Journal article
A randomized, placebo-controlled, double-blind phase IIb trial evaluating the safety and efficacy of tirasemtiv in patients with amyotrophic lateral sclerosis
Amyotrophic lateral sclerosis and frontotemporal degeneration, Vol.17(5-6), pp.426-435
08/17/2016
DOI: 10.3109/21678421.2016.1148169
PMID: 26982815
Abstract
Our objectives were to evaluate the safety and tolerability of tirasemtiv over 12 weeks and its effect on the revised ALS Functional Rating Scale (ALSFRS-R) and other secondary functional measures. This randomized, double-blind, placebo-controlled trial enrolled adults with ALS and slow vital capacity (SVC) > 50% from 73 centers in eight countries. Patients who tolerated open-label tirasemtiv 125 mg b.i.d. for one week were randomized to double-blind treatment either to placebo or tirasemtiv, escalating to a maximum tolerated dose up to 250 mg b.i.d. The primary endpoint was the change from baseline in ALSFRS-R; secondary endpoints included SVC, maximum voluntary ventilation, sniff nasal inspiratory pressure, isometric muscle strength, and sub-maximum handgrip fatigue. Of 711 patients enrolled, 596 were randomized and received at least one dose of double-blind treatment. The primary endpoint showed no treatment effect (tirasemtiv: −2.98 ± 0.28, placebo: −2.40 ± 0.25, p = 0.114); however, SVC and muscle strength declined significantly more slowly on tirasemtiv (95% CI p = 0.0006, p = 0.0158, respectively). Dropouts and serious adverse events occurred more frequently in the tirasemtiv group. In conclusion, this was a negative study with respect to the primary endpoint; however, the effects on SVC and muscle strength suggest a potentially important effect of tirasemtiv warranting further evaluation over a longer period in ALS.
Details
- Title: Subtitle
- A randomized, placebo-controlled, double-blind phase IIb trial evaluating the safety and efficacy of tirasemtiv in patients with amyotrophic lateral sclerosis
- Creators
- Jeremy M Shefner - Barrow Neurological InstituteAndrew A Wolff - Cytokinetics, IncLisa Meng - Cytokinetics, IncAmy Bian - Cytokinetics, IncJacqueline Lee - Cytokinetics, IncDonna Barragan - Cytokinetics, IncJinsy A Andrews - Cytokinetics, IncBenefit-ALS Study Group
- Contributors
- Christopher S Nance (Contributor) - University of Iowa, Neurology
- Resource Type
- Journal article
- Publication Details
- Amyotrophic lateral sclerosis and frontotemporal degeneration, Vol.17(5-6), pp.426-435
- Publisher
- Taylor & Francis
- DOI
- 10.3109/21678421.2016.1148169
- PMID
- 26982815
- ISSN
- 2167-8421
- eISSN
- 2167-9223
- Language
- English
- Date published
- 08/17/2016
- Academic Unit
- Neurology
- Record Identifier
- 9984020612002771
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