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

NCT03891108 | Completed Phase 1 FDA Drug

• 1 other identifier: CV013-038
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

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.

Conditions

Heart Failure

Outcome Measures

Primary Outcomes (10)

• 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 Outcomes (6)

• Number of Participants with Adverse Events (AEs)

  Day 1 up to Day 13

• Number of Participants with Serious AEs (SAEs)

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

• Number of Participants With Significant Changes in Clinical Laboratory Values

  Day 1 up to Day 13

• Number of Participants with Significant Changes in Vital Signs

  Day 1 up to Day 13

• Number of Participants with Significant Changes in Electrocardiograms (ECGs)

  Day 1 up to Day 13

Study Arms (4)

Treatment A: BMS-986231 Formulation A

ACTIVE COMPARATOR

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

Treatment B: BMS-986231 Formulation B

EXPERIMENTAL

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

Treatment C: BMS-986231 Formulation C

EXPERIMENTAL

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

Treatment D: BMS 986231 Formulation D

EXPERIMENTAL

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

Interventions

BMS-986231 Formulation A DRUG

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

Treatment A: BMS-986231 Formulation A

BMS-986231 Formulation B DRUG

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

Treatment B: BMS-986231 Formulation B

BMS-986231 Formulation C DRUG

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

Treatment C: BMS-986231 Formulation C

BMS-986231 Formulation D DRUG

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

Treatment D: BMS 986231 Formulation D

Eligibility Criteria

• Age: 18 Years - 40 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Bristol-Myers Squibb: lead

Study Sites (1)

PRA Health Sciences

Salt Lake City, Utah, 84124, United States

Location

Related Links

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

MeSH Terms

Conditions

Heart Failure

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 25, 2019
• First Posted: March 26, 2019
• Study Start: February 28, 2019
• Primary Completion: July 29, 2019
• Study Completion: July 29, 2019
• Last Updated: October 1, 2019

Record last verified: 2019-09

Locations

US (1)