Abstracts

Rationale: Antiepileptic drug (AED) use may be associated with substantial changes in body weight that may increase risk of morbidity and reduce adherence to the treatment regimen. Eslicarbazepine acetate (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. We report the effect of ESL on changes in body weight during two Phase III clinical trials. Methods: Body weight data were collected during clinic visits in six Phase III studies of ESL in patients with treatment-refractory POS. Changes of ≥7% from baseline in weight were deemed potentially clinically significant (per FDA guidance). In three studies (2093-301, -302, -304), patients received double-blind ESL or placebo (PBO) alongside baseline AEDs for 14 weeks; open-label (OL) extensions allowed flexible dosing. In two dose-blind conversion-to-ESL monotherapy studies (093-045, -046), patients received ESL for 18 weeks (10 weeks as monotherapy; 1200 or 1600 mg QD); the OL extension study (093-050) allowed flexible dosing of ESL (800–2400 mg) as well as the introduction of other medications, including AEDs. Results: In studies of adjunctive ESL (Table 1), 1–5% of patients taking ESL experienced a ≥7% reduction in body weight, versus 1% of patients taking PBO. Conversely, 9–12% of patients taking ESL and 6% of patients taking PBO experienced a ≥7% increase. In the OL extension studies, 81% of patients taking adjunctive ESL had a ≥7% change in body weight (53% had an increase; 28% a reduction); however, the potential impact of concomitant medication changes could not be accounted for in these patients. In conversion-to-ESL-monotherapy studies (Table 1), 5% of patients taking ESL 1200 mg and 3% taking ESL 1600 mg experienced a ≥7% reduction in weight, whereas 3% taking 1200 mg and 9% taking 1600 mg experienced a ≥7% increase in weight. In the 1-year OL extension, 60% of patients taking ESL monotherapy had ≥7% change in body weight (40% had an increase; 20% a reduction) and similarly, the potential impact of concomitant medication changes could not be accounted for in these patients. Conclusions: In the adjunctive trials, compared with PBO, larger proportions of patients taking ESL either gained or lost weight, and these percentages were more prominent during the OL extensions. In the monotherapy trials, there were also patients who either gained or lost weight relative to baseline, and these changes also became more evident during the 1-year OL extension phase, although changes in ESL dose and in baseline medications were allowed and could have affected these results. Given these variable clinical trial data, no definitive conclusions regarding weight changes during treatment with ESL can be made. Funding: Funding was provided by Sunovion Pharmaceuticals Inc.