A Randomized, Double-Blinded, Placebo-Controlled, Single Ascending Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of BMS-986308 in Healthy Participants
Overview
- Phase
- Phase 1
- Intervention
- Furosemide
- Conditions
- Healthy Participants
- Sponsor
- Bristol-Myers Squibb
- Enrollment
- 46
- Locations
- 1
- Primary Endpoint
- Incidence of clinically significant changes in clinical laboratory results: Clinical Chemistry tests
- Status
- Completed
- Last Updated
- 4 years ago
Overview
Brief Summary
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.
Investigators
Eligibility Criteria
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
Arms & Interventions
Part A Furosemide
Intervention: Furosemide
Part B (SAD)
Single Ascending Dose (SAD)
Intervention: BMS-986308
Part B (SAD)
Single Ascending Dose (SAD)
Intervention: Placebo (for BMS-986308)
Outcomes
Primary Outcomes
Incidence of clinically significant changes in clinical laboratory results: Clinical Chemistry tests
Time Frame: Up to 19 days
Part B
Incidence of clinically significant changes in vital signs: Respiratory rate
Time Frame: Up to 19 days
Part B
Incidence of clinically significant changes in vital signs: Supine blood pressure
Time Frame: Up to 19 days
Part B
Incidence of clinically significant changes in vital signs: Orthostatic hypotension measurements performed as per clinical research unit's standard operating procedure
Time Frame: Up to 19 days
Part B
Incidence of clinically significant changes in electrocardiogram (ECG) parameters: PR interval
Time Frame: Up to 19 days
Part B PR interval is the time from the onset of the P wave to the start of the QRS complex
Incidence of clinically significant changes in electrocardiogram (ECG) parameters: QRS
Time Frame: Up to 19 days
Part B QRS can be defined as the electrical impulse as it spreads through the ventricles, indicating ventricular depolarization
Incidence of clinically significant changes in electrocardiogram (ECG) parameters: QT interval
Time Frame: Up to 19 days
Part B The QT interval is the time from the start of the Q wave to the end of the T wave
Incidence of clinically significant changes in electrocardiogram (ECG) parameters: QTcF
Time Frame: Up to 19 days
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
Incidence of clinically significant changes in cardiac telemetry
Time Frame: Up to 19 days
Part B
Incidence of clinically significant changes in physical examination findings
Time Frame: Up to 19 days
Part B
Incidence of Adverse Events (AEs)
Time Frame: Up to 19 days
Part B
Incidence of serious adverse events (SAEs)
Time Frame: Up to 19 days
Part B
Incidence of death
Time Frame: Up to 19 days
Part B
Incidence of adverse events (AEs) leading to discontinuation
Time Frame: Up to 19 days
Part B
Incidence of clinically significant changes in clinical laboratory results: Hematology tests
Time Frame: Up to 19 days
Part B
Incidence of clinically significant changes in vital signs: Heart rate
Time Frame: Up to 19 days
Part B
Incidence of clinically significant changes in clinical laboratory results: Urinalysis tests
Time Frame: Up to 19 days
Part B