Abstracts

Rationale: We are conducting an ongoing multicenter, open-label, phase 3 study to assess long-term safety of conversion to lacosamide (LCM) monotherapy for partial-onset seizures (EP0057; NCT02124564). Here, we present results of an interim analysis from the study.  Methods: Japanese patients, aged ≥16 years, with uncontrolled partial-onset seizures, with or without secondary generalization receiving a single antiepileptic drug (AED) were eligible to participate in the study. During a 4-week titration period, LCM was orally administered twice daily in 2 equally divided doses, initiated at 100 mg/day and titrated by 100 mg/day each week up to 400 mg/day. Any baseline AED was tapered and discontinued over a 4 to 12-week baseline AED withdrawal period (which may have overlapped with the LCM titration period). Patients who completed the baseline AED withdrawal period entered the LCM monotherapy period, which consisted of a 52-week evaluation period and a follow-up period. During the AED withdrawal and LCM monotherapy periods, the LCM dose could be adjusted to between 200 and 600 mg/day. We assessed primary safety variables, including treatment emergent adverse events (TEAEs), withdrawals due to TEAEs, and serious TEAEs. We evaluated pharmacokinetics and efficacy as secondary outcomes. Results: Of the 19 Japanese patients who participated in the study (see Table 1 for baseline data), 13 (68.4%) completed the 52-week evaluation period and are in the follow-up period. Meanwhile, 6 patients (31.6%) discontinued due to a lack of efficacy (n=3), TEAEs (n=2; dizziness), or consent withdrawal (n=1). The overall mean (SD) duration of LCM exposure was 427.8 (208.2) days. The maximum daily dose was 400 mg/day for 8 patients (42.1%), 500 mg/day for 3 patients (15.8%), and 600 mg/day for 8 patients (42.1%). All 19 patients reported TEAEs and 16 (84.2%) reported TEAEs considered to be LCM-related (Table 2). The most commonly reported TEAEs during the study were dizziness (n=9, 47.4%) and somnolence (n=6, 31.6%), both of which were most frequently reported during the titration period. The majority of TEAEs were mild (73.7%) or moderate (21.1%) in intensity. Only 1 patient reported a serious TEAE (convulsion) and no patient died during the study. The LCM plasma concentration data showed that nearly all LCM concentrations were within the expected ranges. Regarding efficacy, of the 11 patients who were exposed to LCM for at least 12 months (364 days) in the monotherapy period, 5 (45.5%) remained seizure-free for 12 consecutive months from the start of the monotherapy period (2/13 patients completing the 52-week evaluation period were not included in the 12-month efficacy analysis as they did not meet the criterion of at least 364 days of LCM exposure). Conclusions: In this interim analysis, long-term LCM monotherapy at doses up to 600 mg/day showed favorable safety and tolerability, and maintained seizure reduction over time in Japanese adults with partial-onset seizures, with or without secondary generalization. Funding: UCB Pharma-sponsored.