Abstracts

Rationale: The purpose of this trial was to assess efficacy and tolerability of extended-release levetiracetam (LEV XR) 1000 mg once daily as add-on therapy in patients (12-70 years old) with refractory partial-onset seizures (POS). Methods: This multi-centre, double-blind, placebo-controlled, randomized (1:1), parallel group trial enrolled patients with refractory POS uncontrolled on 1-3 AEDs. Eligible patients had to have at least 8 POS during the 8-week prospective baseline. Randomized patients received once daily LEV XR 1000 mg/day (2 x 500 mg) or placebo (PBO) for 12 weeks. Efficacy assessments included changes from baseline in POS frequency/week, responder rates, categorical responses, and seizure freedom. Tolerability and safety assessment included adverse events (AE), laboratory parameters, and vital signs. Results: Of 188 subjects screened, 158 (59 female, 99 males; mean [±SD] age 33 [±13] years; ITT) were randomized to LEV XR (n=79) or PBO(n=79). 71 (89.9%) patients on LEV XR and 72 (91.1%) on PBO completed trial. 67 patients on LEV XR and 69 PBO patients who did not have major protocol violations impacting the primary efficacy analysis were included in the per protocol (PP) population. Median percent reduction in POS frequency/week for patients on LEV XR was 46.1% compared with 33.4% on PBO (ITT). The estimated (2-sided 95% CI) percent reduction over PBO in POS frequency/week was 14.4% (0.9%, 26.0%) in the ITT population (p=0.038) and 18.6% (6.7%, 28.9%) in the PP population (p=0.003). The difference in distribution between LEV XR and PBO in categorized response (percentage of patients with <-25%, -25 to <25%, 25% to <75%, 75% to <100%, and 100% POS frequency reduction, ITT) was statistically significant (p=0.033). 43.0% LEV XR patients had at least 50% reduction in weekly POS frequency compared with 29.1% on PBO (Fig. 1). 24.1% LEV XR and 11.4% PBO patients had at least 75% reduction in POS frequency. 10.1% LEV XR and 1.3% PBO patients were free of POS during the entire 12-week treatment period. Overall, the incidence of the treatment-emergent AEs reported in the two treatment groups was similar (53.2% LEV XR; 54.4% PBO) and most were of mild to moderate intensity. The AEs most common and reported more frequently in LEV XR- than PBO-treated patients were somnolence, influenza, nasopharyngitis, irritability, nausea and dizziness (Table 1). No clinically relevant abnormalities in ECG, vital signs, body weight, physical and neurological exams were reported. Conclusions: LEV XR, a new once daily extended-release formulation of levetiracetam, was efficacious and well tolerated as add-on therapy in patients (12-70 years old) with refractory POS. Study sponsored by UCB.