Abstracts

Rationale: ESL is a once-daily (QD) oral antiepileptic drug (AED) for adjunctive treatment of partial-onset seizures (POS). ESL is not approved as monotherapy. CBZ is commonly used in the treatment of POS. In previous conversion-to-monotherapy AED studies, prior CBZ use has increased the hazard rate of study exit by 8% (95% CI: -19.4%, 35.4%) (French J, et al. Epilepsia 2010;51:1936–43). This exploratory post-hoc analysis examined the efficacy and tolerability of ESL monotherapy in patients previously taking one or two AEDs, one of which was CBZ.Methods: Studies 093-045 and -046 were randomized, double-blind, conversion-to-ESL monotherapy studies that used a historical control. Eligible patients (16–70 years) with POS not well controlled by 1–2 AEDs were randomized (2:1) to ESL 1600mg or 1200mg QD (double blind period: 2-week titration; 6-week AED conversion [other AEDs withdrawn]; 10-week monotherapy). Exit rate (proportion of patients meeting ≥1 of five exit criteria signifying worsening seizure control; primary endpoint), change in standardized seizure frequency (SSF; seizure count per 28 days) and responder rates (proportion of patients with ≥50% reduction in SSF; secondary endpoints), and treatment-emergent AE (TEAE) incidence were calculated for patients who were/were not taking CBZ at entry (+CBZ/-CBZ). The efficacy (patients who began AED conversion) and intent-to-treat (ITT; patients who received ≥1 dose of ESL) populations were used for efficacy and safety analyses, respectively.Results: Overall, 27% of patients (ITT and efficacy populations) were taking CBZ at entry; in the efficacy population (n=332), 81 patients converted from CBZ alone and 10 from CBZ taken in combination with another baseline AED; -CBZ group, n=241. The overall hazard ratio for study exit between the +CBZ and -CBZ groups, was 1.49 (95% CI: 0.93, 2.39; p=0.10). Median changes in SSF indicated improved seizure control between baseline and the double-blind period, regardless of which AED patients withdrew from; magnitude of median seizure reduction was numerically less for +CBZ than for -CBZ, for both doses (ESL 1200mg: +CBZ -14.4 [n=37], -CBZ -45.2 [n=77]; ESL 1600mg: +CBZ -26.7 [n=54], -CBZ -50.2 [n=162]). Responder rates were also numerically less for +CBZ vs -CBZ (ESL 1200mg: +CBZ 18.9% [n=37], -CBZ 44.2% [n=77]; ESL 1600mg: +CBZ 22.2% [n=54], -CBZ 49.4% [n=164]). Prior CBZ use was associated with a slightly lower overall TEAE incidence (+CBZ: 75.0%, -CBZ: 80.0%); individual TEAE incidences differed slightly for +CBZ vs -CBZ (Figure 1).Conclusions: The hazard ratio for study exit, for +CBZ vs -CBZ, was 1.49 (p=0.10). Although the magnitude of seizure reduction was lower in the +CBZ (vs -CBZ) group, some improvement in seizure control (vs baseline) was seen in patients who converted to ESL from CBZ. In addition, overall TEAE incidence was slightly lower for +CBZ than for -CBZ. Study sponsored by Sunovion Pharmaceuticals Inc.