Safety and Efficacy of TUDCA as add-on Treatment in Patients Affected by ALS

Inclusion Criteria:

• Probable laboratory-supported, probable, or definite ALS, as defined by El EscorialRevised ALS diagnostic criteria at screening visit (month -3)
• Disease duration ≤ 18 months at screening visit (month -3)
• Able to perform reproducible pulmonary function tests at screening visit (month -3)
• Forced vital capacity or slow vital capacity ≥70% of normal at screening visit (month -3)
• Stable on riluzole treatment for 3 months in the lead-in period
• Signed informed consent at screening visit (month -3)

Exclusion Criteria:

• Treatment with edaravone
• Other causes of neuromuscular weakness
• Presence of other neurodegenerative diseases
• Significant cognitive impairment, clinical dementia or psychiatric illness
• Severe cardiac or pulmonary disease
• Other diseases precluding functional assessments
• Other life-threatening diseases
• Any use of non-invasive ventilation (e.g. continuous positive airway pressure,non-invasive bi-level positive airway pressure or non-invasive volume ventilation) forany portion of the day, or mechanical ventilation via tracheostomy, or on any form ofoxygen supplementation
• Gastrointestinal disorder that is likely to impair absorption of study drug from thegastrointestinal tract
• Has taken any investigational study drug within 30 days or five half-lives of theprior agent, whichever is longer, prior to dosing
• Any clinically significant laboratory abnormality
• Other concurrent investigational medications
• Active peptic ulcer
• Previous surgery or infections of small intestine
• Patients unable to easily swallow the treatment pills
• Acute inflammation of the gallbladder or bile ducts
• Occurrence of frequent biliary colic, biliary infections, severe pancreaticabnormalities
• Bile duct obstruction, calcified X-ray opaque gallstones and reduced mobility of thegallbladder
• Subjects who weigh 88 lbs (40 kg) or less
• Aspartate aminotransferase or alanine aminotransferase concentrations more than 3times the upper limit of normal
• Creatinine clearance 50 ml/min or less
• Any clinically significant neurological, haematological, autoimmune, endocrine,cardiovascular, neoplastic, renal, gastrointestinal, or other disorder that, in theInvestigator's opinion, could interfere with the subject's participation in the study,place the subject at increased risk, or confound interpretation of study results
• Consideration by the investigator, for any reason, that the subject is an unsuitablecandidate to receive TUDCA or that the subject is unable or unlikely to comply withthe dosing schedule or study evaluations
• The patient of reproductive potential is sexually active and is not willing to usehighly effective contraception during the study and up to 90 days after the day oflast dose
• The patient is pregnant or breast feeding