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Long‐term safety of perampanel and seizure outcomes in refractory partial‐onset seizures and secondarily generalized seizures: Results from phase III extension study 307

2014; Wiley; Volume: 55; Issue: 7 Linguagem: Inglês

10.1111/epi.12643

1528-1167

Gregory L. Krauss, Emilio Perucca, Elinor Ben‐Menachem, Patrick Kwan, Jerry J. Shih, Jean‐François Clément, Xuefeng Wang, Makarand Bagul, Michelle Gee, Jin Zhu, David Squillacote,

Drug Transport and Resistance Mechanisms

Summary Objective To evaluate safety, tolerability, seizure frequency, and regional variations in treatment responses with the AMPA antagonist, perampanel, in a large extension study during up to 3 years of treatment. Methods Patients ≥12 years old with partial‐onset seizures despite treatment with 1–3 antiepileptic drugs at baseline completed a perampanel phase III trial and entered extension study 307 ( NCT 00735397). Patients were titrated to 12 mg/day (or their individual maximum tolerated dose) during the blinded conversion period, followed by open‐label maintenance. Exposure, safety (adverse events [AEs], vital signs, weight, electrocardiography [ ECG] , laboratory values) and seizure outcomes were analyzed; key measures were assessed by geographic regions. Results Among 1,216 patients, median exposure was 1.5 years (range 1 week to 3.3 years), with >300 patients treated for >2 years. Treatment retention was 58.5% at cutoff. AEs reported in ≥10% of patients were dizziness, somnolence, headache, fatigue, irritability, and weight increase. Only dizziness and irritability caused discontinuation in >1% of patients (3.9% and 1.3%, respectively). The only serious AE s reported in >1% of patients were epilepsy‐related (convulsion, 3.0%; status epilepticus, 1.1%). No clinically relevant changes in vital signs, ECG or laboratory parameters were seen. After titration/conversion, responder rate and median percentage change from baseline in seizure frequency were stable: 46% for both measures at 9 months (in 980 patients with ≥9 months' exposure) and 58% and 60%, respectively, at 2 years (in the 337 patients with 2 years' exposure). Median percentage reduction in frequency of secondarily generalized ( SG ) seizures ranged from 77% at 9 months (N = 422) to 90% at 2 years (N = 141). Among the 694 patients with maintenance data ≥1 year, 5.3% were seizure‐free for the entire year. Significance No new safety signals emerged during up to 3 years of perampanel exposure in 39 countries. Seizure responses remained stable, with marked reductions, particularly in SG seizures. A PowerPoint slide summarizing this article is available for download in the Supporting Information section here .