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

Bristol-Myers Squibb60 enrolled

Overview

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.

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 Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Heart Failure

Interventions

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.

Eligibility

Sex: ALLMin age: 18 YearsMax age: 40 YearsHealthy volunteers:

Medical Language ↔ Plain English

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

Locations (1)

PRA Health Sciences

Salt Lake City, Utah, United States

Outcomes

Primary Outcomes

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

Cmax is the maximum plasma concentration.

Time frame: 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.

Time frame: 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.

Time frame: 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).

Time frame: 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.

Time frame: 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.

Time frame: 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)

Data from ClinicalTrials.gov

This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.

Secondary Outcomes

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.