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

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 additional 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.

Key Inclusion Criteria:

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

Key Exclusion Criteria:

• Life expectancy <3 months
• 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
• Any prior treatment with CK-2017357
• Use of non-invasive positive pressure ventilation (NIPPV) for any part of the day or night

Other protocol-defined inclusion/exclusion criteria may apply.