{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T18:58:56Z","timestamp":1790276336256,"version":"4.1.0"},"reference-count":20,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2022,12,28]],"date-time":"2022-12-28T00:00:00Z","timestamp":1672185600000},"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":[[2023,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Introduction\/Aims<\/jats:title><jats:p>An intravenous (IV) formulation of edaravone has been shown to slow the rate of physical functional decline in amyotrophic lateral sclerosis (ALS). An oral suspension formulation of edaravone was recently approved by the United States Food and Drug Administration for use in patients with ALS. This study assessed the safety and tolerability of oral edaravone.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>This global, open\u2010label, phase 3 study evaluated the long\u2010term safety and tolerability of oral edaravone in adults with ALS who had a baseline forced vital capacity \u226570% of predicted and disease duration \u22643\u00a0y. The primary safety analysis was assessed at weeks 24 and 48. Patients received a 105\u2010mg dose of oral edaravone in treatment cycles replicating the dosing of IV edaravone.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The study enrolled 185 patients (64.3% male; mean age, 59.9\u00a0y; mean disease duration, 1.56\u2009y). The most common treatment\u2010emergent adverse events (TEAEs) at week 48 were fall (22.2%), muscular weakness (21.1%) and constipation (17.8%). Serious TEAEs were reported by 25.9% of patients; the most common were worsening ALS symptoms, dysphagia, dyspnea, and respiratory failure. Twelve TEAEs leading to death were reported. Forty\u2010six (24.9%) patients reported TEAEs that were considered related to study drug; the most common were fatigue, dizziness, headache, and constipation. Sixteen (8.6%) patients discontinued study drug due to TEAEs. No serious TEAEs were related to study drug.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>This study indicated that oral edaravone was well tolerated during 48\u2009wk of treatment, with no new safety concerns identified.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mus.27768","type":"journal-article","created":{"date-parts":[[2022,12,12]],"date-time":"2022-12-12T04:59:40Z","timestamp":1670821180000},"page":"124-129","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["Oral edaravone demonstrated a favorable safety profile in patients with amyotrophic lateral sclerosis after 48\u2009weeks of treatment"],"prefix":"10.1002","volume":"67","author":[{"given":"Angela","family":"Genge","sequence":"first","affiliation":[{"name":"Clinical Research and ALS Clinic Montreal Neurological Institute and Hospital  Montreal Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8365-6707","authenticated-orcid":false,"given":"Gary L.","family":"Pattee","sequence":"additional","affiliation":[{"name":"Neurological Sciences Department University of Nebraska Medical Center  Lincoln Nebraska USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gen","family":"Sobue","sequence":"additional","affiliation":[{"name":"Department of Neurology Nagoya University Graduate School of Medicine  Nagoya Japan"},{"name":"Department of Neurology Aichi Medical University  Nagakute Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masashi","family":"Aoki","sequence":"additional","affiliation":[{"name":"Department of Neurology Tohoku University School of Medicine  Sendai Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiide","family":"Yoshino","sequence":"additional","affiliation":[{"name":"Department of Neurology Yoshino Neurology Clinic  Chiba Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philippe","family":"Couratier","sequence":"additional","affiliation":[{"name":"Department of Neurology University Hospital of Limoges  Limoges France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Lunetta","sequence":"additional","affiliation":[{"name":"Istituti Clinici Scientifici Maugeri IRCCS Neurorehabilitation Unit of Milano  Milan Italy"},{"name":"NEMO Clinical Center Fondazione Serena Onlus  Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susanne","family":"Petri","sequence":"additional","affiliation":[{"name":"Clinic for Neurology Hannover Medical School  Hannover Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Selness","sequence":"additional","affiliation":[{"name":"Clinical and Technical Operations Mitsubishi Tanabe Pharma Development America, Inc.  Jersey City New Jersey USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sachin","family":"Bidani","sequence":"additional","affiliation":[{"name":"Clinical Development, Mitsubishi Tanabe Pharma Development America, Inc.  Jersey City New Jersey USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manabu","family":"Hirai","sequence":"additional","affiliation":[{"name":"Clinical Research &amp; Development, Mitsubishi Tanabe Pharma Corporation  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takeshi","family":"Sakata","sequence":"additional","affiliation":[{"name":"Global Products Management Department, Mitsubishi Tanabe Pharma Corporation  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alejandro","family":"Salah","sequence":"additional","affiliation":[{"name":"Medical Affairs Mitsubishi Tanabe Pharma America, Inc.  Jersey City New Jersey USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3051-3953","authenticated-orcid":false,"given":"Stephen","family":"Apple","sequence":"additional","affiliation":[{"name":"Medical Affairs Mitsubishi Tanabe Pharma America, Inc.  Jersey City New Jersey USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Art","family":"Wamil","sequence":"additional","affiliation":[{"name":"Neurology, Medical Science, Mitsubishi Tanabe Pharma Development America, Inc.  Jersey City New Jersey USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander","family":"Kalin","sequence":"additional","affiliation":[{"name":"Drug Safety, Mitsubishi Tanabe Pharma Development America, Inc.  Jersey City New Jersey USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlayne E.","family":"Jackson","sequence":"additional","affiliation":[{"name":"Department of Neurology University of Texas Health Science Center at San Antonio  San Antonio Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,12,28]]},"reference":[{"key":"e_1_2_13_2_1","unstructured":"Center for Drug Evaluation and Research (CDER). Rilutek (Riluzole) Marketing Approval.2017.https:\/\/www.accessdata.fda.gov\/scripts\/opdlisting\/oopd\/detailedIndex.cfm?cfgridkey=072792. Accessed November 22 2022."},{"key":"e_1_2_13_3_1","unstructured":"Center for Drug Evaluation and Research (CDER). Radicava (Edaravone) Injection Approval Letter.2017.https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/nda\/2017\/209176Orig1s000Approv.pdf. Accessed November 22 2022."},{"key":"e_1_2_13_4_1","doi-asserted-by":"publisher","DOI":"10.1080\/17482960600881870"},{"key":"e_1_2_13_5_1","doi-asserted-by":"publisher","DOI":"10.3109\/21678421.2014.959024"},{"key":"e_1_2_13_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(17)30115-1"},{"key":"e_1_2_13_7_1","doi-asserted-by":"publisher","DOI":"10.1080\/21678421.2017.1362000"},{"key":"e_1_2_13_8_1","doi-asserted-by":"publisher","DOI":"10.1080\/21678421.2017.1361441"},{"key":"e_1_2_13_9_1","doi-asserted-by":"publisher","DOI":"10.1080\/21678421.2019.1645858"},{"key":"e_1_2_13_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpdd.925"},{"key":"e_1_2_13_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpdd.952"},{"key":"e_1_2_13_12_1","volume-title":"Safety Study of Oral Edaravone Administered in Subjects with ALS. 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