Abstracts

Rationale: Evaluation of sustained efficacy in long-term open-label extension trials of antiepileptic drugs is confounded by patient drop-out. This can result in the appearance of progressive improvement over time as nonresponders drop-out of the trial. To examine the long-term efficacy of lacosamide in phase II-III open-label extension trials, data were evaluated based on cohorts of subjects who were exposed to lacosamide for at least 6, 12, 18, 24, 30, and 36 months. Methods: Pooled data for patients treated with lacosamide in completed double-blind trials and corresponding ongoing open-label extension trials were used. For subjects who received lacosamide in the double-blind trials, data from both the double-blind and open-label trials were included in the analysis. For subjects who received placebo in the double-blind trials, data from the transition period at the end of the double-blind trial and from the open-label trial were used. For each cohort (6, 12, 18, 24, 30, or 36 months), data from the first day of lacosamide exposure to the cut-off date for the interim analysis (17 Apr 2006) were included. Subjects in the longer duration cohorts were also included in the shorter duration cohorts. Efficacy endpoints included percent change in seizure frequency and responder rates (percent of patients with ≥50% and ≥75% reduction in partial seizure frequency) from baseline to the maintenance period. Data are presented at 3 month timepoints. Results: At the time of the interim analysis a total of 1327 subjects had been exposed to lacosamide in either double-blind or OL trials. Of these 978 had been entered and treated in open-label trials, and 892 patients had been exposed to lacosamide and had efficacy data available for a total of at least 6 months, with n= 607, 302, 235, 154, and 86 patients exposed with efficacy data for 12, 18, 24, 30, and 36 months, respectively. The median percent reduction in seizure frequency for the first 3 months of treatment was 40.8%, 45.2%, 46.5%, 48.2%, 48.3%, and 46.5% for the 6, 12, 18, 24, 30, and 36 month cohort respectively. In each cohort median percent reduction in seizure frequency appeared sustained, such that the corresponding median percent reduction for the last 3 months of treatment was 40.7%, 51.3%, 58.3%, 65.9%, 69.8%, and 59.7% for each cohort, respectively. Similarly, the proportion of subjects who experienced ≥50% reduction in partial seizure frequency (responders) compared to baseline was sustained over subsequent timepoints in each cohort. The ≥50% responder rate ranged from 41% to 48% across cohorts for the first 3 months of treatment compared with 42% to 70% for the last 3 months of treatment. Likewise, the proportion of ≥75% responders ranged from 17% ¬to 24% across cohorts for the first 3 months of treatment compared with 22% to 42% for the last 3 months. Conclusions: Lacosamide produced long-term, sustained efficacy in cohorts of patients with partial-onset seizures who completed 6 to 36 months of treatment.