Abstracts

Rationale: Lacosamide is an antiepileptic drug (AED) approved for the adjunctive treatment of partial-onset seizures. In a previously completed Phase III double-blind, randomized trial (SP754; NCT00136019; Chung et al., Epilepsia 2010), treatment with adjunctive lacosamide significantly reduced the frequency of partial-onset seizures. We report final efficacy results for the subsequent open-label extension (OLE) trial (SP756; NCT00522275) with lacosamide exposure through 5 years. Methods: Patients completing the maintenance phase of the US Phase III double-blind clinical trial (Chung et al., Epilepsia 2010), who elected to enter the OLE trial were transitioned to a lacosamide dose of 200 mg/day. Lacosamide could be decreased to 100 mg/day or increased up to 800 mg/day (in 100 mg/day per week increments), and concomitant medications could be increased or decreased on an individual basis. Safety evaluation during long-term exposure was the primary objective of the trial (results reported separately); efficacy endpoints included percent change in 28-day partial seizure frequency, responder rate (percentage of patients with a ?50% or a ?75% reduction in partial seizure frequency from Baseline of the previous trial); and seizure-free status for yearly completer cohorts. Data were analyzed for those patients receiving at least one dose of open-label lacosamide with at least one post-Baseline efficacy assessment. Results: A total of 308 patients were exposed to lacosamide in this OLE trial. Of these, 307 had post-Baseline efficacy data available. The median modal dose of lacosamide (patient modal dose = the dose the patient used most often during the trial) was 500 mg/day, and 39% of patients had a modal dose ?600 mg/day. Median treatment duration was 1075 days. Most patients (82%) were receiving 2-3 concomitant AEDs at Baseline of the previous trial, and 50% had tried 7 or more lifetime AEDs. The ?50% and ?75% responder rates were 48.2% and 24.4% for the entire treatment period; responder rates increased over time for patients completing each time point. Of those patients exposed to lacosamide for at least 2 years, 6/193 (3.1%) remained seizure free from the first dose of open-label lacosamide through at least 2 years. Conclusions: Long-term treatment with lacosamide in this open-label study was associated with a reduction in seizures and maintenance of efficacy.