Abstracts

Rationale: Lacosamide is currently under regulatory review as an adjunctive treatment for partial-onset seizures. With a different mechanism of action from existing antiepileptic drugs (selective enhancement of sodium channel slow-inactivation and modulation of CRMP-2), the efficacy of lacosamide should be independent of the antiepileptic drug (AED) to which it is added. This analysis examines lacosamide efficacy in Phase II/III clinical trials by concomitant AED. Methods: Three similarly-conducted placebo-controlled double-blind trials (SP667, SP754, SP755) evaluated the efficacy and safety of lacosamide in adults age ≥16 years with partial-onset seizures with or without secondary generalization. All trials included a 400 mg/day lacosamide dose group. Subjects were taking 1 to 3 concomitant AEDs. Reduction in seizure frequency from Baseline to the Maintenance Phase and responder rates (≥50% reduction in seizure frequency) were evaluated for all subjects randomized to 400 mg/day lacosamide by the most frequently used concomitant AEDs. Results: The pooled population was comprised of 466 subjects randomized to lacosamide 400 mg/day and 359 subjects randomized to placebo. Of these 825 subjects, 17%, 59% and 24% were taking 1, 2 or 3 concomitant AEDs, respectively. The most commonly used concomitant AEDs for this sample were carbamazepine (33%), lamotrigine (33%), levetiracetam (30%), valproate (23%), topiramate (23%), and oxcarbazepine (17%). For the pooled analysis, the overall median percent reduction (per 28 days) in seizure frequency from Baseline to the Maintenance Phase was 36.8% for lacosamide 400 mg/day versus 18.4% for placebo (P<.0001). When analyzed by concomitant AED use, lacosamide showed a similar magnitude of reduction versus placebo regardless of AED to which it was added; carbamazepine (36.5% lacosamide 400 mg/day vs 21.7%, placebo), lamotrigine (33.3% vs 18.3%), levetiracetam (37.6% vs 17.6%), valproate (45.3% vs 21.3%), topiramate (41.4% vs 28.5%), and oxcarbazepine (27.2% vs 12.5%). The percentage of ≥50% responders was 39.7% for lacosamide 400 mg/day and 22.6% for placebo (