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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Cytokinetics
ClinicalTrials.gov Identifier:
NCT00941681
First received: July 15, 2009
Last updated: February 6, 2013
Last verified: February 2013
  Purpose

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.


Condition Intervention Phase
Heart Failure
Drug: CK-1827452
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: An Open Label Study to Investigate the Pharmacokinetics of CK-1827452 Administered Orally to Patients With Stable Heart Failure

Resource links provided by NLM:


Further study details as provided by Cytokinetics:

Primary Outcome Measures:
  • C Max (Day 1, Dose 1) [ Time Frame: 1 day ] [ Designated as safety issue: No ]
    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.

  • T Max (Day 1, Dose 1) [ Time Frame: 1 day ] [ Designated as safety issue: No ]
    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.

  • AUC (Day 1, Dose 1) [ Time Frame: 1 day ] [ Designated as safety issue: No ]
    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.

  • C Max (Day 10) [ Time Frame: 1 day ] [ Designated as safety issue: No ]
    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).

  • T Max (Day 10) [ Time Frame: 1 day ] [ Designated as safety issue: No ]
    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).

  • AUC (Day 10) [ Time Frame: 1 day ] [ Designated as safety issue: No ]
    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).


Secondary Outcome Measures:
  • Evaluate the Safety and Tolerability of Oral Formulations of CK-1827452 When Dosed to Steady-state in Patients With Stable Heart Failure. [ Time Frame: 1 week ] [ Designated as safety issue: Yes ]

Enrollment: 35
Study Start Date: April 2009
Study Completion Date: October 2009
Primary Completion Date: October 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Cohort 1: MR 50 mg BID
Modified-release (MR) 50 mg dose of CK-1827452 twice a day (BID) for 10 days.
Drug: CK-1827452
50 mg MR CK-1827452 BID for 10 days
Experimental: 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.
Drug: CK-1827452
37.5 mg IR CK-1827452 TID for 10 days
Experimental: Cohort 3: MR 100 mg BID
Modified-release (MR) 100 mg dose of CK-1827452 twice a day (BID) for 10 days
Drug: CK-1827452
100 mg MR CK-1827452 BID for 10 days

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00941681

Locations
Georgia
Cardio-Reanimation Centre
Tbilisi, Georgia
Diagnostic Services Clinic
Tbilisi, Georgia
Tbilisi State Medical University Clinic #1
Tbilisi, Georgia
Sponsors and Collaborators
Cytokinetics
  More Information

No publications provided

Responsible Party: Cytokinetics
ClinicalTrials.gov Identifier: NCT00941681     History of Changes
Other Study ID Numbers: CY 1021
Study First Received: July 15, 2009
Results First Received: October 29, 2010
Last Updated: February 6, 2013
Health Authority: Georgia: Ministry of Health

Keywords provided by Cytokinetics:
omecamtiv mecarbil

Additional relevant MeSH terms:
Heart Failure
Cardiovascular Diseases
Heart Diseases

ClinicalTrials.gov processed this record on November 27, 2014