Abstracts

Rationale: Lacosamide is a new chemical entity undergoing regulatory review as adjunctive treatment for partial-onset seizures. Data from phase II/III trials were analyzed to evaluate change in seizure frequency during the initial weeks of lacosamide exposure. Methods: Three similarly conducted Phase II/III multicenter, randomized, double-blind, placebo-controlled trials, evaluating fixed doses of lacosamide 200 mg/day (SP667, SP755), 400 mg/day (all 3 trials), or 600 mg/day (SP667, SP754) were pooled. All subjects received 100 mg/day during the initial week of lacosamide exposure, followed by weekly titration in 100 mg increments to the assigned target dose. The primary variables-the percentage reduction over placebo from baseline to maintenance phase in seizure frequency per 28 days and the percentage of subjects with ≥50% response to treatment from baseline to maintenance phase-were evaluated for each randomized dose group over the first weeks of lacosamide exposure using data from subject seizure diaries. Results: A total of 935 subjects randomized to lacosamide (200 mg/day, n=267; 400 mg/day, n=466; 600 mg/day, n=202) and 359 randomized to placebo and having at least one post-baseline efficacy assessment were included in this analysis. At the end of the first week of lacosamide exposure, when subjects in all three lacosamide treatment groups were receiving 100 mg/day lacosamide, the percent reduction over placebo in seizure frequency was 17.9% (P<.01). By the end of the second week of exposure, when all lacosamide-treated subjects were receiving 200 mg/day, the percent reduction over placebo in seizure frequency was 20.4% (