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

Bristol-Myers Squibb (BMS)

Status and phase: Completed; Phase 1

Conditions: Heart Failure

Treatments: Drug: BMS-986231 Formulation A; Drug: BMS-986231 Formulation D; Drug: BMS-986231 Formulation B; Drug: BMS-986231 Formulation C

Study type: Interventional

Funder types: Industry

Identifiers

NCT03891108

CV013-038

Details and patient eligibility

About

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.

Full 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.

Enrollment: 60 patients

Sex: All

Ages: 18 to 40 years old

Volunteers: Accepts 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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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60 participants in 4 patient groups

Treatment A: BMS-986231 Formulation A

Active Comparator group

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.

Treatment:

Drug: BMS-986231 Formulation A

Treatment B: BMS-986231 Formulation B

Experimental group

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.

Treatment:

Drug: BMS-986231 Formulation B

Treatment C: BMS-986231 Formulation C

Experimental group

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.

Treatment:

Drug: BMS-986231 Formulation C

Treatment D: BMS 986231 Formulation D

Experimental group

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.

Treatment:

Drug: BMS-986231 Formulation D