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

Primary Purpose

Intermittent Claudication, Peripheral Artery Disease

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Placebo
375 mg CK-2017357
500 mg CK-2017357
Sponsored by
Cytokinetics
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Intermittent Claudication

Eligibility Criteria

40 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Tatum Ridge Internal Medicine
  • Apex Research Institute
  • Stanford Hospital and Clinics
  • Denver Health Medical Center
  • Tampa Bay Medical Research
  • Jacksonville Center for Clinical Research
  • DMI Research, Inc
  • Maine Research Associates
  • University of Massachusetts Memorial Medical Center
  • Henry Ford Hospital
  • Baylor College of Medicine
  • Clinical Trials of Texas, Inc.
  • National Clinical Research - Norfolk, Inc.
  • National Clinical Research - Richmond, Inc.

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm Type

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Arm Label

Treatment Sequence 1

Treatment Sequence 2

Treatment Sequence 3

Treatment Sequence 4

Treatment Sequence 5

Treatment Sequence 6

Arm Description

Dosing Period 1 - Placebo; Dosing Period 2 - 375 mg CK-2017357; Dosing Period 3 - 500 mg CK-2017357

Dosing Period 1 - Placebo; Dosing Period 2 - 500 mg CK-2017357; Dosing Period 3 - 375 mg CK-2017357

Dosing Period 1 - 375 mg CK-2017357; Dosing Period 2 - Placebo; Dosing Period 3 - 500 mg CK-2017357

Dosing Period 1 - 375 mg CK-2017357; Dosing Period 2 - 500 mg CK-2017357; Dosing Period 3 - Placebo

Dosing Period 1 - 500 mg CK-2017357; Dosing Period 2 - Placebo; Dosing Period 3 - 375 mg CK-2017357

Dosing Period 1 - 500 mg CK-2017357; Dosing Period 2 - 375 mg CK-2017357; Dosing Period 3 - Placebo

Outcomes

Primary Outcome Measures

Effect of single dose of CK-2017357 on number of contractions, time and work to onset of claudication during bilateral heel raises
Heel raises will be monitored by an electrogoniometer placed on the index leg and performed once every other second until onset of claudication pain or fatigue as determined by electrogoniometry
Effect of single dose of CK-2017357 on number of contractions, time and work to intolerable claudication pain or maximal calf muscle fatigue
Heel raises will be monitored by an electrogoniometer placed on the index leg and performed once every other second until limited by intolerable claudication pain or fatigue as determined by electrogoniometry
Effect of single dose of CK-2017357 on Six-Minute Walk Test
Patient's self-paced walking distance over 6 minutes

Secondary Outcome Measures

Characterize the relationship, if any, between the plasma concentrations of CK-2017357 and number of contractions, time and work to onset of claudication during bilateral heel raises
Bilateral heel raise assessments will be paired with PK concentrations obtained at or near the same time as the bilateral heel raises assessments and analyzed for concentration related effects
Characterize the relationship, if any, between the plasma concentrations of CK-2017357 and number of contractions, time and work to intolerable claudication pain or maximal calf muscle fatigue during bilateral heel raises
Bilateral heel raise assessments will be paired with PK concentrations obtained at or near the same time as the bilateral heel raises assessments and analyzed for concentration related effects
Characterize the relationship, if any, between the plasma concentrations of CK-2017357 and Six-Minute Walk Test
Six-Minute Walk Test will be paired with PK concentrations obtained at or near the same time Six Minute Walk Test and analyzed for concentration related effects
Number of patients with adverse events

Full Information

First Posted
May 25, 2010
Last Updated
May 9, 2019
Sponsor
Cytokinetics
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1. Study Identification

Unique Protocol Identification Number
NCT01131013
Brief Title
A Study of CK-2017357 in Patients With Peripheral Artery Disease and Symptomatic Claudication
Official Title
A Phase II, Double-Blind, Randomized, Placebo-Controlled, Three-Way Crossover, Pharmacokinetic and Pharmacodynamic Study of CK-2017357 in Patients With Claudication
Study Type
Interventional

2. Study Status

Record Verification Date
May 2019
Overall Recruitment Status
Completed
Study Start Date
May 2010 (undefined)
Primary Completion Date
March 2011 (Actual)
Study Completion Date
March 2011 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Cytokinetics

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Intermittent Claudication, Peripheral Artery Disease

