Abstracts

Rationale: The approval of lacosamide (Vimpat ) as adjunctive treatment of partial-onset seizures (POS) in adults (maximum approved dose 400mg/day) was based on positive results from three pivotal studies in treatment-resistant patients randomized to lacosamide (200, 400, or 600mg/day) and treated with up to 3 concomitant antiepileptic drugs (AEDs). In this ongoing study, the efficacy and tolerability of lacosamide are evaluated in adult patients with POS receiving only one baseline AED. As such, the effects of lacosamide can be determined without the potentially confounding factor of multiple concomitant AEDs and in a less severely affected population, closer to routine clinical practice.Methods: The planned enrollment for this 6-month prospective, non-interventional study is 500 evaluable patients. The monotherapy background AED was chosen by the treating physician prior to inclusion and independent of study procedures. Main outcome variables include reduction in seizure frequency ( 50% and 75% responder rates) compared to 3-month retrospective baseline, seizure freedom for 6 months, Clinical Global Impression of Change (CGIC), and treatment-emergent adverse events (TEAEs). Data for all subjects in the analysis sets and subgroups of interest are presented; all statistical analyses are descriptive.Results: In this second interim report, efficacy (n=329 patients) and safety (n=367 patients) data are reported. At the last study visit (6 months), 70.2% and 59.9% of patients showed a 50% and 75% reduction in seizure frequency compared to baseline, and 40.7% were seizure free for at least 3 months (median lacosamide dose = 200mg [50 600mg]). On the CGIC, physicians judged symptoms as very much improved or much improved in 26.5% and 36.9% of patients. Compared to the overall results, the reduction in seizure frequency was greater with lacosamide adjunctive therapy in elderly patients ( 65 years, n=55), in patients with a short duration of epilepsy ( 5 years, n=130), and in patients who received lacosamide as a first adjunctive treatment (n=112). For these subgroups, 50% responder rates were 78.2%, 75.4% and 81.3%, and seizure freedom rates were 54.5%, 48.5% and 55.4%. The overall incidence of TEAEs was 48.8%, with 30.2% of TEAEs judged by physicians as related to lacosamide. A total of 12.5% of patients discontinued due to a TEAE. The most frequent TEAEs related to lacosamide ( 2%) were fatigue (10.1%, n=37), vertigo (8.7%, n=32), and headache and nausea (2.2%, n=8 each). Conclusions: The results of this second interim analysis indicate improved seizure control with a favorable safety and tolerability profile when lacosamide is used as adjunctive treatment to AED monotherapy in routine clinical practice. These preliminary results are consistent with the first interim analysis based on 109 patients and need to be verified by the final analysis at the end of the study. Funded by UCB Pharma