EFFICACY AND TOLERABILITY OF PERAMPANEL AS ADDITIONAL DRUG OF TEENAGERS WITH DRUG-RESISTANT PARTIAL EPILEPSY: RESULTS OF A RANDOMIZED DOUBLE-BLIND PLACEBO-CONTROLLED STUDY CONDUCTED IN THE RUSSIAN FEDERATION

Abstract

Abstract: the efficacy and tolerability of adjunctive perampanel (PER) in refractory partial epilepsy in Russian adolescents has been investigated. It was the part of three international (global) randomized placebo-controlled prospective phase III trials with prolonged open follow–up phase. Materials and methods: 26 patients with refractory partial seizures (both secondarily generalized and without generalization) aged from 12 to 18 years were included. All of them were unsuccessfully pretreated with 1-3 antiepileptic drugs. They were randomizes either to placebo or to 2, 4, 8, 12 mg of PER daily respectively. After completing the double blind phase they were transferred to open extention phase with titration of daily dose of PER up to 12 mg. Results: PER in doses of 4, 8, and 12 mg/day provided reductions in the frequency of partial-onset seizures compared with placebo – 17.24%, 4.51%, и – 24.89% respectively. Efficaсy became more evident in open phase of the trial – at 78th week of the trial all patients – 23/23 (100%) responded to the treatment with PER (had reduction in seizure frequency 50% and more), proving that efficaсy outcomes may be maintained with long-term treatment. PER was effective in al types of partial seizures, especially in secondarily generalized ones. Adverse events (AEs) were seen in 8/26 (47.1%) of patients receiving PER versus 4/9 (44,4%). The incidence of AEs in open phase was 16/23 (69.6%). The most common AEs (≤ 11,8%) were dizziness, somnolence, aggression. The majority of them were mild or moderate in intensity. There were no clinically important changes in vital signs, ECG measures, or biochemical or hematologic parameters. Conclusion: in adolescents with refractory partial epilepsy PER appeared to be a promising new antiepileptic drug with a new mode of action and unique pharmacological profile.