Abstracts

RATIONALE: Pregabalin is a novel compound with CNS activity. Three trials have demonstrated the efficacy and safety of pregabalin as adjunctive therapy in reducing seizure frequency in patients with refractory partial seizures with or without secondary generalization. These analyses define the early time to onset for pregabalin anticonvulsant activity.
METHODS: Combined results are presented for three randomized, double-blind, placebo-controlled, 12-week treatment, multicenter studies with adjunctive BID and/or TID dosing. During an 8-week baseline period, patients experienced at least 6 partial seizures with no 4-week seizure-free period. Studies 1008-009 (placebo, 600 mg/day TID, or 600 mg/day BID) and 1008-011 (placebo, 150, or 600 mg/day TID) utilized a 1 week titration and 1008-034 (placebo, 50, 150, 300, or 600 mg/day BID) did not use any titration. Statistical analyses were performed on 2 sets of data. Dataset 1 contained patients from the placebo and active pregabalin treatment groups (150 to 600 mg/day dose groups). Dataset 2 contained patients from the placebo and 600 mg/day pregabalin treatment groups. Efficacy was assessed by computing the percentage of patients free of partial seizures on a daily basis. Statistical testing, adjusting for study, was used to compare pregabalin and placebo treatment groups at each day.
RESULTS: In Dataset 1, placebo and active pregabalin treatment groups were combined in these 3 studies for a total of 964 patients (294 placebo and 670 pregabalin). Pregabalin patients attained a mean dose of 185 mg/day (average dose across all pregabalin patients on that day) on Day 1 after randomization, increasing over the first week to a mean dose of 429 mg/day on Day 8. The percentage of pregabalin patients free of partial seizures was 74% on Day 2 and stabilized at an estimated 75% over time. The percentage of placebo patients free of partial seizures on Day 2 was 66%. A statistically significant difference between the pregabalin and placebo treatment groups was observed starting on Day 2 at an average attained dose of 216 mg/day and remained for the duration of the study. Dataset 2 consisted of a total of 689 patients (294 placebo and 395 patients who were randomized to receive 600 mg/day pregabalin). Using this dataset, a statistically significant difference between the pregabalin 600 mg/day treatment groups and placebo was also observed starting on Day 2, although the magnitude of the treatment effect was larger after patients titrated to their maximum dose.
CONCLUSIONS: Pregabalin is highly effective as adjunctive therapy with a demonstrated anticonvulsant effect starting on Day 2 of treatment and which continues for the duration of the studies.
Support: Pfizer Global Research and Development
Disclosure: Salary - Pfizer; Grant - Pfizer; Equity - Pfizer; Consulting - Pfizer; Stock - Pfizer; Honoraria - Pfizer; Other - Pfizer