A study designed to evaluate the effects of BMS-986231 versus placebo on urine output when taken with a single dose of a diuretic (furosemide). BMS-986231 or Placebo are provided in the form of Intravenous Infusions for a duration of 8 hours, with furosemide given after 4 hours, in patients whose heart is unable to pump sufficiently (chronic heart failure); exposed to each of the 2 interventions over the course of the study.
- Conditions
- Heart failure with reduced ejection fraction (HFrEF)MedDRA version: 20.0Level: LLTClassification code 10074631Term: Systolic heart failureSystem Organ Class: 100000004849MedDRA version: 20.0Level: LLTClassification code 10019279Term: Heart failureSystem Organ Class: 100000004849Therapeutic area: Diseases [C] - Cardiovascular Diseases [C14]
- Registration Number
- EUCTR2018-000970-31-GB
- Lead Sponsor
- Bristol-Myers Squibb International Corporation
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 20
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 <45%, as assessed by echocardiography, a multigated acquisition (MUGA) scan or magnetic resonance imaging (MRI) scan within 18 months.
c) On stable chronic guideline-directed therapy for HF including chronic loop diuretics, ACEi, ARBs, MRAs, ARNI or / and ß-blockers as tolerated, with no changes of these medications in the past 2 weeks.
d) Not applicable per Protocol Amendment 3.0
e) Not applicable per Protocol Amendment 3.0
f) Not applicable per Protocol Amendment 3.0
g) Elevated natriuretic peptides (N terminal-pro BNP [NT-proBNP] = 200 pg/mL or brain natriuretic peptide [BNP] = 60 pg/mL). For subjects with atrial fibrillation, NT-proBNP = 400 pg/mL or BNP = 120 pg/mL.
h) Estimated glomerular filtration rate (eGFR) between 30 and 80 mL/min/1.73m2.
3) Age and Reproductive Status
a) Women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of human chorionic gonadotropin [HCG]) within 24 hours prior to the start of each study treatment.
b) Women must not be breastfeeding.
c) WOCBP must agree to follow instructions for methods of highly effective contraception for 31 days after discontinuation (duration of study drug exposure plus 30 days duration of one ovulatory cycle).
d) Males who are sexually active with WOCBP must require these partners to follow instructions for highly effective methods of contraception for 91 days after discontinuation (duration of study drug plus 90 days (duration of sperm turnover).
e) Azoospermic males are exempt from contraceptive requirements. WOCBP who are continuously not heterosexually active are also exempt from contraceptive requirements, but still must undergo pregnancy testing as described in this section.
Investigators shall advise on the use of highly effective methods of contraception, which have a failure rate of < 1% when used consistently and correctly.
Local laws and regulations may require use of alternative and/or additional contraception methods.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 15
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 5
1)Target Disease Exceptions
a) SBP < 115 mm Hg or > 180 mm Hg at screening or pre-randomization.
b) Heart rate < 50 beats per minute (bpm) or > 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 months.
n) Liver disease defined as history of cirrhosis with evidence of portal hypertension such as varices, or encephalopathy, or total bilirubin > 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 < 130 or > 145 mEq/L (mmol/L).
ii)A potassium (K+) concentration < 3.2 or > 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.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method