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A Study of CK-2017357 in Patients With Peripheral Artery Disease and Symptomatic Claudication

This study has been completed.
Sponsor:
Information provided by:
Cytokinetics
ClinicalTrials.gov Identifier:
NCT01131013
First received: May 25, 2010
Last updated: September 16, 2013
Last verified: May 2011
  Purpose

The primary objective of this early-stage clinical study is to demonstrate an effect of single doses of CK-2017357 on measures of skeletal muscle function and fatigability in patients with peripheral artery disease and symptomatic claudication.


Condition Intervention Phase
Intermittent Claudication
Drug: Placebo
Drug: 375 mg CK-2017357
Drug: 500 mg CK-2017357
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase II, Double-Blind, Randomized, Placebo-Controlled, Three-Way Crossover, Pharmacokinetic and Pharmacodynamic Study of CK-2017357 in Patients With Claudication

Resource links provided by NLM:


Further study details as provided by Cytokinetics:

Primary Outcome Measures:
  • The primary objective of this early-stage clinical study is to demonstrate an effect of single doses of CK-2017357 on measures of skeletal muscle function and fatigability in patients with peripheral artery disease and symptomatic claudication. [ Time Frame: 1 day ] [ Designated as safety issue: No ]

    In this hypothesis-generating Phase II study, multiple assessments of skeletal muscle function and fatigability will be made without specifying a single primary pharmacodynamic endpoint. The assessments include:

    • Number of contractions, time and work to onset of claudication during bilateral heel raises
    • Number of contractions, time and work to intolerable claudication pain or maximal calf muscle fatigue as determined by electrogoniometry (end of test) during bilateral heel raises
    • Six-minute walk test


Secondary Outcome Measures:
  • To evaluate and characterize the relationship, if any, between the doses and plasma concentrations of CK-2017357 and its pharmacodynamic effects [ Time Frame: 1 day ] [ Designated as safety issue: No ]
  • To evaluate the safety and tolerability of CK-2017357 administered as single doses to patients with peripheral artery disease and symptomatic claudication [ Time Frame: 4 weeks ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 36
Study Start Date: May 2010
Study Completion Date: March 2011
Primary Completion Date: March 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Three-way crossover
2 oral dose levels of CK-2017357 and placebo
Drug: Placebo
Matching placebo in capsules administered as a single oral dose.
Drug: 375 mg CK-2017357
375 mg CK-2017357 in capsules administered as a single oral dose.
Other Name: tirasemtiv
Drug: 500 mg CK-2017357
500 mg CK-2017357 in capsules administered as a single oral dose.
Other Name: tirasemtiv

Detailed Description:

This study is a Phase II, double-blind, randomized, placebo-controlled, three-way crossover design of two single doses of CK-2017357 in patients with peripheral artery disease and symptomatic claudication. 36 to 72 patients will be randomized at approximately 15 study centers to one of six different treatment sequences. Each treatment sequence consists of three dosing periods in which patients receive single oral doses of placebo, 375 mg and 500 mg of CK-2017357. All six treatment sequences will enroll approximately the same number of patients. A wash out period of at least 6 days (to a maximum of 10 days) will be employed between the individual doses for each patient. This study is designed to assess the effects of CK-2017357 on measures of endurance/fatigue, work output, and walking capacity. The PK and PD relationship of CK-2017357 after two single doses will be assessed versus placebo, and the CK-2017357 concentration versus time data obtained in this study may be used to develop a population PK model to estimate intra- and inter-patient variability of PK parameters in patients with claudication.

  Eligibility

Ages Eligible for Study:   40 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Ability to comprehend and willing to sign an Informed Consent Form (ICF)
  2. Ability to understand written and oral English language
  3. Peripheral arterial disease defined as an ankle-brachial index (ABI) at rest ≤ 0.90 in at least one leg in which the patient experiences claudication
  4. Stable claudication symptoms over past 6 months (Fontaine Stage II) in at least one calf muscle due to documented peripheral artery disease
  5. Females (of non-childbearing potential) or males who are 40 years of age or older
  6. Body mass index (BMI) of 18.0 to 30.0 kg/m2, inclusive
  7. Ability to perform the bilateral heel raise familiarization sufficient to induce typical claudication at a contraction frequency of once every other second
  8. Ability to complete a six-minute walking test
  9. Pre-study clinical laboratory findings (including troponin I [TnI] and creatine phosphokinase [CPK]) within the normal range, or if outside of the normal range, deemed not clinically significant by the Investigator and Sponsor's Medical Monitor
  10. For female patients only: Non-childbearing potential (e.g., documented post-menopausal ≥ 1 year, sterilized, status-post hysterectomy) For male patients only: Agreement either

