Abstracts

Rationale: Lacosamide is being developed as an anticonvulsant for the treatment of seizures and diabetic neuropathic pain. Reviewed here are individual and pooled results of 3 placebo-controlled, double-blind, international clinical trials evaluating the efficacy and safety of adjunctive lacosamide (200-600mg/day) in adults ≥16 years with partial-onset seizures with or without secondary generalization. Methods: Pooled efficacy data from Phase II/III trials (SP667 [200, 400, 600mg/day lacosamide], SP754 [400, 600mg/day], and SP755 [200, 400mg/day]) were analyzed by randomized dose. Trial designs were comparable: 12-week fixed-dose maintenance phase, similar titration schedules (100mg/day weekly increments), similar eligibility criteria, and matching primary efficacy endpoints (change in seizure frequency per 28 days from baseline to maintenance phase and responder rate, defined as the % of subjects with ≥50% seizure reduction from baseline to maintenance phase). Individual and pooled trial data are presented for the full analysis set (FAS), which included all randomized subjects receiving ≥one dose of trial medication with ≥one post-baseline efficacy assessment. Results: The data pool consisted of 1,294 treated subjects (placebo, n=359; 200mg/day lacosamide, n=267; 400mg/day, n=466; 600mg/day, n=202). A total of 88.3%, 82.8%, 77.9%, and 62.4% completed treatment for placebo, 200, 400, and 600mg/day lacosamide groups. Overall, 77% of subjects had tried ≥4 lifetime antiepileptic drugs (AEDs) and 45% had tried ≥7 AEDs. Most subjects (84.5%) were taking 2 or 3 concomitant AEDs during the trial, mainly CBZ (35.2%), LTG (31.2%) and LEV (29.0%). In individual trials, 400 and 600mg/day doses were significantly different from placebo for both primary efficacy endpoints (P<.05, all analyses). The 200mg/day dose demonstrated significant seizure reduction versus placebo in one of the two trials evaluating this dose (SP755; FAS,