Perampanel: expanding therapeutic options for patients with medically refractory secondary generalized convulsive seizures

Acta Neurol Scand Suppl. 2013;(197):36-43. doi: 10.1111/ane.12103.


To evaluate the efficacy of adjunctive, once-daily perampanel against secondarily generalized (SG) seizures in three Phase III trials (studies 304, 305, and 306) and their extension (study 307). The Phase III studies enrolled patients (≥ 12 years) with uncontrolled partial-onset seizures despite treatment with 1-3 concomitant antiepileptic drugs. Patients completing the core Phase III studies were eligible for the extension study. Endpoints included median percent change in SG seizure frequency, 50% responder (proportion of patients achieving a ≥ 50% reduction in SG seizure frequency), 75% response, and seizure-freedom rates. In total, 1480 patients were randomized and treated in the three perampanel Phase III trials. At baseline, 71.9% of placebo-treated and 68.4% of perampanel-treated patients had a history of SG seizures. In the individual core Phase III studies, perampanel (4-12 mg) reduced seizure frequency and improved responder rates. Consistent with this, in pooled analyses of the Phase III data, the median percent change in SG seizure frequency was -48.6%, -62.9%, and -53.3% with perampanel 4, 8, and 12 mg, respectively, vs -19.4% with placebo; 50% responder rates were 49.3%, 60.5%, and 53.7% vs 37.0% with placebo. More perampanel-treated patients had ≥ 75% reductions in SG seizure frequency, and seizure-freedom rates improved, compared with placebo. Improvements in seizure frequency and responder rate were maintained during the extension study. Perampanel consistently demonstrated efficacy against SG seizures when assessed using various endpoints. Furthermore, reductions in seizure frequency and improvements in responder rate were sustained with long-term perampanel treatment.

Publication types

  • Review

MeSH terms

  • Anticonvulsants / therapeutic use*
  • Clinical Trials, Phase III as Topic
  • Epilepsies, Partial / drug therapy*
  • Epilepsy, Generalized / drug therapy*
  • Humans
  • Nitriles
  • Pyridones / therapeutic use*


  • Anticonvulsants
  • Nitriles
  • Pyridones
  • perampanel