Abstracts

RATIONALE: Pregabalin is a novel compound with CNS activity. Three trials have demonstrated the efficacy and safety of pregabalin as add-on treatment in reducing seizure frequency in patients with refractory partial seizures with or without secondary generalization.
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. Pharmacokinetic parameters were estimated using steady-state plasma pregabalin concentrations from randomly collected blood samples. The primary efficacy assessment was the symmetrized percent change (RRatio) in partial seizure frequency and secondary efficacy parameters included Responder Rate (defined as the percentage of patients with a [gte]50% reduction in seizure frequency during treatment compared to baseline).
RESULTS: A total of 1052 patients were randomized to treatment in these 3 studies (758 pregabalin and 294 placebo). The mean age of epilepsy diagnosis was 13.7 years and mean duration of epilepsy was 25.0 years. The mean patient age at study entry was 37.9 years (range: 12-75 years). Approximately 23% of the patients were taking 3 concurrent AEDs at baseline, 27% taking 1, and 50% taking 2. Mean and median baseline seizure rates were 24.4 and 11.2 seizures/month, respectively. Mean RRatio values were as high as -37 and Responder Rate values were as high as 51%, with both parameters showing a statistically significant increase in efficacy with pregabalin dose (p[lte]0.0001). In all 3 studies, statistically significant efficacy resulted by Week 1. The pharmacokinetics of pregabalin were dose-proportional and predictable. Adverse events were generally CNS related, mild to moderate in intensity, and transient. Some adverse events appear to be dose-related while others do not. Withdrawal rates due to adverse events appear to be dose-related and the rate was 1.2% at the recommended starting dose of 150 mg/day BID. Serious adverse events were infrequent and did not show any trend. Overall, 84% of all patients entered optional open-label extension studies.
CONCLUSIONS: Pregabalin administered BID or TID is highly effective as adjunctive therapy with a demonstrated dose-response in seizure frequency reduction. Pregabalin is safe and generally well tolerated.
Support: Supported by Pfizer Global Research and Development.
Disclosure: Salary - Pfizer. Grant - Pfizer. Consulting - Pfizer. Stock - Pfizer. Honoraria - Pfizer. Other - Pfizer.