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

• Sponsor: Bristol-Myers Squibb (Industry)
• Overall Status: Completed
• CT.gov ID: NCT04763226
• Collaborator: (none)
• Enrollment: 46
• Location: 1
• Arms: 2
• Actual Duration (Months): 10.5
• Patients Per Site Per Month: 4.4

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Healthy Participants	Drug: BMS-986308; Other: Placebo (for BMS-986308); Drug: Furosemide	Phase 1

Study Design

• Study Type: Interventional
• Actual Enrollment: 46 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: Apr 14, 2021
• Actual Primary Completion Date: Feb 27, 2022
• Actual Study Completion Date: Feb 27, 2022

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. Incidence of Adverse Events (AEs) [Up to 19 days]

   Part B

2. Incidence of serious adverse events (SAEs) [Up to 19 days]

   Part B

3. Incidence of death [Up to 19 days]

   Part B

4. Incidence of adverse events (AEs) leading to discontinuation [Up to 19 days]

   Part B

5. Incidence of clinically significant changes in clinical laboratory results: Hematology tests [Up to 19 days]

   Part B

6. Incidence of clinically significant changes in clinical laboratory results: Clinical Chemistry tests [Up to 19 days]

   Part B

7. Incidence of clinically significant changes in clinical laboratory results: Urinalysis tests [Up to 19 days]

   Part B

8. Incidence of clinically significant changes in vital signs: Respiratory rate [Up to 19 days]

   Part B

9. Incidence of clinically significant changes in vital signs: Supine blood pressure [Up to 19 days]

   Part B

10. Incidence of clinically significant changes in vital signs: Heart rate [Up to 19 days]

    Part B

11. Incidence of clinically significant changes in vital signs: Orthostatic hypotension measurements performed as per clinical research unit's standard operating procedure [Up to 19 days]

    Part B

12. Incidence of clinically significant changes in electrocardiogram (ECG) parameters: PR interval [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

13. Incidence of clinically significant changes in electrocardiogram (ECG) parameters: QRS [Up to 19 days]

    Part B QRS can be defined as the electrical impulse as it spreads through the ventricles, indicating ventricular depolarization

14. Incidence of clinically significant changes in electrocardiogram (ECG) parameters: QT interval [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

15. Incidence of clinically significant changes in electrocardiogram (ECG) parameters: QTcF [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

16. Incidence of clinically significant changes in cardiac telemetry [Up to 19 days]

    Part B

17. Incidence of clinically significant changes in physical examination findings [Up to 19 days]

    Part B

Other Outcome Measures

1. Incidence of Adverse Events (AEs) [Up to 14 days]

   Part A

2. Incidence of serious adverse events (SAEs) [Up to 72 days]

   Part A

3. Incidence of death [Up to 72 days]

   Part A

4. Incidence of adverse events (AEs) leading to discontinuation [Up to 72 days]

   Part A

5. Incidence of clinically significant changes in vital signs: Respiratory rate [Up to 14 days]

   Part A

6. Incidence of clinically significant changes in vital signs: Supine blood pressure [Up to 14 days]

   Part A

7. Incidence of clinically significant changes in vital signs: Heart rate [Up to 14 days]

   Part A

8. Incidence of clinically significant changes in vital signs: Orthostatic hypotension measurements performed as per clinical research unit's standard operating procedure [Up to 3 days]

   Part A

9. Incidence of clinically significant changes in electrocardiogram (ECG) parameters: PR interval [Up to 14 days]

   Part A PR interval is the time from the onset of the P wave to the start of the QRS complex

10. Incidence of clinically significant changes in electrocardiogram (ECG) parameters: QRS [Up to 14 days]

    Part A QRS can be defined as the electrical impulse as it spreads through the ventricles, indicating ventricular depolarization

11. Incidence of clinically significant changes in electrocardiogram (ECG) parameters: QT interval [Up to 14 days]

    Part A The QT interval is the time from the start of the Q wave to the end of the T wave

12. Incidence of clinically significant changes in electrocardiogram (ECG) parameters: QTcF [Up to 14 days]

    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

13. Incidence of clinically significant changes in cardiac telemetry [Up to 3 days]

    Part A

14. Incidence of clinically significant changes in physical examination findings [Up to 14 days]

    Part A

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 55 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Local Institution - 0001	Lenexa	Kansas	United States	66219

Sponsors and Collaborators

• Bristol-Myers Squibb

Investigators

• Study Director: Bristol-Myers Squibb, Bristol-Myers Squibb

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• BMS Clinical Trial Information
• BMS Clinical Trial Patient Recruiting
• FDA Safety Alerts and Recalls

Publications

None provided.

• Responsible Party: Bristol-Myers Squibb
• ClinicalTrials.gov Identifier: NCT04763226
• Other Study ID Numbers: CV021-004
• First Posted: Feb 21, 2021
• Last Update Posted: Apr 27, 2022
• Last Verified: Apr 1, 2022

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Bristol-Myers Squibb: BMS-986308; Congestive heart failure (CHF); Diuretics; Diuretic resistance; Fluid overload; Furosemide; Persistent congestion
• Additional relevant MeSH terms: Furosemide

Study Results

No Results Posted as of Apr 27, 2022