Abstracts

Rationale: Lacosamide (LCM) is a 3rd generation AED approved for adjunctive therapy in adults with partial-onset seizures (POS; 200-400mg/d). A historical-controlled trial is considered by the FDA as appropriate in providing evidence of AED efficacy as a monotherapy (French et al, Epilepsia, 2010). This historical-controlled, multicenter, double-blind, randomized trial (SP902; NCT00520741) was conducted to assess efficacy and safety of conversion to LCM 400mg/d monotherapy in patients with POS on a stable regimen of 1-2 AEDs.Methods: Patients (16-70 years) experiencing 2 to 40 POS/28 days during the 8-week Baseline were randomized 3:1 to LCM 400 or 300mg/d. The 300mg/d arm was included for blinding and consistency with the historical control studies. During the 3-week Titration, LCM was initiated at 200mg/d and increased (100mg/d weekly increments with no dose reductions allowed) to the randomized dose. The Maintenance Phase included a 6-week AED withdrawal period followed by a 10-week LCM monotherapy period. The Safety Set (SS) included all randomized patients receiving 1 LCM dose. The Full Analysis Set (FAS) included all SS subjects who completed Titration, took 1 dose and started withdrawing background AEDs. The primary efficacy variable was the percentage of the FAS meeting 1 of the 5 predefined exit criteria by Maintenance Day 112; for LCM 400mg/d, a Kaplan-Meier estimate of the primary efficacy variable and a 2-sided 95% CI were calculated. Safety and tolerability were assessed.Results: A total of 425 patients comprised the SS (n=106, 300mg/d; n=319, 400mg/d); 383 of which comprised the FAS (n=99, 300mg/d; n=284, 400mg/d). The most common background AEDs for the 300 and 400mg/d groups, respectively, were levetiracetam (22.2%, 22.9%), carbamazepine (18.2%, 20.1%), and lamotrigine (14.1%, 15.1%). The predicted exit rate for LCM 400mg/d (0.300; 95% CI [0.246, 0.355]) was statistically significantly lower than the historical control exit rate (0.653; Table 1, Figure 1). The median duration of monotherapy was 71.0 days (both dose groups; SD 22.0 in 300mg/d and 20.3 in 400mg/d). The majority of patients were reported as improved on Clinical (CGIC) and Patient (PGIC) Global Impression of Change assessments; CGIC - 75.4% (400mg/day) and 72.7% (300mg/day); PGIC - 74.3% (400mg/day) and 72.7% (300mg/day). The most common treatment-emergent adverse events (TEAEs) in 300mg/d and 400mg/d groups, respectively, were dizziness (17.9%, 26.0%), nausea (12.3%, 13.8%), and headache (17.9%, 13.2%). Discontinuation due to TEAEs occurred in 15.1% and 17.6% of patients in 300 and 400mg/d groups, respectively.Conclusions: LCM 400mg/d was efficacious as monotherapy in patients with POS based on the significantly lower percentage of patients meeting exit criteria compared to the historical control exit rate. LCM was generally well tolerated. The types of AEs reported during this study were similar between the two dose groups and to those in previous LCM adjunctive therapy trials. Funded by UCB Pharma