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Journal article
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, v 12(2), pp 455-460
01 Apr 2015
PMID: 25742919
Featured in Collection : UN Sustainable Development Goals @ Drexel
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. The results of this study suggest that tirasemtiv may improve muscle function in MG and will be used to support further development of tirasemtiv in neuromuscular diseases.
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- Title
- 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
- Creators
- Donald B. Sanders - Duke UniversityJeffrey Rosenfeld - University of California, San FranciscoMazen M. Dimachkie - University of Kansas Medical CenterLisa Meng - CytokineticsFady I. Malik - CytokineticsTirasemtiv Myasthenia Gravis StudyCarolyn Jackson - Environmental and Occupational Health
- Publication Details
- Neurotherapeutics, v 12(2), pp 455-460
- Publisher
- Springer Nature
- Number of pages
- 6
- Grant note
- RC3NS070670 / NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Neurological Disorders & Stroke (NINDS) 1RC3NS070670 - 01 / National Institute of Neurological Disorders and Stroke (NINDS); United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Neurological Disorders & Stroke (NINDS) UL1TR001414 / NATIONAL CENTER FOR ADVANCING TRANSLATIONAL SCIENCES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Center for Advancing Translational Sciences (NCATS)
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Environmental and Occupational Health
- Web of Science ID
- WOS:000353223000017
- Scopus ID
- 2-s2.0-84940006623
- Other Identifier
- 991019173452304721
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- Collaboration types
- Industry collaboration
- Domestic collaboration
- Web of Science research areas
- Clinical Neurology
- Neurosciences
- Pharmacology & Pharmacy