Clinical trial NCT00941681: Pharmacokinetics of Oral CK-1827452 in Patients With Stable Heart Failure
Official title: An Open Label Study to Investigate the Pharmacokinetics of CK-1827452 Administered Orally to Patients With Stable Heart Failure
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Heart Failure
Keywords: omecamtiv mecarbil
Lead sponsor: Cytokinetics
Sponsor class: INDUSTRY
First posted: 2009-07-17
Enrollment: 35
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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

Primary outcomes:
measure: C Max (Day 1, Dose 1)
timeFrame: 1 day
measure: T Max (Day 1, Dose 1)
timeFrame: 1 day
measure: AUC (Day 1, Dose 1)
timeFrame: 1 day
measure: C Max (Day 10)
timeFrame: 1 day
measure: T Max (Day 10)
timeFrame: 1 day
measure: AUC (Day 10)
timeFrame: 1 day
Secondary outcomes:
measure: Evaluate the Safety and Tolerability of Oral Formulations of CK-1827452 When Dosed to Steady-state in Patients With Stable Heart Failure.
timeFrame: 1 week
Other outcomes:
Locations:
city: Tbilisi
country: Georgia
facility: Cardio-Reanimation Centre
city: Tbilisi
country: Georgia
facility: Diagnostic Services Clinic
city: Tbilisi
country: Georgia
facility: Tbilisi State Medical University Clinic #1
Study officials:
References: