Exploratory double-blind, parallel-group, placebo-controlled study of edaravone (MCI-186) in amyotrophic lateral sclerosis (Japan ALS severity classification: Grade 3, requiring assistance for eating, excretion or ambulation)

Abstract

Our objective was to explore the efficacy and safety of edaravone in amyotrophic lateral sclerosis (ALS) patients with a Japan ALS severity classification of Grade 3. In a 24-week, double-blind, randomized study, 25 patients who met all of the following criteria were enrolled: Japan ALS severity classification Grade 3; definite, probable, or probable-laboratory supported ALS (El Escorial/revised Airlie House); forced vital capacity (%FVC) ≥60%; duration of disease ≤3 years at consent; and change in the revised ALS functional rating scale (ALSFRS-R) score of –1 to –4 points during the 12-week pre-observation period. Patients received edaravone (n = 13) or placebo (n = 12) for six cycles. The efficacy outcome was change in the ALSFRS-R score. The least-squares mean change in the ALSFRS-R score ± standard error during the 24-week treatment was –6.52 ± 1.78 in the edaravone group and –6.00 ± 1.83 in the placebo group; the difference of –0.52 ± 2.46 was not statistically significant (p = 0.835). Incidence of adverse events was 92.3% (12/13) in the edaravone group and 100.0% (12/12) in the placebo group. There was no intergroup difference in the changes in the ALSFRS-R score. The incidences of adverse events were similar in the two groups.

Keywords:

• Amyotrophic lateral sclerosis (ALS)
• edaravone
• Japan ALS severity classification Grade 3
• revised ALS functional rating scale (ALSFRS-R)
• MCI-186

Acknowledgements

We thank all participating patients and their family members and participating staff at all study sites; Teresa Oblak of Covance Market Access, Inc., for editorial assistance; Richard Steele of WRS Steele Scientific and Technical Editing for proofreading the manuscript; Koji Takei and Kikumi Tsuda of Mitsubishi Tanabe Pharma Development America for critical review of the manuscript.

Declaration of interest

Mr. Abe received travel funds and speaker honoraria from Mitsubishi Tanabe Pharma Corporation. Mr. Itoyama received speaker honoraria from Mitsubishi Tanabe Pharma Corporation. Mr. Tsuji received travel funds and speaker honoraria from Mitsubishi Tanabe Pharma Corporation. Mr. Sobue received travel funds and speaker honoraria from Mitsubishi Tanabe Pharma Corporation and serves on the scientific advisory board for the Kanae Science Foundation for the Promotion of Medical Science, Naito Science Foundation, and as an advisory board member of Brain, an editorial board member of Degenerative Neurological and Neuromuscular Disease, the Journal of Neurology, and Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration, and has received funding from several Japanese government agencies. Mr. Aoki received travel funds, speaker honoraria, and fees for conducting and consulting on pharmacological testing of edaravone in a rat ALS model from Mitsubishi Tanabe Pharma Corporation and has received research grants from several Japanese government agencies, including an Intramural Research Grant for Neurological Psychiatric Disorders from the National Center of Neurology and Psychiatry (NCNP). Mr. Doyu received travel funds and speaker honoraria from Mitsubishi Tanabe Pharma Corporation. Mr. Hamada is a consultant for Chugai Pharmaceutical Co., Ltd., Taiho Pharmaceutical Co., Ltd., Kowa Company, Ltd., Sanwa Kagaku Kenkyusho Co., Ltd., Maruho Co., Ltd., Daiichi Sankyo Co., Ltd., Eisai Co., Ltd., Mochida Pharmaceutical Co., Ltd., Otsuka Pharmaceutical Co., Ltd., Nippon Shinyaku Pharmaceutical Co., Ltd., and Mitsubishi Tanabe Pharma Corporation. Mr. Tanaka, Mr. Akimoto, Ms. Nakamura, Ms. Sumii, Mr. Takahashi and Mr. Kondo are employees of Mitsubishi Tanabe Pharma Corporation. Mr. Yoshino received travel funds and speaker honoraria from, had co-owned a patent with, and is a consultant for Mitsubishi Tanabe Pharma Corporation.

This study was funded by Mitsubishi Tanabe Pharma Corporation.

Open access publication of this article and editorial support were funded by Mitsubishi Tanabe Pharma America, Inc.