Abstracts

Rationale: Some commonly used antiepileptic drugs (AEDs) may impair cognitive function; therefore, the comprehensive evaluation of cognitive adverse events (AEs) must be a significant consideration in clinical trials of AEDs. Eslicarbazepine acetate (ESL) is a once-daily oral AED, shown to be well tolerated for partial-onset (focal) seizures (POS). In a previous analysis of three Phase III trials of adjunctive ESL, cognition-related treatment-emergent adverse events (TEAEs) were reported infrequently. The current post-hoc analysis examines the frequency of TEAEs potentially related to changes in cognitive function (cognitive TEAEs) in two conversion to ESL monotherapy trials. Methods: This is a post-hoc analysis of data pooled from two Phase III randomized, double-blind conversion to ESL monotherapy trials (093-045 and -046) in adults (16–70 years) with POS uncontrolled by one or two AEDs. Following a baseline period (8 weeks), eligible patients were randomized 2:1 to receive ESL 1,600 mg or 1,200 mg once-daily for 18 weeks (2-week titration, 6-week baseline AED taper, 10-week monotherapy). The pooled intent-to-treat (ITT) population (all randomized patients receiving =1 dose of ESL) was used for all analyses. Cognitive TEAEs and related serious adverse events (SAEs) (categorized using the Medical Dictionary for Regulatory Activities, v13.1) were identified. Inclusion of terms that are not typically regarded as cognition-related was due to an FDA request. Results: The pooled ITT population comprised 365 patients (ESL 1,600 mg, n = 242; ESL 1,200 mg, n = 123). The incidence of cognitive TEAEs was similar between dose groups (ESL 1,600 mg, 7.0%; ESL 1,200 mg, 7.3%) (Table 1). Memory impairment, irritability, skin laceration, and disturbance in attention were the most frequently reported cognitive-related TEAEs; each had an overall incidence < 2%. All other cognitive TEAEs were limited to one or two cases, occurring in < 1% of patients. Skin laceration was the only cognition-related AE reported during the baseline period, with a total incidence of 1.1% (ESL 1,600 mg, 0.8%; ESL 1,200 mg, 1.6%). Overall, the majority of cognitive TEAEs were mild (73.1%) in severity. Severe cognitive TEAEs were reported in three patients: severe amnesia in one patient taking ESL 1,600 mg and severe agitation in one patient in each dose group. No SAEs were reported in either dose group, and no patients in the ESL 1,200 mg dose group had a cognitive TEAE leading to discontinuation; one patient (0.4%) in the ESL 1,600 mg dose group had a cognitive TEAE (aggression) which led to discontinuation. Conclusions: Cognitive TEAEs were reported infrequently in Phase III conversion to ESL monotherapy trials; incidences were similar between dose groups and the majority of reported cognitive TEAEs were mild in severity. Funding: Studies sponsored by Sunovion Pharmaceuticals Inc.