Abstracts

Rationale: The efficacy and safety of rufinamide in patients with Lennox-Gastaut syndrome (LGS) were investigated in a randomized, double-blind core trial and open-label extension.Methods: After a 28-day baseline period, patients with LGS were randomized to either rufinamide (RUF) or placebo (PBO) in conjunction with usual anti-epileptic drugs (AEDs). RUF was titrated to approximately 45 mg/kg/day given bid. Patients completing the core trial (3 months) could enter an open-label extension. All adverse events (AEs) and serious AEs (SAEs) were recorded. Use of concomitant AEDs was also noted; AED dose changes were disallowed during the core trial but were permissible during the extension phase.Results: Core trial (n=138): Patients were exposed to RUF for a median duration of 84 days and received a median dose of 1800 mg/day. The mean age was 14.1 years. Most patients were taking 2 or 3 concomitant AEDs at baseline and/or during the treatment period (n=66, 89.2% RUF vs. n=56, 87.5% PBO). AE rates were similar for RUF (81.1%) vs. PBO (81.3%). The most frequently reported AEs for RUF vs. PBO were somnolence (n=18, 24.3% vs. n=8, 12.5%), vomiting (n=16, 21.6% vs. n=4, 6.3%), pyrexia (n=10, 13.5% vs. n=11, 17.2%) and diarrhea (n=4, 5.4%, vs. n=7, 10.9%). Cognitive AEs were not frequently observed with RUF (17.6% vs PBO 23.4%). Severe AEs were seen in 12.2% (9/74) of RUF and 9.4% (6/64) of PBO-treated patients. Five patients experienced SAEs (RUF n=3 vs. PBO n=2), only one of which experienced SAEs that were considered to be treatment related. Six patients (8%) in the RUF group discontinued due to AEs but none in PBO group. There were no deaths. Extension phase (n=124): The median duration of exposure to RUF was 432 days, with a median dose of 1800 mg/day. The median reduction in total and tonic-atonic seizure frequency was maintained over the extension phase. At least 50% of patients experienced reductions in dose of concomitant AEDs at each 6-month treatment interval. In total, 91.1% of patients experienced an AE (similar to the AE frequency reported in the 3 month core trial) but only 12 patients (9.7%) discontinued treatment due to AEs. The most common AEs were vomiting (n=38, 30.6%), pyrexia (n=32, 25.8%), upper respiratory tract infection (n=27, 21.8%) and somnolence (n=26, 21.0%); 17 patients (13.7%) experienced an SAE, and 2 deaths occurred after 1 year of treatment, both of which considered to be unrelated to study drug. Conclusions: Treatment with RUF was generally well tolerated; AEs were mostly mild to moderate in severity, and infrequently led to discontinuation. The most commonly reported AEs occurring with higher frequency in RUF vs PBO were somnolence and vomiting, which are often associated with AED polytherapy in children. The long-term safety profile of RUF was similar to that observed during the 3-month core trial. Funding: this work was supported by Eisai Ltd