Abstracts

Rationale: Lacosamide is approved for adjunctive treatment of adults with partial-onset seizures. Analyses have shown a significant difference vs. placebo in median percent reduction in seizure frequency and 50% responder rate during the first (100 mg/day) and second (200 mg/day) week of actual lacosamide exposure (Chung et al, CNS Drugs, 2010). This post hoc analysis evaluated efficacy based on percentage seizure-free days during the entire Treatment Period (Titration and Maintenance). Methods: Data were pooled from 3 Phase II/III, randomized, double-blind, placebo-controlled trials (SP667, SP754, SP755), evaluating fixed doses of lacosamide 200, 400 and 600 mg/day. Patients received 100 mg/day during the initial week of lacosamide exposure, followed by weekly titration in 100 mg increments to the assigned dose. Percentage of seizure-free days averaged over the entire Treatment Period and for each week of the Treatment Period was evaluated for the lacosamide group (all doses combined), individual dose groups and placebo. Generalized estimating equation models were used to perform pairwise comparisons of lacosamide group(s) versus placebo. Results: Overall 935 patients randomized to lacosamide (200 mg/day, n=267; 400 mg/day, n=466; 600 mg/day, n=202) and 359 to placebo with at least one seizure diary entry were included in the analysis. Patients had long-standing epilepsy (mean time since diagnosis of >20 years for placebo and lacosamide groups) with 77% reporting ≥4 lifetime AEDs. Median baseline seizure frequency per 28 days was 11.5 for the total population. A significant difference in the percentage of seizure-free days averaged over the Treatment Period was observed from the model (all doses combined versus placebo; P<0.001). During the first week of actual lacosamide exposure, when patients in all three lacosamide treatment groups were receiving 100 mg/day, there was a significantly greater percentage of seizure-free days/week with lacosamide (all doses combined) relative to placebo (