Abstracts

RATIONALE: Pregabalin (PGB), a novel CNS-active compound with anticonvulsant activity, exhibits dose-linear absorption and is not metabolized or protein bound. We report the safety and efficacy results in this study of PGB dosed twice daily (BID) or three-times daily (TID) as add-on therapy in refractory epilepsy patients. METHODS: Pts aged ? 18 yrs with partial seizures (szs) not adequately controlled on 1-3 antiepileptic drugs (AEDs) enrolled into this 43-center, double-blind (DB) parallel-group study. Pts experiencing at least 6 szs during the 8-week prospective baseline, randomized to PGB 300mg BID, PGB 200mg TID, or placebo. Baseline AED therapy was maintained during 12 weeks of DB treatment. Efficacy assessments included RRatio (primary), Responder Rates, and Median Percent Change (secondary). Safety included adverse events (AEs), vitals, ECGs, and clinical labs. RESULTS: A total of 312 pts were randomized and received at least 1 dose of study medication. 76% of pts completed the 12-week study. PGB 600mg/day administered BID or TID resulted in significant reductions in seizure frequency compared to placebo (mean RRatio -28.4, -36.1, 0.6, respectively; p ? 0.0001). An RRatio of -33 corresponds to a 50% reduction in seizure frequency. Responder Rates (?50% reduction in seizure frequency) were also significant for pregabalin BID and TID (p ? 0.001) compared to placebo (43%, 49%, 9%, respectively). Median percent change results with PGB BID and TID compared to placebo were -35.6, -48.1, and -0.8, respectively. PGB BID or TID were similarly well-tolerated. Dizziness, somnolence, and ataxia were the most frequent AEs. The incidence of withdrawals due to AEs were 26%, 19%, and 7% with pregabalin BID, TID, or placebo, respectively. CONCLUSIONS: Pregabalin 600mg/day, administered TID or BID, is highly effective as add-on therapy, is safe and generally well-tolerated. Pregabalin dosed BID or TID provides similar efficacy and safety profiles supporting initial twice daily dosing in all patients.