Intermittent ClaudicationPhase 2NCT01131013

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

A Phase 2 study testing 375 mg CK-2017357 and 500 mg CK-2017357 in people with Intermittent Claudication and Peripheral Artery Disease, run by Cytokinetics at 14 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

Search all trials

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. Read more about this study

Who is it for?: Ages 40 years and older
Conditions the study is for: Intermittent Claudication, Peripheral Artery Disease
What is being tested?: 375 mg CK-2017357 and 500 mg CK-2017357
Type of treatment: Pill or oral medicine
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 61 participants
Where: 14 sitesUnited States
Study dates: May 2010to Mar 2011
Phase: Phase 2
Are there results?: None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 40 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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

Show all 12Show fewer

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

Who cannot join

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

Show all 20Show fewer

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

Trial locations and contacts

14 sites in 1 country.

City, postcode or hospital

14 sites in 1 country

United States14 sites

Maine Research Associates
Auburn, Maine, 04210
Tampa Bay Medical Research
Clearwater, Florida, 33761
Denver Health Medical Center
Denver, Colorado, 80204
Henry Ford Hospital
Detroit, Michigan, 48202
Baylor College of Medicine
Houston, Texas, 77030
Jacksonville Center for Clinical Research
Jacksonville, Florida, 32216
National Clinical Research - Norfolk, Inc.
Norfolk, Virginia, 23502
Tatum Ridge Internal Medicine
Phoenix, Arizona, 85032
DMI Research, Inc
Pinellas Park, Florida, 33782
National Clinical Research - Richmond, Inc.
Richmond, Virginia, 23294
Clinical Trials of Texas, Inc.
San Antonio, Texas, 78229
Apex Research Institute
Santa Ana, California, 92705
Stanford Hospital and Clinics
Stanford, California, 94305
University of Massachusetts Memorial Medical Center
Worcester, Massachusetts, 01655

Other trials in United States

About this study

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

Read the 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
Being tested: Placebo, 375 mg CK-2017357, 500 mg CK-2017357
Medical subject headings: Intermittent Claudication, Peripheral Arterial Disease

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

PlaceboDrug
Matching placebo in capsules administered as a single oral dose.
375 mg CK-2017357Drug
Also called tirasemtiv
375 mg CK-2017357 in capsules administered as a single oral dose.
500 mg CK-2017357Drug
Also called tirasemtiv
500 mg CK-2017357 in capsules administered as a single oral dose.

Study groups in NCT01131013
Study group	Role	What they receive
Treatment Sequence 1	Experimental	Dosing Period 1 - Placebo; Dosing Period 2 - 375 mg CK-2017357; Dosing Period 3 - 500 mg CK-2017357 Receives: 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 Receives: 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 Receives: 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 Receives: 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 Receives: 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 Receives: Drug: Placebo; Drug: 375 mg CK-2017357; Drug: 500 mg CK-2017357

What is being measured

The primary outcome is the main question the study is designed to answer.

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
Measured: 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
Measured: 1 day
Effect of single dose of CK-2017357 on Six-Minute Walk Test
Patient's self-paced walking distance over 6 minutes
Measured: 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
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
Measured: 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
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
Measured: 1 day
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
Measured: 1 day
Number of patients with adverse events
Measured: 4 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

May 2010Mar 2011

First posted26 May 2010 (estimated)
Study startMay 2010
Primary completionMar 2011
Study completionMar 2011

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Publications (2)Papers the sponsor has linked to this study.
Other trials for Intermittent ClaudicationStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Crossover
Masking: Quadruple blind
Who is masked: Participant, Care provider, Investigator, Outcomes assessor
Enrolment: 61 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01131013
Sponsor's protocol ID: CY 4022
Status last verified: May 2019
First submitted: 25 May 2010
Last updated: 14 May 2019
Results posted: No
Data monitoring committee: No

Publications

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
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.
PubMed 24872402

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

Not yet recruiting
Daily Stretching to Improve Walking in Older Patients With Peripheral Artery Disease: The STRETCH PAD Study
Peripheral Artery Disease (PAD), Intermittent Claudication
Recruiting
EVERO Drug-coated Balloon (DCB) Randomized Trial
Peripheral Vascular Disease, Peripheral Arterial Disease
Recruiting
Personalised Multicomponent Exercise Programme in Peripheral Arterial Disease
Peripheral Arterial Disease, Intermittent Claudication
Active, not recruitingPhase 4
Ramipril Treatment of Claudication: Oxidative Damage and Muscle Fibrosis
Peripheral Arterial Disease
RecruitingPhase 3
Improving Mobility After Revascularization in Peripheral Artery Disease
Peripheral Artery Disease, Intermittent Claudication

All Intermittent Claudication trials

Study at a glance

From the registry record, last updated by the sponsor on 14 May 2019. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Phase II, Double-Blind, Randomized, Placebo-Controlled, Three-Way Crossover, Pharmacokinetic and Pharmacodynamic Study of CK-2017357 in Patients With Claudication
ClinicalTrials.gov ID: NCT01131013
Acronym / sponsor ID: CY 4022
Conditions: Intermittent Claudication, Peripheral Artery Disease
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 61 participants (actual)
Lead sponsor: CytokineticsIndustry (pharma, biotech, devices)
Study start: May 2010
Primary completion: Mar 2011 (actual)
Study completion: Mar 2011 (actual)
First posted: 26 May 2010 (estimated)
Results: Not posted in the source record

