Authors
Michael D Weiss, Eric A Macklin, Zachary Simmons, Angela S Knox, David J Greenblatt, Nazem Atassi, Michael Graves, Nicholas Parziale, Johnny S Salameh, Colin Quinn, Robert H Brown Jr, Jane B Distad, Jaya Trivedi, Jeremy M Shefner, Richard J Barohn, Alan Pestronk, Andrea Swenson, Merit E Cudkowicz, Mexiletine ALS Study Group, Mexiletine ALS Study Group, Hong Yu, Amanda Nichols, Jason Walker, Igor Katsovskiy, Ervin Sinani, Alexander Sherman, Annette De Mattos, Daniela Grasso, Katelyn Gilardi, Meghan Hall, Mary Lou Watson, Sharon Downing, Divpreet Kaur, Max Lowden, Divisha Raheja, Helen Stephens, Travis Haines, Martina Wiedau-Pazos, Thomas Hintz, Rebecca Alvarez, Diane McKenna-Yasek, Sharon Nations, Lauren Phillips, Lydia Sharp, Nina Gorham, Mazen M Dimachkie, April L Mcvey, Jeffrey Statland, Mamatha Pasnoor, Omar Jawdat, Maureen Walsh, Julaine M Florence, Jeri Sieren, Heena Olalde
Publication date
2016/4/19
Journal
Neurology
Volume
86
Issue
16
Pages
1474-1481
Publisher
Lippincott Williams & Wilkins
Description
Objective
To determine the safety and tolerability of mexiletine in a phase II double-blind randomized controlled trial of sporadic amyotrophic lateral sclerosis (SALS).
Methods
Sixty participants with SALS from 10 centers were randomized 1:1:1 to placebo, mexiletine 300 mg/d, or mexiletine 900 mg/d and followed for 12 weeks. The primary endpoints were safety and tolerability. Secondary endpoints were pharmacokinetic study from plasma and CSF, ALS Functional Rating Scale–Revised (ALSFRS-R) score, slow vital capacity (SVC), and muscle cramp frequency and severity.
Results
The only serious adverse event among active arm participants was one episode of imbalance. Thirty-two percent of participants receiving 900 mg of mexiletine discontinued study drug vs 5% on placebo (p = 0.026). Pharmacokinetic study demonstrated a peak plasma concentration 2 hours postdose and strong correlation between …
Scholar articles
MD Weiss, EA Macklin, Z Simmons, AS Knox… - Neurology, 2016