Randomized phase 2 study of perampanel for sporadic amyotrophic lateral sclerosis

被引：18

作者：

Aizawa, Hitoshi ^{[1
]}

Kato, Haruhisa ^{[1
]}

Oba, Koji ^{[2
]}

Kawahara, Takuya ^{[3
]}

Okubo, Yoshihiko ^{[1
]}

Saito, Tomoko ^{[1
]}

Naito, Makiko ^{[1
]}

Urushitani, Makoto ^{[4
]}

Tamaoka, Akira ^{[5
]}

Nakamagoe, Kiyotaka ^{[5
]}

Ishii, Kazuhiro ^{[5
]}

Kanda, Takashi ^{[6
]}

Katsuno, Masahisa ^{[7
]}

Atsuta, Naoki ^{[7
]}

Maeda, Yasushi ^{[8
]}

Nagai, Makiko ^{[9
]}

Nishiyama, Kazutoshi ^{[9
]}

Ishiura, Hiroyuki ^{[10
]}

Toda, Tatsushi ^{[10
]}

Kawata, Akihiro ^{[11
]}

Abe, Koji ^{[12
]}

Yabe, Ichiro ^{[13
,14
]}

Takahashi-Iwata, Ikuko ^{[13
,14
]}

Sasaki, Hidenao ^{[13
,14
]}

Warita, Hitoshi ^{[15
]}

Aoki, Masashi ^{[15
]}

Sobue, Gen ^{[7
]}

Mizusawa, Hidehiro ^{[16
]}

Matsuyama, Yutaka ^{[2
]}

Haga, Tomohiro ^{[3
]}

Kwak, Shin ^{[1
]}

机构：

[1] Tokyo Med Univ, Dept Neurol, Tokyo, Japan

[2] Univ Tokyo, Grad Sch Med, Sch Publ Hlth, Dept Biostat, Tokyo, Japan

[3] Univ Tokyo Hosp, Clin Res Support Ctr, Cent Coordinating Unit, Tokyo, Japan

[4] Shiga Univ Med Sci, Dept Neurol, Otsu, Shiga, Japan

[5] Univ Tsukuba, Fac Med, Div Clin Med, Dept Neurol, Tsukuba, Ibaraki, Japan

[6] Yamaguchi Univ, Grad Sch Med, Dept Neurol & Clin Neurosci, Ube, Yamaguchi, Japan

[7] Nagoya Univ, Dept Neurol, Nagoya, Aichi, Japan

[8] Natl Hosp Org, Kumamoto Saishun Med Ctr, Dept Neurol, Kumamoto, Japan

[9] Kitasato Univ, Sch Med, Dept Neurol, Sagamihara, Kanagawa, Japan

[10] Univ Tokyo, Dept Neurol, Tokyo, Japan

[11] Tokyo Metropolitan Neurol Hosp, Dept Neurol, Tokyo, Japan

[12] Univ Okayama, Dept Neurol, Okayama, Japan

[13] Hokkaido Univ, Fac Med, Dept Neurol, Sapporo, Hokkaido, Japan

[14] Hokkaido Univ, Grad Sch Med, Sapporo, Hokkaido, Japan

[15] Tohoku Univ Hosp, Dept Neurol, Sendai, Miyagi, Japan

[16] Natl Ctr Neurol & Psychiat, Tokyo, Japan

来源：

JOURNAL OF NEUROLOGY | 2022年 / 269卷 / 02期

关键词：

Perampanel; Sporadic amyotrophic lateral sclerosis; AMPA receptor; Efficacy; Safety; AMPA RECEPTORS; MOTOR-NEURONS; DOUBLE-BLIND; EPIDEMIOLOGY; EFFICACY; SAFETY; GENES; DEATH; ADAR2;

D O I：

10.1007/s00415-021-10670-y

中图分类号：

R74 [神经病学与精神病学];

学科分类号：

摘要：

Objective To evaluate the efficacy and safety of perampanel in patients with sporadic amyotrophic lateral sclerosis (SALS). Methods This randomized, double-blind, placebo-controlled, multicenter, phase 2 clinical study was conducted at 12 sites. Patients with probable or definite ALS as defined by revised El Escorial criteria were enrolled. Sixty-six patients were randomly assigned (1:1:1) to receive placebo, 4 mg perampanel, or 8 mg perampanel daily for 48 weeks. Adverse events (AEs) were recorded throughout the trial period. The primary efficacy outcome was the change in Amyotrophic Lateral Sclerosis Rating Scale-Revised (ALSFRS-R) score after 48 weeks of treatment. Results One patient withdrew before starting the treatment. Of 65 patients included, 18 of 22 patients randomized to placebo (82%), 14 of 22 patients randomized to 4 mg perampanel (64%), and 7 of 21 patients randomized to 8 mg perampanel (33%) completed the trial. There was a significant difference in the change of ALSFRS-R scores [- 8.4 (95% CI - 13.9 to - 2.9); p = 0.015] between the placebo and the perampanel 8 mg group, primarily due to worsening of the bulbar subscore in the perampanel 8 mg group. Serious AEs were more frequent in the perampanel 8 mg group than in the placebo group (p = 0.0483). Conclusions Perampanel was associated with a significant decline in ALSFRS-R score and was linked to worsening of the bulbar subscore in the 8 mg group.

引用

页码：885 / 896

页数：12

共 35 条

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