Efficacy and safety of pregabalin versus levetiracetam as adjunctive therapy in patients with partial seizures: a randomized, double-blind, noninferiority trial.

To assess the comparative efficacy and safety of pregabalin and levetiracetam for the reduction of seizure frequency in patients with partial seizures. This was a randomized, double-blind, flexible-dose, parallel-group noninferiority study of pregabalin and levetiracetam (randomized 1:1) as adjunctive treatment in adult patients with refractory partial seizures. The study included a 6-week baseline phase, 4-week dose-escalation phase, and 12-week maintenance phase. The primary endpoint was the proportion of patients with a ≥ 50% reduction in 28-day seizure rate during the 12-week maintenance phase, as compared with baseline. Noninferiority of pregabalin was declared if the lower limit of the 95% confidence interval (CI) for the difference in responder rates was greater than the prespecified noninferiority margin of -12%. A key secondary endpoint was the percent change from baseline in 28-day seizure rate during the dose-escalation and maintenance phases. Five hundred nine patients were randomized to pregabalin (n = 254) or levetiracetam (n = 255) and 418 (208 pregabalin, 210 levetiracetam) completed the maintenance phase. With both pregabalin and levetiracetam, the proportion of patients with a ≥ 50% reduction in 28-day seizure rate was 0.59 (difference between groups [95% CI], 0.00 [-0.08 to 0.09]). Because the lower bound of the 95% CI was greater than the prespecified noninferiority margin of -12%, pregabalin was not inferior to levetiracetam. There was no significant difference between pregabalin and levetiracetam in the percent change in 28-day seizure rate (median difference [95% CI], 4.1 [-2.6 to 10.9], p = 0.3571). In a post hoc analysis, the proportion of patients who were seizure-free for the maintenance phase was lower with pregabalin (8.4%) than with levetiracetam (16.2%), p = 0.0155. Safety profiles were similar and consistent with prior trials. These results indicate that pregabalin is noninferior, and has a similar tolerability, to levetiracetam as adjunctive therapy in reducing seizure frequency in patients with partial seizures.