A Study to Evaluate the Safety, Tolerability, Drug Levels, and Drug Effects of BMS-986308 in Healthy Participants

A Randomized, Double-Blinded, Placebo-Controlled, Single Ascending Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of BMS-986308 in Healthy Participants

The purpose of this study is to evaluate the safety, tolerability, drug levels, and drug effects of BMS-986308 compared to placebo in healthy participants.

Study Overview

• Status: Completed
• Conditions: Healthy Participants
• Intervention / Treatment: Drug: Furosemide; Drug: BMS-986308; Other: Placebo (for BMS-986308)

• Study Type: Interventional
• Enrollment (Actual): 46
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Kansas
    • Lenexa, Kansas, United States, 66219
      • Local Institution - 0001

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

For more information regarding Bristol-Myers Squibb Clinical Trial participation, please visit www.BMSStudyConnect.com

Inclusion Criteria:

• Must be in good health, as determined by no clinically significant deviations from normal in medical history, physical examination, electrocardiograms (ECGs), and clinical laboratory determinations
• Must have a body mass index (BMI) of 18.0 kg/m^2 to 32.0 kg/m^2, inclusive, at screening. BMI = weight (kg)/height (m)^2
• Must have normal renal function at screening (and study admission) as evidenced by an estimated glomerular filtration rate (eGFR) ≥ 80 mL/min/1.73 m^2 calculated with the Chronic Kidney Disease Epidemiology Collaboration formula

Exclusion Criteria:

• Any significant acute or chronic medical illness
• Presence or need for urinary catheterization, urinary tract abnormality, or disorder interfering with urination
• History of tinnitus or hearing impairment, including deafness
• History or risks factors for Torsade de Pointes and Long QT syndrome (such as electrolyte imbalances, etc)
• History of, or active, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection
• Consumption of caffeine or xanthine-containing food or beverages within 72 hours prior to study treatment administration
• Use of any prescription drugs or over-the-counter (OTC) acid controllers within 4 weeks prior to study treatment administration except those medications cleared by the Medical Monitor
• Use of any other drugs, including OTC medications within 1 week and herbal preparations, within 2 weeks prior to study treatment administration except those medications cleared by the Medical Monitor
• Use of diuretics (loop diuretics, thiazide diuretics, potassium-sparing diuretics [spironolactone, amiloride]), oral calcium, potassium or magnesium supplements (including multi-vitamins) or use of non-steroidal anti-inflammatory drugs within 72 hours of the first study treatment
• Use of concomitant medications that are strong inhibitors or inducers of cytochrome CYP3A4 or OATP administered within 2 weeks prior to study treatment administration and throughout the study
• Consumption of any nutrients known to modulate cytochrome P450 (CYP) enzymes activity (eg, grapefruit, or grapefruit juice,pomelo juice, star fruit, or Seville [blood] orange products) within 14 days prior to first administration of study treatment
• Evidence of organ dysfunction or any clinically significant deviation from normal in physical examination, vital signs, ECG, or clinical laboratory determinations beyond what is consistent with the target population of healthy volunteers
• History of allergy to furosemide, sulfonamides, other loop diuretics (furosemide cohort only), BMS-986308 or related compounds, components of the suspension or solution, including hydroxypropylmethylcellulose

Other protocol-defined inclusion/exclusion criteria apply

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part A Furosemide	Drug: Furosemide; Specified dose on specified days
Experimental: Part B (SAD); Single Ascending Dose (SAD)	Drug: BMS-986308; Specified dose on specified days; Other: Placebo (for BMS-986308); Specified dose on specified days

