Perampanel for tonic-clonic seizures in idiopathic generalized epilepsy

Jacqueline A. French, Gregory Krauss, Robert T. Wechsler, Xue Feng Wang, Bree Diventura, Christian Brandt, Eugen Trinka, Terence J. O'Brien, Antonio Laurenza, Anna Patten, Francesco Bibbiani

Research output: Contribution to journalArticle

Abstract

Objective: To assess efficacy and safety of adjunctive perampanel in patients with drug-resistant, primary generalized tonic-clonic (PGTC) seizures in idiopathic generalized epilepsy (IGE). Methods: In this multicenter, double-blind study (ClinicalTrials.gov identifier: NCT01393743; funded by Eisai Inc.), patients 12 years or older with PGTC seizures and IGE were randomized to placebo or perampanel during a 4-week titration period (perampanel uptitrated from 2 to 8 mg/d, or highest tolerated dose) and 13-week maintenance period. The primary endpoint was percent change in PGTC seizure frequency per 28 days (titration plus maintenance vs baseline). The key secondary endpoint (primary endpoint for European Union registration) was 50% PGTC seizure responder rate (patients achieving ≥50% reduction in PGTC seizure frequency; maintenance vs baseline). Treatment-emergent adverse events were monitored. Results: Of 164 randomized patients, 162 comprised the full analysis set (placebo, 81; perampanel, 81). Compared with placebo, perampanel conferred a greater median percent change in PGTC seizure frequency per 28 days (-38.4% vs -76.5%; p <0.0001) and greater 50% PGTC seizure responder rate (39.5% vs 64.2%; p 0.0019). During maintenance, 12.3% of placebo-treated patients and 30.9% of perampanel-treated patients achieved PGTC seizure freedom. For the safety analysis (placebo, 82; perampanel, 81), the most frequent treatment-emergent adverse events with perampanel were dizziness (32.1%) and fatigue (14.8%). Conclusions: Adjunctive perampanel was well tolerated and improved control of drug-resistant PGTC seizures in patients with IGE. Classification of evidence: This study provides Class I evidence that adjunctive perampanel reduces PGTC seizure frequency, compared with placebo, in patients with drug-resistant PGTC seizures in IGE.

Original languageEnglish (US)
Pages (from-to)950-957
Number of pages8
JournalNeurology
Volume85
Issue number11
DOIs
StatePublished - Sep 15 2015

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Seizures
Placebos
Maintenance
perampanel
Idiopathic Generalized Epilepsy
Safety
Drug and Narcotic Control
Dizziness
European Union
Double-Blind Method
Pharmaceutical Preparations
Fatigue
Therapeutics

ASJC Scopus subject areas

  • Clinical Neurology

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French, J. A., Krauss, G., Wechsler, R. T., Wang, X. F., Diventura, B., Brandt, C., ... Bibbiani, F. (2015). Perampanel for tonic-clonic seizures in idiopathic generalized epilepsy. Neurology, 85(11), 950-957. https://doi.org/10.1212/WNL.0000000000001930

Perampanel for tonic-clonic seizures in idiopathic generalized epilepsy. / French, Jacqueline A.; Krauss, Gregory; Wechsler, Robert T.; Wang, Xue Feng; Diventura, Bree; Brandt, Christian; Trinka, Eugen; O'Brien, Terence J.; Laurenza, Antonio; Patten, Anna; Bibbiani, Francesco.

In: Neurology, Vol. 85, No. 11, 15.09.2015, p. 950-957.

