Abstracts

The objectives of this study were to evaluate the efficacy and safety of rufinamide versus placebo as monotherapy in patients with refractory partial seizures. Patients [ge]12 years of age with refractory partial seizures who had completed an inpatient evaluation for epilepsy surgery were evaluated during a double-blind, placebo-controlled, parallel-group, monotherapy protocol. After a 48-hour baseline phase (BP), patients were randomized to rufinamide or placebo for 10 days (double-blind phase; DB). During DB, rufinamide doses were titrated from 2400 mg/d (Day 1) to 3200 mg/d (Day 2) and maintained at 3200 mg/d (Days 2-10). Dose reductions to a minimum of 2000 mg/d were permitted. Adjunctive antiepileptic drugs (AEDs), with the exception of lorezepam (up to 8 mg/24 hrs), were not allowed during the first 18 hours postrandomization. Exit criteria consisted of 4 defined sets of types and numbers of seizures. The primary efficacy variable was time to meeting [ge]1 exit criteria. Secondary efficacy variables included percentage of patients meeting 1 exit criterion and therapeutic onset (time to 1^st, 2^nd, 3^rd, and 4^th partial seizure). Standard safety measures were evaluated. Patients (N=104) were randomized to rufinamide (n=52) or placebo (n=52). The mean daily dose of rufinamide during DB was 2970.7 mg/d. Rufinamide-treated patients demonstrated a significantly greater median number of days to meet [ge]1 exit criteria versus placebo-treated patients (4.8 vs 2.4 respectively; [italic]p[/italic]=0.0499). Approximately the same percentage of patients in the rufinamide group (67.3%) as in the placebo group (69.2%) met 1 exit criterion ([italic]p[/italic]=0.8809). The median times to 1^st, 2^nd, and 3^rd partial seizures were significantly greater with rufinamide than with placebo ([italic]p[le] [/italic]0.0348). The most commonly reported adverse events (AEs) ([ge]10%) for both groups were somnolence, nausea, and headache. Clinically relevant abnormal laboratory values were noted in 9 rufinamide-treated patients for alkaline phosphatase, SGOT, SGPT, uric acid, potassium, eosinophils, and WBCs. A clinically notable decrease in systolic blood pressure was observed in 2 rufinamide-treated patients (3.9%). Nonfatal serious AEs occurred in only 1 rufinamide-treated patient. Three rufinamide- and 2 placebo-treated patients discontinued due to nonserious AEs. Rufinamide was significantly more effective than placebo as monotherapy for the treatment of refractory partial seizures as demonstrated by the primary efficacy results. Rufinamide was well tolerated, with the majority of AEs mild to moderate in severity. (Supported by Eisai Inc.)