Abstracts

RATIONALE: Pregabalin, structurally related to the neurotransmitter GABA, is a new compound with anticonvulsant properties. Patients with partial seizures were to be evaluated for the dose-response relationship of efficacy and safety as add-on treatment with pregabalin and compared to placebo.
METHODS: The study was designed as a double-blind, placebo-controlled, parallel-group multicentre study. Patients selected had a diagnosis of refractory partial seizures with or without secondary generalization and continued to receive 1 to 3 standard antiepileptic drugs throughout the study. During an 8-week baseline period, patients experienced at least 6 partial seizures with no seizure-free period exceeding 4-weeks. Patients were randomized and titrated over one week on either placebo, or pregabalin 150, or 600 mg/day, administered three times daily. The efficacy assessment was based on change in 28-day partial seizure-rate from baseline to double blind period: primary was the symmetrized percent change (mean RRatio); secondary was the Responder Rate (percentage of patients with [gte]50% seizure reduction). The primary analysis was performed on data from the intent-to-treat (ITT) population using a main effect ANOVA model. After completion of the double-blind treatment period, patients had the option to continue in an open-label study to adjust the dose for optimization of seizure control or adverse event reduction.
RESULTS: A total of 288 patients were randomized: 99 patients on pregabalin 150 mg/day, 92 patients on 600 mg/day, and 97 patients on placebo. RRatio was significantly better in the pregabalin 150 mg/day group (-11.5, p=0.0007) and 600 mg/day group (-31.4, p[lte]0.0001) than in the placebo group (0.9). Responder Rates for pregabalin were: 14.1% (p=0.087) and 43.5%, (p[lte]0.001) for 150 mg/day or 600 mg/day pregabalin, respectively, vs. 6.2 % for placebo. A statistically significant dose-response (linear trend) was shown (p[lt]0.0001). Most frequently reported adverse events were CNS related and mostly mild to moderate in intensity and transient; no clinically important changes in other safety assessments were observed. Eighty percent of patients across all three groups entered the open-label study (84% placebo; 83% and 75% pregabalin 150 or 600 mg/day, respectively).
CONCLUSIONS: Pregabalin is effective with clear dose-response, is safe and well-tolerated as add-on treatment in patients with refractory partial seizures.
Support: Supported by Pfizer Global Research and Development
Disclosure: Salary - Employee of Pfizer GmbH, Freiburg, Germany. Stock - Have stock options in Pfizer GmbH, Freiburg, Germany.