Abstracts

RATIONALE: Pregabalin is an alpha[sub]2[/sub]-delta ([alpha][sub]2[/sub][delta]) ligand that exhibits analgesic, anxiolytic, and anticonvulsant activity. Three controlled studies have demonstrated the efficacy, safety, and tolerability of pregabalin as add-on treatment for patients with refractory partial seizures with or without secondary generalization. Additional efficacy analyses have been conducted, and are presented, which further demonstrate the robust efficacy results in these 3 studies.
METHODS: In three randomized double-blind placebo-controlled 12-week multicenter studies in adjunctive therapy using pregabalin, patients experienced at least 6 partial seizures with no 4-week seizure-free interval during an 8-week baseline period. Two studies used a 1-week titration (1008-009 and 1008-011) and one study had no titration (1008-034). Randomized doses included placebo and up to 600 mg/day pregabalin. Additional efficacy measures include percent of patients with seizure freedom for a minimum of 28 days from their last seizure in treatment and several response variables from the cumulative distributions of percent change in seizure rates from baseline including 50% reduction (traditional responder rate definition), 75% reduction, and 25% increase (worsening). Results will be presented by study and by randomized dose.
RESULTS: A total of 1052 patients were randomized to treatment (758 pregabalin and 294 placebo). The mean patient age at study entry was 37.9 years (range: 12-75 years) and the mean duration of epilepsy was 25.0 years. Study patients presented with highly refractory epilepsy as was evidenced by the fact that approximately 25% of the patients were taking 3 concurrent AEDs at baseline, 50% were taking 2 AEDs, and 25% were taking 1 AED and the mean and median baseline seizure rates were 24.4 and 11.2 seizures/month, respectively. The percentage of seizure free patients was up to 17% (15 out of 89 patients) in one 600 mg/day group. From the cumulative distribution of percent change from baseline seizure rate, 50% or greater reductions from baseline (i.e. responder rate) were 43-51% for the 600 mg/day pregabalin dose groups compared to 6-14% for placebo groups (p[lte]0.001 compared to placebo). The 75% or greater reductions in seizure rates were 21-33% in the 600 mg/day pregabalin groups and 2-3% in the placebo groups (all p[lte]0.001). The 25% or greater increases from baseline seizure rates (worsening) ranged from 21-33% in the placebo groups compared to only 4-13% in the 600 mg/day pregabalin groups (p-values [lte]0.001 to 0.082).
CONCLUSIONS: These additional efficacy analyses, which include seizure freedom and several other response criteria, demonstrate further evidence in support of the primary conclusions of pregabalin[ssquote]s effectiveness in patients with refractory partial seizures with or without secondary generalization.
[Supported by: Pfizer Global Research and Development]; (Disclosure: Salary - Pfizer (Not MJB), Grant - Pfizer, Consulting - Pfizer, Ownership - Pfizer, Materials - Pfizer, Stock - Pfizer, Royalties - Pfizer, Honoraria - Pfizer (MJB), Other - Pfizer)