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 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:

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.