Pharmacokinetics of Oral CK-1827452 in Patients With Stable Heart Failure
Condition: Heart Failure
MeSH terms: Heart Failure
Intervention: CK-1827452; CK-1827452; CK-1827452
Intervention description: 50 mg MR CK-1827452 BID for 10 days; 37.5 mg IR CK-1827452 TID for 10 days; 100 mg MR CK-1827452 BID for 10 days
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 35.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: omecamtiv mecarbil

Summary:

      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.
    

Eligibility criteria:

        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