Research output: Contribution to journalArticle

French, JA, Krauss, G, Wechsler, RT, Wang, XF, Diventura, B, Brandt, C, Trinka, E, O'Brien, TJ, Laurenza, A, Patten, A & Bibbiani, F 2015, 'Perampanel for tonic-clonic seizures in idiopathic generalized epilepsy', Neurology, vol. 85, no. 11, pp. 950-957. https://doi.org/10.1212/WNL.0000000000001930
French JA, Krauss G, Wechsler RT, Wang XF, Diventura B, Brandt C et al. Perampanel for tonic-clonic seizures in idiopathic generalized epilepsy. Neurology. 2015 Sep 15;85(11):950-957. https://doi.org/10.1212/WNL.0000000000001930
French, Jacqueline A. ; Krauss, Gregory ; Wechsler, Robert T. ; Wang, Xue Feng ; Diventura, Bree ; Brandt, Christian ; Trinka, Eugen ; O'Brien, Terence J. ; Laurenza, Antonio ; Patten, Anna ; Bibbiani, Francesco. / Perampanel for tonic-clonic seizures in idiopathic generalized epilepsy. In: Neurology. 2015 ; Vol. 85, No. 11. pp. 950-957.
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abstract = "Objective: To assess efficacy and safety of adjunctive perampanel in patients with drug-resistant, primary generalized tonic-clonic (PGTC) seizures in idiopathic generalized epilepsy (IGE). Methods: In this multicenter, double-blind study (ClinicalTrials.gov identifier: NCT01393743; funded by Eisai Inc.), patients 12 years or older with PGTC seizures and IGE were randomized to placebo or perampanel during a 4-week titration period (perampanel uptitrated from 2 to 8 mg/d, or highest tolerated dose) and 13-week maintenance period. The primary endpoint was percent change in PGTC seizure frequency per 28 days (titration plus maintenance vs baseline). The key secondary endpoint (primary endpoint for European Union registration) was 50{\%} PGTC seizure responder rate (patients achieving ≥50{\%} reduction in PGTC seizure frequency; maintenance vs baseline). Treatment-emergent adverse events were monitored. Results: Of 164 randomized patients, 162 comprised the full analysis set (placebo, 81; perampanel, 81). Compared with placebo, perampanel conferred a greater median percent change in PGTC seizure frequency per 28 days (-38.4{\%} vs -76.5{\%}; p <0.0001) and greater 50{\%} PGTC seizure responder rate (39.5{\%} vs 64.2{\%}; p 0.0019). During maintenance, 12.3{\%} of placebo-treated patients and 30.9{\%} of perampanel-treated patients achieved PGTC seizure freedom. For the safety analysis (placebo, 82; perampanel, 81), the most frequent treatment-emergent adverse events with perampanel were dizziness (32.1{\%}) and fatigue (14.8{\%}). Conclusions: Adjunctive perampanel was well tolerated and improved control of drug-resistant PGTC seizures in patients with IGE. Classification of evidence: This study provides Class I evidence that adjunctive perampanel reduces PGTC seizure frequency, compared with placebo, in patients with drug-resistant PGTC seizures in IGE.",
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AU - Krauss, Gregory

AU - Wechsler, Robert T.

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AU - Diventura, Bree

AU - Brandt, Christian

AU - Trinka, Eugen

AU - O'Brien, Terence J.

AU - Laurenza, Antonio

AU - Patten, Anna

AU - Bibbiani, Francesco

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N2 - Objective: To assess efficacy and safety of adjunctive perampanel in patients with drug-resistant, primary generalized tonic-clonic (PGTC) seizures in idiopathic generalized epilepsy (IGE). Methods: In this multicenter, double-blind study (ClinicalTrials.gov identifier: NCT01393743; funded by Eisai Inc.), patients 12 years or older with PGTC seizures and IGE were randomized to placebo or perampanel during a 4-week titration period (perampanel uptitrated from 2 to 8 mg/d, or highest tolerated dose) and 13-week maintenance period. The primary endpoint was percent change in PGTC seizure frequency per 28 days (titration plus maintenance vs baseline). The key secondary endpoint (primary endpoint for European Union registration) was 50% PGTC seizure responder rate (patients achieving ≥50% reduction in PGTC seizure frequency; maintenance vs baseline). Treatment-emergent adverse events were monitored. Results: Of 164 randomized patients, 162 comprised the full analysis set (placebo, 81; perampanel, 81). Compared with placebo, perampanel conferred a greater median percent change in PGTC seizure frequency per 28 days (-38.4% vs -76.5%; p <0.0001) and greater 50% PGTC seizure responder rate (39.5% vs 64.2%; p 0.0019). During maintenance, 12.3% of placebo-treated patients and 30.9% of perampanel-treated patients achieved PGTC seizure freedom. For the safety analysis (placebo, 82; perampanel, 81), the most frequent treatment-emergent adverse events with perampanel were dizziness (32.1%) and fatigue (14.8%). Conclusions: Adjunctive perampanel was well tolerated and improved control of drug-resistant PGTC seizures in patients with IGE. Classification of evidence: This study provides Class I evidence that adjunctive perampanel reduces PGTC seizure frequency, compared with placebo, in patients with drug-resistant PGTC seizures in IGE.

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