Abstracts

Rationale: Levetiracetam extended-release tablets (LEV XR; Keppra XR) have been shown to be effective as adjunctive therapy for partial-onset seizures (Peltola et al, 2009). The purpose of this study was to evaluate the efficacy, safety and tolerability of LEV XR during conversion to monotherapy treatment of patients with partial-onset seizures compared with a historical control. Methods: We conducted a double-blind, randomized, multicenter, conversion to monotherapy study using a historical-controlled design (N01280; NCT00419094). Patients (aged 12-75 years) with uncontrolled partial-onset seizures (2-40 partial-onset seizures/4 weeks) on 1-2 AEDs (?50% minimum recommended dose for 2nd AED) were randomized 3:1 to receive once-daily LEV XR 2000 mg/day or 1000 mg/day. The study comprised: 8-week baseline, 2-week LEV XR up-titration, 6-week previous AED(s) tapering and 10-week LEV XR monotherapy. The primary efficacy variable was cumulative exit rate (patients meeting exit criteria) at Day 112 after the start of tapering previous AED(s). The primary analysis compared the cumulative exit rates for LEV XR 2000 mg/day versus the historical control. Exit criteria included increase in seizure frequency, severity, duration, occurrence of status epilepticus or new generalized seizure (versus 6 months pre-randomization). Secondary variables included cumulative exit rate (all drop-outs) at Day 112 for LEV XR 2000 mg/day and safety/tolerability for LEV XR 2000 mg/day and 1000 mg/day. Results: Of 228 patients (mean age 34.1 years; 42.1% male) randomized to LEV XR 2000 mg/day (n=171) and LEV XR 1000 mg/day (n=57), 82.5% and 87.7% completed the study, respectively. The cumulative exit rate for patients meeting exit criteria on LEV XR 2000 mg/day (0.375 [95% CI 0.297, 0.453]; n=158) was significantly lower than historical control (0.653). The results were confirmed in the secondary, worst case analysis with cumulative exit rate (all drop-outs/zero censoring) in LEV XR 2000 mg/day: 0.475 (95% CI 0.397, 0.553). 177/228 (77.6%) patients reported ?1 treatment-emergent adverse event (TEAE) which were mostly of mild to moderate intensity. The most frequently reported TEAEs were (2000/1000 mg/day): somnolence (22.2%/21.1%), headache (18.7%/22.8%) and convulsion (14.0%/17.5%). Only 10/228 (4.4%) patients discontinued study drug because of TEAE. Conclusions: In conversion to monotherapy for partial-onset seizures, significantly fewer patients taking LEV XR 2000 mg/day met the exit criteria compared with historical controls. Both LEV doses were well tolerated. UCB-sponsored Reference: Peltola et al, Epilepsia 2009;50(3):406-14