2019 年 36 巻 4 号 p. 471-476
Perampanel, a selective non–competitive AMPA receptor antagonist, has been reported to prevent the progression of the model mouse for sporadic amyotrophic lateral sclerosis (ALS) (AR2 mice), in which an RNA editing enzyme adenosine deaminase acting on RNA2 (ADAR2) is conditionally knocked out in the motor neurons. Because of therapeutic potency of perampanel for sporadic ALS, we planned to perform a clinical trial with perampanel for sporadic ALS to investigate the safety and the efficacy of perampanel in patients with sporadic ALS. We designed a multicenter randomized, double–blinded, placebo–controlled, parallel–group phase 2 clinical trial (CrinicalTrials.gov. ID NCT03019419, UMIN ID UMIN000025614).
The patients eligible for inclusion criteria and not applicable for exclusion criteria will be enrolled for the interim registration. After 12 weeks of observation period, the patients with the progression on score of ALS functional rating scale–revised (ALSFRS–R) between −2 and −5 will proceed to the registration. Then the patients will be allocated into three groups : placebo (n＝20), 4mg of perampanel (n＝20), and 8mg of perampanel (n＝20). The patients will take placebo or perampanel once daily before bedtime with dose–escalation method. The primary outcome measure is change in ALSFRS–R after 48 weeks of the treatment. This research is supported by the Project Promoting Clinical Trials for Development of New Drugs and Medical Devices (Japan Medical Association) from Japan Agency for Medical Research and development, AMED. This study was started in April 2017, and the recruiting ALS patients was completed in October 2018. The open–labeled continuation study will follow after the phase 2 study. The results of the phase 2 study will be available in early 2020.
