Abstracts

Rationale: Rufinamide is indicated for the adjunctive treatment of seizures associated with Lennox-Gastaut Syndrome (LGS) in pediatric pts 1 year of age and older, and in adults. A multicenter, randomized, double-blind, placebo-controlled trial (Study 022) in pts with inadequately controlled LGS showed that rufinamide was effective and well tolerated. Here, we determine whether adverse events (AEs) experienced during Titration were transient and improved in the Maintenance Period. Methods: The study comprised a 28-day Baseline Phase and an 84-day Double-Blind Treatment Phase (14-day Titration and 70-day Maintenance Periods) where pts received rufinamide (100/200/400 mg twice daily) or placebo. Pts received rufinamide or placebo in addition to their stable dose of 1–3 concomitant anti-seizure drugs. During Titration, doses were increased based on weight (forced titration), and at the end of the Titration Period this dose was used during the entire Maintenance Period. Treatment-emergent AEs (TEAEs) were recorded during the Titration or Maintenance Periods. Results: During Titration, 74 pts were randomized to rufinamide (median age [range] 13.0 [4.0–35.0] years; 37.8% female) and 64 to placebo (median age [range] 10.5 [4.0–37.0] years; 37.5% female); 3 pts (rufinamide, n=1; placebo, n=2) discontinued during Titration. Fifty-five (74.3%) rufinamide- and 39 (60.9%) placebo-treated pts had TEAEs during Titration; 40 (54.8%) rufinamide- and 36 (58.1%) placebo-treated pts had TEAEs during Maintenance. TEAEs for ≥5% of pts are shown in Table 1. Most common TEAEs during Titration were somnolence and vomiting for rufinamide, and somnolence, pyrexia, and fatigue for placebo. During Maintenance, pyrexia was the most common TEAE in both cohorts. For rufinamide, fewer pts experienced vomiting, somnolence, fatigue, diarrhea, appetite decreased, anorexia, ataxia, and rash during Maintenance vs. Titration. Pyrexia increased in both groups from Titration to Maintenance. For placebo, incidence of upper respiratory tract infections and diarrhea increased from Titration to Maintenance. Incidence of nasopharyngitis was similar in Titration and Maintenance Periods for rufinamide but increased in placebo-treated pts during Maintenance. For rufinamide, mean (standard deviation) time to AE onset (any TEAE) was 22.3 (16.8) days and resolution of AEs during Maintenance was 27.5 (15.1) days; these were 30.3 (17.6) and 34.6 (17.8) days, respectively, for placebo. Conclusions: Most AEs experienced by rufinamide-treated pts in the Titration Period were reduced or absent during the Maintenance Period. This suggests that AEs associated with rufinamide are transient and resolve with continued treatment. Future studies could investigate if slower titration of rufinamide could reduce TEAEs even further. Funding: Eisai Inc.