Clinical trial NCT03891108: 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
Overall status: COMPLETED
Phase: PHASE1
Conditions: Heart Failure
Lead sponsor: Bristol-Myers Squibb
Sponsor class: INDUSTRY
First posted: 2019-03-26
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Maximum Plasma Concentration (Cmax) of BMS-986231 and its Metabolites (BMT-284730, BMT-279554, and CAR-000463)
timeFrame: Day 1 to Day 5
measure: Average Concentration Over a Dosing Interval (Css-av) of BMS-986231 and its Metabolites (BMT-284730, BMT-279554, and CAR-000463)
timeFrame: Day 1 to Day 5
measure: 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)
timeFrame: Day 1 to Day 5
measure: 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)
timeFrame: Day 1 to Day 5
measure: Terminal Elimination Phase Half-Life (T-HALF) of BMS-986231 and its Metabolites (BMT-284730, BMT-279554, and CAR-000463)
timeFrame: Day 1 to Day 5
measure: Time to Reach Cmax in Plasma (Tmax) of BMS-986231 and its Metabolites (BMT-284730, BMT-279554, and CAR-000463)
timeFrame: Day 1 to Day 5
measure: 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)
timeFrame: Day 1 to Day 5
measure: Total Systemic Clearance (CLT) of BMS-986231
timeFrame: Day 1 to Day 5
measure: Apparent Volume of Distribution During the Terminal Phase (Vz) of BMS-986231
timeFrame: Day 1 to Day 5
measure: Volume of Distribution at Steady State (Vss) of BMS-986231
timeFrame: Day 1 to Day 5
Secondary outcomes:
measure: Number of Participants with Adverse Events (AEs)
timeFrame: Day 1 up to Day 13
measure: Number of Participants with Serious AEs (SAEs)
timeFrame: From signature of informed consent up to 30 days post last treatment
measure: Number of Participants With Significant Changes in Clinical Laboratory Values
timeFrame: Day 1 up to Day 13
measure: Number of Participants with Significant Changes in Vital Signs
timeFrame: Day 1 up to Day 13
measure: Number of Participants with Significant Changes in Electrocardiograms (ECGs)
timeFrame: Day 1 up to Day 13
measure: Number of Participants with Significant Changes in Physical Examinations
timeFrame: Day 1 up to Day 13
Other outcomes:
Locations:
city: Salt Lake City
country: United States
facility: PRA Health Sciences
state: Utah
Study officials:
References: