| Eligibility |
Inclusion Criteria:
- The patient has signed an Informed Consent Form/Patient Information Sheet for this
study approved by the governing Institutional Review Board (IRB) or Independent Ethics
Committee (IEC)
- =18 years old at the time of consent
- Heart failure (HF) for = 3 months and New York Heart Association class II or III at
enrollment
- Left ventricular ejection fraction < / = 35% by most recent echocardiogram within 3
months of enrollment. For patients with cardiac resynchronization therapy (CRT), left
ventricular ejection fraction (LVEF) assessment for eligibility must be performed at
least 3 months after device implantation
- Treated for HF with optimal, stable pharmacological therapy. In general, optimal
treatment will include a beta-blocker and an Angiotensin Converting Enzyme (ACE)
inhibitor and/or an Angiotensin Receptor Blocker (ARB) at doses shown to be
efficacious in Heart Failure (HF) trials, unless not tolerated. Stable medical therapy
is defined as having no new HF drug class introduced 4 weeks prior to enrollment,
although doses of all drugs may be adjusted throughout the trial
- Considered to be an appropriate candidate for study enrollment as determined by the
patient's clinical laboratory findings, vital signs and electrocardiograms (ECGs)
within normal range, or if outside of the normal range not deemed clinically
significant in the opinion of the Investigator
- For female patients only: The patient is post-menopausal (= 1 year) or sterilized, or
if she is of childbearing potential, she is not breastfeeding, her pregnancy test is
negative, she has no intention to become pregnant during the course of the study and
within 1 week following the last dose of omecamtiv mecarbil, and she is using highly
effective methods of birth control. Postmenopausal female is defined as 12 continuous
months of spontaneous amenorrhea confirmed by a serum follicle-stimulating hormone
(FSH) result > 40mIU/mL, or at least 6 weeks postsurgical bilateral oophorectomy (with
or without hysterectomy) as documented in medical history (verified with an operative
note, if available)
- For male patients only: Male patients agree for the duration of the study and 11 weeks
after the last dose of omecamtiv mecarbil to use a condom during sexual intercourse
with female partners who are of reproductive potential and to have female partners use
an additional effective means of contraception (eg, diaphragm plus spermicide, or oral
contraceptives) or the male subject must agree to abstain from sexual intercourse for
the duration of the study and 11 weeks after the last dose of omecamtiv mecarbil.
Exclusion Criteria:
- HF hospitalization, acute coronary syndrome, myocardial infarction, percutaneous
intervention coronary revascularization, transient ischemic attack or stroke, cardiac
arrhythmia within 6 weeks prior to enrollment , or major surgery including thoracic or
cardiac within 8 weeks prior to enrollment
- Symptoms of angina at rest or with minimal activity (Canadian Cardiovascular Society
class III and IV)
- Severe aortic or mitral stenosis or clinically significant valvular heart disease that
might lead to surgical correction within 12 months of enrollment
- Hypertrophic obstructive cardiomyopathy, active myocarditis, constrictive
pericarditis, or clinically significant congenital heart disease
- Refractory, end-stage, heart failure defined as subjects who are appropriate
candidates in the opinion of the investigator for ventricular assist devices,
continuous inotropic therapy, or hospice care
- CRT implantation within 3 months or implantable cardioverter defibrillator (ICD)
within 4 weeks prior to enrollment
- Likely to receive cardiac transplant within 6 months after enrollment
- Recipient of any major organ transplant (eg, lung, liver, heart, bone marrow, renal)
- Known to be hepatitis B surface antigen, hepatitis C virus, or human immunodeficiency
virus (HIV) positive, or a known diagnosis of acquired immunodeficiency syndrome
- Recent (within 3 months) history of alcohol or illicit drug abuse
- Concomitant non-cardiovascular disease that is expected to reduce life expectancy to
less than 1 year
- Routinely scheduled outpatient intravenous (IV) infusions for HF (eg, inotropes,
vasodilators [eg, nesiritide], diuretics) or routinely scheduled ultrafiltration
- Subjects on digoxin therapy with a steady state plasma level (approximately 6 hours
post-dose) that exceeds 1.0 ng/mL at screening
- Chronic antiarrhythmic therapy, with the exception of amiodarone
- Currently taking, or has taken within 14 days prior to enrollment, a potent Cytochrome
P450 3A4 (CYP3A4) inhibitor
- Currently taking, or has taken within 28 days prior to enrollment, a potent CYP3A4
inducer
- Prior treatment with omecamtiv mecarbil
- Currently enrolled in, or at least 60 days or 5 half-lives, whichever is greater,
since ending participation in other investigational device or drug trial(s) or
receiving other investigational agent
- Systolic blood pressure > 150 mm Hg or < 80 mm Hg, or diastolic blood pressure > 95 mm
Hg, assessed on two separate occasions prior to enrollment
- Supine heart rate = 100 beats per minute after 5 minutes of rest or an untreated
symptomatic bradyarrhythmia within 1 month prior to enrollment
- Troponin I at screening > upper limit of normal (ULN)
- Total bilirubin = 1.5 times ULN, or an Alanine transaminase (ALT) or Aspartate
transaminase (AST) = 3 times ULN
- Estimated glomerular filtration rate (GFR) = 30 ml/min/1.73 m2 calculated by the
Modification of Diet in Renal Disease (MDRD) equation
- In the opinion of the Investigator, a condition that compromises the ability of the
subject to give written informed consent or to comply with study procedures
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