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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03891108
Recruitment Status : Completed
First Posted : March 26, 2019
Last Update Posted : October 1, 2019
Sponsor:
Information provided by (Responsible Party):
Bristol-Myers Squibb

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.

Condition or disease Intervention/treatment Phase
Heart Failure Drug: BMS-986231 Formulation A Drug: BMS-986231 Formulation B Drug: BMS-986231 Formulation C Drug: BMS-986231 Formulation D Phase 1

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 60 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : February 28, 2019
Actual Primary Completion Date : July 29, 2019
Actual Study Completion Date : July 29, 2019

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.




Primary Outcome Measures :
  1. Maximum Plasma Concentration (Cmax) of BMS-986231 and its Metabolites (BMT-284730, BMT-279554, and CAR-000463) [ Time Frame: Day 1 to Day 5 ]
    Cmax is the maximum plasma concentration.

  2. Average Concentration Over a Dosing Interval (Css-av) of BMS-986231 and its Metabolites (BMT-284730, BMT-279554, and CAR-000463) [ Time Frame: Day 1 to Day 5 ]
    Css-av is defined as the average concentration over a dosing interval.

  3. 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) [ Time Frame: Day 1 to Day 5 ]
    AUC(INF) is defined as area under the plasma concentration-time curve from time 0 (dosing) extrapolated to infinity.

  4. 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) [ Time Frame: Day 1 to Day 5 ]
    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).

  5. Terminal Elimination Phase Half-Life (T-HALF) of BMS-986231 and its Metabolites (BMT-284730, BMT-279554, and CAR-000463) [ Time Frame: Day 1 to Day 5 ]
    T-HALF is terminal elimination phase half-life.

  6. Time to Reach Cmax in Plasma (Tmax) of BMS-986231 and its Metabolites (BMT-284730, BMT-279554, and CAR-000463) [ Time Frame: Day 1 to Day 5 ]
    Tmax is defined as time to reach Cmax in plasma.

  7. 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) [ Time Frame: Day 1 to Day 5 ]
    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.

  8. Total Systemic Clearance (CLT) of BMS-986231 [ Time Frame: Day 1 to Day 5 ]
    CLT is total systemic clearance.

  9. Apparent Volume of Distribution During the Terminal Phase (Vz) of BMS-986231 [ Time Frame: Day 1 to Day 5 ]
    Vz is apparent volume of distribution during the terminal phase.

  10. Volume of Distribution at Steady State (Vss) of BMS-986231 [ Time Frame: Day 1 to Day 5 ]
    Vss is volume of distribution at steady state.


Secondary Outcome Measures :
  1. Number of Participants with Adverse Events (AEs) [ Time Frame: Day 1 up to Day 13 ]
    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.

  2. Number of Participants with Serious AEs (SAEs) [ Time Frame: From signature of informed consent up to 30 days post last treatment ]
    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).

  3. Number of Participants With Significant Changes in Clinical Laboratory Values [ Time Frame: Day 1 up to Day 13 ]
    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.

  4. Number of Participants with Significant Changes in Vital Signs [ Time Frame: Day 1 up to Day 13 ]
    Vital signs include body temperature, respiratory rate, and semi-supine blood pressure, and heart rate.

  5. Number of Participants with Significant Changes in Electrocardiograms (ECGs) [ Time Frame: Day 1 up to Day 13 ]
    A reflex 12-lead ECG will be conducted to confirm any significant changes in ECGs.

  6. Number of Participants with Significant Changes in Physical Examinations [ Time Frame: Day 1 up to Day 13 ]
    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.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 40 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03891108


Locations
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United States, Utah
PRA Health Sciences
Salt Lake City, Utah, United States, 84124
Sponsors and Collaborators
Bristol-Myers Squibb
Additional Information:
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Responsible Party: Bristol-Myers Squibb
ClinicalTrials.gov Identifier: NCT03891108    
Other Study ID Numbers: CV013-038
First Posted: March 26, 2019    Key Record Dates
Last Update Posted: October 1, 2019
Last Verified: September 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Heart Failure
Heart Diseases
Cardiovascular Diseases