Perampanel for adjunctive treatment of partial-onset seizures: A pooled dose-response analysis of phase III studies

Lynn D. Kramer, Andrew Satlin, Gregory L. Krauss, Jacqueline French, Emilio Perucca, Elinor Ben-Menachem, Patrick Kwan, Jerry J. Shih, Antonio Laurenza, Haichen Yang, Jin Zhu, David Squillacote

Research output: Contribution to journalArticlepeer-review

Abstract

Objective To better understand the relationship between efficacy and perampanel dose, integrated actual (last) dose data from three phase III trials and an extension study (blinded Conversion Period; open-label Maintenance Period) were analyzed. Methods Seizure frequency data were analyzed in patients who were randomized to and completed the 13-week Maintenance Period of the phase III studies on perampanel 8 mg, and who received an actual (last) dose of 12 mg during (1) the extension 16-week blinded Conversion Period or (2) weeks 1-13 of the extension Maintenance Period. Due to a treatment-by-region interaction (p = 0.042), analyses excluded patients from the Latin America region (n = 162/1,480; 10.9% of the treated cohort). Results Of 372 patients randomized to 8 mg in the phase III studies, 273 completed the Maintenance Period at 8 mg and 267 entered the extension study. In patients who then had an actual (last) dose of 12 mg during the extension blinded Conversion Period (n = 217), median percent change in seizure frequency per 28 days improved from -32.4% (8 mg, phase III Maintenance Period) to -44.2% (12 mg, extension blinded Conversion Period); 50% responder rates increased slightly from 37.3% to 42.9%. In patients who completed the phase III studies on 8 mg and had an actual (last) dose of 12 mg during weeks 1-13 of the extension Maintenance Period (n = 181), median percent change in seizure frequency per 28 days improved from -34.1% (phase III Maintenance Period) to -46.0% (weeks 1-13 extension Maintenance Period); 50% responder rates were 39.2% and 46.4%. Seizure control remained substantially unchanged in patients who completed the phase III studies at 12 mg and continued on that dose during the extension. Significance Increasing perampanel dose from 8 to 12 mg can produce additional benefits in seizure control in at least some patients who tolerate the higher dose.

Original languageEnglish
Pages (from-to)423-431
Number of pages9
JournalEpilepsia
Volume55
Issue number3
DOIs
Publication statusPublished - 2014

Keywords

  • Actual (last) dose
  • Antiepileptic
  • Efficacy
  • Epilepsy
  • α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid

ASJC Scopus subject areas

  • Clinical Neurology
  • Neurology

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