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

Heart Failure Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03891108
• Other study ID #: CV013-038
• Status: Completed
• Phase: Phase 1
• Start date: February 28, 2019
• Est. completion date: July 29, 2019

Study information

• Verified date: September 2019
• Source: Bristol-Myers Squibb
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 60
• Est. completion date: July 29, 2019
• Est. primary completion date: July 29, 2019
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 40 Years

Eligibility

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

Related Conditions & MeSH terms

• Heart Failure

Intervention

Drug:
• BMS-986231 Formulation A
Participants will be administered BMS-986231 Formulation A as IV infusion for 48 hours.
• BMS-986231 Formulation B
Participants will be administered BMS-986231 Formulation B as IV infusion for 48 hours.
• BMS-986231 Formulation C
Participants will be administered BMS-986231 Formulation C as IV infusion for 48 hours.
• BMS-986231 Formulation D
Participants will be administered BMS-986231 Formulation D as IV infusion for 48 hours.

Locations

Country	Name	City	State
United States	PRA Health Sciences	Salt Lake City	Utah

Sponsors (1)

Lead Sponsor	Collaborator
Bristol-Myers Squibb

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	Total Systemic Clearance (CLT) of BMS-986231	CLT is total systemic clearance.	Day 1 to Day 5
Primary	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
Primary	Volume of Distribution at Steady State (Vss) of BMS-986231	Vss is volume of distribution at steady state.	Day 1 to Day 5
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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

External Links

•   BMS Clinical Trial Information
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