TY - JOUR
T1 - Assessment of the long-term efficacy and safety of adjunctive perampanel in tonic-clonic seizures
T2 - Analysis of four open-label extension studies
AU - Rektor, Ivan
AU - Krauss, Gregory L.
AU - Inoue, Yushi
AU - Kaneko, Sunao
AU - Williams, Betsy
AU - Patten, Anna
AU - Malhotra, Manoj
AU - Laurenza, Antonio
AU - Wechsler, Robert T.
N1 - Funding Information:
The authors would like to thank the patients who participated in these studies and their families, as well as all study investigators and their teams. Francesco Bibbiani, formerly an employee of Eisai Inc., contributed to the study design and interpretation of the results. Medical writing support, under the direction of the authors, was provided by David Pertab, PhD, of CMC AFFINITY, McCann Health Medical Communications, and Fiona Scott, PhD, on behalf of CMC AFFINITY, funded by Eisai Inc., in accordance with Good Publication Practice (GPP3) guidelines. Studies 207, 307, 335 OLEx, and 332 OLEx, as well as the present analysis, were funded by Eisai Inc. The data reported in this paper have previously been presented at the 70th Annual Meeting of the American Epilepsy Society, Houston, Texas, December 2‐6, 2016; the 69th Annual Meeting of the American Academy of Neurology, Boston, Massachusetts, April 22‐28, 2017; the Association of British Neurologists Annual Meeting, Liverpool, UK, May 3‐5, 2017; and the 32nd International Epilepsy Congress, Barcelona, Spain, September 2‐6, 2017. In addition, some of the data for GTCS were previously presented at the 12th European Congress on Epileptology, Prague, Czech Republic, September 11‐15, 2016.
Funding Information:
The authors would like to thank the patients who participated in these studies and their families, as well as all study investigators and their teams. Francesco Bibbiani, formerly an employee of Eisai Inc., contributed to the study design and interpretation of the results. Medical writing support, under the direction of the authors, was provided by David Pertab, PhD, of CMC AFFINITY, McCann Health Medical Communications, and Fiona Scott, PhD, on behalf of CMC AFFINITY, funded by Eisai Inc., in accordance with Good Publication Practice (GPP3) guidelines. Studies 207, 307, 335 OLEx, and 332 OLEx, as well as the present analysis, were funded by Eisai Inc. The data reported in this paper have previously been presented at the 70th Annual Meeting of the American Epilepsy Society, Houston, Texas, December 2-6, 2016; the 69th Annual Meeting of the American Academy of Neurology, Boston, Massachusetts, April 22-28, 2017; the Association of British Neurologists Annual Meeting, Liverpool, UK, May 3-5, 2017; and the 32nd International Epilepsy Congress, Barcelona, Spain, September 2-6, 2017. In addition, some of the data for GTCS were previously presented at the 12th European Congress on Epileptology, Prague, Czech Republic, September 11-15, 2016.
Publisher Copyright:
© 2020 The Authors. Epilepsia published by Wiley Periodicals LLC on behalf of International League Against Epilepsy
PY - 2020/7/1
Y1 - 2020/7/1
N2 - Objective: This post hoc analysis evaluated long-term efficacy and safety in patients with focal to bilateral tonic-clonic seizures (FBTCS) or generalized tonic-clonic seizures (GTCS) who entered open-label extension (OLEx) studies to receive long-term adjunctive perampanel. Methods: Patients aged 12 years and older who completed phase II or III randomized, double-blind, placebo-controlled studies could enter an OLEx study, each comprising a blinded conversion period followed by an open-label maintenance period (32-424 weeks; maximum perampanel dose = 12 mg/d). Exposure, seizure outcomes, and treatment-emergent adverse events (TEAEs) were analyzed. Results: Baseline characteristics were generally balanced between patients with FBTCS (n = 720) and GTCS (n = 138). Mean (standard deviation) cumulative duration of perampanel exposure was 102.3 (70.3) weeks (FBTCS) and 83.9 (38.4) weeks (GTCS). Retention rates were 50.0% for up to 4 years (FBTCS) and 49.2% for up to 2 years (GTCS). Across OLEx treatment durations, median reductions in seizure frequency per 28 days were 66.7% (FBTCS) and 80.6% (GTCS). Fifty percent and 75% responder and seizure-freedom rates were 59.5%, 45.3%, and 18.4%, respectively (FBTCS), and 72.5%, 51.5%, and 16.7%, respectively (GTCS). Efficacy was sustained for up to 4 years (FBTCS) and up to 3 years (GTCS), even when accounting for early dropouts. TEAE incidence was highest during Year 1 (FBTCS, 85.3%; GTCS, 86.2%); most common were dizziness and somnolence. During Year 1, serious TEAEs were reported in 81 (11.3%; FBTCS) and 10 (7.2%; GTCS) patients. TEAEs were consistent with the known safety profile of perampanel; no new safety signals were identified with long-term treatment. Significance: This post hoc analysis suggests long-term (up to 4 years) adjunctive perampanel (up to 12 mg/d) is efficacious and well tolerated in patients (aged 12 years and older) with FBTCS or GTCS.
AB - Objective: This post hoc analysis evaluated long-term efficacy and safety in patients with focal to bilateral tonic-clonic seizures (FBTCS) or generalized tonic-clonic seizures (GTCS) who entered open-label extension (OLEx) studies to receive long-term adjunctive perampanel. Methods: Patients aged 12 years and older who completed phase II or III randomized, double-blind, placebo-controlled studies could enter an OLEx study, each comprising a blinded conversion period followed by an open-label maintenance period (32-424 weeks; maximum perampanel dose = 12 mg/d). Exposure, seizure outcomes, and treatment-emergent adverse events (TEAEs) were analyzed. Results: Baseline characteristics were generally balanced between patients with FBTCS (n = 720) and GTCS (n = 138). Mean (standard deviation) cumulative duration of perampanel exposure was 102.3 (70.3) weeks (FBTCS) and 83.9 (38.4) weeks (GTCS). Retention rates were 50.0% for up to 4 years (FBTCS) and 49.2% for up to 2 years (GTCS). Across OLEx treatment durations, median reductions in seizure frequency per 28 days were 66.7% (FBTCS) and 80.6% (GTCS). Fifty percent and 75% responder and seizure-freedom rates were 59.5%, 45.3%, and 18.4%, respectively (FBTCS), and 72.5%, 51.5%, and 16.7%, respectively (GTCS). Efficacy was sustained for up to 4 years (FBTCS) and up to 3 years (GTCS), even when accounting for early dropouts. TEAE incidence was highest during Year 1 (FBTCS, 85.3%; GTCS, 86.2%); most common were dizziness and somnolence. During Year 1, serious TEAEs were reported in 81 (11.3%; FBTCS) and 10 (7.2%; GTCS) patients. TEAEs were consistent with the known safety profile of perampanel; no new safety signals were identified with long-term treatment. Significance: This post hoc analysis suggests long-term (up to 4 years) adjunctive perampanel (up to 12 mg/d) is efficacious and well tolerated in patients (aged 12 years and older) with FBTCS or GTCS.
KW - AMPA receptor antagonist
KW - antiseizure medication
KW - focal to bilateral tonic-clonic seizures
KW - generalized tonic-clonic seizures
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U2 - 10.1111/epi.16573
DO - 10.1111/epi.16573
M3 - Article
C2 - 32645213
AN - SCOPUS:85087713929
SN - 0013-9580
VL - 61
SP - 1491
EP - 1502
JO - Epilepsia
JF - Epilepsia
IS - 7
ER -