-986231 Formulation DParticipants will be administered BMS-986231 Formulation D as IV infusion for 48 hours. | Drug | Treatment D: BMS 986231 Formulation D |
Primary outcome
Maximum Plasma Concentration (Cmax) of BMS-986231 and its Metabolites (BMT-284730, BMT-279554, and CAR-000463)
Time frame: Day 1 to Day 5
Cmax is the maximum plasma concentration.
Average Concentration Over a Dosing Interval (Css-av) of BMS-986231 and its Metabolites (BMT-284730, BMT-279554, and CAR-000463)
Time frame: Day 1 to Day 5
Css-av is defined as the average concentration over a dosing interval.
Area Under the Plasma Concentration-Time Curve From Time 0 (Dosing) Extrapolated to Infinity (AUC(INF)) of BMS-986231 and its Metabolites (BMT-284730, BMT-279554, and CAR-000463)
Time frame: Day 1 to Day 5
AUC(INF) is defined as area under the plasma concentration-time curve from time 0 (dosing) extrapolated to infinity.
Area Under the Concentration-Time Curve From Time 0 (Dosing) to the Time of the Last Quantifiable Concentration Observed (AUC(0-T)) of BMS-986231 and its Metabolites (BMT-284730, BMT-279554, and CAR-000463)
Time frame: Day 1 to Day 5
AUC(0-T) is defined as area under the concentration-time curve from time 0 (dosing) to the time of the last quantifiable concentration observed (T).
Terminal Elimination Phase Half-Life (T-HALF) of BMS-986231 and its Metabolites (BMT-284730, BMT-279554, and CAR-000463)
Time frame: Day 1 to Day 5
T-HALF is terminal elimination phase half-life.
Time to Reach Cmax in Plasma (Tmax) of BMS-986231 and its Metabolites (BMT-284730, BMT-279554, and CAR-000463)
Time frame: Day 1 to Day 5
Tmax is defined as time to reach Cmax in plasma.
Metabolite to Parent Molar Ratio of AUC(INF) (MRAUC[INF]) and Metabolite to Parent Molar Ratio of Css-av (MRCssav) of Metabolites of BMS-986231 (BMT-284730, BMT-279554, and CAR-000463)
Time frame: Day 1 to Day 5
MRAUC(INF) is determined using AUC(INF) for metabolite / AUC(INF) for BMS-986231. MRCss-av is determined using Css-av for metabolite / Css-av for BMS-986231.
Total Systemic Clearance (CLT) of BMS-986231
Time frame: Day 1 to Day 5
CLT is total systemic clearance.
Apparent Volume of Distribution During the Terminal Phase (Vz) of BMS-986231
Time frame: Day 1 to Day 5
Vz is apparent volume of distribution during the terminal phase.
Volume of Distribution at Steady State (Vss) of BMS-986231
Time frame: Day 1 to Day 5
Vss is volume of distribution at steady state.
6 secondary outcomes
Number of Participants with Adverse Events (AEs)
Time frame: Day 1 up to Day 13
Number of Participants with Serious AEs (SAEs)
Time frame: From signature of informed consent up to 30 days post last treatment
Number of Participants With Significant Changes in Clinical Laboratory Values
Time frame: Day 1 up to Day 13
Number of Participants with Significant Changes in Vital Signs
Time frame: Day 1 up to Day 13
Number of Participants with Significant Changes in Electrocardiograms (ECGs)
Time frame: Day 1 up to Day 13
Number of Participants with Significant Changes in Physical Examinations
Time frame: Day 1 up to Day 13
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Oct 2019.
- 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.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing BMS-986231 Formulation A, BMS-986231 Formulation B and BMS-986231 Formulation C in people with Heart Failure, run by Bristol-Myers Squibb at 1 site in United States.
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 8 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: finished, as of the sponsor's last update on 1 Oct 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. 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. 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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Maximum Plasma Concentration (Cmax) of BMS-986231 and its Metabolites (BMT-284730, BMT-279554, and CAR-000463) (time frame: Day 1 to Day 5). The study lists 10 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 1 Oct 2019.