- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01089010
A Study of CK-2017357 in Patients With Amyotrophic Lateral Sclerosis (ALS)
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 Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
-
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Arizona
-
Phoenix, Arizona, United States, 85018
- Phoenix Neurological Associates, Ltd.
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California
-
Fresno, California, United States, 93701
- University Neurology Associates
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San Francisco, California, United States, 94115
- California Pacific Medical Center
-
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Florida
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Jacksonville, Florida, United States, 32224
- Mayo Clinic Florida
-
-
Kentucky
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Lexington, Kentucky, United States, 40536
- University of Kentucky
-
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Maryland
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Baltimore, Maryland, United States, 21287
- Johns Hopkins Hospital
-
-
Massachusetts
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Boston, Massachusetts, United States, 02114
- Massachusetts General Hospital
-
-
Missouri
-
Saint Louis, Missouri, United States, 63110
- Washington University
-
-
New York
-
Syracuse, New York, United States, 13210
- SUNY Upstate Medical Center
-
-
North Carolina
-
Durham, North Carolina, United States, 27705
- Duke University
-
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Oregon
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Portland, Oregon, United States, 97213
- Providence ALS Center
-
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Pennsylvania
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Philadelphia, Pennsylvania, United States, 19102
- Drexel University College of Medicine, Dept of Neurology
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University Park, Pennsylvania, United States, 17033
- Penn State
-
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Texas
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San Antonio, Texas, United States, 78229
- The University of Texas Health Science Center at San Antonio
-
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Vermont
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Burlington, Vermont, United States, 05401
- University of Vermont
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Crossover Assignment
- Masking: Quadruple
Arms and Interventions
Participant Group / 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.
|
Matching placebo in capsules administered as a single oral dose.
250 mg CK-2017357 in capsules administered as a single oral dose.
Other Names:
500 mg CK-2017357 in capsules administered as a single oral dose.
Other Names:
|
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.
|
Matching placebo in capsules administered as a single oral dose.
250 mg CK-2017357 in capsules administered as a single oral dose.
Other Names:
500 mg CK-2017357 in capsules administered as a single oral dose.
Other Names:
|
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.
|
Matching placebo in capsules administered as a single oral dose.
250 mg CK-2017357 in capsules administered as a single oral dose.
Other Names:
500 mg CK-2017357 in capsules administered as a single oral dose.
Other Names:
|
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.
|
Matching placebo in capsules administered as a single oral dose.
250 mg CK-2017357 in capsules administered as a single oral dose.
Other Names:
500 mg CK-2017357 in capsules administered as a single oral dose.
Other Names:
|
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.
|
Matching placebo in capsules administered as a single oral dose.
250 mg CK-2017357 in capsules administered as a single oral dose.
Other Names:
500 mg CK-2017357 in capsules administered as a single oral dose.
Other Names:
|
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.
|
Matching placebo in capsules administered as a single oral dose.
250 mg CK-2017357 in capsules administered as a single oral dose.
Other Names:
500 mg CK-2017357 in capsules administered as a single oral dose.
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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.
|
2 days
|
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.
|
2 days
|
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.
|
2 days
|
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.
|
2 days
|
Slow Vital Capacity (SVC)
Time Frame: 2 days
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SVC is measured using the Puritan Bennett Renaissance II Spirometry System and accessories.
|
2 days
|
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.
|
2 days
|
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
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2 days
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Maximum Voluntary Muscle Contraction (MVC)
Time Frame: 2 days
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MVC is measured using the MicroFET 2 HHD.
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2 days
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Repeated Sub-Maximum Grip Strength Fatigability
Time Frame: 2 days
|
Sub-Maximum Grip Strength Fatigability is measured using the DynEx Electronic Hand.
Dynamometer
|
2 days
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Number of patients with adverse events
Time Frame: 4 weeks
|
4 weeks
|
|
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.
|
2 days
|
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.
|
2 days
|
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.
|
2 days
|
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.
|
2 days
|
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.
|
2 days
|
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.
|
2 days
|
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.
|
2 days
|
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.
|
2 days
|
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.
|
2 days
|
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
|
2 days
|
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
|
2 days
|
Collaborators and Investigators
Sponsor
Investigators
- Study Chair: Jeremy M Shefner, MD, PhD, State University of New York - Upstate Medical University
Publications and helpful links
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- CY 4021
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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