{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T14:12:42Z","timestamp":1788790362882,"version":"build-2803163510"},"reference-count":16,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2025,12,23]],"date-time":"2025-12-23T00:00:00Z","timestamp":1766448000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2025,12,23]],"date-time":"2025-12-23T00:00:00Z","timestamp":1766448000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Muscle and Nerve"],"published-print":{"date-parts":[[2026,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Introduction\/Aims<\/jats:title>\n                    <jats:p>An On\/Off dosing regimen of intravenous (IV) edaravone and edaravone oral suspension is currently approved in the US for treatment of amyotrophic lateral sclerosis (ALS). Placebo\u2010controlled clinical trials showed that IV edaravone slows physical functional decline. Study MT\u20101186\u2010A04 continued to examine the efficacy and safety of investigational once daily and approved on\/off dosing of edaravone oral suspension in patients with ALS.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Study MT\u20101186\u2010A04 (NCT05151471) was a phase 3b, multicenter, randomized, double\u2010blind, parallel group extension study for up to an additional 48\u2009weeks following 48\u2010week Study MT\u20101186\u2010A02 that randomized patients to investigational once daily or approved 105\u2010mg on\/off dosing of edaravone oral suspension. Patients who met Study MT\u20101186\u2010A04 eligibility criteria, including Study MT\u20101186\u2010A02 completion, continued in the same treatment regimen as Study MT\u20101186\u2010A02. The primary efficacy endpoint for MT\u20101186\u2010A04 was time from randomization in Study MT\u20101186\u2010A02 to a \u2265\u200912\u2010point decrease in ALS Functional Rating Scale\u2010Revised (ALSFRS\u2010R) or death, whichever happened first.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Over 96\u2009weeks, including Study MT\u20101186\u2010A02, daily dosing did not show a statistically significant difference vs. approved on\/off dosing for the primary endpoint (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.78). Edaravone oral suspension was well tolerated, and no new safety concerns were identified in either group.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>Similar to Study MT\u20101186\u2010A02, once daily edaravone oral suspension in extension Study MT\u20101186\u2010A04 did not show superiority in terms of the primary efficacy endpoint, but had equivalent efficacy, safety, and tolerability, compared with the approved On\/Off regimen. The results reinforce the appropriateness of the approved dosing regimen.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/mus.70120","type":"journal-article","created":{"date-parts":[[2025,12,23]],"date-time":"2025-12-23T13:06:02Z","timestamp":1766495162000},"page":"534-543","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Phase 3b Extension Study\n                    <scp>MT<\/scp>\n                    \u20101186\u2010\n                    <scp>A04<\/scp>\n                    to Evaluate the Continued Efficacy and Safety of Edaravone Oral Suspension for Up to an Additional 48\u2009Weeks in Patients With Amyotrophic Lateral Sclerosis"],"prefix":"10.1002","volume":"73","author":[{"given":"Angela","family":"Genge","sequence":"first","affiliation":[{"name":"Montreal Neurological Institute\u2010Hospital  Montreal Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2001-8470","authenticated-orcid":false,"given":"Jeffrey","family":"Rothstein","sequence":"additional","affiliation":[{"name":"Department of Neurology, School of Medicine Johns Hopkins University  Baltimore Maryland USA"}],"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"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8096-8366","authenticated-orcid":false,"given":"Lorne","family":"Zinman","sequence":"additional","affiliation":[{"name":"Sunnybrook Health Sciences Centre University of Toronto  Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2252-0846","authenticated-orcid":false,"given":"Marvin","family":"Chum","sequence":"additional","affiliation":[{"name":"McMaster University Health Sciences Centre  Hamilton Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9579-5341","authenticated-orcid":false,"given":"Adriano","family":"Chi\u00f2","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 Japan"},{"name":"Aichi Medical University  Nagakute Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masashi","family":"Aoki","sequence":"additional","affiliation":[{"name":"Tohoku University School of Medicine  Sendai Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiide","family":"Yoshino","sequence":"additional","affiliation":[{"name":"Yoshino Neurology Clinic  Chiba Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manabu","family":"Doyu","sequence":"additional","affiliation":[{"name":"Department of Neurology Aichi Medical University  Nagakute Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Selness","sequence":"additional","affiliation":[{"name":"Tanabe Pharma America, Inc.  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