{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T18:21:11Z","timestamp":1786386071201,"version":"build-2736575974"},"reference-count":14,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2025,6,6]],"date-time":"2025-06-06T00:00:00Z","timestamp":1749168000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Muscle and Nerve"],"published-print":{"date-parts":[[2025,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Introduction\/Aims<\/jats:title><jats:p>An On\/Off dosing regimen of intravenous (IV) edaravone and edaravone oral suspension is approved in the US for the treatment of amyotrophic lateral sclerosis (ALS). Placebo\u2010controlled clinical trials showed IV edaravone slows the rate of physical functional decline. This study evaluated whether investigational daily dosing displayed superior efficacy vs. approved on\/off dosing of edaravone oral suspension, and assessed safety and tolerability, over 48\u2009weeks in patients with ALS.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Study MT\u20101186\u2010A02 (NCT04569084) was a multicenter, phase 3b, double\u2010blind, parallel group, superiority study that randomized patients to edaravone oral suspension (105\u2010mg dose) administered Once Daily or the same edaravone oral suspension dose administered according to the approved On\/Off regimen including placebo to mimic daily drug dosing. Patients had definite or probable ALS, baseline forced vital capacity \u2265\u200970%, and baseline disease duration \u2264\u20092\u2009years. The primary endpoint was a combined assessment of function and survival (CAFS) at week 48, which included change in ALS Functional Rating Scale\u2010Revised (ALSFRS\u2010R) and time to death.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>CAFS at week 48 indicated Once Daily dosing did not show a statistically significant difference vs. approved on\/off dosing (<jats:italic>p<\/jats:italic>\u2009=\u20090.777). Both dosing regimens provided comparable change from baseline ALSFRS\u2010R total score to week 48 (least squares mean difference: 0.27 [95% CI \u22121.43 to 1.97]). Edaravone oral suspension was well tolerated, and no new safety concerns were identified in either group.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>Daily edaravone oral suspension did not show superiority and had equivalent safety and tolerability vs. the approved On\/Off regimen, reinforcing the appropriateness of the approved dosing regimen.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mus.28448","type":"journal-article","created":{"date-parts":[[2025,6,6]],"date-time":"2025-06-06T03:34:59Z","timestamp":1749180899000},"page":"433-442","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Efficacy and Safety of Once Daily Dosing vs. Approved On\/Off Dosing of Edaravone Oral Suspension Up to 48\u2009Weeks in Patients With Amyotrophic Lateral Sclerosis (Study <scp>MT<\/scp>\u20101186\u2010<scp>A02<\/scp>)"],"prefix":"10.1002","volume":"72","author":[{"given":"Jeffrey","family":"Rothstein","sequence":"first","affiliation":[{"name":"Department of Neurology, School of Medicine Johns Hopkins University  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angela","family":"Genge","sequence":"additional","affiliation":[{"name":"Montreal Neurological Institute and Hospital  Montreal Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shari","family":"De Silva","sequence":"additional","affiliation":[{"name":"Woodland Research Northwest  Rogers Arkansas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lorne","family":"Zinman","sequence":"additional","affiliation":[{"name":"Sunnybrook Health Sciences Centre University of Toronto  Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marvin","family":"Chum","sequence":"additional","affiliation":[{"name":"McMaster University Health Sciences Centre  Hamilton Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adriano","family":"Chio","sequence":"additional","affiliation":[{"name":"Universit\u00e0 Degli Studi di Torino, Centro Regionale Esperto per la Sclerosi Laterale Amiotrofica (CRESLA)  Turino Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gen","family":"Sobue","sequence":"additional","affiliation":[{"name":"Nagoya University Graduate School of Medicine  Nagoya Aichi Japan"},{"name":"Aichi Medical University  Nagakute Aichi Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masashi","family":"Aoki","sequence":"additional","affiliation":[{"name":"Tohoku University School of Medicine  Sendai Miyagi Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiide","family":"Yoshino","sequence":"additional","affiliation":[{"name":"Neurology Clinic  Chiba Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manabu","family":"Doyu","sequence":"additional","affiliation":[{"name":"Department of Neurology Aichi Medical University  Nagakute Aichi Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Selness","sequence":"additional","affiliation":[{"name":"Mitsubishi Tanabe Pharma America, Inc.  Jersey City New Jersey USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vesna","family":"Todorovic","sequence":"additional","affiliation":[{"name":"Mitsubishi Tanabe Pharma Europe, Ltd.  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nissim","family":"Sasson","sequence":"additional","affiliation":[{"name":"NStat Solutions, Biostatistical Services  Rehovot Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manabu","family":"Hirai","sequence":"additional","affiliation":[{"name":"Mitsubishi Tanabe Pharma America, Inc.  Jersey City New Jersey USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5701-5332","authenticated-orcid":false,"given":"Fumihiro","family":"Takahashi","sequence":"additional","affiliation":[{"name":"Mitsubishi Tanabe Pharma America, Inc.  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