Dose Titration Study to Test Safety and Effects of CK-2017357 in Patients With Amyotrophic Lateral Sclerosis (ALS)

Patients will be randomized to one of two dosing groups, active CK-2017357 or placebo, in a
3:1 ratio. Prior to study drug dosing, patients will be required to decrease their riluzole
dose to 50 mg QD for 7 days; after this 7 day period patients will either receive placebo or
start the titration on active CK-2017357 while continuing to take riluzole at 50 mg QD.

Potential patients will be screened to assess their eligibility to enter the study within 21
days prior to Day -7, when they will begin taking riluzole at the decreased dose of 50 mg QD.
Patients will be randomized in a 3:1 ratio to CK-2017357 (Group 1) or placebo (Group 2). On
Day 1, patients will begin taking a total daily dose of 250 mg (125 mg BID) of CK-2017357 or
matching placebo tablets BID for 7 days. Then they will take a total daily dose of 375 mg
(125 mg morning [AM] and 250 mg evening [PM]) of CK-2017357 or matching placebo tablets BID
for 7 days, and finally, they will take a total daily dose of 500 mg (250 mg BID) of
CK-2017357 or matching placebo tablets BID for 7 days. A final dose of 250 mg of CK-2017357
or placebo will be taken in the morning on Day 22 at the study site.

Dose-escalation of CK-2017357 or placebo may be stopped, or the dose reduced to a lower
level, based on tolerability. All patients who return to a lower dose will stay on that dose
for the remainder of the study.

Patients will remain on the decreased dose of riluzole until the follow-up visit
approximately 7 days after Day 22.

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. Able to swallow tablets with water

6. Currently taking and tolerating a stable dose of 50 mg BID riluzole

7. Willing and able to reduce daily dose of riluzole to 50mg QD for 5 weeks

8. Not currently taking or willing and able to remain off theophylline-containing
medications during study participation

9. Patient has a caregiver who is capable of observing and reporting patient status

10. Upright Slow Vital Capacity (SVC) >50% of predicted for age, height, and sex

11. Able to perform pulmonary function tests

Exclusion Criteria:

1. Life expectancy <3 months

2. Receipt of investigational study drug 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. Any use of non-invasive positive pressure ventilation (NIPPV), such as Continuous
Positive Airway Pressure (CPAP) or Bilevel Positive Airway Pressure (BiPAP)

Other protocol-defined inclusion/exclusion criteria may apply.