Pharmacokinetics of Oral CK-1827452 in Patients With Stable Heart Failure

NCT ID: NCT00941681

Last Updated: 2013-02-12

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 35 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-04-30
• Study Completion Date: 2009-10-31

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.

Conditions

Heart Failure

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Cohort 1: MR 50 mg BID

Modified-release (MR) 50 mg dose of CK-1827452 twice a day (BID) for 10 days.

Group Type: EXPERIMENTAL

CK-1827452

Intervention Type: DRUG

50 mg MR CK-1827452 BID for 10 days

Cohort 2: IR 37.5 mg TID

Immediate-release (IR) 37.5 mg dose of CK-1827452 three times a day (TID) for 10 days.

Group Type: EXPERIMENTAL

CK-1827452

Intervention Type: DRUG

37.5 mg IR CK-1827452 TID for 10 days

Cohort 3: MR 100 mg BID

Modified-release (MR) 100 mg dose of CK-1827452 twice a day (BID) for 10 days

Group Type: EXPERIMENTAL

CK-1827452

Intervention Type: DRUG

100 mg MR CK-1827452 BID for 10 days

Interventions

CK-1827452

50 mg MR CK-1827452 BID for 10 days

Intervention Type: DRUG

CK-1827452

37.5 mg IR CK-1827452 TID for 10 days

Intervention Type: DRUG

CK-1827452

100 mg MR CK-1827452 BID for 10 days

Intervention Type: DRUG

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Cytokinetics

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Cardio-Reanimation Centre

Tbilisi, , Georgia

Diagnostic Services Clinic

Tbilisi, , Georgia

Tbilisi State Medical University Clinic #1

Tbilisi, , Georgia

Countries

Georgia

Other Identifiers

CY 1021

Identifier Type: -

Identifier Source: org_study_id