Abstracts

Rationale: Epilepsy is a chronic condition that can require life-long treatment with antiepileptic drugs (AEDs); therefore, it is important to evaluate the long-term safety and efficacy of drug therapies. Lacosamide is an AED approved for the adjunctive treatment of patients with partial-onset seizures (POS). The effects of open-label treatment with lacosamide exposure up to 8 years have been evaluated in a pooled POS patient population.Methods: Patients entered one of three open-label extension trials (SP615, NCT00552305; SP756, NCT00522275; SP774, NCT00515619) following completion of a corresponding phase II/III double-blind trial of adjunctive lacosamide for POS. Dosage adjustments of lacosamide (100 800mg/day) and/or concomitant AEDs were allowed to optimize tolerability and seizure reduction. Safety evaluations included treatment-emergent adverse events (TEAEs), vital signs, body weight, clinical laboratory data, and electrocardiograms. Efficacy evaluations for yearly completer cohorts included the percent change from Baseline in 28-day seizure frequency, ?50% and ?75% response to treatment, and seizure-free status.Results: A total of 1,054 patients initiated open-label lacosamide treatment, representing 2997.8 patient-years exposure. The minimum treatment duration was 3 days and the maximum was 2,913 days or ~8 years. At Baseline of the lead-in trials, 62% of patients were taking two concomitant AEDs while 22% were taking three. The median modal dose was 400mg/day, and the median maximum daily dose was 500mg/day. At >1, >3, and >5 years of open-label treatment, 75%, 53%, and 18% of patients were exposed to lacosamide, respectively. The decrease in percentage of patients exposed to lacosamide after 5 years was due to a combination of patients prematurely discontinuing and patients completing the study because of the commercial availability of lacosamide. Primary reasons for discontinuation were lack of efficacy (28%), consent withdrawal (12%), and TEAEs (11%). Common TEAEs (?15%) were dizziness (37%), headache (19%), nasopharyngitis (16%) and diplopia (15%). TEAEs that led to discontinuation in ?0.5% of patients were dizziness (1.7%) and convulsion (0.9%). The Baseline median 28-day seizure frequency was 11.5. The median percent reduction from Baseline for 1-year, 2-year, 3-year, 4-year and 5-year completers was 52%, 56%, 60%, 63% and 65%, respectively. The ?50% responder rate was 53%, 57%, 60%, 64% and 65% for 1-year, 2-year, 3-year, 4-year and 5-year completers, while the ?75% responder rate was 26%, 29%, 31%, 34% and 41%. Of patients exposed to lacosamide for 1, 2, 3, 4 or 5 years, 3.0%, 3.1%. 2.5%, 2.1% and 1.6% remained seizure free.Conclusions: For patients with partial-onset seizures, long-term open-label treatment with lacosamide up to 8 years was generally well tolerated and associated with a reduction in seizure frequency and maintenance of efficacy. No new safety concerns were identified with long-term lacosamide treatment. Funded by UCB