Abstracts

Rationale: Pregabalin is approved in the United States and European Union as adjunctive treatment of partial onset seizures (POS) in adults. Previously, in a placebo-controlled study of pediatric subjects, pregabalin 10mg/kg/day showed statistically significant improvement in the frequency of all POS, and pregabalin 10mg/kg/day and 2.5mg/kg/day were well tolerated. Here, we report the efficacy analyses of pregabalin in subtypes of POS. Methods: This double-blind, international study had 3 periods: 1) an 8-week baseline, 2) a 12-week double-blind (2-week dose escalation and 10-week fixed-dose), and 3) a 1-week taper. Subjects were children (aged 4–16 years) who experienced POS being treated with a stable regimen of 1–3 antiepileptic drugs. Study treatments were pregabalin 2.5mg/kg/day (maximum 150mg/day) or 10mg/kg/day (maximum 600mg/day), or placebo. A 40% higher weight-normalized dose (ie 3.5 or 14mg/kg/day) was utilized for subjects weighing   Results: Overall, 295 patients were enrolled with a mean age of 10.2 years with 55% being male and 69% being white. 104, 97, and 94 patients received pregabalin 2.5mg/kg/day, 10-mg/kg/day, and placebo, respectively. For all POS and for most POS subtypes, pregabalin resulted in a numerically greater percentage of subjects who exhibited categorical decreases in seizure frequency vs placebo (Table 1, green). Decreases tended to be more consistent for pregabalin 10mg/kg/day than 2.5mg/kg/day. A small percentage of subjects experienced a ≥25% increase in seizure frequency, with a numerically larger percentage of these subjects in the placebo group (15.1%) than in either pregabalin group (2.5mg/kg/day, 7.8%; 10mg/kg/day, 11.5%). Relatively few subjects were seizure-free (100% decrease) with any treatment. Pregabalin was well tolerated as assessed by incidence of adverse events and clinical laboratory, vital sign, ECG data, and other safety assessments. Conclusions: Relative to placebo, pregabalin 2.5 and 10mg/kg/day tended to show a consistent, numerically larger percentage of subjects who experienced decreased frequency of POS and POS subtypes. In general, no POS subtype appeared less responsive or non-responsive to pregabalin vs placebo, including complex POS and POS that secondarily generalize which may have greater concerns for morbidity. The overall treatment response for POS and by seizure subtype compared favorably with that reported previously for pregabalin-treated adult patients with POS. Pregabalin was generally safe and well tolerated in pediatric subjects with POS. Funding: This study was funded by Pfizer.