Pharmacokinetics (PK) and Tolerability of Intravenous (IV) and Oral CK-1827452 in Patients With Ischemic Cardiomyopathy and Angina

This study has been completed.
Sponsor:
Information provided by:
Cytokinetics
ClinicalTrials.gov Identifier:
NCT00682565
First received: May 20, 2008
Last updated: February 3, 2010
Last verified: February 2010
  Purpose

This study investigates whether symptom-limited exercise capacity in ischemic cardiomyopathy patients with angina is deleteriously affected by treatment with CK-1827452.


Condition Intervention Phase
Heart Failure
Myocardial Ischemia
Angina Pectoris
Drug: CK-1827452
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Tolerability and CK-1827452 Plasma Concentrations During Intravenous and Immediate-Release Oral CK-1827452 in Patients With Ischemic Cardiomyopathy and Angina

Resource links provided by NLM:


Further study details as provided by Cytokinetics:

Primary Outcome Measures:
  • Participants Stopping Exercise Treadmill Test 3 (ETT-3) for Angina at Stage Earlier Than Baseline Exercise Treadmill Test (ETT-B) [ Time Frame: 1 day ]

Secondary Outcome Measures:
  • Participants Stopping ETT-3 for Any Reason at Stage Earlier Than ETT-B [ Time Frame: 1 day ]
  • Change in Exercise Duration During ETT-3 vs. ETT-B [ Time Frame: 1 day ]
  • Participants Stopping ETT-3 for Angina at Any Stage [ Time Frame: 1 day ]
  • Participants With 1 mm ST Segment Depression During ETT-3 [ Time Frame: 1 day ]

Enrollment: 94
Study Start Date: April 2008
Study Completion Date: March 2009
Primary Completion Date: November 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Mid Dose CK-1827452 or Placebo
CK-1827452 or placebo 20 hour infusion followed by 6 days three times a day oral dose and a final single oral dose
Drug: CK-1827452
I.V. infusion for 2 hours at 24mg/hr followed by 18 hours at 6mg/hr
Drug: CK-1827452
12.5mg oral immediate release capsule
Drug: Placebo
I.V. infusion for 20 hours
Drug: Placebo
Matching placebo oral immediate release capsule
Experimental: High Dose CK-1827452 or Placebo
CK-1827452 or placebo 20 hour infusion followed by 6 days three times a day oral dose and a final single oral dose
Drug: CK-1827452
I.V. infusion for 2 hours at 48mg/hr followed by 18 hours at 11mg/hr
Drug: CK-1827452
25mg oral immediate release capsule
Drug: Placebo
I.V. infusion for 20 hours
Drug: Placebo
Matching placebo oral immediate release capsule

  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.
  3. The patient has ischemic heart disease documented by any one or more of the following:

    • A history of myocardial infarction documented by elevated CPK-MB, troponin I or T, or the presence of electrocardiographic Q waves consistent with myocardial infarction.
    • Coronary angiography demonstrating at least 1 major epicardial coronary artery (i.e., left main, left anterior descending, left circumflex, or right coronary artery) with a stenosis of at least 60% diameter or greater but excluding stenosis of the left main coronary artery unless revascularized by coronary artery bypass grafting.
  4. The patient has a history of ≥ 1 episode of exercise induced angina within 2 months prior to the initial screening visit.
  5. The patient has been taking a beta blocker and an ACE inhibitor (and/or an ARB) for at least 4 weeks. If prescribed, diuretics must have been administered for at least 4 weeks prior to the initial screening visit.
  6. The patient is NYHA Class II-III at the time of enrollment and has been so for ≥ 3 months prior to the initial screening visit.
  7. The patient has a history of a left ventricular ejection fraction (LVEF) ≤ 35%.
  8. The patient has a history of EITHER a left ventricular end-diastolic diameter ≥ 55 mm, OR a left ventricular end-diastolic diameter index ≥ 32 mm/m2.
  9. The patient can be expected to complete at least 4 minutes of a Modified Naughton ETT (see Appendix B).
  10. 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.

