Abstracts

Rufinamide, a structurally novel antiepileptic drug (AED) under investigation, demonstrates broad-spectrum anticonvulsant activity in animal models. The efficacy and safety of rufinamide (800 mg/d) as adjunctive therapy was evaluated for patients with inadequately controlled primary generalized tonic-clonic (GTC) seizures . This multicenter, double-blind, placebo-controlled study of rufinamide (initiated and maintained at 800 mg/d, BID) consisted of a 56-day baseline phase and a 140-day double-blind phase. The study was open to patients [ge]4 years of age with a diagnosis of inadequately controlled primary GTC seizures who were treated with 1 or 2 concomitant, fixed-dosage AEDs. To be randomized, patients had to have experienced at least 3 GTC seizures during the baseline phase, with at least 1 occurrence during each 28-day baseline period. The primary efficacy end point was the percent change from baseline in GTC seizure frequency per 28 days. Adverse events (AEs) and laboratory measures for patients receiving any amount of study drug were used to assess safety. A total of 153 patients were randomized and received at least one dose of study drug: rufinamide, n=78; placebo, n=75. Mean age of treated patients was 29.3 years (range, 4-63 y) and the median number of GTC seizures per 28 days during baseline was 3.5 (range, 1.5-84) and 4.0 (range, 1.5-74) for the rufinamide and placebo groups, respectively. The primary efficacy variable did not show a significant difference between rufinamide (median reduction, 36.4%) and placebo (25.6%; [italic]p[/italic]=0.633). Sixty-four patients (82.1%) in the rufinamide group and 61 placebo patients (81.3%) experienced at least 1 AE. Nonfatal serious AEs were reported by 7 rufinamide-treated and 4 placebo patients, but none were considered related to the study drug. Three patients in each treatment group discontinued due to AEs and 1 placebo patient died. Adverse events (reported by [ge]10% of patients) in the rufinamide group versus placebo were headache (21.8% vs 22.7%), somnolence (16.7% vs 13.3%), nausea (16.7% vs 8.0%), dizziness (12.8% vs 10.7%), and vomiting (10.3% vs 6.7%). No treatment-emergent and clinically relevant alterations were seen in laboratory parameters. A greater median reduction in GTC seizure frequency was seen in rufinamide-treated patients compared to those receiving placebo, but the difference was not statistically significant. Safety assessments were comparable between treatment groups. (Supported by Eisai Inc.)