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PK and Tolerability of IV and Oral CK-1827452 in Patients With Ischemic Cardiomyopathy and Angina

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ClinicalTrials.gov Identifier: NCT00682565
Recruitment Status : Completed
First Posted : May 22, 2008
Results First Posted : February 25, 2010
Last Update Posted : August 21, 2018
Sponsor:
Information provided by (Responsible Party):
Cytokinetics

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

Condition or disease Intervention/treatment Phase
Heart Failure Myocardial Ischemia Angina Pectoris Drug: CK-1827452 24mg and 6 mg iv infusion Drug: CK-1827452 12.5mg capsule Drug: CK-1827452 48 mg and 11 mg iv infusion Drug: CK-1827452 25mg capsule Drug: Placebo iv infusion Drug: Placebo capsule Phase 2

Detailed Description:
The primary objective of this study is to assess the effect of intravenous (i.v.) CK-1827452 on symptom-limited exercise tolerance in patients with ischemic cardiomyopathy and angina. The secondary objectives are to assess the tolerability of CK-1827452 administered three times daily (tid) to steady state in an immediate-release (IR), blend-in-capsule oral formulation to outpatients with ischemic cardiomyopathy and angina and to assess CK-1827452 plasma concentrations at trough and 1 hour after dosing with CK-1827452 administered tid to steady state in an IR, blend-in-capsule oral formulation to outpatients with ischemic cardiomyopathy and angina.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 94 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, 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
Study Start Date : April 2008
Actual Primary Completion Date : November 2008
Actual Study Completion Date : March 2009

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Mid Dose CK-1827452 or Placebo
CK-1827452 I.V. infusion for 2 hours at 24mg/hr followed by 18 hours at 6mg/hr or placebo, followed by 6 days three times a day oral dose and a final single oral dose
Drug: CK-1827452 24mg and 6 mg iv infusion
I.V. infusion for 2 hours at 24mg/hr followed by 18 hours at 6mg/hr
Other Name: omecamtiv mecarbil

Drug: CK-1827452 12.5mg capsule
12.5mg oral immediate release capsule
Other Name: omecamtiv mecarbil

Drug: Placebo iv infusion
Matching placebo iv infusion

Drug: Placebo capsule
Matching placebo oral immediate release capsule

Experimental: High Dose CK-1827452 or Placebo
CK-1827452 I.V. infusion for 2 hours at 48mg/hr followed by 18 hours at 11mg/hr or placebo, followed by 6 days three times a day oral dose and a final single oral dose
Drug: CK-1827452 48 mg and 11 mg iv infusion
I.V. infusion for 2 hours at 48mg/hr followed by 18 hours at 11mg/hr
Other Name: omecamtiv mecarbil

Drug: CK-1827452 25mg capsule
25mg oral immediate release capsule
Other Name: omecamtiv mecarbil

Drug: Placebo iv infusion
Matching placebo iv infusion

Drug: Placebo capsule
Matching placebo oral immediate release capsule




Primary Outcome Measures :
  1. Participants Stopping Exercise Treadmill Test 3 (ETT-3) for Angina at Stage Earlier Than Baseline Exercise Treadmill Test (ETT-B) [ Time Frame: 1 day ]
    The Modified Naughton Exercise Treadmill Test was employed in this study. Exercise Treadmill Test 3 (ETT-3) was performed during the last 2 hours of the 20-hour infusion of study drug or placebo. Baseline Exercise Treadmill Test (ETT-B) was performed prior to dosing.


Secondary Outcome Measures :
  1. Participants Stopping ETT-3 for Any Reason at Stage Earlier Than ETT-B [ Time Frame: 1 day ]
    The Modified Naughton Exercise Treadmill Test was employed in this study. Exercise Treadmill Test 3 (ETT-3) was performed during the last 2 hours of the 20-hour infusion of study drug or placebo. Baseline Exercise Treadmill Test (ETT-B) was performed prior to dosing.

  2. Increase in Exercise Duration During ETT-3 vs. ETT-B [ Time Frame: 1 day ]
  3. Participants Stopping ETT-3 for Angina at Any Stage [ Time Frame: 1 day ]

    This Outcome Measure includes all participants who stopped ETT-3 for angina at any stage, not only those who stopped at a stage earlier than ETT-B.

    Note: All 9 subjects who stopped ETT-3 for angina also stopped ETT-B for angina.


  4. Participants With 1 mm ST Segment Depression During ETT-3 [ Time Frame: 1 day ]
    ST Segment Depression measured by Electrocardiography while performing ETT-3.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00682565


Locations
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Georgia
Tbilisi State Medical University Clinic #1
Tbilisi, Georgia, 0102
Cardio-Reanimation Centre
Tbilisi, Georgia, 0141
Cardiology Clinic
Tbilisi, Georgia, 0144
National Center of Therapy
Tbilisi, Georgia, 0159
Multiprofile Clinical Hospital of Tbilisi #2
Tbilisi, Georgia, 0164
Diagnostic Services Clinic
Tbilisi, Georgia, 0179
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
Federal Center of Heart, Blood and Endocrinology n.a. Almazov
St. Petersburg, Russian Federation
Research Centre for Cardiology n.a. Almazov under Roszdrav
St. Petersburg, Russian Federation
Volgograd Regional Cardiology Center
Volgograd, Russian Federation
Sponsors and Collaborators
Cytokinetics
Investigators
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Study Chair: Andrew A Wolff, MD, FACC Cytokinetics, Inc.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Cytokinetics
ClinicalTrials.gov Identifier: NCT00682565     History of Changes
Other Study ID Numbers: CY 1221
First Posted: May 22, 2008    Key Record Dates
Results First Posted: February 25, 2010
Last Update Posted: August 21, 2018
Last Verified: February 2010
Additional relevant MeSH terms:
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Heart Diseases
Cardiomyopathies
Angina Pectoris
Myocardial Ischemia
Ischemia
Cardiovascular Diseases
Pathologic Processes
Vascular Diseases
Chest Pain
Pain
Neurologic Manifestations
Signs and Symptoms