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Adverse Events (AEs)	Part B	Up to 19 days
Incidence of serious adverse events (SAEs)	Part B	Up to 19 days
Incidence of death	Part B	Up to 19 days
Incidence of adverse events (AEs) leading to discontinuation	Part B	Up to 19 days
Incidence of clinically significant changes in clinical laboratory results: Hematology tests	Part B	Up to 19 days
Incidence of clinically significant changes in clinical laboratory results: Clinical Chemistry tests	Part B	Up to 19 days
Incidence of clinically significant changes in clinical laboratory results: Urinalysis tests	Part B	Up to 19 days
Incidence of clinically significant changes in vital signs: Respiratory rate	Part B	Up to 19 days
Incidence of clinically significant changes in vital signs: Supine blood pressure	Part B	Up to 19 days
Incidence of clinically significant changes in vital signs: Heart rate	Part B	Up to 19 days
Incidence of clinically significant changes in vital signs: Orthostatic hypotension measurements performed as per clinical research unit's standard operating procedure	Part B	Up to 19 days
Incidence of clinically significant changes in electrocardiogram (ECG) parameters: PR interval	Part B PR interval is the time from the onset of the P wave to the start of the QRS complex	Up to 19 days
Incidence of clinically significant changes in electrocardiogram (ECG) parameters: QRS	Part B QRS can be defined as the electrical impulse as it spreads through the ventricles, indicating ventricular depolarization	Up to 19 days
Incidence of clinically significant changes in electrocardiogram (ECG) parameters: QT interval	Part B The QT interval is the time from the start of the Q wave to the end of the T wave	Up to 19 days
Incidence of clinically significant changes in electrocardiogram (ECG) parameters: QTcF	Part B QTcF = Corrected QT interval using the Fridericia formula. QT interval is the time from the start of the Q wave to the end of the T wave	Up to 19 days
Incidence of clinically significant changes in cardiac telemetry	Part B	Up to 19 days
Incidence of clinically significant changes in physical examination findings	Part B	Up to 19 days

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Adverse Events (AEs)	Part A	Up to 14 days
Incidence of serious adverse events (SAEs)	Part A	Up to 72 days
Incidence of death	Part A	Up to 72 days
Incidence of adverse events (AEs) leading to discontinuation	Part A	Up to 72 days
Incidence of clinically significant changes in vital signs: Respiratory rate	Part A	Up to 14 days
Incidence of clinically significant changes in vital signs: Supine blood pressure	Part A	Up to 14 days
Incidence of clinically significant changes in vital signs: Heart rate	Part A	Up to 14 days
Incidence of clinically significant changes in vital signs: Orthostatic hypotension measurements performed as per clinical research unit's standard operating procedure	Part A	Up to 3 days
Incidence of clinically significant changes in electrocardiogram (ECG) parameters: PR interval	Part A PR interval is the time from the onset of the P wave to the start of the QRS complex	Up to 14 days
Incidence of clinically significant changes in electrocardiogram (ECG) parameters: QRS	Part A QRS can be defined as the electrical impulse as it spreads through the ventricles, indicating ventricular depolarization	Up to 14 days
Incidence of clinically significant changes in electrocardiogram (ECG) parameters: QT interval	Part A The QT interval is the time from the start of the Q wave to the end of the T wave	Up to 14 days
Incidence of clinically significant changes in electrocardiogram (ECG) parameters: QTcF	Part A QTcF = Corrected QT interval using the Fridericia formula. QT interval is the time from the start of the Q wave to the end of the T wave	Up to 14 days
Incidence of clinically significant changes in cardiac telemetry	Part A	Up to 3 days
Incidence of clinically significant changes in physical examination findings	Part A	Up to 14 days

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): April 14, 2021
• Primary Completion (Actual): February 27, 2022
• Study Completion (Actual): February 27, 2022

Study Registration Dates

• First Submitted: February 4, 2021
• First Submitted That Met QC Criteria: February 18, 2021
• First Posted (Actual): February 21, 2021

Study Record Updates

• Last Update Posted (Actual): April 27, 2022
• Last Update Submitted That Met QC Criteria: April 26, 2022
• Last Verified: April 1, 2022

More Information

Terms related to this study

• Keywords: Diuretics; Fluid overload; Furosemide; BMS-986308; Congestive heart failure (CHF); Diuretic resistance; Persistent congestion
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Natriuretic Agents; Membrane Transport Modulators; Diuretics; Sodium Potassium Chloride Symporter Inhibitors; Furosemide
• Other Study ID Numbers: CV021-004

Drug and device information, study documents

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