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Crossover Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
61 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Treatment Sequence 1
Arm Type
Experimental
Arm Description
Dosing Period 1 - Placebo; Dosing Period 2 - 375 mg CK-2017357; Dosing Period 3 - 500 mg CK-2017357
Arm Title
Treatment Sequence 2
Arm Type
Experimental
Arm Description
Dosing Period 1 - Placebo; Dosing Period 2 - 500 mg CK-2017357; Dosing Period 3 - 375 mg CK-2017357
Arm Title
Treatment Sequence 3
Arm Type
Experimental
Arm Description
Dosing Period 1 - 375 mg CK-2017357; Dosing Period 2 - Placebo; Dosing Period 3 - 500 mg CK-2017357
Arm Title
Treatment Sequence 4
Arm Type
Experimental
Arm Description
Dosing Period 1 - 375 mg CK-2017357; Dosing Period 2 - 500 mg CK-2017357; Dosing Period 3 - Placebo
Arm Title
Treatment Sequence 5
Arm Type
Experimental
Arm Description
Dosing Period 1 - 500 mg CK-2017357; Dosing Period 2 - Placebo; Dosing Period 3 - 375 mg CK-2017357
Arm Title
Treatment Sequence 6
Arm Type
Experimental
Arm Description
Dosing Period 1 - 500 mg CK-2017357; Dosing Period 2 - 375 mg CK-2017357; Dosing Period 3 - Placebo
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Matching placebo in capsules administered as a single oral dose.
Intervention Type
Drug
Intervention Name(s)
375 mg CK-2017357
Other Intervention Name(s)
tirasemtiv
Intervention Description
375 mg CK-2017357 in capsules administered as a single oral dose.
Intervention Type
Drug
Intervention Name(s)
500 mg CK-2017357
Other Intervention Name(s)
tirasemtiv
Intervention Description
500 mg CK-2017357 in capsules administered as a single oral dose.
Primary Outcome Measure Information:
Title
Effect of single dose of CK-2017357 on number of contractions, time and work to onset of claudication during bilateral heel raises
Description
Heel raises will be monitored by an electrogoniometer placed on the index leg and performed once every other second until onset of claudication pain or fatigue as determined by electrogoniometry
Time Frame
1 day
Title
Effect of single dose of CK-2017357 on number of contractions, time and work to intolerable claudication pain or maximal calf muscle fatigue
Description
Heel raises will be monitored by an electrogoniometer placed on the index leg and performed once every other second until limited by intolerable claudication pain or fatigue as determined by electrogoniometry
Time Frame
1 day
Title
Effect of single dose of CK-2017357 on Six-Minute Walk Test
Description
Patient's self-paced walking distance over 6 minutes
Time Frame
1 day
Secondary Outcome Measure Information:
Title
Characterize the relationship, if any, between the plasma concentrations of CK-2017357 and number of contractions, time and work to onset of claudication during bilateral heel raises
Description
Bilateral heel raise assessments will be paired with PK concentrations obtained at or near the same time as the bilateral heel raises assessments and analyzed for concentration related effects
Time Frame
1 day
Title
Characterize the relationship, if any, between the plasma concentrations of CK-2017357 and number of contractions, time and work to intolerable claudication pain or maximal calf muscle fatigue during bilateral heel raises
Description
Bilateral heel raise assessments will be paired with PK concentrations obtained at or near the same time as the bilateral heel raises assessments and analyzed for concentration related effects
Time Frame
1 day
Title
Characterize the relationship, if any, between the plasma concentrations of CK-2017357 and Six-Minute Walk Test
Description
Six-Minute Walk Test will be paired with PK concentrations obtained at or near the same time Six Minute Walk Test and analyzed for concentration related effects
Time Frame
1 day
Title
Number of patients with adverse events
Time Frame
4 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
40 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Ability to comprehend and willing to sign an Informed Consent Form (ICF) Ability to understand written and oral English language 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 Stable claudication symptoms over past 6 months (Fontaine Stage II) in at least one calf muscle due to documented peripheral artery disease Females (of non-childbearing potential) or males who are 40 years of age or older Body mass index (BMI) of 18.0 to 30.0 kg/m2, inclusive Ability to perform the bilateral heel raise familiarization sufficient to induce typical claudication at a contraction frequency of once every other second Ability to complete a six-minute walking test 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 