- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00682565
PK and Tolerability of IV and Oral CK-1827452 in Patients With Ischemic Cardiomyopathy and Angina
July 24, 2018 updated by: Cytokinetics
Tolerability and CK-1827452 Plasma Concentrations During Intravenous and Immediate-Release Oral CK-1827452 in Patients With Ischemic Cardiomyopathy and Angina
This study investigates whether symptom-limited exercise capacity in ischemic cardiomyopathy patients with angina is deleteriously affected by treatment with CK-1827452.
Study Overview
Status
Completed
Conditions
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.
Study Type
Interventional
Enrollment (Actual)
94
Phase
- Phase 2
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
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Tbilisi, Georgia, 0102
- Tbilisi State Medical University Clinic #1
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Tbilisi, Georgia, 0141
- Cardio-Reanimation Centre
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Tbilisi, Georgia, 0159
- National Center of Therapy
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Tbilisi, Georgia, 0179
- Diagnostic Services Clinic
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Tbilisi, Georgia, 0144
- Cardiology Clinic
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Tbilisi, Georgia, 0164
- Multiprofile Clinical Hospital of Tbilisi #2
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Barnaul, Russian Federation
- Altay Territory Cardiology Dispensary
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Barnaul, Russian Federation
- City Hospital #1
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Moscow, Russian Federation
- City Clinical Hospital #59
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Moscow, Russian Federation
- City Clinical Hospital #64
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Moscow, Russian Federation
- Moscow Municipal Clinical Hospital #4
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St. Petersburg, Russian Federation
- Federal Center of Heart, Blood and Endocrinology n.a. Almazov
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St. Petersburg, Russian Federation
- Research Centre for Cardiology n.a. Almazov under Roszdrav
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Volgograd, Russian Federation
- Volgograd Regional Cardiology Center
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years and older (Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
Inclusion Criteria:
- 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.
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.
- The patient has a history of ≥ 1 episode of exercise induced angina within 2 months prior to the initial screening visit.
- 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.
- 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.
- The patient has a history of a left ventricular ejection fraction (LVEF) ≤ 35%.
- 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.
- The patient can be expected to complete at least 4 minutes of a Modified Naughton ETT (see Appendix B).
- 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:
- The patient has acute myocarditis; clinically significant restrictive, constrictive, or hypertrophic obstructive cardiomyopathy; or clinically significant congenital heart disease.
- The patient has a SBP > 160 mmHg, documented on at least 3 separate occasions, at least 10 minutes apart.
- The patient has a DBP > 90 mmHg, documented on at least 3 separate occasions, at least 10 minutes apart.
- 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.
- The patient has severe aortic or mitral stenosis.
- The patient has had an acute coronary syndrome, transient ischemic attack, or revascularization procedure within 6 weeks of the Initial Screening Visit (Visit 1).
- The patient has significant co-morbid conditions (i.e., lung disease, arthritis, peripheral vascular disease) that may limit his or her treadmill exercise capacity.
- The patient has renal impairment defined by a calculated creatinine clearance < 30 cc/min or a need for renal replacement therapy.
- 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.
- The patient has received an investigational drug or device within 30 days or 5 half-lives, whichever is greater, of randomization.
- The patient weighs > 120 kg.
- The patient has a body temperature > 38 ° C, confirmed by at least 2 successive measurements, at least 10 minutes apart.
- The patient has any laboratory abnormality which, in the opinion of the investigator, should preclude his or her participation in the study.
- The patient has had any prior treatment with CK-1827452.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Quadruple
Arms and Interventions
Participant Group / 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
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I.V. infusion for 2 hours at 24mg/hr followed by 18 hours at 6mg/hr
Other Names:
12.5mg oral immediate release capsule
Other Names:
Matching placebo iv infusion
Matching placebo oral immediate release capsule
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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
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Matching placebo iv infusion
Matching placebo oral immediate release capsule
I.V. infusion for 2 hours at 48mg/hr followed by 18 hours at 11mg/hr
Other Names:
25mg oral immediate release capsule
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Participants Stopping Exercise Treadmill Test 3 (ETT-3) for Angina at Stage Earlier Than Baseline Exercise Treadmill Test (ETT-B)
Time Frame: 1 day
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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.
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1 day
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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.
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1 day
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Increase in Exercise Duration During ETT-3 vs. ETT-B
Time Frame: 1 day
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1 day
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Participants Stopping ETT-3 for Angina at Any Stage
Time Frame: 1 day
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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. |
1 day
|
Participants With 1 mm ST Segment Depression During ETT-3
Time Frame: 1 day
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ST Segment Depression measured by Electrocardiography while performing ETT-3.
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1 day
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Investigators
- Study Chair: Andrew A Wolff, MD, FACC, Cytokinetics, Inc.
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start
April 1, 2008
Primary Completion (Actual)
November 1, 2008
Study Completion (Actual)
March 1, 2009
Study Registration Dates
First Submitted
May 20, 2008
First Submitted That Met QC Criteria
May 21, 2008
First Posted (Estimate)
May 22, 2008
Study Record Updates
Last Update Posted (Actual)
August 21, 2018
Last Update Submitted That Met QC Criteria
July 24, 2018
Last Verified
February 1, 2010
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- CY 1221
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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