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

• Status: Completed
• Trial end date: 2011-03-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Cytokinetics

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