Heart failure and impaired systolic function 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) Heart failure with reduced ejection fraction (LVEF on echocardiogram of 40% or less)c) Stable guideline directed therapy for heart failure including oral diuretics, ACEi, ARBs, ARNi, MRAs , and ß blockers as tolerated), with no dose changes of these medications in the past 2 weeks d) Have screening values of NT pro-BNP = 125 pg/mL (15 pmol/L) or BNP = 35 pg/mL (10 pmol/L). e) In sinus rhythm at the start of the infusion 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 HCG) within 24 hours prior to the start of study treatment. b) Women must not be breastfeeding c) Women of childbearing potential (WOCBP) must agree to follow instructions for methods of contraception for 32 days after discontinuation (duration of study drug plus 30 days duration of one ovulatory cycle). d) Males who are sexually active with WOCBP must agree to follow instructions for methods of contraception (Appendix 4) 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 counsel WOCBP, and male participants who are sexually active with WOCBP, on the importance of pregnancy prevention and the implications of an unexpected pregnancy. Investigators shall advise on the use of highly effective methods of contraception, (Appendix 4 which have a failure rate of =65 years) no F.1.3.1 Number of subjects for this age range 2
Exclusion criteria
Exclusion criteria: 1) Target Disease Exceptions a) Systolic blood pressure (SBP) 90 bpm at screening orpre-randomization c) Permanent Atrial Fibrillation, Atrial Flutter or having Atrial Fibrillation, Atrial Flutter before start of the infusion d) Permanent paced rhythm (VVI, DDD or BiV pacing) e) NYHA Class IV symptoms of heart failure 2) Medical History and Concurrent Disease a) Primary HF etiology attributable to either restrictive/obstructive cardiomyopathy, idiopathic hypertrophic or uncorrected severe valvular disease as defined by AHA/ACC/ESC criteria. (Note: A restrictive mitral inflow pattern is not exclusionary) b) Pericardial tamponade or constrictive pericarditis c) Large post-MI LV aneurisms d) Intra-cardiac thrombus e) Prior mitral valve repair, mitral or aortic prosthesis of any type. f) LV assist device or prior heart transplant g) Hospitalized for acute decompensated heart failure in the previous month h) Hospitalized with acute coronary syndrome, coronary evascularization or acute myocardial infarction during the previous 90 days prior to screening i) Have a history of a cerebral vascular accident (CVA or stroke) or of a transient ischemic attack (TIA) during the previous 90 days prior to screening j) Considered clinically unstable for any condition k) Serious comorbid non cardiovascular disease in which the life expectancy of the subject is 3 mg/dL (> 51 µmol/L) or significant elevation of liver enzymes (AST, ALT > 3 times the upper limit of normal) m) Prior solid organ transplant 3) Prior/Concomitant Therapy a) Treatment with oral phosphodiesterase type 5 (PDE5) inhibitor sildenafil, vardenafil or avanafil within 24 hours of study drug infusion or treated with tadalafil within 4 days of study drug infusion b) Treatment with intravenous inotropic therapy (dobutamine, milrinone, levosimendan) in the previous month or planned treatment in next 3 months. c) Current treatment with chronic oral, transdermal or sublingual nitrates, except at the discretion of the investigator and treating physician, nitrates could be temporarily interrupted. In which case, an interruption of 3 days is required prior to start of study drug. 4) Physical and Laboratory Test Findings a) Estimated glomerular filtration rate (eGFR) 145 mEq/L (mmol/L) ii) A potassium (K+) concentration 5.5 mEq/L (mmol/L) c) Have severe anemia, as documented by a hemoglobin < 9 g/dL (< 5.59 mmol/L) 5) Allergies and Adverse Drug Reaction a) Any history of allergic reaction to BMS-986231, or its components, Captisol® or potassium acetate. b) Allergic reactions to organic nitrates 6) 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.,
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Evaluate the effects of BMS-986231 on the left ventricular (LV) systolic function by stroke volume index (SVI) assessed by echocardiography compared to placebo.;Secondary Objective: - Evaluate the effects of BMS-986231 on the left ventricular (LV) systolic function by stroke volume index (SVI) assessed by echocardiography compared to nitroglycerin (NTG). - Evaluate the effects of BMS-986231 on selected other left ventricular systolic and diastolic indices compared to placebo and NTG;Primary end point(s): Mean SVI derived from the velocity time integral at the left ventricular outflow tract (LVOT VTI) at the end of the 5-hours infusion of BMS- 986231, versus placebo.;Timepoint(s) of evaluation of this end point: At the end of the 5-hours infusion | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - Mean SVI derived from LVOT VTI at the end of the 5-hours infusion of BMS-986231, versus NTG. - Mean LVEF, computed by Simpson’s method at the end of the 5-hours infusion of BMS-986231, versus placebo and NTG. - Mean cardiac power index at the end of the 5-hours infusion of BMS-986231, versus placebo and NTG. - Mean Diastolic indices: E/A, annular e' velocity and E/e' ratio at the end of the 5-hours infusion of BMS-986231, versus placebo and NTG. - Mean LV global longitudinal strain, computed using STE at the end of the 5-hours infusion of BMS-986231, versus placebo and NTG.;Timepoint(s) of evaluation of this end point: At the end of the 5-hours infusion | — |
Countries
Japan, Netherlands, United Kingdom, United States
Contacts
Public ContactGCT-SU
Bristol-Myers Squibb International Corporation
Outcome results
None listed