A Double-Blinded, Randomized, Placebo-Controlled Trial to Evaluate Efficacy, Safety, and Tolerability of Single Doses of Tirasemtiv in Patients with Acetylcholine Receptor-Binding Antibody-Positive Myasthenia Gravis

Neurotherapeutics : the Journal of the American Society for Experimental NeuroTherapeutics
Donald B SandersTirasemtiv in Myasthenia Gravis Study Group

Abstract

Tirasemtiv is a fast skeletal troponin activator that sensitizes the sarcomere to calcium and increases muscle force following subtetanic nerve input. In an animal model of myasthenia gravis (MG), single oral doses of tirasemtiv improved muscle force and reduced fatigability. The purpose of this study was to determine the effect of single doses of tirasemtiv on skeletal muscle function and fatigability in patients with generalized MG. Thirty-two patients with acetylcholine receptor-antibody positive MG and muscle weakness received single doses of tirasemtiv (250 mg or 500 mg) or placebo in a double-blind, randomized treatment sequence with each treatment separated by at least 1 week. Outcome measures included the Quantitative MG Score (QMG), MG Composite, Manual Muscle Testing, and forced vital capacity. At 6 h after dosing, tirasemtiv produced dose-related improvements from baseline in the QMG score (slope: -0.49 QMG point per 250 mg; p = 0.02) and in percent predicted forced vital capacity (slope: 2.2% per 250 mg; p = 0.04). QMG improved >3 points in twice as many patients after 500 mg tirasemtiv than after placebo. Both doses of tirasemtiv were well tolerated; there were no premature terminations or serious adverse events. T...Continue Reading

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Citations

Oct 30, 2015·Neurotherapeutics : the Journal of the American Society for Experimental NeuroTherapeutics·Jeffrey T GuptillMatthew N Meriggioli
Dec 26, 2015·Journal of Neurology·Sophie BinksJacqueline Palace
Sep 14, 2015·Drugs & Aging·Nuha M Alkhawajah, Joel Oger
Sep 18, 2015·Lancet Neurology·Nils Erik Gilhus, Jan J Verschuuren
Jul 4, 2016·European Journal of Medicinal Chemistry·Vijay KumarFaizan Ahmad
Dec 22, 2017·Muscle & Nerve·Leo H Wang, Michael D Weiss
May 3, 2019·Nature Reviews. Disease Primers·Nils Erik GilhusJan J G M Verschuuren
Jun 28, 2017·Current Opinion in Neurology·Amelia Evoli
Sep 25, 2020·Amyotrophic Lateral Sclerosis & Frontotemporal Degeneration·Jeremy M ShefnerStacy A Rudnicki
Apr 25, 2017·Journal of Neuromuscular Diseases·Josine M de Winter, Coen A C Ottenheijm
Aug 1, 2020·Frontiers in Neurology·Maria Elena Farrugia, John A Goodfellow

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NCT01268280

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SAS

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