PT  - JOURNAL ARTICLE
AU  - French, Jacqueline A.
AU  - Krauss, Gregory L.
AU  - Biton, Victor
AU  - Squillacote, David
AU  - Yang, Haichen
AU  - Laurenza, Antonio
AU  - Kumar, Dinesh
AU  - Rogawski, Michael A.
TI  - Adjunctive perampanel for refractory partial-onset seizures
AID  - 10.1212/WNL.0b013e3182635735
DP  - 2012 Aug 07
TA  - Neurology
PG  - 589--596
VI  - 79
IP  - 6
4099  - http://n.neurology.org/content/79/6/589.short
4100  - http://n.neurology.org/content/79/6/589.full
SO  - Neurology2012 Aug 07; 79
AB  - Objective: To assess efficacy and safety of once-daily 8 or 12 mg perampanel, a noncompetitive α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) receptor antagonist, when added to concomitant antiepileptic drugs (AEDs) in the treatment of drug-resistant partial-onset seizures. Methods: This was a multicenter, double-blind, placebo-controlled trial (ClinicalTrials.gov identifier: NCT00699972). Patients (≥12 years, with ongoing seizures despite 1–3 AEDs) were randomized (1:1:1) to once-daily perampanel 8 mg, 12 mg, or placebo. Following baseline (6 weeks), patients entered a 19-week double-blind phase: 6-week titration (2 mg/week increments to target dose) followed by a 13-week maintenance period. Percent change in seizure frequency was the primary endpoint; 50% responder rate was the primary endpoint for EU registration. Results: Of 388 patients randomized and treated, 387 provided seizure frequency data. Using this intent-to-treat population over the double-blind phase, the median percent change in seizure frequency was −21.0%, −26.3%, and −34.5% for placebo and perampanel 8 and 12 mg, respectively (p = 0.0261 and p = 0.0158 for 8 and 12 mg vs placebo, respectively). Fifty percent responder rates during the maintenance period were 26.4%, 37.6%, and 36.1%, respectively, for placebo, perampanel 8 mg, and perampanel 12 mg; these differences were not statistically significant for 8 mg (p = 0.0760) or 12 mg (p = 0.0914). Sixty-eight (17.5%) patients discontinued, including 40 (10.3%) for adverse events. Most frequent treatment-emergent adverse events were dizziness, somnolence, irritability, headache, fall, and ataxia. Conclusions: This trial demonstrated that once-daily, adjunctive perampanel at doses of 8 or 12 mg improved seizure control in patients with uncontrolled partial-onset seizures. Doses of perampanel 8 and 12 mg were safe, and tolerability was acceptable. Classification of evidence: This study provides Class I evidence that once-daily 8 and 12 mg doses of adjunctive perampanel are effective in patients with uncontrolled partial-onset seizures. AE=adverse event; AED=antiepileptic drug; AMPA=α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid; ANCOVA=analysis of covariance; CGIC=Clinical Global Impression of Change; CI=confidence interval; EU=European Union; ITT=intent-to-treat; PGIC=Patient Global Impression of Change; QOLIE-31-P=Quality of Life in Epilepsy questionnaire; SAE=serious adverse event; TEAE=treatment-emergent adverse event