Study of Safety, Tolerability & Efficacy of CK-2017357 in Amyotrophic Lateral Sclerosis (ALS)

The length of the study, including screening, dosing, and follow-up, is approximately 20
weeks. After a one-week open-label phase during which all patients will receive CK-2017357
125 milligrams (mg) twice daily, patients will be randomized one to one (fifty-fifty) to
receive double-blind CK-2017357 or matching placebo. The CK-2017357/placebo dose will be
increased no faster than weekly to each patient's highest tolerated daily dose, with a
maximum of 250 mg twice daily. The dose may be decreased based on tolerability. Patients
will continue treatment at the highest tolerated dose to complete a total of 12 weeks of
double-blind treatment. Patients may be on riluzole or not on riluzole at study entry.
Patients not on riluzole must stay off riluzole. Patients on riluzole who are getting
double-blind CK-2017357 will be given riluzole at half the labeled dosage (50 mg once a day
instead of 50 mg twice a day). Blood tests for safety will be performed. Information about
any side effects that may occur will also be collected.

Inclusion Criteria:

1. Able to comprehend and willing to sign an Informed Consent Form (ICF)

2. Male or female 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. Upright Slow Vital Capacity (SVC) >60 % of predicted for age, height and sex

5. At least 4 of the 12 ALSFRS-R questions must be scored 2 or 3

6. Diminished but measurable maximum voluntary grip strength in at least one hand; i.e.,
between 10 and 40 pounds (females) and 10 and 60 pounds (males)

7. Able to swallow tablets without crushing

8. A caregiver (if one is needed) who can and will observe and report the patient's
status

9. Pre-study clinical laboratory findings within normal range or, if outside of the
normal range, deemed not clinically significant by the Investigator

10. Male patients must agree for the duration of the study and 10 weeks after the end of
the study to use a condom during sexual intercourse with female partners who are of
reproductive potential and to have female partners use an additional effective means
of contraception (e.g., diaphragm plus spermicide, or oral contraceptives) or the
male patient must agree to abstain from sexual intercourse during and for 10 weeks
after the end of the study

11. Female patients must be post-menopausal (≥ 1 year) or sterilized, or, if of
childbearing potential, not be breastfeeding, have a negative pregnancy test, have no
intention to become pregnant during the course of the study, and use contraceptive
drugs or devices as detailed in item 10 for the duration of the study and for 10
weeks after the end of the study

12. Patients must be either on a stable dose of riluzole 50 mg twice daily for at least
30 days prior to screening or have not taken riluzole for at least 30 days prior to
screening and are willing not to begin riluzole use during the conduct of this study.

Exclusion Criteria:

1. Any use of non-invasive positive pressure ventilation (NIPPV, e.g. continuous
positive airway pressure [CPAP] or bilevel positive airway pressure [BiPAP]) for any
portion of the day, or mechanical ventilation via tracheostomy, or on any form of
oxygen supplementation

2. Patients with a diaphragm pacing system (DPS) at study entry or who anticipate DPS
placement during the course of the study

3. Body Mass Index (BMI) of 19.0 kg/m2 or lower

4. Unwilling to discontinue theophylline-containing medications during study
participation

5. Serum chloride < 100 mmol/L

6. Neurological impairment due to a condition other than ALS, including history of
transient ischemic attack (TIA) within the past year

7. Presence at screening of any medically significant cardiac, pulmonary,
gastrointestinal (GI), musculoskeletal, or psychiatric illness that might interfere
with the patient's ability to comply with study procedures or that might confound the
interpretation of clinical safety or efficacy data

8. Has taken any investigational study drug within 30 days or 5 half-lives of the prior
agent, whichever is greater, prior to dosing

9. Previously received CK-2017357 in any previous clinical trial