Abstracts

Rationale: ESL is a once-daily (QD) oral antiepileptic drug (AED), approved in the EU, US and Canada as adjunctive treatment of partial-onset seizures (POS). ESL is not approved as monotherapy. Following oral dosing, eslicarbazepine, R-licarbazepine, and oxcarbazepine account for 94%, 5% and 1% of ESL exposure, and 78%, 19% and 4% of OXC exposure, respectively (Nunes T, et al. Epilepsia. 2013;54:108–16). The tolerability of ESL taken transiently with OXC has not been previously evaluated. This exploratory post-hoc analysis examines the safety and tolerability of ESL monotherapy in patients who had previously been taking one or two AEDs, one of which was OXC; as well as when patients were taking ESL with OXC (ESL titration and OXC taper periods).Methods: Studies 093-045 and -046 were randomized, double-blind, conversion-to-ESL monotherapy studies which used a historical control. Patients (16–70 years) with POS not well controlled by 1–2 AEDs were randomized (2:1) to ESL 1600mg or 1200mg QD (2-week titration; 6-week AED taper [other AEDs withdrawn]; 10-week monotherapy). In both trials, treatment-emergent adverse event (TEAE) incidence was calculated for patients who were/were not taking OXC at entry (+OXC/-OXC).Results: Overall, 365 patients received ≥1 dose of study medication (intent-to-treat population); 22 patients (6.0%) were on baseline OXC and 343 patients (94.0%) were receiving other baseline AEDs. Overall TEAE incidence (proportion of patients who had ≥1 TEAEs) was 86.4% for +OXC and 78.1% for -OXC. During the titration and baseline AED(s) taper periods, overall TEAE incidence was greater for + than -OXC (72.7% vs 57.1%, and 68.2% vs 53.9%, respectively). In the monotherapy period, overall TEAE incidence was 64.7% and 57.6% for + and -OXC, respectively; there were only a small number of +OXC patients in this period (n=17). One patient for +OXC (4.5%) and 20 for -OXC (5.8%) had severe TEAEs. TEAEs led to the discontinuation of 2 (9.1%) and 45 (13.1%) patients for + and -OXC, respectively. No serious TEAEs were reported for +OXC. Figure 1 shows incidences of TEAEs reported by >10% of patients in the + or -OXC groups; the incidence difference between groups was >10% for dizziness, vomiting and diplopia.Conclusions: During the initial study phases (ESL titration and AED[s] taper periods), overall TEAE incidence was greater among patients who were converting to ESL from OXC than among patients who converted from a baseline AED regimen that did not include OXC; this difference was driven largely by higher incidences of dizziness, vomiting and diplopia in the +OXC group. After conversion to ESL monotherapy, tolerability appeared to be comparable between subgroups, whether or not patients had previously been taking OXC. Study sponsored by Sunovion Pharmaceuticals Inc.