Abstracts

Rationale: To evaluate the efficacy and safety/tolerability of brivaracetam (BRV) as adjunctive treatment for partial-onset seizures (POS) using pooled data from three Phase 3 studies in the overall population and the elderly patient subgroup.Methods: Data were pooled from three studies (NCT004900351, NCT004642692, NCT012613253) of adults with POS uncontrolled by 1–2 AEDs randomized to placebo (PBO) or BRV 5, 20, 50, 100, or 200 mg/day. Data reported here are for the proposed therapeutic dose range of 50–200 mg/day. The efficacy population included all patients from the primary efficacy analyses, not receiving concomitant levetiracetam (LEV). The safety population included all patients taking ≥1 dose of study drug, regardless of LEV status. The elderly efficacy and safety subgroups comprised all patients ≥65 years old from these populations.Results: Overall, patients (efficacy population; n=1160) were 50.6% female; 72.5% white/Caucasian/Hispanic; 0–1, 2–4 and ≥5 previous AEDs were taken by 24.3%, 38.3% and 37.4%, respectively. The most common concomitant AEDs were carbamazepine (41.0%), lamotrigine (25.5%), valproate (22.9%), oxcarbazepine (15.9%), and topiramate (14.5%). Baseline median (IQR) POS frequency/28 days was 9.6 (5.5, 24.3) PBO vs 8.9 (5.5, 17.3) 50 mg/day; 8.9 (5.5, 20.6) 100 mg/day; and 9.3 (5.5, 18.8) 200 mg/day. Median (IQR) percent reduction in POS frequency from baseline was 17.2 (-8.3, 44.2) for PBO (n=418) vs 34.7 (7.0, 62.4) 50 mg/day (n=161); 37.6 (0.8, 72.0) 100 mg/day (n=332); and 35.6 (4.8, 66.2) 200 mg/day (n=249). In the overall safety population (n=1262), mean (SD) drug exposure (days) was 84.2 (15.6) for PBO and 83.0 (16.6) for BRV. The study completion rate was 94.7% for PBO, 90.4% for BRV. Treatment-emergent adverse events (TEAEs) were reported by 59.7% (n=459) of PBO and 67.1% (n=803) of BRV patients. TEAEs in ≥5% patients on BRV (for PBO vs BRV, respectively) were somnolence (7.0% vs 14.2%), dizziness (5.9% vs 10.8%), headache (9.6% vs 9.3%), and fatigue (2.6% vs 8.3%). In the elderly efficacy subgroup (n=31, across the four treatment groups), median percent reduction in POS frequency from baseline was 14.0 (-10.2, 49.7) for PBO (n=7) vs 25.5 (6.3, 71.3) 50 mg/day (n=4); 49.6 (32.1, 72.1) 100 mg/day (n=14); and 74.9 (27.8, 85.1) 200 mg/day (n=6). In the elderly safety subgroup (n=32), mean (SD) drug exposure (days) was 81.1 (12.0) for PBO and 82.6 (18.0) for BRV, similar to the overall safety population. In this subgroup, 7/8 (87.5%) PBO patients and 23/24 (95.8%) BRV patients completed the study. TEAEs in ≥5% of elderly patients on BRV were hyponatremia (0 vs 2 patients), paraesthesia (0 vs 2), headache (1 vs 2), and somnolence (2 vs 2) for PBO vs BRV, respectively.Conclusions: BRV was efficacious and generally well tolerated in both the overall pooled population and the small subgroup of elderly patients. UCB supported. 1Ryvlin P et al. Epilepsia 2014;55(1):47-56. 2Biton V et al. Epilepsia 2014;55(1):57-66. 3Klein P et al. Epilepsy Curr 2015;15:379.