Tolerability and safety of perampanel: Two randomized dose-escalation studies

Gregory Krauss, M. Bar, V. Biton, J. A. Klapper, I. Rektor, N. Vaiciene-Magistris, D. Squillacote, D. Kumar

Research output: Contribution to journalArticle

Abstract

Objectives- To evaluate, for the first time in patients with epilepsy, the tolerability and safety of escalating doses of oral perampanel, a novel, selective, non-competitive AMPA antagonist, as adjunctive therapy for refractory partial-onset seizures. Materials and methods - Two consecutive, randomized, double-blind, dose-escalation studies recruited adults (18-70 years) with uncontrolled partial-onset seizures receiving one to three concomitant antiepileptic drugs. In study 206, patients were treated for 12 weeks (8-week dose-titration, 4-week dose-maintenance) with placebo or perampanel (up to 4mg/day, dosed once- or twice-daily). In study 208, patients received placebo or perampanel once-daily (up to 12mg) for 16 weeks (12-week titration, 4-week maintenance). Results - Overall, 153 patients were randomized into study 206 (perampanel twice-daily, n=51; perampanel once-daily, n=51; placebo, n=51). Study 208 included 48 patients (perampanel once-daily, n=38; placebo, n=10). The highest dose in study 206 - 4mg/day - was well tolerated, with similar proportions of patients tolerating once-daily (82.4%) and twice-daily (82.4%) perampanel and placebo (82.4%) treatments. In study 208 most patients tolerated doses of ≥6mg perampanel once-daily in a Kaplan-Meier analysis. In both studies, the most common adverse events were CNS-related; most were of mild/moderate severity. Conclusions - Perampanel was well tolerated across doses of 4-12mg/day. The studies showed preliminary evidence of efficacy and identified doses to be evaluated in larger clinical studies.

Original languageEnglish (US)
Pages (from-to)8-15
Number of pages8
JournalActa Neurologica Scandinavica
Volume125
Issue number1
DOIs
StatePublished - Jan 2012

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Safety
Placebos
Seizures
Maintenance
perampanel
alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid
Kaplan-Meier Estimate
Anticonvulsants
Epilepsy
Therapeutics

Keywords

  • Antiepileptic drugs
  • Efficacy
  • Partial-onset
  • Perampanel
  • Refractory
  • Safety

ASJC Scopus subject areas

  • Clinical Neurology
  • Neurology

Cite this

Krauss, G., Bar, M., Biton, V., Klapper, J. A., Rektor, I., Vaiciene-Magistris, N., ... Kumar, D. (2012). Tolerability and safety of perampanel: Two randomized dose-escalation studies. Acta Neurologica Scandinavica, 125(1), 8-15. https://doi.org/10.1111/j.1600-0404.2011.01588.x

Tolerability and safety of perampanel : Two randomized dose-escalation studies. / Krauss, Gregory; Bar, M.; Biton, V.; Klapper, J. A.; Rektor, I.; Vaiciene-Magistris, N.; Squillacote, D.; Kumar, D.

In: Acta Neurologica Scandinavica, Vol. 125, No. 1, 01.2012, p. 8-15.

Research output: Contribution to journalArticle

Krauss, G, Bar, M, Biton, V, Klapper, JA, Rektor, I, Vaiciene-Magistris, N, Squillacote, D & Kumar, D 2012, 'Tolerability and safety of perampanel: Two randomized dose-escalation studies', Acta Neurologica Scandinavica, vol. 125, no. 1, pp. 8-15. https://doi.org/10.1111/j.1600-0404.2011.01588.x
Krauss, Gregory ; Bar, M. ; Biton, V. ; Klapper, J. A. ; Rektor, I. ; Vaiciene-Magistris, N. ; Squillacote, D. ; Kumar, D. / Tolerability and safety of perampanel : Two randomized dose-escalation studies. In: Acta Neurologica Scandinavica. 2012 ; Vol. 125, No. 1. pp. 8-15.
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