Open-label 24-week extension study of edaravone (MCI-186) in amyotrophic lateral sclerosis

• Published in: Amyotrophic lateral sclerosis and frontotemporal degeneration Vol. 18; no. sup1; pp. 55 - 63
• Format: Journal Article
• Language: English
• Published: England Taylor & Francis 31.10.2017
• Subjects: Adult; Aged; Amyotrophic lateral sclerosis (ALS), edaravone, extension active-treatment period; Amyotrophic Lateral Sclerosis - diagnosis; Amyotrophic Lateral Sclerosis - drug therapy; Amyotrophic Lateral Sclerosis - mortality; Antipyrine - adverse effects; Antipyrine - analogs & derivatives; Antipyrine - therapeutic use; Double-Blind Method; Female; Free Radical Scavengers - adverse effects; Free Radical Scavengers - therapeutic use; Humans; Male; Middle Aged; Nasopharyngitis - chemically induced; Respiration Disorders - chemically induced; revised ALS functional rating scale (ALSFRS-R), MCI-186; Survival Rate - trends; revised ALS functional rating scale (ALSFRS-R), MCI-186; Amyotrophic lateral sclerosis (ALS), edaravone, extension active-treatment period
• ISSN: 2167-8421; 2167-9223
• DOI: 10.1080/21678421.2017.1364269

We aimed to explore the longer-term efficacy and safety of edaravone in an active-treatment extension period following the double-blind period of the second phase III study. Patients who met all the following criteria (scores ≥2 points on all 12 items of the revised amyotrophic lateral sclerosis functional rating scale [ALSFRS-R], forced vital capacity ≥80%, definite or probable ALS, and disease duration ≤2 years) were randomised to 60 mg intravenous edaravone or placebo for six cycles in the double-blind period, and then offered the opportunity to proceed to this 24-week open-label extension period. One hundred and twenty-three of 137 patients continued to the extension period: 65 edaravone-edaravone (E-E group) and 58 placebo-edaravone (P-E group). Change (mean ± standard deviation; SD) in the ALSFRS-R score from baseline in the double-blind period was -4.1 ± 3.4 and -6.9 ± 5.1 in the E-E group and P-E group, respectively, while it was -8.0 ± 5.6 in the E-E group and -10.9 ± 6.9 in the P-E group over the whole 48-week period. The ALSFRS-R score changed almost linearly throughout Cycles 1-12 in the E-E group. The most commonly reported adverse events were constipation, dysphagia, and contusion. There was no sudden deterioration in the ALSFRS-R score of the E-E group. No safety concerns related to edaravone were detected.