CK-2017357

The number of participants with adverse events was used as the measure for the long-term safety and tolerability of tirasemtiv.

SVC was measured using a spirometer (in units of liters). Following 3 to 5 breaths at rest, the patients were instructed to take as deep an inspiration as possible followed by a maximum exhalation (blowing out all the air in their lungs). Values obtained were converted to % predicted values (ie, the test result as a percent of predicted values for patients of similar demographic and baseline characteristics \[eg, height, age, sex\], based on Knudson 83 normative values).

The ALSFRS-R is used to measure the progression and severity of disease; it consists of 12 questions, assessing a patient's capability and independence in functional activities relevant to ALS, categorized in 4 domains: gross motor tasks, fine motor tasks, bulbar functions, and respiratory function. Each question is scored from 0 (indicating incapable or dependent) to 4 (normal). The total score ranges from 0 to 48, with higher scores reflecting more normal function and lower scores reflecting more impaired function.

Safety and tolerability of CK-2017357 after multiple oral doses to steady state in patients with ALS

Heel raises will be monitored by an electrogoniometer placed on the index leg and performed once every other second until onset of claudication pain or fatigue as determined by electrogoniometry

Heel raises will be monitored by an electrogoniometer placed on the index leg and performed once every other second until limited by intolerable claudication pain or fatigue as determined by electrogoniometry

Patient's self-paced walking distance over 6 minutes

An instrument for evaluating the functional status of patients with ALS. Minimum score is 0 and maximum score is 40. The higher the score the more function is retained.

Measured using the DynEx Electronic Hand Dynamometer. Patients asked to squeeze the device with the maximum possible force to establish the maximum voluntary contraction.

Handgrip fatigue is measured using the DynEx Electronic Hand Dynamometer. Patient is asked to squeeze the device until they can no longer stay above 60% of target or 120 seconds.

Patient is asked to hold one arm outstretched in front of them at a 90 degree angle. The time the arm falls below 90 degrees for \> 2 seconds will be recorded, up to a total evaluation time of 2 minutes. This is then repeated with the other arm.

SVC is measured using the Puritan Bennett Renaissance II Spirometry System and accessories.

MVV is the volume of air that can be exhaled during 12 seconds of rapid deep breathing. The actual volume is extrapolated to one minute. the Puritan Bennett Renaissance II Spirometry System and accessories is used for this measurement.

SNIP is measured at Functional Residual Capacity, the bottom of the tidal breathing cycle, through one plugged nostril while the other remains open using the Micro Medical MicroRPM Respiratory Pressure Meter

MVC is measured using the MicroFET 2 HHD.

Sub-Maximum Grip Strength Fatigability is measured using the DynEx Electronic Hand. Dynamometer