Abstracts

Rationale: Treatment-emergent adverse events (TEAEs) are generally thought to be more frequent when antiepileptic drugs (AEDs) are used adjunctively (compared to monotherapy) and AEDs may be expected to exhibit optimal seizure control when taken at their appropriate maintenance dose. Eslicarbazepine acetate (ESL) is a once-daily (QD) oral AED for partial-onset (focal) seizures (POS). In conversion-to-ESL monotherapy trials, ESL was used concomitantly with other AEDs during the titration and baseline AED taper periods. This pooled analysis examines whether seizure frequency and tolerability differ between study periods in two Phase III conversion-to-ESL monotherapy trials. Methods: Studies 093-045 and -046 were randomized, double-blind, conversion-to-ESL monotherapy studies. Eligible patients (aged 16–70 years) with POS refractory to 1–2 AEDs were randomized (2:1) to ESL 1600 mg or 1200 mg QD (2-week titration; 6-week baseline AED taper; 10-week monotherapy). Change in standardized seizure frequency (SSF; seizures per 28 days), responder rates (proportion of patients with =50% reduction in SSF) and TEAE incidences were calculated. The efficacy (patients who entered the baseline AED taper period) and intent-to-treat (ITT; patients who received =1 dose of ESL) populations were used for efficacy and safety analyses, respectively. Results: The efficacy and ITT populations comprised 332 and 365 patients, respectively. Changes in SSF and responder rates during each study period are reported in Table 1. Reductions in SSF from baseline and responder rates did not notably differ between the three study periods in the ESL 1600 mg group; in the ESL 1200 mg group, reductions in SSF and responder rates appeared to be greater during the monotherapy period than during the titration and baseline AED taper periods. Incidences of TEAEs and TEAEs leading to discontinuation, by study period, are reported in Table 2. The incidence of dizziness (both ESL doses), as well as the overall incidence of TEAEs leading to discontinuation (ESL 1600 mg only), appeared to be lower during the monotherapy period than during the titration and baseline AED taper periods. Conclusions: ESL (1600 mg and 1200 mg QD) was effective and well tolerated during the monotherapy period of Phase III conversion to ESL monotherapy trials. In the ESL 1200 mg group, seizure reduction was greater during the monotherapy period than during the titration and baseline AED taper periods. Incidences of dizziness and TEAEs leading to discontinuation were lower during the monotherapy period than during the titration and AED taper periods. Funding: Studies sponsored by Sunovion Pharmaceuticals Inc.