A Study of CK-2017357 in Patients With Amyotrophic Lateral Sclerosis (ALS)
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The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. |
ClinicalTrials.gov Identifier: NCT01089010 |
Recruitment Status :
Completed
First Posted : March 18, 2010
Last Update Posted : May 10, 2019
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Condition or disease | Intervention/treatment | Phase |
---|---|---|
Amyotrophic Lateral Sclerosis | Drug: Placebo Drug: 250 mg CK-2017357 Drug: 500 mg CK-2017357 | Phase 2 |
Study Type : | Interventional (Clinical Trial) |
Actual Enrollment : | 67 participants |
Allocation: | Randomized |
Intervention Model: | Crossover Assignment |
Masking: | Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor) |
Primary Purpose: | Treatment |
Official Title: | A Phase II, Double-Blind, Randomized, Placebo-Controlled, Three-Way Crossover, Pharmacokinetic and Pharmacodynamic Study of CK-2017357 in Patients With Amyotrophic Lateral Sclerosis (ALS) |
Study Start Date : | March 2010 |
Actual Primary Completion Date : | November 2010 |
Actual Study Completion Date : | November 2010 |

Arm | Intervention/treatment |
---|---|
Experimental: Treatment Sequence 1
Treatment sequence 1 consisted of three dosing periods in which patients received single oral doses of placebo, 250 mg, and 500 mg of CK-2017357, in that order, with approximately one week between each dose. Each patient acted as their own control, as all doses were represented in each treatment sequence.
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Drug: Placebo
Matching placebo in capsules administered as a single oral dose. Drug: 250 mg CK-2017357 250 mg CK-2017357 in capsules administered as a single oral dose.
Other Name: tirasemtiv Drug: 500 mg CK-2017357 500 mg CK-2017357 in capsules administered as a single oral dose.
Other Name: tirasemtiv |
Experimental: Treatment Sequence 2
Treatment sequence 2 consisted of three dosing periods in which patients received single oral doses of placebo, 500 mg, and 250 mg of CK-2017357, in that order, with approximately one week between each dose. Each patient acted as their own control, as all doses were represented in each treatment sequence.
|
Drug: Placebo
Matching placebo in capsules administered as a single oral dose. Drug: 250 mg CK-2017357 250 mg CK-2017357 in capsules administered as a single oral dose.
Other Name: tirasemtiv Drug: 500 mg CK-2017357 500 mg CK-2017357 in capsules administered as a single oral dose.
Other Name: tirasemtiv |
Experimental: Treatment Sequence 3
Treatment sequence 3 consisted of three dosing periods in which patients received single oral doses of 250 mg, placebo and 500 mg of CK-2017357, in that order, with approximately one week between each dose. Each patient acted as their own control, as all doses were represented in each treatment sequence.
|
Drug: Placebo
Matching placebo in capsules administered as a single oral dose. Drug: 250 mg CK-2017357 250 mg CK-2017357 in capsules administered as a single oral dose.
Other Name: tirasemtiv Drug: 500 mg CK-2017357 500 mg CK-2017357 in capsules administered as a single oral dose.
Other Name: tirasemtiv |
Experimental: Treatment Sequence 4
Treatment sequence 4 consisted of three dosing periods in which patients received single oral doses of 250 mg, 500 mg and placebo of CK-2017357, in that order, with approximately one week between each dose. Each patient acted as their own control, as all doses were represented in each treatment sequence.
|
Drug: Placebo
Matching placebo in capsules administered as a single oral dose. Drug: 250 mg CK-2017357 250 mg CK-2017357 in capsules administered as a single oral dose.
Other Name: tirasemtiv Drug: 500 mg CK-2017357 500 mg CK-2017357 in capsules administered as a single oral dose.
Other Name: tirasemtiv |
Experimental: Treatment Sequence 5
Treatment sequence 5 consisted of three dosing periods in which patients received single oral doses of 500 mg, placebo, and 250 mg of CK-2017357, in that order, with approximately one week between each dose. Each patient acted as their own control, as all doses were represented in each treatment sequence.
|
Drug: Placebo
Matching placebo in capsules administered as a single oral dose. Drug: 250 mg CK-2017357 250 mg CK-2017357 in capsules administered as a single oral dose.
Other Name: tirasemtiv Drug: 500 mg CK-2017357 500 mg CK-2017357 in capsules administered as a single oral dose.
Other Name: tirasemtiv |
Experimental: Treatment Sequence 6
Treatment sequence6 consisted of three dosing periods in which patients received single oral doses of 500 mg, 250 mg, and placebo of CK-2017357, in that order, with approximately one week between each dose. Each patient acted as their own control, as all doses were represented in each treatment sequence.
|
Drug: Placebo
Matching placebo in capsules administered as a single oral dose. Drug: 250 mg CK-2017357 250 mg CK-2017357 in capsules administered as a single oral dose.