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: Asymptomatic peripheral artery disease classified as Fontaine Stage I Critical leg ischemia classified as Fontaine Stage III-IV (rest pain, tissue necrosis or gangrene) Non-atherosclerotic causes of arterial occlusive disease "Atypical leg pain," defined as significant residual leg discomfort at rest Leg, hip, or knee surgery within 6 months prior to randomization Any revascularization procedure (coronary or peripheral) within 3 months prior to randomization Life-threatening ventricular arrhythmias, unstable angina, stroke, and/or myocardial infarction within 3 months prior to randomization 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 Severe COPD or other respiratory impairment defined as receiving supplemental oxygen therapy at home or by clinical assessment of the Investigator Poorly controlled hypertension (defined as supine resting BP >180 mmHg systolic or > 100 mmHg diastolic, or both) Hypotension (defined as supine resting BP < 95 mmHg systolic or < 55 mmHg diastolic, or both, or symptomatic hypotension [standing, supine, or orthostatic]) 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 Type 1 diabetes (juvenile onset, insulin-dependent), or poorly controlled Type 2 diabetes (defined as HbA1c > 9.0% in the past 3 months) Hepatic insufficiency (defined as ALT or AST > 3x ULN, or total bilirubin > 3 mg/dL) Renal insufficiency (defined as serum creatinine > 2.5 mg/dL or receiving dialysis) Anemia (defined as hemoglobin < 12.0 g/dL) 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 Previous treatment with gene therapy or other vascular endothelial growth factor (VEGF)-related therapy Any prior treatment with CK-2017357 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
William Hiatt, MD
Organizational Affiliation
Colorado Prevention Center
Official's Role
Study Director
First Name & Middle Initial & Last Name & Degree
Alan Hirsch, MD
Organizational Affiliation
University of Minnesota
Official's Role
Principal Investigator
Facility Information:
Facility Name
Tatum Ridge Internal Medicine
City
Phoenix
State/Province
Arizona
ZIP/Postal Code
85032
Country
United States
Facility Name
Apex Research Institute
City
Santa Ana
State/Province
California
ZIP/Postal Code
92705
Country
United States
Facility Name
Stanford Hospital and Clinics
City
Stanford
State/Province
California
ZIP/Postal Code
94305
Country
United States
Facility Name
Denver Health Medical Center
City
Denver
State/Province
Colorado
ZIP/Postal Code
80204
Country
United States
Facility Name
Tampa Bay Medical Research
City
Clearwater
State/Province
Florida
ZIP/Postal Code
33761
Country
United States
Facility Name
Jacksonville Center for Clinical Research
City
Jacksonville
State/Province
Florida
ZIP/Postal Code
32216
Country
United States
Facility Name
DMI Research, Inc
City
Pinellas Park
State/Province
Florida
ZIP/Postal Code
33782
Country
United States
Facility Name
Maine Research Associates
City
Auburn
State/Province
Maine
ZIP/Postal Code
04210
Country
United States
Facility Name
University of Massachusetts Memorial Medical Center
City
Worcester
State/Province
Massachusetts
ZIP/Postal Code
01655
Country
United States
Facility Name
Henry Ford Hospital
City
Detroit
State/Province
Michigan
ZIP/Postal Code
48202
Country
United States
Facility Name
Baylor College of Medicine
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
Clinical Trials of Texas, Inc.
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78229
Country
United States
Facility Name
National Clinical Research - Norfolk, Inc.
City
Norfolk
State/Province
Virginia
ZIP/Postal Code
23502
Country
United States
Facility Name
National Clinical Research - Richmond, Inc.
City
Richmond
State/Province
Virginia
ZIP/Postal Code
23294
Country
United States

12. IPD Sharing Statement

Citations:
Citation
Hiatt WR, Hirsch AT, Bauer TA, Malik F, Lee J, Lin Y, Han FX, Chen MM, Jones D, Cedarbaum JM, Wolff AA. Efficacy and Tolerability of the Novel Fast Skeletal Muscle Troponin Activator, CK-2017357, in Patients with Claudication. 22nd Annual Sessions of the Society for Vascular Medicine. Boston, MA, June 2011
Results Reference
result
PubMed Identifier
24872402
Citation
Bauer TA, Wolff AA, Hirsch AT, Meng LL, Rogers K, Malik FI, Hiatt WR. Effect of tirasemtiv, a selective activator of the fast skeletal muscle troponin complex, in patients with peripheral artery disease. Vasc Med. 2014 Aug;19(4):297-306. doi: 10.1177/1358863X14534516. Epub 2014 May 28.
Results Reference
derived

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

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