Long‐term safety of perampanel and seizure outcomes in refractory partial‐onset seizures and secondarily generalized seizures: Results from phase III extension study 307. Issue 7 (27th May 2014)

• Record Type: Journal Article
• Authors: Krauss, Gregory L.; Perucca, Emilio; Ben‐Menachem, Elinor; Kwan, Patrick; Shih, Jerry J.; Clément, Jean‐François; Wang, Xuefeng; Bagul, Makarand; Gee, Michelle; Zhu, Jin; Squillacote, David
• Is Part Of: Epilepsia. Volume 55:Issue 7(2014:Jul.)
• Page Start: 1058
• Page End: 1068
• Publication Date: 2014-05-27
• Subjects: Epilepsy -- Periodicals; 616.853
• DOI: 10.1111/epi.12643
• Languages: English
• ISSNs: 0013-9580

Abstract

<abstract abstract-type="main" id="epi12643-abs-0001"> <title>Summary</title> <sec id="epi12643-sec-0001" sec-type="section"> <title>Objective</title> <p>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.</p> </sec> <sec id="epi12643-sec-0002" sec-type="section"> <title>Methods</title> <p>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 (NCT00735397). 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.</p> </sec> <sec id="epi12643-sec-0003" sec-type="section"> <title>Results</title> <p>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 AEs 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.</p> </sec> <sec id="epi12643-sec-0004" sec-type="section"> <title>Significance</title> <p>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.</p> <p>A PowerPoint slide summarizing this article is available for download in the Supporting Information section <ext-link ext-link-type="uri" xlink:href="http://dx.doi.org/10.1111/epi.12643/supinfo" xlink:type="simple" xmlns:xlink="http://www.w3.org/1999/xlink">here</ext-link>.</p> </sec> </abstract>