Other Name: tirasemtiv Drug: 500 mg CK-2017357 500 mg CK-2017357 in capsules administered as a single oral dose.
Other Name: tirasemtiv |
- ALSFRS-R [ Time Frame: 2 days ]An instrument for evaluating the functional status of patients with ALS. Minimum score is 0 and maximum score is 40. The higher the score the more function is retained.
- Maximum grip strength [ Time Frame: 2 days ]Measured using the DynEx Electronic Hand Dynamometer. Patients asked to squeeze the device with the maximum possible force to establish the maximum voluntary contraction.
- Maximum grip strength fatigability [ Time Frame: 2 days ]Handgrip fatigue is measured using the DynEx Electronic Hand Dynamometer. Patient is asked to squeeze the device until they can no longer stay above 60% of target or 120 seconds.
- Shoulder extension fatigue [ Time Frame: 2 days ]Patient is asked to hold one arm outstretched in front of them at a 90 degree angle. The time the arm falls below 90 degrees for > 2 seconds will be recorded, up to a total evaluation time of 2 minutes. This is then repeated with the other arm.
- Slow Vital Capacity (SVC) [ Time Frame: 2 days ]SVC is measured using the Puritan Bennett Renaissance II Spirometry System and accessories.
- Maximum Voluntary Ventilation (MVV) [ Time Frame: 2 days ]MVV is the volume of air that can be exhaled during 12 seconds of rapid deep breathing. The actual volume is extrapolated to one minute. the Puritan Bennett Renaissance II Spirometry System and accessories is used for this measurement.
- Sniff Inspiratory Pressure (SNIP) [ Time Frame: 2 days ]SNIP is measured at Functional Residual Capacity, the bottom of the tidal breathing cycle, through one plugged nostril while the other remains open using the Micro Medical MicroRPM Respiratory Pressure Meter
- Maximum Voluntary Muscle Contraction (MVC) [ Time Frame: 2 days ]MVC is measured using the MicroFET 2 HHD.
- Repeated Sub-Maximum Grip Strength Fatigability [ Time Frame: 2 days ]Sub-Maximum Grip Strength Fatigability is measured using the DynEx Electronic Hand. Dynamometer
- Characterize the relationship, if any, between the plasma concentration of CK-2017357 and ALSFRS-R. [ Time Frame: 2 days ]ALSFRS-R assessments will be paired with PK concentrations obtained at or near the same time as the ALSFRS-R assessments and analyzed for concentration related effects.
- Characterize the relationship, if any, between the plasma concentration of CK-2017357 and maximum grip strength [ Time Frame: 2 days ]Maximum grip strength assessments will be paired with PK concentrations obtained at or near the same time as the maximum grip strength assessments and analyzed for concentration related effects.
- Characterize the relationship, if any, between the plasma concentration of CK-2017357 and maximum grip strength fatigability [ Time Frame: 2 days ]Maximum grip strength fatigability assessments will be paired with PK concentrations obtained at or near the same time as the maximum grip strength fatigability assessments and analyzed for concentration related effects.
- Characterize the relationship, if any, between the plasma concentration of CK-2017357 and shoulder extension fatigue [ Time Frame: 2 days ]Shoulder extension fatigue assessments will be paired with PK concentrations obtained at or near the same time as the shoulder extension fatigue assessments and analyzed for concentration related effects.
- Characterize the relationship, if any, between the plasma concentration of CK-2017357 and slow vital capacity [ Time Frame: 2 days ]Slow vital capacity assessments will be paired with PK concentrations obtained at or near the same time as the slow vital capacity assessments and analyzed for concentration related effects.
- Characterize the relationship, if any, between the plasma concentration of CK-2017357 and maximum voluntary ventilation [ Time Frame: 2 days ]Maximum voluntary ventilation assessments will be paired with PK concentrations obtained at or near the same time as the maximum voluntary ventilation assessments and analyzed for concentration related effects.
- Characterize the relationship, if any, between the plasma concentration of CK-2017357 and sniff inspiratory pressure [ Time Frame: 2 days ]Sniff inspiratory pressure assessments will be paired with PK concentrations obtained at or near the same time as the sniff inspiratory pressure assessments and analyzed for concentration related effects.
- Characterize the relationship, if any, between the plasma concentration of CK-2017357 and maximum voluntary muscle contraction [ Time Frame: 2 days ]Maximum voluntary muscle contraction assessments will be paired with PK concentrations obtained at or near the same time as the maximum voluntary muscle contraction assessments and analyzed for concentration related effects.
- Characterize the relationship, if any, between the plasma concentration of CK-2017357 and repeated sub-maximum grip strength fatigability [ Time Frame: 2 days ]Repeated sub-maximum grip strength fatigability assessments will be paired with PK concentrations obtained at or near the same time as the repeated sub-maximum grip strength fatigability assessments and analyzed for concentration related effects.
