TY - JOUR
T1 - 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
AU - Usui, Naotaka
AU - Akamatsu, Naoki
AU - Nakasato, Nobukazu
AU - Ohnishi, Akihiro
AU - Kaneko, Sunao
AU - Hiramatsu, Hidetaka
AU - Saeki, Kazunori
AU - Miyagishi, Hideaki
AU - Inoue, Yushi
N1 - Funding Information:
Medical writing support, under the direction of the authors, was provided by David Pertab, PhD, of CMC AFFINITY, a division of Complete Medical Communications Ltd., Glasgow, UK, funded by Eisai Inc., in accordance with Good Publication Practice (GPP3) guidelines.
Publisher Copyright:
© 2018 The Authors
Copyright:
Copyright 2018 Elsevier B.V., All rights reserved.
PY - 2018/11
Y1 - 2018/11
N2 - 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.
AB - 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.
KW - AMPA receptor
KW - Antiepileptic drugs
KW - Epilepsy
KW - Perampanel
UR - http://www.scopus.com/inward/record.url?scp=85053834538&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85053834538&partnerID=8YFLogxK
U2 - 10.1016/j.seizure.2018.09.012
DO - 10.1016/j.seizure.2018.09.012
M3 - Article
C2 - 30267941
AN - SCOPUS:85053834538
VL - 62
SP - 26
EP - 32
JO - Seizure : the journal of the British Epilepsy Association
JF - Seizure : the journal of the British Epilepsy Association
SN - 1059-1311
ER -