• 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. [ Time Frame: 2 days ] [ Designated as safety issue: No ]

  In this hypothesis-generating early Phase II study, multiple assessments of skeletal muscle function will be made without specifying a single primary endpoint, including:

  1. ALS Functional Assessment
  2. Maximum Grip Strength (bilateral)
  3. Maximum Grip Strength Fatigability (bilateral)
  4. Shoulder Extension Fatigue (bilateral)
  5. Slow Vital Capacity
  6. Maximal Voluntary Ventilation
  7. Sniff Inspiratory Pressure
  8. Maximum Voluntary Muscle Contraction of multiple bilateral muscle groups using Hand Held Dynamometry
  9. Repeated Sub-Maximum Grip Strength Fatigability (bilateral)
  
  

• To evaluate and characterize the relationship, if any, between the plasma concentration of CK-2017357 and its pharmacodynamic effects (PK/PD relationship) [ Time Frame: 2 day ] [ Designated as safety issue: No ]
  
• To evaluate the safety and tolerability of 2 doses of CK-2017357 given as single doses administered orally to patients with ALS [ Time Frame: 4 weeks ] [ Designated as safety issue: Yes ]
  
• To evaluate the effect of CK-2017357 on patient and investigator determined global functional assessment [ Time Frame: 2 days ] [ Designated as safety issue: No ]
  

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.