Mexiletine in Sporadic Amyotrophic Lateral Sclerosis (SALS)

Inclusion Criteria: * Sporadic Amyotrophic Lateral Sclerosis (SALS) diagnosed as possible, laboratory-supported probable, probable, or definite ALS as defined by revised El Escorial criteria. * Age 18 years or older. * Disease duration ≤ 36 months from ALS symptom onset. * Capable of providing informed consent and following trial procedures. * Subjects must not have taken riluzole for at least 30 days or be on a 50 milligrams twice daily dose of riluzole for at least 60 days prior to randomization (riluzole-naïve subjects are permitted in the study). * Subjects must not have taken medication for muscle cramping such as cyclobenzaprine, baclofen, carisoprodol, or methocarbamol, for at least 30 days prior to randomization or be on a stable dose for at least 60 days prior to randomization. * Geographic accessibility to the site. * Women must not become pregnant for the duration of the study and must be willing to use two contraceptive therapies and have a negative pregnancy test throughout the course of the study. * Slow vital capacity (SVC) measure greater than or equal to 50% of predicted for gender, height, and age at the screening visit. * Subjects medically able to undergo lumbar puncture (LP) as determined by the investigator (for example, no bleeding disorder, allergy to local anesthetics, a skin infection at or near the LP site, or evidence of high intracranial pressure). * Must be able to swallow capsules throughout the course of the study, according to Principal Investigator (PI) judgment. * Must have a caregiver assist with dispensing the study drug. Exclusion Criteria: * Invasive ventilator dependence, such as tracheostomy. * Creatinine level greater than 1.5 milligram/deciliter. * Serum glutamic oxaloacetic transaminase or (aspartate transaminase) / serum glutamic pyruvic transaminase (alanine aminotransferase) greater than 3 times the upper limit of normal at screening. * History of known sensitivity or intolerability to mexiletine or lidocaine. * Any history of either substance abuse within the past year, unstable psychiatric disease, cognitive impairment, or dementia. * Clinically significant conduction abnormalities on electrocardiogram or a known history of cardiac arrhythmia. * Known history of epilepsy. * Known history of congestive heart failure (CHF) or history of myocardial infarction within the past 24 months. * Use of mexiletine for 60 days prior to Baseline Visit. * Exposure to any other experimental agent (off-label use or investigational) including high dose creatine (greater than 10 grams a day) within 30 days prior to Baseline Visit. * Use of amiodarone, flecainide, duloxetine, tizanidine, or clozapine. * Pregnant women or women currently breastfeeding. * Placement of Diaphragm Pacing System (DPS) device less than 60 days prior to Baseline Visit. * Planned DPS device implantation after Baseline Visit.