Heart failure with reduced ejection fraction (HFrEF) MedDRA version: 20.0 Level: LLT Classification code 10074631 Term: Systolic heart failure System Organ Class: 100000004849 MedDRA version: 20.0 Level: LLT Classification code 10019279 Term: Heart failure System Organ Class: 100000004849
Conditions
Sponsors
Bristol-Myers Squibb International Corporation
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1) Signed Written Informed Consent a) Subjects will be required to provide a written informed consent. 2)Type of Participant and Target Disease Characteristics a) Males and Females, ages 18 or age of majority or older. b) Left ventricular EF =65 years) yes F.1.3.1 Number of subjects for this age range 5
Exclusion criteria
Exclusion criteria: 1)Target Disease Exceptions a) SBP 180 mm Hg at screening or pre-randomization. b) Heart rate 120 bpm at screening or pre-randomization. c) Primary HF etiology attributable to either restrictive/obstructive cardiomyopathy, idiopathic hypertrophic or uncorrected severe valvular disease as defined by American Heart Association (AHA)/American College of Cardiology (ACC)/European Society of Cardiology (ESC) criteria. d) Patients with urinary/prostate disorders with urinary retention/significant bladder dysfunction or urinary incontinence. e) Inability to comply with the serial urine collection procedures. f) Pericardial tamponade or constrictive pericarditis. g) Left ventricular (LV) assist device or prior heart transplant. h) Hospitalized for acute decompensated HF in the previous month. i) New York Heart Association (NYHA) Class IV symptoms of HF. j) Hospitalized with acute coronary syndrome, coronary revascularization or acute myocardial infarction during the previous 90 days prior to screening. k) Have a history of a cerebral vascular accident (cerebrovascular accident [CVA] or stroke) or of a transient ischemic attack (TIA) during the previous 90 days prior to screening. l) Considered clinically unstable for any condition. m) Serious comorbid non-cardiovascular disease in which the life expectancy of the subject is 3 mg/dL (> 34.2 µmol/L) or significant elevation of liver enzymes (aspartate aminotransferase [AST], alanine aminotransferase [ALT] > 3 times the upper limit of normal). o) Prior solid organ transplant. 2)Prior/Concomitant Therapy a) Patients taking thiazides / metolazone or potassium-sparing diuretics (with the exception of spironolactone or eplerenone at doses = 50 mg/day which are allowed). 3)Physical and Laboratory Test Findings a) Have persistent abnormal serum electrolytes not resolved between screening and start of the study drug infusion, as defined by any of the following: i)A sodium (Na+) concentration 145 mEq/L (mmol/L). ii)A potassium (K+) concentration 5.5 mEq/L (mmol/L). b) Have severe anemia, as documented by a hemoglobin < 9 g/dL (< 5.59 mmol/L). 4)Allergies and Adverse Drug Reaction a) Any history of allergic reaction to components of BMS-986231, Captisol® or potassium acetate. b) Any history of allergic reactions to furosemide. 5)Other Exclusion Criteria a) Prisoners or participants who are involuntarily incarcerated. (Note: under certain specific circumstances a person who has been imprisoned may be included or permitted to continue as a participant. Strict conditions apply and Bristol-Myers Squibb’s approval is required). b) Participants who are compulsorily detained for treatment of either a psychiatric or physical (e.g., infectious disease) illness. c) Participation in an investigational clinical drug study within 30 days or 5 elimination half-lives, (whichever is longer) prior to randomization. d) Prior participation and treatment in a study using BMS-986231. e) Alcohol beverage consumption within 6 hours prior to randomization. f) Body weight < 45 kg or = 140 kg. g) Site personel and their families.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Evaluate the effects of HNO donor BMS-986231 on 4-hour urine output in patients with HFrEF after administration of 40 mg of IV furosemide ;Secondary Objective: - Assess the effect of BMS-986231 on fractional excretion of Na (FeNa) - Assess the effect of BMS-986231 on fractional excretion of K (FeK) - Assess the effects of BMS-986231 on furosemide urinary and plasma concentration and the ratio urinary sodium to urinary furosemide - Assess safety of BMS-986231;Primary end point(s): 4-hour urinary output following intravenous administration of 40 mg furosemide to HFrEF patients receiving BMS-986231 infusion compared to placebo;Timepoint(s) of evaluation of this end point: At the end of the 8-hour infusion | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - FeNa in patients with HFrEF while on BMS 986231 compared to placebo - FeK in patients with HFrEF while on BMS 986231 compared to placebo - Furosemide urinary and plasma concentration in patients with HFrEF while on BMS-986231 compared to placebo - Ratio Urinary Na to Urinary furosemide after BMS 986231 compared to placebo - Clinically relevant hypotension during infusion, AEs, clinical laboratory values, vital signs, ECGs, telemetry, physical examinations.;Timepoint(s) of evaluation of this end point: During and at the end of the 8-hour infusion | — |
Countries
United Kingdom
Contacts
Public ContactGCT-SU
Bristol-Myers Squibb International Corporation
Outcome results
None listed