title: Retigabine as adjunctive therapy in adults with partial-onset seizures: integrated analysis of three pivotal controlled trials.
abstract: We assessed the efficacy and tolerability of retigabine (RTG; international non-proprietary name)/ezogabine (EZG; US adopted name) as adjunctive therapy in adults with partial-onset seizures in an integrated analysis of three trials. Studies 205, 301 (NCT00232596), and 302 (NCT00235755) were randomized, double-blind, placebo-controlled studies in adults having ≥4 partial-onset seizures per 28 days and receiving 1-3 antiepileptic drugs with/without vagus nerve stimulator. Patients underwent titration to RTG/EZG 600, 900, or 1200 mg/day or to placebo followed by 8 or 12 weeks maintenance. For efficacy analyses, placebo was compared with RTG/EZG 600 and 900 mg/day in Studies 205 and 302, and RTG/EZG 1200 mg/day in Studies 205 and 301. Responder rates (≥50% reduction in baseline seizure frequency) were 35% and 45% for RTG/EZG 600 and 900 mg/day, respectively (placebo=21%; p<0.001), and 50% for RTG/EZG 1200 mg/day (placebo=24%, p<0.001). Reductions in 28-day total partial-seizure frequency (medians: placebo=14%; 600 mg/day=26%, p=0.003; 900 mg/day=37%, p<0.001; placebo=15%; 1200 mg/day=39%, p<0.001) were significantly greater with all RTG/EZG doses vs. placebo from baseline to the double-blind phase, and similarly during the maintenance phase. The most commonly reported (>10%) treatment-emergent adverse events were dizziness, somnolence, headache, and fatigue. RTG/EZG demonstrated efficacy and was generally tolerated as adjunctive therapy in adults with partial-onset seizures in this integrated analysis.
authors.affiliation: University of Pennsylvania, 461 Timber Lane, Devon, PA 19333, USA. rjportermd@aol.com
authors.forename: Roger J
authors.initials: RJ
authors.lastname: Porter
authors.forename: David E
authors.initials: DE
authors.lastname: Burdette
authors.forename: Antonio
authors.initials: A
authors.lastname: Gil-Nagel
authors.forename: Susan T
authors.initials: ST
authors.lastname: Hall
authors.forename: Robin
authors.initials: R
authors.lastname: White
authors.forename: Soraya
authors.initials: S
authors.lastname: Shaikh
authors.forename: Sarah E
authors.initials: SE
authors.lastname: DeRossett
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000927:Anticonvulsants / Q000009:adverse effects / Q000627:therapeutic use*; D002219:Carbamates / Q000009:adverse effects / Q000627:therapeutic use*; D004311:Double-Blind Method; D023381:Endpoint Determination; D004828:Epilepsies, Partial / Q000188:drug therapy*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010655:Phenylenediamines / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome; D055986:Vital Signs; D055815:Young Adult
chemical_list: D000927:Anticonvulsants; D002219:Carbamates; D010655:Phenylenediamines; C101866:ezogabine