Pharmacokinetics of Oral CK-1827452 in Patients With Stable Heart Failure
Pharmacokinetics of Oral CK-1827452 in Patients With Stable Heart Failure
This study is designed to understand the pharmacokinetics of different oral formulations of
 CK-1827452 being considered for future studies in patients with heart failure. This study
 will compare the pharmacokinetics and safety and tolerability of both modified-release (MR)
 and immediate-release (IR) oral formulations of CK-1827452.
Inclusion Criteria:

 1. 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)

 2. The patient is at least 18 years old at the time of consent

 3. Left ventricular ejection fraction (LVEF) ≤ 35% as determined by the Investigator
 within 3 weeks prior to enrollment

 4. Treated for at least 4 weeks with a beta blocker and an ACE inhibitor (and/or an ARB)
 unless not tolerated. If prescribed, diuretics must have been administered according
 to a consistent regimen for at least 4 weeks.

 5. Diagnosed with heart failure for ≥ 3 months prior to enrollment

 6. Patient is considered to be an appropriate candidate for study enrollment as
 determined by the patient's clinical laboratory findings, vital signs and ECGs within
 normal range, or if outside of the normal range not deemed clinically significant in
 the opinion of the Investigator

 7. 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
 she is using contraceptive drugs or devices. For male patients only: Male patients
 agree for the duration of the study and 10 weeks after the end of the study 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 10 weeks after the end of
 the study.

 Exclusion Criteria:

 1. Patient has been hospitalised for heart failure, acute coronary syndrome, myocardial
 infarction, coronary revascularisation, transient ischemic attack or stroke, cardiac
 arrhythmia, or major surgery within 6 weeks prior to enrollment

 2. Poorly controlled hypertension defined as blood pressure > 150/95 mmHg, documented on
 at least 2 separate occasions prior to enrollment

 3. The patient has a supine heart rate ≥ 100 beats per minute after 10 minutes of rest

 4. Patient has a troponin I at screening that is above the upper limit of normal

 5. The patient has severe aortic or mitral stenosis

 6. The patient has active myocarditis; clinically significant restrictive, constrictive,
 or hypertrophic obstructive cardiomyopathy; clinically significant congenital heart
 disease; history of major organ transplantation

 7. The patient has Canadian Cardiovascular Society Class IV angina

 8. Patient is on chronic anti-arrhythmic therapy, with the exception of amiodarone

 9. Patient has impaired renal function defined as an estimated GFR ≤ 30 ml/min/1.73 m2
 calculated by the Modification of Diet in Renal Disease (MDRD) equation

 10. Patient is currently taking, or has taken within 14 days prior to enrollment, a potent
 CYP3A4 inhibitor (medication or food). Patient is currently taking, or has taken
 within 28 days prior to enrollment, a potent CYP3A4 inducer (medication or food).

 11. The patient has hepatic impairment defined as a total bilirubin > 3 mg/dL, or an ALT
 or AST > 2 times the upper limit of normal

 12. Concomitant non-cardiovascular disease that is expected to reduce life expectancy to
 less than 1 year

 13. The patient has received an investigational drug or device within 30 days or 5
 half-lives, whichever is greater, of enrollment

 14. Patient has, 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, including scheduled self-administration of oral CK-1827452

 15. The patient has had any prior treatment with CK-1827452