Mexiletine for the Treatment of Muscle Cramps in ALS

Inclusion Criteria

• ALS diagnosed according to El Escorial criteria (Awaji version) as: Possible, Probable, or Definite.
• Experiencing cramps as a moderate or severe symptom as defined by willingness to take a medication for the symptom
• ≥2 cramps per week during run in week
• Life expectancy > 6 months, estimated by clinician
• Able to take drug capsule by mouth
• No significant EKG abnormality on screening
• aspartate aminotransferase / alanine aminotransferase <2x upper limit of normal measured at screening
• Having successfully filled out the cramp diary and cramp and fasciculation scales on six out of the last seven days of run in period

Exclusion Criteria

• Inability to communicate by telephone or email
• Allergy/ known sensitivity to mexiletine
• Prior use of mexiletine
• AV block unless subject has pacemaker
• Cardiac arrhythmia
• Prior myocardial infarction
• Other significant EKG abnormality
• Liver disease
• History of leucopenia (WBC <3,500/mm3)
• Epilepsy
• Other serious and unstable medical condition
• Pregnant woman
• Breastfeeding woman
• Active drug or alcohol use or dependence that, in the opinion of the site investigator, would interfere with adherence to study requirements
• Use of quinidine (alone or as a component of Nuedexta®) during the study
• Inability or unwillingness of subject to give written informed consent
• Woman of childbearing potential, not willing to use at least two approved methods of contraception
• Use of a prohibited medication during study