Efficacy and safety of perampanel in adolescent patients with drug-resistant partial seizures in three double-blind, placebo-controlled, phase III randomized clinical studies and a combined extension study. (July 2015)

• Record Type: Journal Article
• Authors: Rosenfeld, William; Conry, Joan; Lagae, Lieven; Rozentals, Guntis; Yang, Haichen; Fain, Randi; Williams, Betsy; Kumar, Dinesh; Zhu, Jin; Laurenza, Antonio
• Is Part Of: European journal of paediatric neurology. Volume 19:Number 4(2015:Jul.)
• Page Start: 435
• Page End: 445
• Publication Date: 2015-07
• Subjects: Pediatric neurology -- Periodicals; Nervous System Diseases -- Periodicals; Child -- Periodicals; Infant -- Periodicals; Neurologie pédiatrique -- Périodiques; Pediatric neurology; Electronic journals; Periodicals; Electronic journals; 618.928
• DOI: 10.1016/j.ejpn.2015.02.008
• Languages: English
• ISSNs: 1090-3798

Abstract

<abstract xml:lang="en" abstract-type="author" id="abs0010"> <title id="sectitle0010">Abstract</title> <sec> <title id="sectitle0015">Objective</title> <p id="abspara0010">Assess perampanel's efficacy and safety as adjunctive therapy in adolescents (ages 12–17) with drug-resistant partial seizures.</p> </sec> <sec> <title id="sectitle0020">Methods</title> <p id="abspara0015">Adolescent patients enrolled in multinational, double-blind, placebo-controlled, phase III core studies (studies 304, 305, or 306) completed 19-week, double-blind phase (6-week titration/13-week maintenance) with once-daily perampanel or placebo. Upon completion, patients were eligible for the extension (study 307), beginning with 16-week, blinded conversion, during which placebo patients switched to perampanel. Patients then entered the open-label treatment.</p> </sec> <sec> <title id="sectitle0025">Results</title> <p id="abspara0020">Of 1480 patients from the core studies, 143 were adolescents. Pooled adolescent data from these core studies demonstrated median percent decreases in seizure frequency for perampanel 8 mg (34.8%) and 12 mg (35.6%) were approximately twice that of placebo (18.0%). Responder rates increased with perampanel 8 mg (40.9%) and 12 mg (45.0%) versus placebo (22.2%). Adolescents receiving concomitant enzyme-inducing antiepileptic drugs (AEDs) had smaller reductions in seizure frequency (8 mg:31.6%; 12 mg:26.8%) than those taking non-inducing AEDs (8 mg:54.6%; 12 mg:52.7%). Relative to pre-perampanel baseline, seizure frequency and responder rates during the extension (Weeks 1–52) improved with perampanel. Most commonly reported adverse events in adolescents during the core studies were dizziness (20.4%), somnolence (15.3%), aggression (8.2%), decreased appetite (6.1%), and rhinitis (5.1%). Dizziness (13.2%), somnolence (11.6%), and aggression (6.6%) most often led to perampanel interruption/dose adjustment during the extension.</p> </sec> <sec> <title id="sectitle0030">Significance</title> <p id="abspara0025">Data demonstrated adjunctive perampanel treatment in adolescents with drug-resistant partial seizures produced better seizure control versus placebo, sustained seizure frequency improvements, and a generally favorable safety profile. Results were comparable to the overall study population.</p> <p id="abspara0030">Clinical Trial Registration: clinicaltrials.gov Identifiers: Study 304: <ext-link ext-link-type="unknown" id="intref0010" xlink:type="simple" xlink:href="ctgov:NCT00699972" xmlns:xlink="http://www.w3.org/1999/xlink">NCT00699972</ext-link>; 305: <ext-link ext-link-type="unknown" id="intref0015" xlink:type="simple" xlink:href="ctgov:NCT00699582" xmlns:xlink="http://www.w3.org/1999/xlink">NCT00699582</ext-link>; 306: <ext-link ext-link-type="unknown" id="intref0020" xlink:type="simple" xlink:href="ctgov:NCT00700310" xmlns:xlink="http://www.w3.org/1999/xlink">NCT00700310</ext-link>; Study 307: <ext-link ext-link-type="unknown" id="intref0025" xlink:type="simple" xlink:href="ctgov:NCT00735397" xmlns:xlink="http://www.w3.org/1999/xlink">NCT00735397</ext-link>.</p> </sec> </abstract>