Perampanel Study 207: long-term open-label evaluation in patients with epilepsy

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Evaluate interim long-term tolerability, safety and efficacy of adjunctive perampanel, a novel α-amino-3-hydroxy-5-methyl-5-isoxazolepropionic acid (AMPA)-receptor antagonist, in patients with refractory partial-onset seizures. Study 207, an open-label extension (OLE) study (ClinicalTrials.gov identifier: NCT00368472), enrolled patients (18-70years) who completed one of two randomized, placebo-controlled, dose-escalation Phase II studies. The OLE Treatment Phase comprised a 12-week Titration Period (2mg increments of perampanel every 2weeks to 12mg/day, maximum) and a Maintenance Period, during which patients continued treatment up to a planned maximum of 424weeks (~8years). Interim analysis data cut-off date was 1 December, 2010. Of 180 patients completing the Phase II studies, 138 enrolled in study 207. At the time of interim analyses (approximately 4years after study start), over a third (n=53, 38.4%) remained on perampanel; 41.3% (n=57) of patients had >3years of exposure; and 13.0% (n=18) had at least 4years' exposure. Mean±standard deviation (SD) duration of exposure was 116±75weeks and mean±SD dose during the OLE Maintenance Period was 7.3±3.3mg. No new safety signals emerged with long-term treatment. Consistent with previous studies, the most common treatment-emergent adverse events were as follows: dizziness, headache and somnolence. Overall median (range) per cent change from baseline in seizure frequency per 28days during open-label treatment was -31.5% (-99.2 to 512.2). Long-term - up to 4years - adjunctive perampanel had a favourable tolerability profile in patients with refractory partial-onset seizures. Improvements in seizure control were maintained with long-term treatment.