Abstracts

Pregabalin is a novel compound that binds to the alpha[sub]2[/sub]-delta subunit protein of voltage-gated calcium channels, and it has demonstrated anticonvulsant, analgesic, and anxiolytic activity. This report describes analyses performed to determine whether time since diagnosis of epilepsy (epilepsy duration) or number of concomitant AEDs (both of which can be indicators of epilepsy severity) influenced the degree of patient response to add-on treatment with pregabalin. Pooled data here reported were from three randomized, double-blind, placebo-controlled, add-on trials, each consisting of 8-week baseline and 12-week double-blind phases. Patients were refractory to 2 AEDs at maximally tolerated doses, experienced [ge]6 partial seizures during baseline with no 4-week seizure-free period, and were currently receiving 1-3 AEDs. Data from the three trials were pooled across dose regimens. Patients were randomized to placebo or 50, 150, 300, or 600 mg/day pregabalin (PGB). The primary population was intent-to-treat (ITT) defined as all patients randomized to treatment and who received at least one dose of study medication. Efficacy was assessed by seizure-frequency reduction from baseline. Seizure reduction was analyzed by dose using ANCOVA, with refractoriness measured by duration of epilepsy in years or number of concomitant AEDs as explanatory variables to determine if efficacy varied with refractoriness. Duration of epilepsy ranged from 0.6 years to 71 years (mean 25 years). Interaction between duration of epilepsy by dose was not statistically significant ([italic]P[/italic]=0.8968), suggesting that the treatment effect is similar regardless of epilepsy duration. Approximately 27% of patients were on one AED, 50% on two, and 23% on three AEDs. Interaction between number of concurrent AEDs and dose was also not significant ([italic]P[/italic]=0.7651), indicating that number of AEDs does not affect seizure reduction within doses of pregabalin. In this population of patients with epilepsy refractory to treatment, pregabalin[rsquo]s efficacy was not a function of epilepsy severity as measured by epilepsy duration and number of concomitant AEDs. (Supported by Pfizer, Inc)