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. In a previous Phase IIIb, open-label, 12-week study (NCT01653262), patients ≥16 years with epilepsy (n=29), receiving 1−>3 AEDs, and who had nonpsychotic behavioral adverse events (BAEs) associated with levetiracetam (LEV) were switched to BRV without titration.1 Most patients (93.1%) who switched from LEV to BRV had clinically meaningful reduction in BAEs. Patients who completed the study could enter this Phase IIIb, long-term follow-up (LTFU) study (NCT01728077). Final results of this LTFU study are reported. Methods: Patients received flexible-dose adjunctive BRV 50−200 mg/day in 2 equal doses. Safety/tolerability, efficacy, and health-related quality of life (HRQoL) assessments were done at protocol-specified time points until study closure. Results: Twenty-six patients (89.7%) completed the previous study, and all 26 entered this LTFU study. Total exposure: 54.1 patient-years; 22, 21, 19, 18 and 5 patients received BRV for ≥3, 6, 12, 24 and 36 months, respectively. Thirteen patients (50%) discontinued LTFU, most commonly due to subject choice (n=5) or lack of efficacy (n=4). Baseline mean (SD) age was 36.5 (11.9) years; 53.8% male (safety population, n=26). 19/26 patients received modal dose 200 mg/day (maximum 200 mg/day). 21/26 patients (80.8%) reported TEAEs (4/26, 15.4% drug-related). The most common TEAEs (≥10%) were headache (30.8%), back pain, convulsion, urinary tract infection (all 15.4%), bronchitis, dizziness, fatigue, nausea, and upper respiratory tract infection (all 11.5%). Serious TEAEs were reported in 7/26 (26.9%) patients (0% drug-related). One patient (3.8%) discontinued BRV and died due to TEAEs of cardio-pulmonary arrest/drowning. No BAEs were reported as TEAEs. No TEAEs potentially associated with cognitive impairment were reported. Median reduction from baseline in focal seizure frequency/28 days over the treatment period was 56.3%; ≥50% responder rate was 54.5% (Figure). Median reduction from baseline in primary generalized seizure days over the treatment period was 90.9%; ≥50% responder rate was 83.3% (Figure). At 24 months, ≥6 and ≥12 months continuous seizure freedom, respectively, was seen for 8/13 (61.5%) and 5/13 (38.5%) patients with focal seizures, and 3/5 (60%) and 3/5 (60%) patients with generalized seizures. QOLIE-31P scores increased from baseline to the last available value (Table), with the largest change in medication effects. Conclusions: BRV had a safety profile consistent with previous studies when administered for up to 36 months to patients who had switched from LEV to BRV due to BAEs. No BAEs were reported during LTFU. Seizure frequency tended to decrease over time. There were substantial improvements in HRQoL, measured by QOLIE-31P scores. Results from this small, open-label study should be interpreted with caution.  1Yates SL et al. Epilepsy Behav 2015;52:165−8 Funding: Study sponsored by UCB Pharma