Abstracts

Rationale: Age-related changes, such as reduced drug clearance and a lower threshold for developing side effects, impact on antiepileptic drug (AED) choice in elderly patients (French JA, Gazzola DM. Continuum [Minneap Minn] 2013;19:643–55). It is therefore important to investigate the safety and tolerability of AEDs in elderly populations. Eslicarbazepine acetate (ESL) is a once-daily (QD) oral AED, approved in the EU, US and Canada as adjunctive treatment of partial-onset seizures (POS). The tolerability of ESL was found to be similar in elderly and non-elderly patients from non-epilepsy studies (Andermann E, et al. Neurology 2014;82[10 Suppl.]:P3.240).Methods: This exploratory post-hoc analysis of pooled data from three double-blind Phase III studies (BIA-2093-301, -302 and -304) evaluates the safety and tolerability of adjunctive ESL in elderly (≥60 years) and non-elderly (18–59 years) patients with ≥4 POS/month, taking 1–3 AEDs. Patients received placebo (PBO) or ESL 400 mg (studies -301 and -302 only), 800 mg, or 1200 mg QD (Rogin J, et al. Epilepsy Curr 2014;14[Suppl.1]:209. Abstract 2.126). The incidence of treatment-emergent adverse events (TEAEs) was calculated for elderly and non-elderly patients in the safety population (all patients who received at least one dose of study drug). PBO-adjusted incidence was determined as [incidence with ESL (800 mg or 1200 mg)] – [incidence with PBO].Results: 4% of patients were aged ≥60 years (PBO, 18/426; ESL, 40/1021; Table 1). Elderly patients received a mean ESL dose of 816 mg/day for a mean of 84.1 days (overall exposure = 9.2 patient-years). At baseline, levetiracetam was used more frequently in elderly patients, and valproic acid in non-elderly patients. The overall incidence of TEAEs was similar in elderly and non-elderly patients; TEAEs with an incidence ≥10% in both elderly and non-elderly patients treated with ESL were dizziness, somnolence, nausea and headache (Table 2). The overall PBO-adjusted incidence of TEAEs was ≥10% greater in elderly than non-elderly patients (total ESL group [patients taking ESL 400 mg, 800 mg or 1200 mg QD], 27.5 vs 15.1%). The PBO-adjusted incidence of the following TEAEs was ≥10% greater in elderly than non-elderly patients treated with: ESL 1200 mg: insomnia (26.7 vs -0.2%), diplopia (26.7 vs 8.3%), blurred vision (20.0 vs 2.9%), ataxia (20.0 vs 3.5%), dysarthria (13.3 vs 2.1%); ESL 800 mg: nausea (19.0 vs 3.7%), fall (14.3 vs 0.6%), headache (14.3 vs 2.3%), somnolence (12.7 vs 2.0%).Conclusions: Although the qualitative nature of TEAEs with ESL was similar in elderly and non-elderly patients, there was a higher PBO-adjusted incidence of some TEAEs in the elderly subgroup. These findings should be interpreted with caution given the low number of elderly patients. Studies sponsored by Sunovion Pharmaceuticals Inc.