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

NCT00941681 | Completed Phase 2 Results

• 1 other identifier: CY 1021
• Study Type: interventional
• Target: 35
• Locations: 1 country
• Sites: 3

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

Keywords

omecamtiv mecarbil

Outcome Measures

Primary Outcomes (6)

• 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

• 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

• 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

• 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

• 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

• 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

Secondary Outcomes (1)

• Evaluate the Safety and Tolerability of Oral Formulations of CK-1827452 When Dosed to Steady-state in Patients With Stable Heart Failure.

  1 week

Study Arms (3)

Cohort 1: MR 50 mg BID

EXPERIMENTAL

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

Drug: CK-1827452

Cohort 2: IR 37.5 mg TID

EXPERIMENTAL

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

Drug: CK-1827452

Cohort 3: MR 100 mg BID

EXPERIMENTAL

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

Drug: CK-1827452

Interventions

CK-1827452 DRUG

50 mg MR CK-1827452 BID for 10 days

Cohort 1: MR 50 mg BID

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)
• The patient is at least 18 years old at the time of consent
• Left ventricular ejection fraction (LVEF) ≤ 35% as determined by the Investigator within 3 weeks prior to enrollment
• 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.
• Diagnosed with heart failure for ≥ 3 months prior to enrollment
• 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
• 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.

You may not qualify if:

• 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
• Poorly controlled hypertension defined as blood pressure \> 150/95 mmHg, documented on at least 2 separate occasions prior to enrollment
• The patient has a supine heart rate ≥ 100 beats per minute after 10 minutes of rest
• Patient has a troponin I at screening that is above the upper limit of normal
• The patient has severe aortic or mitral stenosis
• The patient has active myocarditis; clinically significant restrictive, constrictive, or hypertrophic obstructive cardiomyopathy; clinically significant congenital heart disease; history of major organ transplantation
• The patient has Canadian Cardiovascular Society Class IV angina
• Patient is on chronic anti-arrhythmic therapy, with the exception of amiodarone
• 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
• 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).
• 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
• Concomitant non-cardiovascular disease that is expected to reduce life expectancy to less than 1 year
• The patient has received an investigational drug or device within 30 days or 5 half-lives, whichever is greater, of enrollment
• 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
• The patient has had any prior treatment with CK-1827452

Sponsors & Collaborators

• Cytokinetics: lead

Study Sites (3)

Cardio-Reanimation Centre

Tbilisi, Georgia

Location

Diagnostic Services Clinic

Tbilisi, Georgia

Location

Tbilisi State Medical University Clinic #1

Tbilisi, Georgia

Location

MeSH Terms

Conditions

Heart Failure

Interventions

omecamtiv mecarbil

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases

Results Point of Contact

• Title: Project Manager
• Organization: Cytokinetics, Inc.

650-624-2918

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 15, 2009
• First Posted: July 17, 2009
• Study Start: April 1, 2009
• Primary Completion: October 1, 2009
• Study Completion: October 1, 2009
• Last Updated: February 12, 2013
• Results First Posted: December 21, 2010

Record last verified: 2013-02

Locations

GE (3)