Perampanel for Sporadic Amyotrophic Lateral Sclerosis (138)

Objective: To investigate the safety and the efficacy of perampanel in patients with sporadic amyotrophic lateral sclerosis. Background: There are limited treatments for amyotrophic lateral sclerosis (ALS). Perampanel, selective non-competitive α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptor antagonist, has been reported to rescue motor dysfunction and neuropathology in sporadic ALS model mice, in which is an RNA editing enzyme adenosine deaminase acting on RNA 2 is conditionally knocked out in motor neurons, suggesting therapeutic potency of perampanel for sporadic ALS. Design/Methods: We conducted a multicenter randomized, double-blinded, placebo-controlled, parallel-group phase 2 clinical trial to evaluate the efficacy and safely of perampanel at doses of 4mg and 8mg per day, as compared with placebo, in patients with sporadic ALS. Sporadic ALS patients, aged 40 years to 78 years who have clinically definite ALS, clinically probable ALS, or clinically probable-laboratory supported ALS as a specified in the revised El Escorial Airline House diagnostic criteria, were registered. The primary outcome measure is the change in ALS functional rating scale-revised (ALSFRS-R) scores after 48 weeks of the treatment. Secondary outcomes include change in ALSFRS-R slope, manual muscle test, and percent-predicted forced vital capacity. Mixed effect model repeated measures analysis was used for statistics. Results: Of 79 patients eligible for interim registration, 66 patients underwent randomization to assign to 3 groups: 8mg of perampanel, 4mg of perampanel, and placebo. This study will be completed in January 2020. The results this study will be available in February 2010. (Funded by Japan Agency for Medical Research and Development, AMED; CrinicalTrials.gov number, NCT03019419.) Conclusions: The conclusions will be updated at the 72nd annual meeting of American Academy of Neurology. Disclosure: Dr. Aizawa has nothing to disclose. Dr. Kato has nothing to disclose. Dr. Oba has nothing to disclose. Dr. Kawahara has nothing to disclose. Dr. Okubo has nothing to disclose. Dr. Saito has nothing to disclose. Dr. Urushitani has nothing to disclose. Dr. Tamaoka has nothing to disclose. Dr. Nakamagoe has nothing to disclose. Dr. Ishii has nothing to disclose. Dr. Kanda has nothing to disclose. Dr. Katsuno has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Speaker’s honoraria (Biogen and Takeda).. Dr. Katsuno has received research support from Research funding (Dainippon Sumitomo, Novartis Pharma K.K., Otsuka, Sanofi, and Takeda).. Dr. Atsuta has nothing to disclose. Dr. Maeda has nothing to disclose. Dr. Nagai has nothing to disclose. Dr. Nishiyama has received research support from Daiichi Sankyo Co., Ltd., Otsuka Pharmaceutical Company, Ltd., Dainippon Sumitomo Pharma, Co., Ltd., and Eisai Co., Ltd.. Dr. Ishiura has nothing to disclose. Dr. Toda has nothing to disclose. Dr. Kawata has nothing to disclose. Dr. Abe has nothing to disclose. Dr. Yabe has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with AbbVie Inc. and Takeda Pharmaceutical Company Limitied.. Dr. Yabe has received research support from Daiichi Sankyo Company, Ltd., Mitsubishi Tanabe Pharma Corporation., AstraZeneca K.K., and Ono Pharmaceutical Co., Ltd.. Dr. Takahashi has nothing to disclose. Dr. Sasaki has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Sumitomo Dainippon Pharma Co., Ltd., Takeda Pharmaceutical Company Limited., FP Pharmaceutical Corporation, Nippon Chemiphar Co., Ltd., and Mitsubishi Tanabe Pharma Corporation.. Dr. Sasaki has received research support from Kyowa Hakko Kirin Co., Ltd., Takeda Pharmaceutical Company Limited., Astellas Pharma Inc., Sumitomo Dainippon Pharma Co., Ltd., Japan Blood Products Organization, Nippon Boehringer Ingelheim Co., Ltd., Otsuka Pharmaceutical Co., Ltd., Nihon Pharmaceutical. Dr. Warita has nothing to disclose. Dr. Aoki has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Eisai Inc., Mitsubishi Tanabe Pharma Corporation, Astellas Pharma Inc., Takeda Pharmaceutical Company Ltd, Sanofi K.K., and Dainippon Sumitomo Pharma Co. Ltd. Dr. Sobue has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Mitsubishi Tanabe Pharma Co; Takeda Pharmaceutical Company Limited. Dr. Mizusawa has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Eisai Co. EA Pharma Co. Novartis Pharma Co. Sanofi Co. Tenable Mitsubishi Pharma Co. FP Parma Co. Nihon Pharma Co.. Dr. Mizusawa has received personal compensation in an editorial capacity for Chugai Igaku Co. Igakushoin Co. Nankodo Co.. Dr. Matsuyama has nothing to disclose. Dr. Kwak has nothing to disclose.