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Efficacy and safety of adjunctive perampanel for the treatment of refractory partial seizures: A pooled analysis of three phase III studies
Author(s) -
Steinhoff Bernhard J.,
BenMenachem Elinor,
Ryvlin Philippe,
Shorvon Simon,
Kramer Lynn,
Satlin Andrew,
Squillacote David,
Yang Haichen,
Zhu Jin,
Laurenza Antonio
Publication year - 2013
Publication title -
epilepsia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.687
H-Index - 191
eISSN - 1528-1167
pISSN - 0013-9580
DOI - 10.1111/epi.12212
Subject(s) - perampanel , placebo , refractory (planetary science) , post hoc analysis , medicine , anesthesia , epilepsy , adjunctive treatment , antagonist , adverse effect , psychiatry , physics , alternative medicine , pathology , astrobiology , receptor
Summary Purpose Three phase III studies (304 [ ClinicalTrials.gov identifier: NCT 00699972], 305 [ NCT 00699582], 306 [ NCT 00700310]) 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. Methods 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. Key Findings 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 ( TEAE s) were dizziness, somnolence, and headache. Most TEAE s were mild/moderate; relatively few patients experienced severe TEAE s (placebo, 5.4%; perampanel, 8.9%) or serious TEAE s (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. Significance Perampanel reduced partial seizure frequency and improved responder rates compared with placebo, with an acceptable tolerability profile.