Efficacy and safety of Brivaracetam as an adjunctive therapy in patients with focal-onset seizures: a phase III, multi-center, randomized, double-blind, placebo-controlled trial.

BACKGROUND

Preclinical experiments have revealed that Brivaracetam (BRV) exhibited a significant anti-seizure function in animal models and was more effective and safer than other synaptic vesicle protein 2A (SV2A) ligands, including levetiracetam (LEV), this study aims to evaluate the efficacy and safety of generic BRV tablets in Chinese patients with focal-onset seizure.

METHODS

This phase III, randomized, double-blind, placebo-controlled clinical trial conducted in 21 medical centers evaluated BRV (200 mg/day) as an adjunctive therapy in Chinese adult patients with focal-onset seizures, with or without secondary generalization, despite treatment with one or two permitted concomitant anti-seizure medications (ASMs). After an 8-week screening baseline, patients were 1:1 randomized to BRV 200 mg/day or placebo for a 12-week treatment period. The primary efficacy endpoint was the percent reduction in seizure frequency per 28 days from baseline. Safety evaluations included the adverse events (AEs), side effects, and the regular monitoring of clinical symptoms, vital signs, physical examinations, laboratory tests, electrocardiograms, and mood.

RESULTS

Of 179 randomized patients, 178 were included in the final analysis (90 in BRV; 88 in placebo), while one patient in placebo group was excluded for not receiving the study drug. The percent reduction in seizure frequency per 28 days from baseline was 40.67% in the BRV group compared to the placebo group. The 12-week responder rate was significantly higher with BRV than placebo [48.89% vs. 23.86%, Odds Ratio (OR) = 3.12, 95% Confidence Interval (CI): 1.63-5.99, P = 0.0006]. There's no statistical significance of reported AEs in the BRV and placebo groups. Seizure freedom was achieved by 10 (11.11%) and 2 (2.27%) patients in the BRV and placebo groups, respectively (P = 0.0325). Discontinuations due to AEs (6.67% vs. 0, P = 0.0287) and special concern AEs (32.22% vs. 9.09%, P = 0.0002) were higher with BRV than placebo. Dizziness, somnolence, and nausea were reported more frequently with BRV than placebo.

CONCLUSIONS

Generic BRV demonstrated a better efficacy and comparable safety in treating focal-onset seizure in Chinese patients.