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A Pharmacokinetics, Safety and Tolerability Study of Multiple Formulations of BMS-986231 in Healthy Participants

Primary Purpose

Heart Failure

Status

Completed

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

BMS-986231 Formulation A

BMS-986231 Formulation B

BMS-986231 Formulation C

BMS-986231 Formulation D

About this trial

This is an interventional treatment trial for Heart Failure

Eligibility Criteria

18 Years - 40 Years (Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

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.

Exclusion Criteria:

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

Sites / Locations

PRA Health Sciences

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Active Comparator

Experimental

Arm Label

Treatment A: BMS-986231 Formulation A

Treatment B: BMS-986231 Formulation B

Treatment C: BMS-986231 Formulation C

Treatment D: BMS 986231 Formulation D

Arm Description

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.

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.

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.

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.

Outcomes

Primary Outcome Measures

Maximum Plasma Concentration (Cmax) of BMS-986231 and its Metabolites (BMT-284730, BMT-279554, and CAR-000463)

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)

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)

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)

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)

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)

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)

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

CLT is total systemic clearance.

Apparent Volume of Distribution During the Terminal Phase (Vz) of BMS-986231

Vz is apparent volume of distribution during the terminal phase.

Volume of Distribution at Steady State (Vss) of BMS-986231

Vss is volume of distribution at steady state.

Secondary Outcome Measures

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.

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).

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.

Number of Participants with Significant Changes in Vital Signs

Vital signs include body temperature, respiratory rate, and semi-supine blood pressure, and heart rate.

Number of Participants with Significant Changes in Electrocardiograms (ECGs)

A reflex 12-lead ECG will be conducted to confirm any significant changes in ECGs.

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.

Full Information

NCT ID

NCT03891108

First Posted

March 25, 2019

Last Updated

September 27, 2019

Sponsor

Bristol-Myers Squibb

1. Study Identification

Unique Protocol Identification Number

NCT03891108

Brief Title

A Pharmacokinetics, Safety and Tolerability Study of Multiple Formulations of BMS-986231 in Healthy Participants

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

Study Type

Interventional

2. Study Status

Record Verification Date

September 2019

Overall Recruitment Status

Completed

Study Start Date

February 28, 2019 (Actual)

Primary Completion Date

July 29, 2019 (Actual)

Study Completion Date

July 29, 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

Data Monitoring Committee

5. Study Description

Brief 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.

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.

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

Treatment

Study Phase

Phase 1

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

60 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Treatment A: BMS-986231 Formulation A

Arm Type

Active Comparator

Arm Description

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.

Arm Title

Treatment B: BMS-986231 Formulation B

Arm Type

Experimental

Arm Description

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.

Arm Title

Treatment C: BMS-986231 Formulation C

Arm Type

Experimental

Arm Description

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.

Arm Title

Treatment D: BMS 986231 Formulation D

Arm Type

Experimental

Arm Description

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.

Intervention Type

Drug

Intervention Name(s)

BMS-986231 Formulation A

Intervention Description

Participants will be administered BMS-986231 Formulation A as IV infusion for 48 hours.

Intervention Type

Drug

Intervention Name(s)

BMS-986231 Formulation B

Intervention Description

Participants will be administered BMS-986231 Formulation B as IV infusion for 48 hours.

Intervention Type

Drug

Intervention Name(s)

BMS-986231 Formulation C

Intervention Description

Participants will be administered BMS-986231 Formulation C as IV infusion for 48 hours.

Intervention Type

Drug

Intervention Name(s)

BMS-986231 Formulation D

Intervention Description

Participants will be administered BMS-986231 Formulation D as IV infusion for 48 hours.

Primary Outcome Measure Information:

Title

Maximum Plasma Concentration (Cmax) of BMS-986231 and its Metabolites (BMT-284730, BMT-279554, and CAR-000463)

Description

Cmax is the maximum plasma concentration.

Time Frame

Day 1 to Day 5

Title

Average Concentration Over a Dosing Interval (Css-av) of BMS-986231 and its Metabolites (BMT-284730, BMT-279554, and CAR-000463)

Description

Css-av is defined as the average concentration over a dosing interval.

Time Frame

Day 1 to Day 5

Title

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)

Description

AUC(INF) is defined as area under the plasma concentration-time curve from time 0 (dosing) extrapolated to infinity.

Time Frame

Day 1 to Day 5

Title

Description

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).

Time Frame

Day 1 to Day 5

Title

Terminal Elimination Phase Half-Life (T-HALF) of BMS-986231 and its Metabolites (BMT-284730, BMT-279554, and CAR-000463)

Description

T-HALF is terminal elimination phase half-life.

Time Frame

Day 1 to Day 5

Title

Time to Reach Cmax in Plasma (Tmax) of BMS-986231 and its Metabolites (BMT-284730, BMT-279554, and CAR-000463)

Description

Tmax is defined as time to reach Cmax in plasma.

Time Frame

Day 1 to Day 5

Title

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)

Description

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.

Time Frame

Day 1 to Day 5

Title

Total Systemic Clearance (CLT) of BMS-986231

Description

CLT is total systemic clearance.

Time Frame

Day 1 to Day 5

Title

Apparent Volume of Distribution During the Terminal Phase (Vz) of BMS-986231

Description

Vz is apparent volume of distribution during the terminal phase.

Time Frame

Day 1 to Day 5

Title

Volume of Distribution at Steady State (Vss) of BMS-986231

Description

Vss is volume of distribution at steady state.

Time Frame

Day 1 to Day 5

Secondary Outcome Measure Information:

Title

Number of Participants with Adverse Events (AEs)

Description

Time Frame

Day 1 up to Day 13

Title

Number of Participants with Serious AEs (SAEs)

Description

Time Frame

From signature of informed consent up to 30 days post last treatment

Title

Number of Participants With Significant Changes in Clinical Laboratory Values

Description

Time Frame

Day 1 up to Day 13

Title

Number of Participants with Significant Changes in Vital Signs

Description

Vital signs include body temperature, respiratory rate, and semi-supine blood pressure, and heart rate.

Time Frame

Day 1 up to Day 13

Title

Number of Participants with Significant Changes in Electrocardiograms (ECGs)

Description

A reflex 12-lead ECG will be conducted to confirm any significant changes in ECGs.

Time Frame

Day 1 up to Day 13

Title

Number of Participants with Significant Changes in Physical Examinations

Description

Time Frame

Day 1 up to Day 13

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

40 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: 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. Exclusion Criteria: 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

Facility Information:

Facility Name

PRA Health Sciences

City

Salt Lake City

State/Province

Utah

ZIP/Postal Code

84124

Country

United States

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 Pharmacokinetics, Safety and Tolerability Study of Multiple Formulations of BMS-986231 in Healthy Participants

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