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. Therapy with AEDs, in particular EIAEDs, can result in detrimental changes in bone turnover and lipid metabolism, leading to an increased risk of conditions such as osteoporosis and vascular disease. This exploratory post-hoc analysis examines the impact of ESL monotherapy on laboratory markers of bone turnover and lipid metabolism, and the effects of converting to ESL monotherapy from an EIAED (i.e., carbamazepine or phenytoin).Methods: After an 8-week BL, patients (16–70 years; POS not well controlled by 1–2 AEDs [only one sodium channel blocker allowed]) in the Phase III studies BIA-2093-045 and -046 were randomized (2:1) to receive ESL 1600 mg or 1200 mg QD (2-week titration; 6-week conversion [BL AEDs withdrawn]; 10-week monotherapy). Those who completed/discontinued/exited after ≥3 weeks of ESL treatment could enter the ongoing, 12-month, open-label extension (OLE) study -050, and remain on ESL monotherapy (800–2400 mg QD [flexible dosing schedule]; re-introduction of 1–2 additional, non-oxcarbazepine AEDs allowed). Markers of bone turnover and lipid metabolism (Tables 1 and 2) were measured at BL, 18 weeks (end of double-blind [DB] period), and after 12 months of OL treatment. Pooled data are presented by BL EIAED use; OL data are presented for patients who took ESL monotherapy during the OLE without re-introducing other AEDs.Results: 365 patients received ≥1 dose of ESL (1600 mg or 1200 mg QD); 130 (36%) took an EIAED at BL (+EIAED group) and 235 (64%) did not (-EIAED group). 274 patients entered the OLE; as of 03/21/2014, 180 patients had completed 1 year of treatment. At BL, mean values for most markers of bone turnover and lipid metabolism were higher in the +EIAED group versus the -EIAED group (Tables 1 and 2). After 18 weeks of DB ESL, changes in markers of bone turnover were variable in the -EIAED and +EIAED groups (Table 1). After 12 months of ESL monotherapy most bone turnover markers were increased versus BL in both groups. In the -EIAED group all markers of lipid metabolism were increased versus BL after both 18 weeks and 12 months of ESL monotherapy (Table 2). In contrast, in the +EIAED group lipid markers were mostly decreased versus BL at both time points.Conclusions: Most markers of bone turnover were increased versus BL after a year of OL ESL monotherapy; the impact of BL EIAED use on these markers during ESL monotherapy was variable. All lipid markers evaluated were increased versus BL during ESL monotherapy, both at 18 weeks and a year, in patients who were not taking an EIAED at BL, and most were decreased at both time points in the +EIAED group. This suggests an intermediate effect of ESL on these markers, consistent with a mild-to-moderate degree of enzyme induction. Studies sponsored by Sunovion Pharmaceuticals Inc.