Abstracts

Rationale: Brivaracetam (BRV), a selective, high-affinity ligand for synaptic vesicle protein 2A, is a new antiepileptic drug (AED) for adjunctive treatment of focal (partial-onset) seizures in adults. Two Phase III, randomized, double-blind, multicenter, historical controlled, conversion-to-monotherapy studies were conducted in patients (=16 years) with uncontrolled focal seizures (NCT00698581; NCT00699283). Patients who completed either study or who met a protocol-defined exit criterion were eligible to enter a long-term follow-up (LTFU) study (NCT00761774) of BRV. This analysis of data from the LTFU study was conducted to evaluate the long-term safety and tolerability of BRV monotherapy. Methods: In the LTFU study, patients received flexible-dose BRV at a recommended starting dose of 100 mg/day, which could be adjusted within the range of 50–200 mg/day with weekly up- or down-titrations of 50 mg/day. Patients could enter the LTFU study on BRV monotherapy or adjunctive therapy; additional AEDs could be prescribed at any time during the LTFU study if clinically indicated. Treatment-emergent adverse events (TEAEs) were evaluated for the subgroup of patients who completed the monotherapy period of either of the parent studies and received BRV monotherapy in the LTFU study. TEAEs were summarized by time interval of onset during the first 12 months of monotherapy exposure in the LTFU study. Results: A total of 150 patients were randomized into the two parent studies; of these, 50 completed the monotherapy period of a parent study and entered the LTFU study on BRV monotherapy. At baseline, patients (mean [standard deviation] age 43.5 [13.0] years; 56.0% female) had median (range) focal seizure frequency/28 days of 6.0 (2.0–25.5). Of these, 50 (100%), 37 (74%), 33 (66%), and 27 (54%) patients were still receiving BRV monotherapy at 1, 4, 7, and 10 months, respectively. At least one TEAE was reported by 26 (52%), 15 (40.5%), 14 (42.4%), and 9 (33.3%) patients with onset in the 1–3 month, 4–6 month, 7–9 month, and 10–12 month time intervals, respectively. The most common TEAEs (=5% of patients in any time interval) were convulsion, fatigue, contusion, abdominal pain, nasopharyngitis, back pain, and dizziness (Table). Five serious TEAEs were reported in three patients: congestive cardiac failure, vomiting and chronic obstructive pulmonary disease (one patient), convulsion (one patient), and urinary tract infection (one patient). Depression was the only TEAE that led to BRV discontinuation (n=1). Conclusions: The TEAE profile for BRV monotherapy was consistent with BRV’s known safety profile in adjunctive therapy. Funding: Study supported by UCB Pharma