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

Heart Failure Clinical Trial

Official title:

An Open Label Study to Investigate the Pharmacokinetics of CK-1827452 Administered Orally to Patients With Stable Heart Failure

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00941681
• Other study ID #: CY 1021
• Status: Completed
• Phase: Phase 2
• First received: July 15, 2009
• Last updated: February 6, 2013
• Start date: April 2009
• Est. completion date: October 2009

Study information

• Verified date: February 2013
• Source: Cytokinetics
• Contact: n/a
• Is FDA regulated: No
• Health authority: Georgia: Ministry of Health
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 35
• Est. completion date: October 2009
• Est. primary completion date: October 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Pharmacokinetics Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Heart Failure

Intervention

Drug:
• CK-1827452
50 mg MR CK-1827452 BID for 10 days
• CK-1827452
37.5 mg IR CK-1827452 TID for 10 days
• CK-1827452
100 mg MR CK-1827452 BID for 10 days

Locations

Country	Name	City	State
Georgia	Cardio-Reanimation Centre	Tbilisi
Georgia	Diagnostic Services Clinic	Tbilisi
Georgia	Tbilisi State Medical University Clinic #1	Tbilisi

Sponsors (1)

Lead Sponsor	Collaborator
Cytokinetics

Country where clinical trial is conducted

Georgia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	C Max (Day 1, Dose 1)	Maximum plasma concentration (C max) measured in nanograms per milliliter (ng/mL) post first dose and pre second dose on day 1. Doses are approximately 12 hours apart in cohort 1 and 3 and 8 hours apart in cohort 2.	1 day	No
Primary	T Max (Day 1, Dose 1)	Time of observed maximum plasma concentration (T max) measured in hours (hr) post first dose and pre second dose on day 1. Doses are approximately 12 hours apart in cohort 1 and 3 and 8 hours apart in cohort 2.	1 day	No
Primary	AUC (Day 1, Dose 1)	Area under the curve (AUC) measured in hours * nanograms per milliliter (hr*ng/mL) post first dose and pre second dose on day 1. Doses are approximately 12 hours apart in cohort 1 and 3 and 8 hours apart in cohort 2.	1 day	No
Primary	C Max (Day 10)	Maximum plasma concentration (C max) measured in nanograms per milliliter (ng/mL) post dose on day 10. Only one dose was administered on day 10 (final dose of study).	1 day	No
Primary	T Max (Day 10)	Time of observed maximum plasma concentration (T max) measured in hours (hr) post dose on day 10. Only one dose was administered on day 10 (final dose of study).	1 day	No
Primary	AUC (Day 10)	Area under the curve (AUC) measured in hours * nanograms per milliliter (hr*ng/mL) post dose on day 10. Only one dose was administered on day 10 (final dose of study).	1 day	No
Secondary	Evaluate the Safety and Tolerability of Oral Formulations of CK-1827452 When Dosed to Steady-state in Patients With Stable Heart Failure.		1 week	Yes