Abstracts

Rationale: Eslicarbazepine acetate (ESL) is a once-daily, oral antiepileptic drug (AED) for focal seizures. Here, we report safety and tolerability outcomes from a recently completed Phase 4 study of ESL taken as a first adjunctive therapy with levetiracetam (LEV) or lamotrigine (LTG) monotherapy, or as later adjunctive therapy in treatment-resistant patients with focal seizures, in a real-world setting. This is the first time that adjunctive ESL has been evaluated at an early stage in the treatment trajectory in North American patients. Methods: A multicenter, open-label, non-randomized Phase 4 study of adjunctive ESL in patients aged ≥18 years with focal seizures in the USA and Canada (NCT03116828). Patients with prior exposure to ESL or currently using oxcarbazepine were excluded. Arm 1: ESL as first adjunctive therapy with LEV (n = 28) or LTG (n = 14) in patients with inadequate response to treatment. Arm 2: ESL as a later adjunctive therapy, following prior use of 1–2 AEDs in patients who required an additional therapeutic option (n = 59). The trial comprised screening (1–2 weeks), titration (2 weeks), maintenance (24 weeks), and ESL taper/safety follow-up (4 weeks) periods. Results: The safety population included 102 patients (Arm 1: n = 43; Arm 2: n = 59). Median age was 40.5 years (Arm 1: 40.0 years; Arm 2: 41.0 years) and 58.8% of patients were female (Arm 1: 53.5%; Arm 2: 62.7%). The majority of patients were white (Arm 1: 65.1%; Arm 2: 61.0%), 13.7% were Hispanic or Latino (Arm 1: 16.3%; Arm 2: 11.9%), and the majority had an epilepsy duration <20 years (Arm 1: 83.7%; Arm 2: 62.7%). In Arm 1, 65.1% of patients were taking LEV and 32.6% were taking LTG. In Arm 2, 37.3% of patients were taking one baseline AED and 62.7% were taking >1 baseline AED. Complex partial seizures were the most serious seizure type during baseline in the majority of patients (Arm 1: 58.1%; Arm 2: 70.7%). Treatment-emergent adverse events (TEAEs) were reported more frequently in Arm 2 (81.4%; n = 48) than in Arm 1 (69.8%; n = 30). The most frequently reported TEAEs were dizziness, nausea, headache, somnolence, fatigue, nasopharyngitis, vomiting, and anxiety; most were reported more frequently in Arm 2 (Figure 1). In Arm 1, TEAEs were reported more frequently in patients who were taking ESL in combination with LTG (13/14 patients; 92.9%) than in those taking ESL in combination with LEV (16/28 patients; 57.1%). In Arm 2, the incidence of TEAEs was comparable between patients taking ESL in combination with LTG (16/21 patients; 76.2%) or LEV (18/24 patients; 75.0%). There were no deaths during the study. Conclusions: Treatment with ESL was generally well tolerated when taken as a first adjunctive therapy with LEV or LTG monotherapy, or as a later adjunctive therapy for focal seizures. Overall incidences of TEAEs were greater in patients taking ESL as later therapy, the majority of whom were taking ESL as adjunctive therapy to more than a single agent. Taking ESL as a first adjunctive therapy with LEV was associated with a lower frequency of TEAEs than taking ESL as a first adjunctive therapy with LTG. Whereas, TEAE frequency was comparable between patients taking ESL with LEV or LTG as a later therapy. The overall types and frequencies of TEAEs were comparable to those reported in previous trials. Funding: Study funded by Sunovion Pharmaceuticals Inc.