A Study to Evaluate the Effects of Multiple Doses of CK-2017357 in Patients With Amyotrophic Lateral Sclerosis (ALS)

• ALSFRS-R [ Time Frame: 21 days ] [ Designated as safety issue: No ]
• Measurement of muscle fatigue [ Time Frame: 21 days ] [ Designated as safety issue: No ]
• Measurement of pulmonary function [ Time Frame: 21 days ] [ Designated as safety issue: No ]
• Patient global assessment [ Time Frame: 21 days ] [ Designated as safety issue: No ]
• Investigator global assessment [ Time Frame: 21 days ] [ Designated as safety issue: No ]

The study will generate data on safety and tolerability after multiple daily doses of CK-2017357 in patients with ALS. Patients will be randomized into one of four different treatment groups, receiving daily oral doses of either placebo, 125 mg, 250 mg, or 375 mg of CK-2017357 for 14 days.

In Part A, approximately 24 patients will be randomized to one of four different treatment groups. After a 7-day washout of riluzole, patients in each treatment group will receive daily oral doses of placebo, 125 mg, 250 mg, or 375 mg of CK-2017357 for 14 days. Patients will take daily doses of CK-2017357 or placebo (Day 1 through Day 14) and will return to the study site on Day 2, Day 8 and Day 15. All patients will return for a follow-up visit 7 days (± 2 days) after their last dose.

In Part B, approximately 24 patients will be randomized to one of four different treatment groups as in Part A. Patients in Part B will be required to decrease their riluzole dose to 50 mg once a day (QD) for 7 days prior to randomization. After this 7 day period, patients will take riluzole at 50 mg QD concurrently with their morning dose of blinded study drug.

• Drug: Placebo
  Three matching placebo tablets once daily for 14 days (Part A) or three matching placebo tablets once daily for 14 days taken concurrently with 50 mg riluzole (Part B)
• Drug: CK-2017357
  One 125 mg CK-2017357 tablet and two matching placebo tablets once daily for 14 days (Part A) or one 125 mg CK-2017357 tablet and two matching placebo tablets once daily for 14 days taken concurrently with 50 mg riluzole (Part B)
• Drug: CK-2017357
  Two 125 mg CK-2017357 tablets and one matching placebo tablet once daily for 14 days (Part A) or two 125 mg CK-2017357 tablets and one matching placebo tablet once daily for 14 days taken concurrently with 50 mg riluzole (Part B)
• Drug: CK-2017357
  Three 125 mg CK-2017357 tablets once daily for 14 days (Part A) or three 125 mg CK-2017357 tablets once daily for 14 days taken concurrently with 50 mg riluzole (Part B)

• Placebo Comparator: Matching Placebo
  Intervention: Drug: Placebo
• Experimental: Active Drug Low Dose
  Intervention: Drug: CK-2017357
• Experimental: Active Drug Mid Dose
  Intervention: Drug: CK-2017357
• Experimental: Active Drug High Dose
  Intervention: Drug: CK-2017357

Key Inclusion Criteria:

1. Able to comprehend and willing to sign an Informed Consent Form (ICF)
2. Males or females 18 years of age or older
3. 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)
4. Maximum voluntary grip strength in at least one hand between 10 & 40 pounds (females) and 10 & 60 pounds (males)
5. Upright Slow Vital Capacity (SVC) >50% of predicted for age, height, and sex
6. Able to swallow tablets with water
7. Willing and able to remain off riluzole for 4 weeks (Part A only)
8. Currently taking and tolerating a stable dose of 50 mg BID riluzole (Part B only)
9. Willing and able to reduce daily dose of riluzole to 50 mg for 4 weeks (Part B only)
10. Willing and able to refrain from caffeine-containing products during study participation
11. Willing and able to remain off warfarin and theophylline-containing medications during study participation
12. Has a caregiver who is capable of observing and reporting patient status, and also assisting in the proper use of nocturnal oximetry equipment
13. Able to perform pulmonary function tests

Key Exclusion Criteria:

1. Life expectancy <3 months
2. Participation in any trial in which receipt of investigational study drug occurred within 30 days or 5 half-lives of the prior agent, whichever is greater, prior to dosing
3. Any prior treatment with CK-2017357
4. Use of non-invasive positive pressure ventilation (NIPPV) for any part of the day or night

Other protocol-defined inclusion/exclusion criteria may apply.