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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.

Publication ,  Journal Article
Sanders, DB; Rosenfeld, J; Dimachkie, MM; Meng, L; Malik, FI; Tirasemtiv in Myasthenia Gravis Study Group
Published in: Neurotherapeutics
April 2015

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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Published In

Neurotherapeutics

DOI

EISSN

1878-7479

Publication Date

April 2015

Volume

12

Issue

2

Start / End Page

455 / 460

Location

United States

Related Subject Headings

  • Young Adult
  • Receptors, Cholinergic
  • Pyrazines
  • Protein Binding
  • Outcome Assessment, Health Care
  • Neurology & Neurosurgery
  • Myasthenia Gravis
  • Muscle, Skeletal
  • Middle Aged
  • Male
 

Citation

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Sanders, D. B., Rosenfeld, J., Dimachkie, M. M., Meng, L., Malik, F. I., & Tirasemtiv in Myasthenia Gravis Study Group. (2015). 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, 12(2), 455–460. https://doi.org/10.1007/s13311-015-0345-y
Sanders, Donald B., Jeffrey Rosenfeld, Mazen M. Dimachkie, Lisa Meng, Fady I. Malik, and Tirasemtiv in Myasthenia Gravis Study Group. “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 12, no. 2 (April 2015): 455–60. https://doi.org/10.1007/s13311-015-0345-y.
Sanders DB, Rosenfeld J, Dimachkie MM, Meng L, Malik FI, Tirasemtiv in Myasthenia Gravis Study Group. 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. 2015 Apr;12(2):455–60.
Sanders DB, Rosenfeld J, Dimachkie MM, Meng L, Malik FI, Tirasemtiv in Myasthenia Gravis Study Group. 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. 2015 Apr;12(2):455–460.
Journal cover image

Published In

Neurotherapeutics

DOI

EISSN

1878-7479

Publication Date

April 2015

Volume

12

Issue

2

Start / End Page

455 / 460

Location

United States

Related Subject Headings

  • Young Adult
  • Receptors, Cholinergic
  • Pyrazines
  • Protein Binding
  • Outcome Assessment, Health Care
  • Neurology & Neurosurgery
  • Myasthenia Gravis
  • Muscle, Skeletal
  • Middle Aged
  • Male