Abstracts

Rufinamide, a structurally novel antiepileptic drug (AED) under investigation, demonstrates broad-spectrum anticonvulsant activity in animal models. This study was designed to assess the efficacy and safety of high- versus low-dose rufinamide monotherapy in patients with inadequately controlled partial seizures with or without secondary generalization. In this multicenter, double-blind, randomized, parallel-group study, patients with inadequately controlled partial seizures on 1 or 2 AEDs were randomized to a low dose (n=70; 300 mg/d) or a high dose, (n=72; 3200 mg/d) of rufinamide for 112 days. Concomitant AED regimens were simultaneously tapered and discontinued over a 42-day period beginning at randomization. Patients either completed 112 days of treatment or were allowed to exit the study by meeting criteria based on severity and frequency of seizures. The primary efficacy outcome was the percentage of patients meeting 1 exit criterion; the secondary efficacy outcome was the time to meeting 1 exit criterion. Safety was assessed by the presence and frequency of adverse events (AEs), physical examinations, vital signs, electrocardiogram (ECG) recordings, and laboratory assessments. A total of 142 patients (age, [ge]12 years) entered the study. The percentage of patients meeting 1 exit criterion was 66.7% and 72.5% for the high- and low-dose groups, respectively; the difference was not significant ([italic]p[/italic]=0.4402). Median time to meeting 1 exit criterion showed a trend favoring high dose (56 days) versus low dose (32 days), but was not statistically significant ([italic]p[/italic]=0.0968). The most commonly reported AEs ([ge]10% of patients in either group) for high dose versus low dose were nausea (23.6% vs 7.1%), headache (19.4% vs 8.6%), and fatigue (15.3% vs 2.9%). There were no deaths during the course of this study. Nonfatal, serious AEs occurred in 4 patients receiving 3200 mg/d rufinamide and in 2 patients receiving 300 mg/d rufinamide. Three patients from the 3200 mg/d group were discontinued from the study due to nonserious AEs. No clinically relevant changes in vital signs, ECG recordings, or laboratory parameters were noted Efficacy analysis showed no significant difference between groups in the percentage of patients meeting 1 of the exit criteria. Adverse events were comparable between the 2 groups, with a greater incidence of AEs in the high-dose group. (Supported by Eisai Inc.)