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

NCT ID: NCT01131013

Last Updated: 2019-05-14

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 61 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-05-31
• Study Completion Date: 2011-03-31

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.

Conditions

Intermittent Claudication; Peripheral Artery Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Treatment Sequence 1

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

Group Type: EXPERIMENTAL

Placebo

Intervention Type: DRUG

Matching placebo in capsules administered as a single oral dose.

375 mg CK-2017357

Intervention Type: DRUG

375 mg CK-2017357 in capsules administered as a single oral dose.

500 mg CK-2017357

Intervention Type: DRUG

500 mg CK-2017357 in capsules administered as a single oral dose.

Treatment Sequence 2

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

Group Type: EXPERIMENTAL

Placebo

Intervention Type: DRUG

Matching placebo in capsules administered as a single oral dose.

375 mg CK-2017357

Intervention Type: DRUG

375 mg CK-2017357 in capsules administered as a single oral dose.

500 mg CK-2017357

Intervention Type: DRUG

500 mg CK-2017357 in capsules administered as a single oral dose.

Treatment Sequence 3

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

Group Type: EXPERIMENTAL

Placebo

Intervention Type: DRUG

Matching placebo in capsules administered as a single oral dose.

375 mg CK-2017357

Intervention Type: DRUG

375 mg CK-2017357 in capsules administered as a single oral dose.

500 mg CK-2017357

Intervention Type: DRUG

500 mg CK-2017357 in capsules administered as a single oral dose.

Treatment Sequence 4

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

Group Type: EXPERIMENTAL

Placebo

Intervention Type: DRUG

Matching placebo in capsules administered as a single oral dose.

375 mg CK-2017357

Intervention Type: DRUG

375 mg CK-2017357 in capsules administered as a single oral dose.

500 mg CK-2017357

Intervention Type: DRUG

500 mg CK-2017357 in capsules administered as a single oral dose.

Treatment Sequence 5

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

Group Type: EXPERIMENTAL

Placebo

Intervention Type: DRUG

Matching placebo in capsules administered as a single oral dose.

375 mg CK-2017357

Intervention Type: DRUG

375 mg CK-2017357 in capsules administered as a single oral dose.

500 mg CK-2017357

Intervention Type: DRUG

500 mg CK-2017357 in capsules administered as a single oral dose.

Treatment Sequence 6

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

Group Type: EXPERIMENTAL

Placebo

Intervention Type: DRUG

Matching placebo in capsules administered as a single oral dose.

375 mg CK-2017357

Intervention Type: DRUG

375 mg CK-2017357 in capsules administered as a single oral dose.

500 mg CK-2017357

Intervention Type: DRUG

500 mg CK-2017357 in capsules administered as a single oral dose.

Interventions

Placebo

Matching placebo in capsules administered as a single oral dose.

Intervention Type: DRUG

375 mg CK-2017357

375 mg CK-2017357 in capsules administered as a single oral dose.

Intervention Type: DRUG

500 mg CK-2017357

500 mg CK-2017357 in capsules administered as a single oral dose.

Intervention Type: DRUG

Other Intervention Names

tirasemtiv; tirasemtiv

Eligibility 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

• Minimum Eligible Age: 40 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Cytokinetics

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

William Hiatt, MD

Role: STUDY_DIRECTOR

Colorado Prevention Center

Alan Hirsch, MD

Role: PRINCIPAL_INVESTIGATOR

University of Minnesota

Locations

Tatum Ridge Internal Medicine

Phoenix, Arizona, United States

Apex Research Institute

Santa Ana, California, United States

Stanford Hospital and Clinics

Stanford, California, United States

Denver Health Medical Center

Denver, Colorado, United States

Tampa Bay Medical Research

Clearwater, Florida, United States

Jacksonville Center for Clinical Research

Jacksonville, Florida, United States

DMI Research, Inc

Pinellas Park, Florida, United States

Maine Research Associates

Auburn, Maine, United States

University of Massachusetts Memorial Medical Center

Worcester, Massachusetts, United States

Henry Ford Hospital

Detroit, Michigan, United States

Baylor College of Medicine

Houston, Texas, United States

Clinical Trials of Texas, Inc.

San Antonio, Texas, United States

National Clinical Research - Norfolk, Inc.

Norfolk, Virginia, United States

National Clinical Research - Richmond, Inc.

Richmond, Virginia, United States

Countries

United States

References

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

Reference Type: RESULT

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.

Reference Type: DERIVED

PMID: 24872402 (View on PubMed)

Other Identifiers

CY 4022

Identifier Type: -

Identifier Source: org_study_id