A Study of CK-2017357 in Patients With Amyotrophic Lateral Sclerosis (ALS)
- Conditions
- Amyotrophic Lateral Sclerosis
- Interventions
- Drug: PlaceboDrug: 250 mg CK-2017357Drug: 500 mg CK-2017357
- Registration Number
- NCT01089010
- Lead Sponsor
- Cytokinetics
- Brief Summary
The primary objective of this study is to demonstrate a pharmacodynamic effect of CK 2017357 on measures of skeletal muscle function or fatigability in patients with ALS.
- Detailed Description
This study is a Phase II, double-blind, randomized, placebo-controlled, three-way crossover study of CK-2017357 in patients with ALS. 36 to 72 patients will be randomized to one of six different treatment sequences. Each treatment sequence consists of three dosing periods; in each dosing period¸ patients receive a single oral dose of placebo, 250 mg of CK-2017357, or 500 mg of CK-2017357. All six treatment sequences will enroll approximately the same number of patients. A washout period of at least 6 days (to a maximum of 10 days) will be employed between the doses for each patient. This study is designed to assess the effect of CK-2017357 on maximal voluntary muscle strength, on the development of fatigue at maximal and sub-maximal voluntary muscle contraction, and on selected pulmonary function parameters. The plasma concentration of CK-2017357 will be measured at selected time points after each of two single doses of CK-2017357 in men and women. The plasma concentration versus time data obtained in this study may be used to develop a population PK model and estimate inter-subject variability of PK parameters in this target patient population, in particular between male and female study patients.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 67
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- CROSSOVER
- Arm && Interventions
Group Intervention Description Treatment Sequence 1 500 mg CK-2017357 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. Treatment Sequence 1 Placebo 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. Treatment Sequence 1 250 mg CK-2017357 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. Treatment Sequence 2 Placebo 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. Treatment Sequence 3 Placebo 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. Treatment Sequence 3 500 mg CK-2017357 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. Treatment Sequence 4 Placebo 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. Treatment Sequence 4 250 mg CK-2017357 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. Treatment Sequence 5 Placebo 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. Treatment Sequence 5 250 mg CK-2017357 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. Treatment Sequence 6 Placebo 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. Treatment Sequence 3 250 mg CK-2017357 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. Treatment Sequence 6 500 mg CK-2017357 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. Treatment Sequence 2 250 mg CK-2017357 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. Treatment Sequence 2 500 mg CK-2017357 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. Treatment Sequence 6 250 mg CK-2017357 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. Treatment Sequence 4 500 mg CK-2017357 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. Treatment Sequence 5 500 mg CK-2017357 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.
- Primary Outcome Measures
Name Time Method Slow Vital Capacity (SVC) 2 days SVC is measured using the Puritan Bennett Renaissance II Spirometry System and accessories.
Maximum Voluntary Ventilation (MVV) 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.
ALSFRS-R 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 Voluntary Muscle Contraction (MVC) 2 days MVC is measured using the MicroFET 2 HHD.
Maximum grip strength 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.
Shoulder extension fatigue 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.
Maximum grip strength fatigability 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.
Sniff Inspiratory Pressure (SNIP) 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
Repeated Sub-Maximum Grip Strength Fatigability 2 days Sub-Maximum Grip Strength Fatigability is measured using the DynEx Electronic Hand. Dynamometer
- Secondary Outcome Measures
Name Time Method Characterize the relationship, if any, between the plasma concentration of CK-2017357 and repeated sub-maximum grip strength fatigability 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.
Effect of CK-2017357 on investigator determined global functional assessment 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
Characterize the relationship, if any, between the plasma concentration of CK-2017357 and maximum voluntary ventilation 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 maximum grip strength fatigability 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 maximum voluntary muscle contraction 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.
Effect of CK-2017357 on patient determined global functional assessment 2 days Patients will be asked to assess whether they feel the same, better or worse as compared to how they felt pre-dose
Characterize the relationship, if any, between the plasma concentration of CK-2017357 and maximum grip strength 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 sniff inspiratory pressure 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.
Number of patients with adverse events 4 weeks Characterize the relationship, if any, between the plasma concentration of CK-2017357 and ALSFRS-R. 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 shoulder extension fatigue 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 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.
Trial Locations
- Locations (15)
University Neurology Associates
🇺🇸Fresno, California, United States
Johns Hopkins Hospital
🇺🇸Baltimore, Maryland, United States
Massachusetts General Hospital
🇺🇸Boston, Massachusetts, United States
SUNY Upstate Medical Center
🇺🇸Syracuse, New York, United States
Drexel University College of Medicine, Dept of Neurology
🇺🇸Philadelphia, Pennsylvania, United States
University of Vermont
🇺🇸Burlington, Vermont, United States
California Pacific Medical Center
🇺🇸San Francisco, California, United States
Phoenix Neurological Associates, Ltd.
🇺🇸Phoenix, Arizona, United States
Duke University
🇺🇸Durham, North Carolina, United States
The University of Texas Health Science Center at San Antonio
🇺🇸San Antonio, Texas, United States
Providence ALS Center
🇺🇸Portland, Oregon, United States
University of Kentucky
🇺🇸Lexington, Kentucky, United States
Penn State
🇺🇸University Park, Pennsylvania, United States
Washington University
🇺🇸Saint Louis, Missouri, United States
Mayo Clinic Florida
🇺🇸Jacksonville, Florida, United States