Levetiracetam extended release conversion to monotherapy for the treatment of patients with partial-onset seizures: a double-blind, randomised, multicentre, historical control study.

This double-blind, randomised, multicentre, conversion to monotherapy, historical control study (N01280; NCT00419094) evaluated the efficacy, safety and tolerability of levetiracetam extended release (LEV XR) 2000mg/day once daily for the treatment of patients with partial-onset seizures compared with a historical control. Patients aged 12-75 years with 2-40 partial-onset seizures per 4 weeks, taking 1-2 antiepileptic drugs (AEDs) and receiving a stable dosage for ≥4 weeks prior to screening were randomised in a 3:1 ratio to LEV XR 2000 or 1000 mg/day. The study comprised baseline (8 weeks), LEV XR up-titration (2 weeks), baseline AED tapering (6 weeks), LEV XR monotherapy (10 weeks), and entry into open-label follow-up study or down-titration (1 week). The primary efficacy variable was the cumulative exit rate at Day 112 due to predefined exit criteria compared with the historical control. Of the 171 patients randomised to LEV XR 2000 mg/day and 57 randomised to 1000 mg/day, 141 (82.5%) and 50 (87.7%) completed the study. The cumulative exit rate for patients on LEV XR 2000 mg/day (0.375 [95% CI 0.297, 0.453]) was significantly lower than historical control (0.653). Both LEV doses were well tolerated. The most common adverse events during the treatment period were somnolence (21.9%), headache (19.7%) and convulsion (14.9%).