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

Peripheral Artery Disease Clinical Trial

Official title:

A Phase II, Double-Blind, Randomized, Placebo-Controlled, Three-Way Crossover, Pharmacokinetic and Pharmacodynamic Study of CK-2017357 in Patients With Claudication

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01131013
• Other study ID #: CY 4022
• Status: Completed
• Phase: Phase 2
• Start date: May 2010
• Est. completion date: March 2011

Study information

• Verified date: May 2019
• Source: Cytokinetics
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 61
• Est. completion date: March 2011
• Est. primary completion date: March 2011
• Accepts healthy volunteers: No
• Gender: All
• Age group: 40 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Intermittent Claudication
• Peripheral Arterial Disease
• Peripheral Artery Disease

Intervention

Drug:
• Placebo
Matching placebo in capsules administered as a single oral dose.
• 375 mg CK-2017357
375 mg CK-2017357 in capsules administered as a single oral dose.
• 500 mg CK-2017357
500 mg CK-2017357 in capsules administered as a single oral dose.

Locations

Country	Name	City	State
United States	Maine Research Associates	Auburn	Maine
United States	Tampa Bay Medical Research	Clearwater	Florida
United States	Denver Health Medical Center	Denver	Colorado
United States	Henry Ford Hospital	Detroit	Michigan
United States	Baylor College of Medicine	Houston	Texas
United States	Jacksonville Center for Clinical Research	Jacksonville	Florida
United States	National Clinical Research - Norfolk, Inc.	Norfolk	Virginia
United States	Tatum Ridge Internal Medicine	Phoenix	Arizona
United States	DMI Research, Inc	Pinellas Park	Florida
United States	National Clinical Research - Richmond, Inc.	Richmond	Virginia
United States	Clinical Trials of Texas, Inc.	San Antonio	Texas
United States	Apex Research Institute	Santa Ana	California
United States	Stanford Hospital and Clinics	Stanford	California
United States	University of Massachusetts Memorial Medical Center	Worcester	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
Cytokinetics

Country where clinical trial is conducted

United States, 

References & Publications (1)

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

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	1 day
Primary	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	1 day
Primary	Effect of single dose of CK-2017357 on Six-Minute Walk Test	Patient's self-paced walking distance over 6 minutes	1 day
Secondary	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	1 day
Secondary	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	1 day
Secondary	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	1 day
Secondary	Number of patients with adverse events		4 weeks