Ventilatory Investigation of Tirasemtiv and Assessment of Longitudinal Indices After Treatment for a Year

Exclusion Criteria

• •At the time of screening, any use of non-invasive positive pressure ventilation (NIPPV, e.g. continuous positive airway pressure \[CPAP\] or bi-level positive airway pressure \[BiPAP\]) for any portion of the day, or mechanical ventilation via tracheostomy, or on any form of oxygen supplementation
• •Patients with a diaphragm pacing system (DPS) at study entry or who anticipate DPS placement during the course of the study
• •BMI of 20.0 kg/m2 or lower
• •Unwilling or unable to discontinue tizanidine and theophylline-containing medications during study participation
• •Serum chloride outside the normal reference range
• •Neurological impairment due to a condition other than ALS, including history of transient ischemic attack within the past year
• •Presence at screening of any medically significant cardiac, pulmonary, 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, including, but not limited to:
• •1. Poorly controlled hypertension
• •2. NYHA Class II or greater congestive heart failure
• •3. Chronic obstructive pulmonary disease or asthma requiring daily use bronchodilator medications
• •4. GI disorder that might impair absorption of study drug
• •5. History of significant liver disease defined by bilirubin \> 2 times the upper limit of normal (ULN) or ALT or AST \> 3 times the ULN on repeat testing
• •6. Poorly controlled diabetes mellitus
• •7. History of vertigo within three months of study entry
• •8. History of syncope without an explainable or treated cause
• •9. History of untreated intracranial aneurysm or poorly controlled seizure disorder
• •10. Amputation of a limb
• •11. Cognitive impairment, related to ALS or otherwise, sufficient to impair the patient's ability to give informed consent and to understand and/or comply with study procedures
• •12. Cancer with metastatic potential (other than basal cell carcinoma, carcinoma in situ of the cervix, or squamous cell carcinoma of the skin excised with clean margins) diagnosed and treated within the last two years
• •13. Any other condition, impairment or social circumstance that, in the opinion of the Investigator, would render the patient not suitable to participate in the study
• •14. Patient judged to be actively suicidal or a suicide risk by the Investigator
• •Has taken any investigational study drug within 30 days or five half-lives of the prior agent, whichever is greater, prior to dosing
• •Prior participation in any form of stem cell therapy for the treatment of ALS
• •Previously received tirasemtiv in any previous clinical trial