A Study of CK-2017357 in Patients With Amyotrophic Lateral Sclerosis (ALS)

This study is a Phase II, double-blind, randomized, placebo-controlled, three-way crossover
study of CK-2017357 in patients with ALS. 36 to 72 patients will be randomized to one of six
different treatment sequences. Each treatment sequence consists of three dosing periods; in
each dosing period¸ patients receive a single oral dose of placebo, 250 mg of CK-2017357, or
500 mg of CK-2017357. All six treatment sequences will enroll approximately the same number
of patients. A washout period of at least 6 days (to a maximum of 10 days) will be employed
between the doses for each patient. This study is designed to assess the effect of CK-2017357
on maximal voluntary muscle strength, on the development of fatigue at maximal and
sub-maximal voluntary muscle contraction, and on selected pulmonary function parameters. The
plasma concentration of CK-2017357 will be measured at selected time points after each of two
single doses of CK-2017357 in men and women. The plasma concentration versus time data
obtained in this study may be used to develop a population PK model and estimate
inter-subject variability of PK parameters in this target patient population, in particular
between male and female study patients.

Inclusion Criteria:

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

- 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) (Brooks, et al.,
2000)

- Males or Females 18 years of age or older

- Body mass index (BMI) of 18.0 to 30.0 kg/m2, inclusive

- Maximum voluntary grip strength between 10 & 40 pounds (females) and 10 & 60 pounds
(males)

- Able to maintain grip contraction for 15 seconds

- Upright Slow Vital Capacity (SVC) ≥40% of predicted for age, height, and sex

- Able to perform pulmonary function tests

- Pre-study clinical laboratory findings (including troponin I (TnI) and CPK) within
normal range, or if outside of the normal range, deemed not clinically significant by
the Investigator

- For female patients only: The patient is post-menopausal (≥ 1 year) or sterilized, or
if she is of childbearing potential, she is not breastfeeding, her pregnancy test is
negative, she has no intention to become pregnant during the course of the study, and
she is using contraceptive drugs or devices. For male patients only: Male patients
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 for 10 weeks after the end of
the study.

Exclusion Criteria:

- Significant hepatic/renal insufficiency as defined by Upper Limit of Normal (ULN)
laboratory findings

- Life expectancy <3 months

- Participation in any trial in which receipt of investigational study drug occurred
within 30 days prior to dosing

- Any prior treatment with CK-2017357

- In the opinion of the Investigator, the patient is not suitable to participate in the
study