Abstracts

Rationale: Lacosamide is an antiepileptic drug (AED) licensed in the European Union and United States in 2008. A high response rate and good tolerability of adjunctive lacosamide therapy in adults with uncontrolled partial-onset seizures (POS) has been reported by previous trials and post-marketing studies in western countries. This study (EP0008; NCT01710657) evaluated the efficacy and safety of adjunctive lacosamide treatment in Chinese and Japanese adults with uncontrolled POS, with or without secondary generalization.Methods: In this double-blind, placebo-controlled study, adults aged 16-70 years with uncontrolled POS and were treating with 1-3 other AEDs, were recruited from 72 study centers in China and Japan. After 8 weeks of baseline, patients were randomly assigned in a 1:1:1 ratio to receive adjunctive lacosamide 400 mg/day (200 mg twice per day), 200 mg/day (100 mg twice per day) or placebo for 4 weeks of titration (started at 100mg/day), followed by 12 weeks of maintenance. The primary outcome was the change in seizure frequency per 28 days from baseline to maintenance phase. Evaluation of efficacy and safety were performed on the full analysis set (FAS) and safety set (SS), respectively.Results: Five hundred and forty-seven patients received treatment (SS), 544 had ≥1 post-baseline efficacy measurement (FAS), and 485 (88.7%) completed the study. No significant difference was found in the demographics and clinical characteristics of the 3 patients groups at baseline. Among 544 patients (FAS) , 77.8% were taking 2 or 3 concomitant AEDs. The median change in seizure frequency per 28 days from baseline to maintenance phase was -4.50 (range -97.5, 28.2), -3.33 (range -754.3, 165.2) and -1.22 (range -93.0, 39.8) in the lacosamide 400 mg/day, 200 mg/day and placebo groups, respectively. The percentages reduction in seizure frequency over placebo per 28 days from baseline to maintenance phase were significant for lacosamide 400 mg/day (39.6% [95% CI 30.5%, 47.6%], p<0.001) and lacosamide 200 mg/day (29.4% [95% CI 18.7%, 38.7%], p<0.001). Higher responder rates were observed in lacosamide groups versus placebo (Figure 1). The proportions of patients who were seizure free during the maintenance period was 5.4%, 4.7%, and 0% in those groups receiving lacosamide 400 mg/day, 200 mg/day and placebo, respectively. The most common treatment-emergent adverse events for all lacosamide treated patients were dizziness (25.9%), nasopharyngitis (14.3%) and somnolence (10.2%).Conclusions: Adjunctive lacosamide (400 and 200 mg/day) was efficacious in reducing POS frequency in Chinese and Japanese patients with a safety and tolerability profile consistent with previous trials.