Clinical trial NCT04763226: A Study to Evaluate the Safety, Tolerability, Drug Levels, and Drug Effects of BMS-986308 in Healthy Participants
Official title: A Randomized, Double-Blinded, Placebo-Controlled, Single Ascending Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of BMS-986308 in Healthy Participants
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Participants
Keywords: BMS-986308
Congestive heart failure (CHF)
Diuretics
Diuretic resistance
Fluid overload
Furosemide
Persistent congestion
Lead sponsor: Bristol-Myers Squibb
Sponsor class: INDUSTRY
First posted: 2021-02-21
Enrollment: 46
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Incidence of Adverse Events (AEs)
timeFrame: Up to 19 days
measure: Incidence of serious adverse events (SAEs)
timeFrame: Up to 19 days
measure: Incidence of death
timeFrame: Up to 19 days
measure: Incidence of adverse events (AEs) leading to discontinuation
timeFrame: Up to 19 days
measure: Incidence of clinically significant changes in clinical laboratory results: Hematology tests
timeFrame: Up to 19 days
measure: Incidence of clinically significant changes in clinical laboratory results: Clinical Chemistry tests
timeFrame: Up to 19 days
measure: Incidence of clinically significant changes in clinical laboratory results: Urinalysis tests
timeFrame: Up to 19 days
measure: Incidence of clinically significant changes in vital signs: Respiratory rate
timeFrame: Up to 19 days
measure: Incidence of clinically significant changes in vital signs: Supine blood pressure
timeFrame: Up to 19 days
measure: Incidence of clinically significant changes in vital signs: Heart rate
timeFrame: Up to 19 days
measure: Incidence of clinically significant changes in vital signs: Orthostatic hypotension measurements performed as per clinical research unit's standard operating procedure
timeFrame: Up to 19 days
measure: Incidence of clinically significant changes in electrocardiogram (ECG) parameters: PR interval
timeFrame: Up to 19 days
measure: Incidence of clinically significant changes in electrocardiogram (ECG) parameters: QRS
timeFrame: Up to 19 days
measure: Incidence of clinically significant changes in electrocardiogram (ECG) parameters: QT interval
timeFrame: Up to 19 days
measure: Incidence of clinically significant changes in electrocardiogram (ECG) parameters: QTcF
timeFrame: Up to 19 days
measure: Incidence of clinically significant changes in cardiac telemetry
timeFrame: Up to 19 days
measure: Incidence of clinically significant changes in physical examination findings
timeFrame: Up to 19 days
Secondary outcomes:
Other outcomes:
measure: Incidence of Adverse Events (AEs)
timeFrame: Up to 14 days
measure: Incidence of serious adverse events (SAEs)
timeFrame: Up to 72 days
measure: Incidence of death
timeFrame: Up to 72 days
measure: Incidence of adverse events (AEs) leading to discontinuation
timeFrame: Up to 72 days
measure: Incidence of clinically significant changes in vital signs: Respiratory rate
timeFrame: Up to 14 days
measure: Incidence of clinically significant changes in vital signs: Supine blood pressure
timeFrame: Up to 14 days
measure: Incidence of clinically significant changes in vital signs: Heart rate
timeFrame: Up to 14 days
measure: Incidence of clinically significant changes in vital signs: Orthostatic hypotension measurements performed as per clinical research unit's standard operating procedure
timeFrame: Up to 3 days
measure: Incidence of clinically significant changes in electrocardiogram (ECG) parameters: PR interval
timeFrame: Up to 14 days
measure: Incidence of clinically significant changes in electrocardiogram (ECG) parameters: QRS
timeFrame: Up to 14 days
measure: Incidence of clinically significant changes in electrocardiogram (ECG) parameters: QT interval
timeFrame: Up to 14 days
measure: Incidence of clinically significant changes in electrocardiogram (ECG) parameters: QTcF
timeFrame: Up to 14 days
measure: Incidence of clinically significant changes in cardiac telemetry
timeFrame: Up to 3 days
measure: Incidence of clinically significant changes in physical examination findings
timeFrame: Up to 14 days
Locations:
city: Lenexa
country: United States
facility: Local Institution - 0001
state: Kansas
Study officials:
affiliation: Bristol-Myers Squibb
name: Bristol-Myers Squibb
role: STUDY_DIRECTOR
References: