Abstracts

Rationale: To evaluate long-term safety and efficacy of lacosamide exposure in subjects with partial-onset seizures participating in an open-label extension trial. Methods: Subjects who had completed an initial trial of lacosamide as adjunctive treatment were enrolled. Investigators could increase or decrease the dose of lacosamide and/or 1 to 3 concomitant AEDs to optimize tolerability and seizure reduction. The allowed lacosamide dose range was 100-800mg/day. An interim analysis of safety and efficacy data was based on data available through October 2006. Safety was evaluated using treatment-emergent adverse events (AE), vital signs and body weight, clinical laboratory data, and ECG. Efficacy was evaluated with continuous and categorical analyses of seizure frequency based on subject diary data. Results: Of the 370 subjects enrolled, 284 (76.8%) subjects had >12 months exposure to lacosamide, 224 (60.5%) subjects had >24 months exposure to lacosamide and 140 (37.8%) subjects had >36 months exposure to lacosamide. The median modal dose was 400mg/day; 30.8% of subjects had a median modal dose ≥600mg/day to 800mg/day lacosamide. The most common AEs (≥10% of total population) were dizziness, headache, fatigue, nasopharyngitis, diplopia, upper respiratory tract infection, nausea, coordination abnormal, contusion, vision blurred, vomiting, skin laceration, and sinusitis. In general, the most common AEs were similar to those reported in double-blind trials although direct comparison is limited due to differences in trial design, duration, and previous exposure to lacosamide. A total of 11.1% of subjects discontinued for AEs; dizziness (1.6%) was the only event that led to discontinuation in >1%. Long-term lacosamide treatment was not associated with any pattern of change in the median or mean hematology, clinical chemistry, vital sign, and body weight measurements with increasing duration of exposure. On the ECG there was a small increase in median PR interval (5-9ms) across all subjects (all modal doses). The overall median percent reduction from Baseline established in the previous trial in 28 day seizure frequency for the Treatment Period was 45.9%. The overall percentage of subjects with ≥50% response to treatment for the Treatment Period was 46.6%. Conclusions: Data from an interim analysis support that long-term (up to 5.5 years) administration of open-label lacosamide was generally well tolerated and reduced seizure frequency as an adjunctive treatment for partial-onset seizures in patients with epilepsy. (Study supported by: SCHWARZ BIOSCIENCES, Inc.)