    • 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 (e.g., diaphragm plus spermicide, or oral contraceptives) for the duration of the study and 10 weeks after the end of the study or
    • To abstain from sexual intercourse for the duration of the study and 10 weeks after the end of the study

Exclusion Criteria:

  1. Asymptomatic peripheral artery disease classified as Fontaine Stage I
  2. Critical leg ischemia classified as Fontaine Stage III-IV (rest pain, tissue necrosis or gangrene)
  3. Non-atherosclerotic causes of arterial occlusive disease
  4. "Atypical leg pain," defined as significant residual leg discomfort at rest
  5. Leg, hip, or knee surgery within 6 months prior to randomization
  6. Any revascularization procedure (coronary or peripheral) within 3 months prior to randomization
  7. Life-threatening ventricular arrhythmias, unstable angina, stroke, and/or myocardial infarction within 3 months prior to randomization
  8. Moderate/severe symptomatic heart failure defined as NYHA Class III or IV; in patients with NYHA Class I or II heart failure, the screening heel raise familiarization must elicit claudication symptoms and not cardiac symptoms
  9. Severe COPD or other respiratory impairment defined as receiving supplemental oxygen therapy at home or by clinical assessment of the Investigator
  10. Poorly controlled hypertension (defined as supine resting BP >180 mmHg systolic or > 100 mmHg diastolic, or both)
  11. Hypotension (defined as supine resting BP < 95 mmHg systolic or < 55 mmHg diastolic, or both, or symptomatic hypotension [standing, supine, or orthostatic])
  12. Exercise tolerance (including ability to perform heel raise and six-minute walk test) that, in the opinion of the Investigator, is significantly limited by other co-morbid conditions or diseases other than claudication
  13. Type 1 diabetes (juvenile onset, insulin-dependent), or poorly controlled Type 2 diabetes (defined as HbA1c > 9.0% in the past 3 months)
  14. Hepatic insufficiency (defined as ALT or AST > 3x ULN, or total bilirubin > 3 mg/dL)
  15. Renal insufficiency (defined as serum creatinine > 2.5 mg/dL or receiving dialysis)
  16. Anemia (defined as hemoglobin < 12.0 g/dL)
  17. Participation in any other investigational study drug or device trial in which receipt of an investigational study drug or device occurred within 30 days prior to dosing
  18. Previous treatment with gene therapy or other vascular endothelial growth factor (VEGF)-related therapy
  19. Any prior treatment with CK-2017357
  20. Recent history of alcoholism or drug abuse, or significant behavioral or psychiatric problems, or other conditions which in the Investigator's opinion may impair ability to adequately comply with the requirements of the study
  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: NCT01131013

Locations
United States, Arizona
Tatum Ridge Internal Medicine
Phoenix, Arizona, United States, 85032
United States, California
Apex Research Institute
Santa Ana, California, United States, 92705
Stanford Hospital and Clinics
Stanford, California, United States, 94305
United States, Colorado
Denver Health Medical Center
Denver, Colorado, United States, 80204
United States, Florida
Tampa Bay Medical Research
Clearwater, Florida, United States, 33761
Jacksonville Center for Clinical Research
Jacksonville, Florida, United States, 32216
DMI Research, Inc
Pinellas Park, Florida, United States, 33782
United States, Maine
Maine Research Associates
Auburn, Maine, United States, 04210
United States, Massachusetts
University of Massachusetts Memorial Medical Center
Worcester, Massachusetts, United States, 01655
United States, Michigan
Henry Ford Hospital
Detroit, Michigan, United States, 48202
United States, Texas
Baylor College of Medicine
Houston, Texas, United States, 77030
Clinical Trials of Texas, Inc.
San Antonio, Texas, United States, 78229
United States, Virginia
National Clinical Research - Norfolk, Inc.
Norfolk, Virginia, United States, 23502
National Clinical Research - Richmond, Inc.
Richmond, Virginia, United States, 23294
Sponsors and Collaborators
Cytokinetics
Investigators
Study Director: William Hiatt, MD Colorado Prevention Center (CPC)
Principal Investigator: Alan Hirsch, MD University of Minnesota - Clinical and Translational Science Institute
  More Information

No publications provided

Responsible Party: Andrew Wolff, MD, FACC, Cytokinetics, Inc.
ClinicalTrials.gov Identifier: NCT01131013     History of Changes
Other Study ID Numbers: CY 4022
Study First Received: May 25, 2010
Last Updated: September 16, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Intermittent Claudication
Arterial Occlusive Diseases
Arteriosclerosis
Cardiovascular Diseases
Signs and Symptoms
Vascular Diseases

ClinicalTrials.gov processed this record on November 20, 2014