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

Objectives 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. Materials and methods Study 207, an open‐label extension (OLE) study (ClinicalTrials.gov identifier: NCT00368472), enrolled patients (18–70 years) who completed one of two randomized, placebo‐controlled, dose‐escalation Phase II studies. The OLE Treatment Phase comprised a 12‐week Titration Period (2 mg increments of perampanel every 2 weeks to 12 mg/day, maximum) and a Maintenance Period, during which patients continued treatment up to a planned maximum of 424 weeks (~8 years). Interim analysis data cut‐off date was 1 December, 2010. Results Of 180 patients completing the Phase II studies, 138 enrolled in study 207. At the time of interim analyses (approximately 4 years after study start), over a third (n = 53, 38.4%) remained on perampanel; 41.3% (n = 57) of patients had >3 years of exposure; and 13.0% (n = 18) had at least 4 years' exposure. Mean ± standard deviation (SD) duration of exposure was 116 ± 75 weeks and mean ± SD dose during the OLE Maintenance Period was 7.3 ± 3.3 mg. 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 28 days during open‐label treatment was −31.5% (−99.2 to 512.2). Conclusions Long‐term – up to 4 years – adjunctive perampanel had a favourable tolerability profile in patients with refractory partial‐onset seizures. Improvements in seizure control were maintained with long‐term treatment.