Exclusion Criteria:

  1. The patient has acute myocarditis; clinically significant restrictive, constrictive, or hypertrophic obstructive cardiomyopathy; or clinically significant congenital heart disease.
  2. The patient has a SBP > 160 mmHg, documented on at least 3 separate occasions, at least 10 minutes apart.
  3. The patient has a DBP > 90 mmHg, documented on at least 3 separate occasions, at least 10 minutes apart.
  4. The patient has levels of troponin I or T, or CPK-MB > the upper limit of normal at any time from 6 weeks prior to the Initial Screening Visit (Visit 1) and up to randomization.
  5. The patient has severe aortic or mitral stenosis.
  6. The patient has had an acute coronary syndrome, transient ischemic attack, or revascularization procedure within 6 weeks of the Initial Screening Visit (Visit 1).
  7. The patient has significant co-morbid conditions (i.e., lung disease, arthritis, peripheral vascular disease) that may limit his or her treadmill exercise capacity.
  8. The patient has renal impairment defined by a calculated creatinine clearance < 30 cc/min or a need for renal replacement therapy.
  9. The patient has known hepatic impairment defined by a total bilirubin > 3 mg/dL, or an ALT or AST > 2 times the upper limit of normal.
  10. The patient has received an investigational drug or device within 30 days or 5 half-lives, whichever is greater, of randomization.
  11. The patient weighs > 120 kg.
  12. The patient has a body temperature > 38 ° C, confirmed by at least 2 successive measurements, at least 10 minutes apart.
  13. The patient has any laboratory abnormality which, in the opinion of the investigator, should preclude his or her participation in the study.
  14. The patient has had any prior treatment with CK-1827452.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00682565

Locations
Georgia
Cardio-Reanimation Centre
Tbilisi, Georgia, 0141
National Center of Therapy
Tbilisi, Georgia, 0159
Diagnostic Services Clinic
Tbilisi, Georgia, 0179
Multiprofile Clinical Hospital of Tbilisi #2
Tbilisi, Georgia, 0164
Tbilisi State Medical University Clinic #1
Tbilisi, Georgia, 0102
Cardiology Clinic
Tbilisi, Georgia, 0144
Russian Federation
Altay Territory Cardiology Dispensary
Barnaul, Russian Federation
City Hospital #1
Barnaul, Russian Federation
City Clinical Hospital #59
Moscow, Russian Federation
City Clinical Hospital #64
Moscow, Russian Federation
Moscow Municipal Clinical Hospital #4
Moscow, Russian Federation
Research Centre for Cardiology n.a. Almazov under Roszdrav
St. Petersburg, Russian Federation
Federal Center of Heart, Blood and Endocrinology n.a. Almazov
St. Petersburg, Russian Federation
Volgograd Regional Cardiology Center
Volgograd, Russian Federation
Sponsors and Collaborators
Cytokinetics
  More Information

No publications provided

Responsible Party: Andrew Wolff, M.D., F.A.C.C., Chief Medical Officer, Cytokinetics, Inc.
ClinicalTrials.gov Identifier: NCT00682565     History of Changes
Other Study ID Numbers: CY 1221
Study First Received: May 20, 2008
Results First Received: November 30, 2009
Last Updated: February 3, 2010
Health Authority: Georgia: Ministry of Health

Additional relevant MeSH terms:
Angina Pectoris
Myocardial Ischemia
Coronary Artery Disease
Heart Failure
Ischemia
Cardiomyopathies
Heart Diseases
Cardiovascular Diseases
Vascular Diseases
Chest Pain
Pain
Signs and Symptoms
Coronary Disease
Arteriosclerosis
Arterial Occlusive Diseases
Pathologic Processes

ClinicalTrials.gov processed this record on April 15, 2014