Abstracts

Rationale: In conversion-to-monotherapy trials of antiepileptic drugs (AEDs), the standard primary endpoint is the cumulative rate of trial exit due to worsening of seizures. In order to provide a more clinically meaningful picture of change in treatment efficacy following the conversion, we evaluated changes from baseline in seizure frequency among all patients in the efficacy populations of two Phase III conversion-to-monotherapy studies of eslicarbazepine acetate (ESL), categorized by degree of improvement or worsening. ESL is a once-daily (QD) oral AED approved as adjunctive treatment for partial-onset seizures (POS) in the USA, Europe, and Canada, and as monotherapy for POS in the USA. Methods: A post-hoc analysis was conducted on pooled data from two conversion-to-ESL-monotherapy studies (093-045 and -046). 271 adults (?-16 years) with refractory POS (?-4 seizures/month while receiving stable doses of 1 or 2 AEDs in the 4 weeks before screening) were treated with ESL (1200 mg or 1600 mg QD) for 18 weeks (2-week titration: previous AEDs withdrawn over the next 6 weeks, ESL monotherapy administered for 10 weeks). Seizures were recorded using daily diaries. We evaluated the proportions of patients with different degrees of improvement or worsening in standardized seizure frequency (SSF; change between baseline and monotherapy periods). Results: Overall, during the monotherapy period, 69/91 patients (76%) taking ESL 1200 mg QD and 142/180 (79%) taking ESL 1600 mg QD experienced a reduction in SSF, with median changes of -47% for ESL 1200 mg and -46% for ESL 1600 mg compared with baseline (Table 1). Among patients who improved relative to baseline, 10% (n = 9) of the ESL 1200 mg QD group and 11% (n = 20) of the ESL 1600 mg QD group experienced a 100% reduction in SSF (i.e., seizure freedom), while 36% (n = 33) and 36% (n = 64) experienced reductions of ?-50% to < 100%, and 30% (n = 27) and 32% (n = 58) experienced SSF reductions of < 50%, respectively. Among those with increases in SSF from baseline, 13% (n = 11) of the ESL 1200 mg QD group and 13% (n = 24) of the ESL 1600 mg QD group experienced an increase < 50%, while 12% (n = 11) and 8% (n = 14), respectively, experienced an increase of ?-50%. Conclusions: The majority of patients (>75%) showed some degree of improvement (i.e., reduction in seizure frequency) following conversion to ESL monotherapy from 1 or 2 baseline AEDs. Increases in seizure frequency of ?-50% were uncommon (~10% of patients). Funding: Studies sponsored by Sunovion Pharmaceuticals Inc.