Perampanel, when used as adjunctive therapy in the treatment of drug-resistant primary generalized tonic-clonic seizures in patients 12 and older, reduced median seizure frequency, compared with placebo, according to the results of a phase III trial published online ahead of print August 21 in Neurology. Results of the multicenter, randomized, double-blind, placebo-controlled clinical trial of 162 patients who were taking one to three antiepileptic drugs showed that patients taking perampanel achieved a 76% median reduction in primary generalized tonic-clonic seizure frequency per 28 days. This result was statistically significant when compared with a 38% reduction with placebo. Additionally, 64% of patients taking perampanel experienced a 50% or greater reduction in primary generalized tonic-clonic seizure frequency versus 40% with placebo.
“These data showed a significant median reduction in the frequency of primary generalized tonic-clonic seizures in patients that had [perampanel] added to their treatment regimen,” said lead author Jacqueline A. French, MD, Professor at New York University Comprehensive Epilepsy Center and Chief Science Officer of the Epilepsy Foundation. “As the number of treatment options are limited for patients with primary generalized tonic-clonic seizures, [perampanel] may provide a new option for this group.”
Dr. French and colleagues enrolled patients age 12 or older with primary generalized tonic-clonic seizures and idiopathic generalized epilepsy. Study participants were randomized to placebo or perampanel during a four-week titration period. During this period, perampanel was titrated from 2 to 8 mg/day or to the highest tolerated dose. The titration period was followed by a 13-week maintenance period.
The primary end point was percent change in seizure frequency per 28 days. The secondary end point was 50% primary generalized tonic-clonic seizure responder rate, which was defined as patients achieving a 50% or greater reduction in seizure frequency.
The full analysis set included 162 patients. The control and treatment groups each had 81 patients. Compared with placebo, perampanel conferred a greater median percent change in primary generalized tonic-clonic seizure frequency per 28 days (-38.4% for placebo vs -76.5% for perampanel). The 50% seizure responder rate was 39.5% for placebo and 64.2% for perampanel. During the maintenance period, 12.3% of placebo-treated patients and 30.9% of perampanel-treated patients achieved seizure freedom. The most frequently reported treatment-emergent adverse events were dizziness (32.1%) and fatigue (14.8%).
The authors concluded that “this study provides Class I evidence that adjunctive perampanel reduces primary generalized tonic-clonic seizure frequency, compared with placebo, in patients with drug-resistant primary generalized tonic-clonic seizures in idiopathic generalized epilepsy.”
—Glenn S. Williams