Abstracts

Rationale: A historical-controlled, multicenter, double-blind, Phase 3 study (SP902; NCT00520741) demonstrated the efficacy and safety of conversion to lacosamide (LCM) monotherapy in adults with focal seizures. The incidence of the most common treatment-emergent adverse events (TEAEs) was generally higher during LCM titration compared with the LCM Maintenance Period. The objective of this post-hoc analysis was to assess the tolerability profile of LCM during initiation at a dose of 200 mg/day (bid regimen), given that an initial dose of 100 mg/day was applied in double-blind, placebo-controlled studies of adjunctive LCM. Methods: In study SP902, patients (16-70 years) on 1-2 AEDs experiencing ≥2 to ≤40 focal seizures/28 days were randomized to LCM 400 or 300 mg/day (3:1). The second AED was required to be ≤50% of the minimal recommended maintenance dose per the US product label. LCM was initiated at 200 mg/day and increased by 100 mg/day in weekly increments to the randomized dose before withdrawal to LCM monotherapy. This post-hoc analysis was performed on the safety set (SS; all patients who received ≥1 LCM dose). TEAEs were analyzed during the initial 200 mg/day dosing period of the Titration Phase (up to 10 days). Post-hoc analyses of pooled data from Phase 2/3 randomized, double-blind, placebo-controlled studies of adjunctive LCM (initiated at 100 mg/day and increased by 100 mg/day in weekly increments) in adults with focal epilepsy on 1-3 background AEDs were also performed. This analysis assessed the subset of patients on 1 background AED and analyzed the TEAEs during the first 2 weeks (up to 14 days) of adjunctive LCM treatment. Results: Of the 425 patients (SS) enrolled in SP902 (mean age 40.6 years; mean duration since diagnosis 17.2 years; 45.9% discontinued >3 AEDs prior to study entry [AED history]), 312 (73.4%) were on 1 and 113 (26.6%) on 2 background AED(s). During the initial 200 mg/day dosing period 41.2% patients in the overall population reported >1 TEAE; most frequently dizziness (8.2%), nausea (5.6%), fatigue (4.5%), somnolence (4.0%) and headache (3.8%) and 3.1% discontinued due to TEAEs during this period. The tolerability profile of LCM was generally similar in patients on 1 and 2 background AEDs (Table). The incidence of the most common TEAEs and the percentage of patients discontinued due to TEAEs during the initial 200 mg/day LCM dosing period (SP0902) were comparable to those reported for subjects on 1 concomitant AED during the first 2 weeks of adjunctive LCM treatment initiated at a dose of 100 mg/day and increased to 200 mg/day during the second week (pooled, adjunctive therapy, randomized, Phase 2/3 placebo-controlled trials (Table) Conclusions: The results of this post-hoc analysis suggest that the tolerability profile of LCM during treatment initiation is similar when started as adjunctive therapy in bid regimen at a dose of 200 mg/day versus 100 mg/day in adults with focal seizures. Funded by UCB Pharma