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

NCT01131013 | Completed Phase 2

• 1 other identifier: CY 4022
• Study Type: interventional
• Target: 61
• Locations: 1 country
• Sites: 14

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.

Conditions

Intermittent Claudication; Peripheral Artery Disease

Outcome Measures

Primary Outcomes (3)

• 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

• 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

• Effect of single dose of CK-2017357 on Six-Minute Walk Test

  Patient's self-paced walking distance over 6 minutes

  1 day

Secondary Outcomes (4)

• 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

  1 day

• 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

  1 day

• Characterize the relationship, if any, between the plasma concentrations of CK-2017357 and Six-Minute Walk Test

  1 day

• Number of patients with adverse events

  4 weeks

Study Arms (6)

Treatment Sequence 1

EXPERIMENTAL

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

Drug: Placebo; Drug: 375 mg CK-2017357; Drug: 500 mg CK-2017357

Treatment Sequence 2

EXPERIMENTAL

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

Drug: Placebo; Drug: 375 mg CK-2017357; Drug: 500 mg CK-2017357

Treatment Sequence 3

EXPERIMENTAL

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

Drug: Placebo; Drug: 375 mg CK-2017357; Drug: 500 mg CK-2017357

Treatment Sequence 4

EXPERIMENTAL

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

Drug: Placebo; Drug: 375 mg CK-2017357; Drug: 500 mg CK-2017357

Treatment Sequence 5

EXPERIMENTAL

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

Drug: Placebo; Drug: 375 mg CK-2017357; Drug: 500 mg CK-2017357

Treatment Sequence 6

EXPERIMENTAL

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

Drug: Placebo; Drug: 375 mg CK-2017357; Drug: 500 mg CK-2017357

Interventions

Placebo DRUG

Matching placebo in capsules administered as a single oral dose.

Treatment Sequence 1; Treatment Sequence 2; Treatment Sequence 3; Treatment Sequence 4; Treatment Sequence 5; Treatment Sequence 6

375 mg CK-2017357 DRUG

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

Also known as: tirasemtiv

Treatment Sequence 1; Treatment Sequence 2; Treatment Sequence 3; Treatment Sequence 4; Treatment Sequence 5; Treatment Sequence 6

500 mg CK-2017357 DRUG

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

Also known as: tirasemtiv

Treatment Sequence 1; Treatment Sequence 2; Treatment Sequence 3; Treatment Sequence 4; Treatment Sequence 5; Treatment Sequence 6

Eligibility Criteria

• Age: 40 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• Cytokinetics: lead

Study Sites (14)

Tatum Ridge Internal Medicine

Phoenix, Arizona, 85032, United States

Location

Apex Research Institute

Santa Ana, California, 92705, United States

Location

Stanford Hospital and Clinics

Stanford, California, 94305, United States

Location

Denver Health Medical Center

Denver, Colorado, 80204, United States

Location

Tampa Bay Medical Research

Clearwater, Florida, 33761, United States

Location

Jacksonville Center for Clinical Research

Jacksonville, Florida, 32216, United States

Location

DMI Research, Inc

Pinellas Park, Florida, 33782, United States

Location

Maine Research Associates

Auburn, Maine, 04210, United States

Location

University of Massachusetts Memorial Medical Center

Worcester, Massachusetts, 01655, United States

Location

Henry Ford Hospital

Detroit, Michigan, 48202, United States

Location

Baylor College of Medicine

Houston, Texas, 77030, United States

Location

Clinical Trials of Texas, Inc.

San Antonio, Texas, 78229, United States

Location

National Clinical Research - Norfolk, Inc.

Norfolk, Virginia, 23502, United States

Location

National Clinical Research - Richmond, Inc.

Richmond, Virginia, 23294, United States

Location

Related Publications (2)

• 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

  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.

  PMID: 24872402 DERIVED

MeSH Terms

Conditions

Intermittent Claudication; Peripheral Arterial Disease

Interventions

CK-2017357

Condition Hierarchy (Ancestors)

Peripheral Vascular Diseases; Vascular Diseases; Cardiovascular Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Atherosclerosis; Arteriosclerosis; Arterial Occlusive Diseases

Study Officials

• William Hiatt, MD

  Colorado Prevention Center

  STUDY DIRECTOR

• Alan Hirsch, MD

  University of Minnesota

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 25, 2010
• First Posted: May 26, 2010
• Study Start: May 1, 2010
• Primary Completion: March 1, 2011
• Study Completion: March 1, 2011
• Last Updated: May 14, 2019

Record last verified: 2019-05

Locations

US (14)