Abstracts

Rationale: The efficacy and safety of conversion to lacosamide (LCM) monotherapy (400mg/day) in adults with focal seizures have been demonstrated in a historical-controlled, multicenter, double-blind study (SP902;NCT00520741) (Wechsler et al, Epilepsia, In Press). The primary efficacy endpoint was the percentage of patients meeting ≥1 of 5 predefined exit criteria for LCM 400mg/day, which differed from the seizure-frequency based endpoints typical of adjunctive epilepsy studies. The objective of this post-hoc analysis of SP902 data was to assess seizure frequency during the different phases of the withdrawal to LCM monotherapy study. Methods: The study comprised 8-week prospective Baseline, and 19-week Treatment Phase (3-week Titration, 6-week background AED Withdrawal, and 10-week LCM Monotherapy Phases). Patients (16-70 years) on 1-2 AED experiencing ≥2 to ≤40 focal seizures/28 days were randomized (3:1) to LCM 400 or 300mg/day. LCM was initiated at 200mg/day and increased by 100mg/day in weekly increments to the randomized dose. This post-hoc analysis was performed on the safety set (SS; all patients who received ≥1 LCM dose) and on the subpopulation who completed the LCM Monotherapy Phase (Completer Set [CS]). The median seizure frequency/28 days across all patients was assessed for all focal seizures, for complex partial seizures (CPS) and secondarily generalized seizures (sGS) combined (CPS + sGS for patients who reported CPS or sGS during Baseline) and for sGS only (for patients who reported sGS during Baseline). Results: A total of 425 patients (SS) were enrolled and 271 (63.8%) completed the LCM Monotherapy Phase (SS/CS: mean age 40.6/41.2 years; mean duration since first diagnosis 17.2/15.8 years; 45.9%/43.5% discontinued >3 AED prior to study entry [AED history]). During the Treatment Phase 69 (16.2%) patients discontinued due to a treatment-emergent adverse event (TEAE), most frequently being TEAEs coded to convulsion (8.2%), dizziness (1.6%), grand mal convulsion (1.2%) and nausea (0.9%). LCM reduced median focal seizure frequency during the add-on Titration Phase, the background AED Withdrawal Phase with steady LCM doses and the LCM Monotherapy Phase for both groups (SS [Figure 1]; CS [Figure 2]). Generally, similar results were observed with the two LCM doses (400 and 300mg/day). The median focal seizure frequency/28 days during the LCM Monotherapy Phase was reduced compared to the Baseline median by 51% (SS) and 60% (CS) for all seizures; 52% (SS) and 60% (CS) for CPS + sGS; and 60% (SS) and 80% (CS) for sGS. Conclusions: The results of this post-hoc analysis suggested that the median seizure frequency/28 days across all patients was reduced during LCM titration and was maintained throughout conversion to LCM monotherapy and LCM monotherapy maintenance for all seizure types. Seizure outcome data from the completer set must be interpreted with strong caution, as this is an enriched patient subset that excluded those not tolerating or significantly worsening during withdrawal to LCM monotherapy. Funded by UCB Pharma