[S16.005] The Effect of Tirasemtiv on Functional Status in Patients with ALS

Jeremy Shefner,1Jacqueline Lee,2Donna Barragan,2Lisa Meng,2Andrew Wolff,2Jinsy Andrews,2NEALS/Cytokinetics Study Team
1Syracuse, NY, USA, 2South San Francisco, CA, USA

Objective: This study was designed to determine the safety, tolerability, and efficacy of tirasemtiv administered at a maximum tolerated dose up to 500 mg daily in ALS patients.
Background: Tirasemtiv is a fast skeletal muscle activator that sensitizes the sarcomere to calcium and increases the force of muscle contraction at submaximal nerve stimulation frequencies. In both single and repeated dose studies, ALS patients have tolerated it well and dose dependent improvements in muscle strength and functional measures were suggested.
Design/Methods: Approximately 680 ALS patients were recruited from 75 centers in North America and Europe. Slow vital capacity was greater than 50% of predicted, at least one handgrip was moderately weak, and at least 4 items of the ALSFRS-R were of intermediate grade. All patients were treated for 1 week with open label tirasemtiv 125 mg BID prior to randomization. Patients who tolerated open label tirasemtiv were then randomized 1:1 to either placebo or tirasemtiv and began a 3 week dose escalation to a maximum tolerated daily dose of up to 500 mg daily for a total of 12 weeks. Efficacy measures included ALSFRS-R, quantitative respiratory and extremity muscle strength, and measures of endurance. In patients taking riluzole and randomized to tirasemtiv, riluzole dose was reduced to 50 mg daily because tirasemtiv increases riluzole concentrations. No riluzole dose-adjustment was done in placebo patients.
Results: All patients will be enrolled by November 2013, with the last patient completing dosing by March 2014. Safety and efficacy results will be presented.
Conclusions: This study tests the hypothesis that improvements in skeletal muscle performance can have a meaningful effect on ALS patient function.
Study Supported by: Cytokinetics, Inc
Category - Neuromuscular and Clinical Neurophysiology (EMG): ALS/Anterior Horn Diseases

Tuesday, April 29, 2014 4:15 PM

S16: Platform Session: Neuromuscular and Clinical Neurophysiology (3:15 PM-5:00 PM)


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