A Study of CK-1827452 Infusion in Stable Heart Failure

Inclusion Criteria

• Patient is male, or female of non-childbearing potential (two years post-menopausal or surgically sterilized)
• Female patients must have a negative urine pregnancy test prior to entry into the study
• Patient is 18 years old or greater
• Patient has given signed informed consent
• Patient is considered to be in suitable health in the opinion of the investigator, as determined by:
• A pre-study physical examination with no clinical abnormalities which in the opinion of the investigator would preclude participation in the study other than physical symptoms or signs consistent with stable heart failure
• An electrocardiogram (ECG) with no abnormalities in the opinion of the investigator that would impair assessment of stopping criteria
• Patient has pre-study clinical laboratory findings that are within normal range, or if outside of the normal range, should not preclude participation in the study in the opinion of the investigator (see Exclusion Criteria, below, for exceptions)
• Patient has a documented diagnosis of heart failure with an ejection fraction of less than 40%
• Patient has been on a stable dose of a beta blocker and an ACE (angiotensin-converting enzyme) inhibitor or an ARB (angiotensin II receptor blocker) for at least 4 weeks. If prescribed, diuretics must have been administered according to a consistent regimen for at least 4 weeks
• Patient is currently in sinus rhythm
• Patient has interpretable echocardiographic images on a screening echocardiogram

Exclusion Criteria

• Patient has been hospitalized for heart failure, myocardial infarction, coronary revascularization, or another cardiac indication within the last 6 weeks
• Patient has a current history of alcohol use which in the opinion of the investigator would preclude participation in the study
• Patient has a current history of drug abuse
• Patient has donated blood or blood products within 30 days prior to screening
• Patient has Canadian Cardiovascular Society (CCS) Class III or IV angina
• Patient has significant obstructive valvular disease or significant congenital heart disease
• Patient has had a valve replacement
• Patient is pacemaker dependent
• Patient is on chronic anti-arrhythmic therapy, with the exception of amiodarone
• Patient is currently taking, or has taken in the last 7 days, a CYP3A4 inhibitor or inducer medication
• Patient has a history of hypertrophic obstructive cardiomyopathy
• Patient weighs > 120 kg
• Patient has a supine resting systolic blood pressure 5.5 mEq/L
• Patient has a sodium ≤ 133 mEq/L
• Patient has a urea > 15 mmole/L
• Patient has a troponin I or T at screening that is detectable at the investigative site's clinical laboratory
• Patient has a hemoglobin 3 times the upper limit of normal
• Patient is, in the opinion of the investigator, not suitable to participate in the study
• Patient has participated in any clinical study with an investigational drug within three months prior to the first day of dosing with the exception of coronary stent studies Patient has ever received CK-1827452