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Crossover
Masking: Quadruple blind (participant, care provider, investigator, outcomes assessor)
Number of arms: 6

Arm	Type	Receives
Treatment Sequence 1	Experimental	Drug: Placebo, Drug: 375 mg CK-2017357, Drug: 500 mg CK-2017357Dosing Period 1 - Placebo; Dosing Period 2 - 375 mg CK-2017357; Dosing Period 3 - 500 mg CK-2017357
Treatment Sequence 2	Experimental	Drug: Placebo, Drug: 375 mg CK-2017357, Drug: 500 mg CK-2017357Dosing Period 1 - Placebo; Dosing Period 2 - 500 mg CK-2017357; Dosing Period 3 - 375 mg CK-2017357
Treatment Sequence 3	Experimental	Drug: Placebo, Drug: 375 mg CK-2017357, Drug: 500 mg CK-2017357Dosing Period 1 - 375 mg CK-2017357; Dosing Period 2 - Placebo; Dosing Period 3 - 500 mg CK-2017357
Treatment Sequence 4	Experimental	Drug: Placebo, Drug: 375 mg CK-2017357, Drug: 500 mg CK-2017357Dosing Period 1 - 375 mg CK-2017357; Dosing Period 2 - 500 mg CK-2017357; Dosing Period 3 - Placebo
Treatment Sequence 5	Experimental	Drug: Placebo, Drug: 375 mg CK-2017357, Drug: 500 mg CK-2017357Dosing Period 1 - 500 mg CK-2017357; Dosing Period 2 - Placebo; Dosing Period 3 - 375 mg CK-2017357
Treatment Sequence 6	Experimental	Drug: Placebo, Drug: 375 mg CK-2017357, Drug: 500 mg CK-2017357Dosing Period 1 - 500 mg CK-2017357; Dosing Period 2 - 375 mg CK-2017357; Dosing Period 3 - Placebo

Who may qualify

Ages: 40 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (12 listed)

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

Key exclusion criteria (20 listed)

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

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
PlaceboMatching placebo in capsules administered as a single oral dose.	Drug	Treatment Sequence 1, Treatment Sequence 2, Treatment Sequence 3, Treatment Sequence 4, Treatment Sequence 5, Treatment Sequence 6
375 mg CK-2017357Also: tirasemtiv375 mg CK-2017357 in capsules administered as a single oral dose.	Drug	Treatment Sequence 1, Treatment Sequence 2, Treatment Sequence 3, Treatment Sequence 4, Treatment Sequence 5, Treatment Sequence 6
500 mg CK-2017357Also: tirasemtiv500 mg CK-2017357 in capsules administered as a single oral dose.	Drug	Treatment Sequence 1, Treatment Sequence 2, Treatment Sequence 3, Treatment Sequence 4, Treatment Sequence 5, Treatment Sequence 6

Primary outcome

Effect of single dose of CK-2017357 on number of contractions, time and work to onset of claudication during bilateral heel raises
Time frame: 1 day
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
Time frame: 1 day
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
Time frame: 1 day
Patient's self-paced walking distance over 6 minutes

4 secondary outcomes

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
Time frame: 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
Time frame: 1 day
Characterize the relationship, if any, between the plasma concentrations of CK-2017357 and Six-Minute Walk Test
Time frame: 1 day
Number of patients with adverse events
Time frame: 4 weeks

Results and safety

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 14 May 2019.
Results publicationHiatt 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
Derived from this study: PubMed 24872402Bauer 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.

Related trials for Intermittent Claudication

Not yet recruiting
Daily Stretching to Improve Walking in Older Patients With Peripheral Artery Disease: The STRETCH PAD Study
Peripheral Artery Disease (PAD), Intermittent Claudication
Recruiting
EVERO Drug-coated Balloon (DCB) Randomized Trial
Peripheral Vascular Disease, Peripheral Arterial Disease
Recruiting
Personalised Multicomponent Exercise Programme in Peripheral Arterial Disease
Peripheral Arterial Disease, Intermittent Claudication
Active, not recruitingPhase 4
Ramipril Treatment of Claudication: Oxidative Damage and Muscle Fibrosis
Peripheral Arterial Disease
RecruitingPhase 3
Improving Mobility After Revascularization in Peripheral Artery Disease
Peripheral Artery Disease, Intermittent Claudication

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

William Hiatt, MD study director

Colorado Prevention Center

Alan Hirsch, MD principal investigator

University of Minnesota

14 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing 375 mg CK-2017357 and 500 mg CK-2017357 in people with Intermittent Claudication and Peripheral Artery Disease, run by Cytokinetics at 14 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 12 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 14 May 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 14 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Effect of single dose of CK-2017357 on number of contractions, time and work to onset of claudication during bilateral heel raises (time frame: 1 day). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01131013, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 May 2019.