- Number of patients with adverse events [ Time Frame: 4 weeks ]
- Effect of CK-2017357 on patient determined global functional assessment [ Time Frame: 2 days ]Patients will be asked to assess whether they feel the same, better or worse as compared to how they felt pre-dose
- Effect of CK-2017357 on investigator determined global functional assessment [ Time Frame: 2 days ]Investigator will assess whether they the patient appears the same, better or worse as compared to the patient's status at pre-dose

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
Inclusion Criteria
For enrollment, patients were required to satisfy all of the following criteria at baseline:
1. Able to comprehend and willing to sign an Informed Consent Form (ICF)
- A diagnosis of familial or sporadic ALS (defined as meeting the possible, laboratory-supported probable, probable, or definite criteria for a diagnosis of ALS according to the World Federation of Neurology El Escorial criteria) (Brooks, Miller et al. 2000)
- Males or females 18 years of age or older
- Body Mass Index (BMI) of 18.0 to 30.0 kg/m2, inclusive
- Maximum voluntary grip strength in at least one hand between 10 and 40 pounds (females) or 10 and 60 pounds (males)
- Able to swallow capsules with water
- Upright Slow Vital Capacity (SVC) > 40% of predicted for age, height, and sex [See Appendix 16.6.1]
- Able to perform pulmonary function tests
- Pre-study clinical laboratory findings (including troponin I [TnI] and creatine phosphokinase [CPK]) within normal range, or, if outside of the normal range, deemed not clinically significant by the Investigator
- For female patients only: The patient is post-menopausal (≥ 1 year) or sterilized, or if she is of childbearing potential, she is not breastfeeding, her pregnancy test is negative, she has no intention to become pregnant during the course of the study, and she is using contraceptive drugs or devices for the duration of the study and for 10 weeks after the end of the study.
For male patients only: Male patients agree for the duration of the study and 10 weeks after the end of the study 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) or the male patient must agree to abstain from sexual intercourse for 10 weeks after the end of the study.
Exclusion Criteria
Patients satisfying any of the following criteria at baseline were excluded from enrollment:
- Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 3 times the upper limit of normal (ULN)
- Life expectancy < 3 months
- Participation in any trial in which receipt of investigational study drug occurred within 30 days prior to dosing
- Any prior treatment with CK-2017357
- In the opinion of the Investigator, the patient is not suitable to participate in the study

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01089010
United States, Arizona | |
Phoenix Neurological Associates, Ltd. | |
Phoenix, Arizona, United States, 85018 | |
United States, California | |
University Neurology Associates | |
Fresno, California, United States, 93701 | |
California Pacific Medical Center | |
San Francisco, California, United States, 94115 | |
United States, Florida | |
Mayo Clinic Florida | |
Jacksonville, Florida, United States, 32224 | |
United States, Kentucky | |
University of Kentucky | |
Lexington, Kentucky, United States, 40536 | |
United States, Maryland | |
Johns Hopkins Hospital | |
Baltimore, Maryland, United States, 21287 | |
United States, Massachusetts | |
Massachusetts General Hospital | |
Boston, Massachusetts, United States, 02114 | |
United States, Missouri | |
Washington University | |
Saint Louis, Missouri, United States, 63110 | |
United States, New York | |
SUNY Upstate Medical Center | |
Syracuse, New York, United States, 13210 | |
United States, North Carolina | |
Duke University | |
Durham, North Carolina, United States, 27705 | |
United States, Oregon | |
Providence ALS Center | |
Portland, Oregon, United States, 97213 | |
United States, Pennsylvania | |
Drexel University College of Medicine, Dept of Neurology | |
Philadelphia, Pennsylvania, United States, 19102 | |
Penn State | |
University Park, Pennsylvania, United States, 17033 | |
United States, Texas | |
The University of Texas Health Science Center at San Antonio | |
San Antonio, Texas, United States, 78229 | |
United States, Vermont | |
University of Vermont | |
Burlington, Vermont, United States, 05401 |
Study Chair: | Jeremy M Shefner, MD, PhD | State University of New York - Upstate Medical University |
Publications of Results:
Responsible Party: | Cytokinetics |
ClinicalTrials.gov Identifier: | NCT01089010 |
Other Study ID Numbers: |
CY 4021 |
First Posted: | March 18, 2010 Key Record Dates |
Last Update Posted: | May 10, 2019 |
Last Verified: | May 2019 |
Motor Neuron Disease Amyotrophic Lateral Sclerosis Sclerosis Pathologic Processes Neurodegenerative Diseases Nervous System Diseases |
Neuromuscular Diseases Spinal Cord Diseases Central Nervous System Diseases TDP-43 Proteinopathies Proteostasis Deficiencies Metabolic Diseases |