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Seizure. 2018 Nov;62:26-32. doi: 10.1016/j.seizure.2018.09.012. Epub 2018 Sep 16.

Long-term tolerability, safety and efficacy of adjunctive perampanel in the open-label, dose-ascending Study 231 and extension Study 233 in Japanese patients with epilepsy.

Author information

1
National Epilepsy Center, NHO Shizuoka Institute of Epilepsy and Neurological Disorders, Urushiyama 886, Aoi-ku, Shizuoka 420-8688, Japan. Electronic address: n-usui@shizuokamind.org.
2
University of Occupational and Environmental Health, 1-1, Iseigaoka, Yahatanishi-ku, Kitakyushu, Fukuoka 807-0804, Japan. Electronic address: akamatsu@iuhw.ac.jp.
3
Kohnankai Foundation Kohnan Hospital, Miyagi 982-8523, Sendai, Japan. Electronic address: nkst@med.tohoku.ac.jp.
4
The Jikei University School of Medicine, 3-25-8, Nishi-Shimbashi, Minato-ku, Tokyo 105-8461, Japan. Electronic address: aki-0275@jikei.ac.jp.
5
North Tohoku Epilepsy Center, Minato Hospital, 7-15 Niida Matsuyama Shimonoba, Hachinohe, Aomori 031-0813, Japan. Electronic address: sk@seishou.jp.
6
Eisai Co., Ltd., 4-6-10, Koishikawa, Bunkyo-ku, Tokyo 112-8088, Japan. Electronic address: h-hiramatsu@hhc.eisai.co.jp.
7
Eisai Co., Ltd., 4-6-10, Koishikawa, Bunkyo-ku, Tokyo 112-8088, Japan. Electronic address: k-saeki@hhc.eisai.co.jp.
8
Eisai Co., Ltd., 4-6-10, Koishikawa, Bunkyo-ku, Tokyo 112-8088, Japan. Electronic address: h-miyagishi@hhc.eisai.co.jp.
9
National Epilepsy Center, NHO Shizuoka Institute of Epilepsy and Neurological Disorders, Urushiyama 886, Aoi-ku, Shizuoka 420-8688, Japan. Electronic address: yinoue-jes@umin.net.

Abstract

PURPOSE:

To evaluate long-term tolerability, safety and efficacy of adjunctive perampanel in a Phase II, multicentre, open-label, dose-ascending Study 231 (NCT00849212) and its extension (Study 233; NCT00903786) in Japanese patients with refractory partial-onset seizures (POS), with/without secondarily generalised seizures.

METHODS:

In Study 231, patients received adjunctive perampanel ≤12 mg/day during a 10-week treatment period. Patients completing Study 231 could enter Study 233 (≤316-week treatment period). Assessments included monitoring of treatment-related treatment-emergent adverse events (TEAEs), median percent change in seizure frequency per 28 days, 50% responder and seizure-freedom rates. During Study 231, a pharmacokinetic analysis assessed the effects of enzyme-inducing antiepileptic drugs.

RESULTS:

Overall, 23/30 (76.7%) patients completed Study 231; 21/30 (70.0%) received perampanel ≥8 mg/day and 10/30 (33.3%) achieved a maximum tolerated dose of 12 mg/day. Median percent change in seizure frequency per 28 days was -35.0%. 50% responder rate was 37.0%; 4 (13.3%) patients achieved seizure freedom. Twenty-one patients entered Study 233. Mean duration of exposure was 195 weeks; 9 (42.9%) patients received perampanel for ≤208 weeks. Seizure control was sustained for 316 weeks in 3/21 (14.3%) patients; 2 achieved seizure freedom. Treatment-related TEAEs were tolerable; the most common was dizziness (Study 231, 53.3%; Study 233, 14.3%). Mean perampanel plasma concentrations were lower with concomitant carbamazepine vs non-inducers (152.7 ng/mL vs 389.4 ng/mL across perampanel groups); small patient numbers for non-inducers (n = 2) should be considered when interpreting these data.

CONCLUSION:

Adjunctive perampanel demonstrated a favourable safety profile and long-term tolerability in Japanese patients with refractory POS for ≤316 weeks.

KEYWORDS:

AMPA receptor; Antiepileptic drugs; Epilepsy; Perampanel

PMID:
30267941
DOI:
10.1016/j.seizure.2018.09.012
[Indexed for MEDLINE]
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