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

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.

Study Overview

• Status: Completed
• Conditions: Heart Failure
• Intervention / Treatment: Drug: BMS-986231 Formulation A; Drug: BMS-986231 Formulation B; Drug: BMS-986231 Formulation C; Drug: BMS-986231 Formulation D

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 Type: Interventional
• Enrollment (Actual): 60
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Utah
    • Salt Lake City, Utah, United States, 84124
      • PRA Health Sciences

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 40 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Treatment A: BMS-986231 Formulation A; 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.	Drug: BMS-986231 Formulation A; Participants will be administered BMS-986231 Formulation A as IV infusion for 48 hours.
Experimental: Treatment B: BMS-986231 Formulation B; 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.	Drug: BMS-986231 Formulation B; Participants will be administered BMS-986231 Formulation B as IV infusion for 48 hours.
Experimental: Treatment C: BMS-986231 Formulation C; 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.	Drug: BMS-986231 Formulation C; Participants will be administered BMS-986231 Formulation C as IV infusion for 48 hours.
Experimental: Treatment D: BMS 986231 Formulation D; 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.	Drug: BMS-986231 Formulation D; Participants will be administered BMS-986231 Formulation D as IV infusion for 48 hours.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum Plasma Concentration (Cmax) of BMS-986231 and its Metabolites (BMT-284730, BMT-279554, and CAR-000463)	Cmax is the maximum plasma concentration.	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.	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.	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).	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.	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.	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.	Day 1 to Day 5
Total Systemic Clearance (CLT) of BMS-986231	CLT is total systemic clearance.	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.	Day 1 to Day 5
Volume of Distribution at Steady State (Vss) of BMS-986231	Vss is volume of distribution at steady state.	Day 1 to Day 5

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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).	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.	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.	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.	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.	Day 1 up to Day 13

Collaborators and Investigators

• Sponsor: Bristol-Myers Squibb

Publications and helpful links

Helpful Links

• BMS Clinical Trial Information
• BMS Clinical Trial Patient Recruiting
• FDA Safety Alerts and Recalls

Study record dates

Study Major Dates

• Study Start (Actual): February 28, 2019
• Primary Completion (Actual): July 29, 2019
• Study Completion (Actual): July 29, 2019

Study Registration Dates

• First Submitted: March 25, 2019
• First Submitted That Met QC Criteria: March 25, 2019
• First Posted (Actual): March 26, 2019

Study Record Updates

• Last Update Posted (Actual): October 1, 2019
• Last Update Submitted That Met QC Criteria: September 27, 2019
• Last Verified: September 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Heart Failure
• Other Study ID Numbers: CV013-038

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No