Efficacy and safety of adjunctive perampanel for the treatment of refractory partial seizures: A pooled analysis of three phase III studies. Issue 8 (10th May 2013)

• Record Type: Journal Article
• Authors: Steinhoff, Bernhard J.; Ben‐Menachem, Elinor; Ryvlin, Philippe; Shorvon, Simon; Kramer, Lynn; Satlin, Andrew; Squillacote, David; Yang, Haichen; Zhu, Jin; Laurenza, Antonio
• Is Part Of: Epilepsia. Volume 54:Issue 8(2013:Aug.)
• Page Start: 1481
• Page End: 1489
• Publication Date: 2013-05-10
• Subjects: Epilepsy -- Periodicals; 616.853
• DOI: 10.1111/epi.12212
• Languages: English
• ISSNs: 0013-9580

Abstract

<abstract abstract-type="main" xml:lang="en" id="epi12212-abs-0001"> <title>Summary</title> <sec id="epi12212-sec-0001" sec-type="section"> <title>Purpose</title> <p>Three phase III studies (304 [ClinicalTrials.gov identifier: NCT00699972], 305 [NCT00699582], 306 [NCT00700310]) evaluated perampanel, an α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid (AMPA) receptor antagonist, as adjunctive therapy for refractory partial seizures. We report post hoc analyses of pooled study data by randomized dose.</p> </sec> <sec id="epi12212-sec-0002" sec-type="section"> <title>Methods</title> <p>Patients with partial seizures despite receiving 1–3 antiepileptic drugs were randomized to once‐daily placebo, perampanel 8 or 12 mg (studies 304, 305), or placebo, perampanel 2, 4, or 8 mg (study 306). Studies included a 6‐week baseline period and double‐blind treatment phase (6‐week titration; 13‐week maintenance). Primary end points were median change in partial seizure frequency (baseline vs. double‐blind phase) and percentage of patients achieving ≥50% reduction in seizure frequency (baseline vs. maintenance). Here, these end points, together with secondary, exploratory, and safety end points, were assessed using pooled study data.</p> </sec> <sec id="epi12212-sec-0003" sec-type="section"> <title>Key Findings</title> <p>The pooled intent‐to‐treat analysis set (randomized, treated patients with any seizure data) included 1, 478 patients. Median changes in partial seizure frequency were greater with perampanel than placebo (perampanel 4 mg, −23.3%; 8 mg, −28.8%; 12 mg, −27.2%; placebo, −12.8%; p < 0.01, each dose vs. placebo), as were 50% responder rates (perampanel 4 mg, 28.5%; 8 mg, 35.3%; 12 mg, 35.0%; placebo, 19.3%; p < 0.05, each dose vs. placebo). In addition, median changes in complex partial plus secondary generalized seizure frequency were also greater with perampanel than placebo (perampanel 4 mg, −31.2%; 8 mg, −35.6%; 12 mg, −28.6%; placebo, −13.9%). Perampanel was generally well tolerated. The most frequent treatment‐emergent adverse events (TEAEs) were dizziness, somnolence, and headache. Most TEAEs were mild/moderate; relatively few patients experienced severe TEAEs (placebo, 5.4%; perampanel, 8.9%) or serious TEAEs (placebo, 5.0%; perampanel, 5.5%). There were no deaths and no clinically important mean changes in laboratory values, electrocardiography (ECG) findings, or vital signs.</p> </sec> <sec id="epi12212-sec-0004" sec-type="section"> <title>Significance</title> <p>Perampanel reduced partial seizure frequency and improved responder rates compared with placebo, with an acceptable tolerability profile.</p> </sec> </abstract>