Efficacy and tolerability of levetiracetam as adjunctive therapy in Japanese patients with uncontrolled partial-onset seizures.

Aims The aim of this study was to confirm the efficacy and safety of adjunctive levetiracetam in adult Japanese patients with uncontrolled partial-onset seizures. Methods In a double-blind, placebo-controlled, confirmatory trial, eligible patients were randomized to receive levetiracetam 500, 1000, 2000, or 3000 mg/day or placebo for 16 weeks. The primary end-point was percentage reduction from baseline in seizure frequency/week over a 12-week evaluation period. Tolerability assessments were also conducted. Findings of this and a previous randomized, double-blind trial were compared. Results Of 401 patients screened, 352 were randomized and 316 completed the study. Median percentage reduction in seizure frequency/week from baseline was 12.92%, 18.00%, 11.11% and 31.67% in the levetiracetam 500, 1000, 2000 and 3000-mg groups, respectively, compared with 12.50% in the placebo group. Unlike the previous trial, the primary efficacy analysis between the levetiracetam 1000 and 3000-mg and placebo groups did not reach statistical significance (P = 0.067). Exploratory analyses demonstrated that the difference in seizure reduction versus placebo was 14.93% (95% confidence interval, 1.98–27.64; P = 0.025) for the levetiracetam 3000-mg group. All levetiracetam doses were well tolerated. The main difference between the two trials was a high placebo response in the present trial. Conclusions The primary efficacy analysis did not reach statistical significance, a finding that could be attributed to an unexpectedly high placebo response. Nonetheless, exploratory analysis suggests that levetiracetam at 3000 mg/day may, at least marginally, be beneficial for patients with uncontrolled partial-onset seizures.