The KEEPER trial: levetiracetam adjunctive treatment of partial-onset seizures in an open-label community-based study.

PURPOSE: Three randomized, placebo-controlled trials have demonstrated the safety and efficacy of levetiracetam, a new antiepileptic medication, as add-on therapy for partial-onset seizures. The purpose of this study was to gather additional safety and efficacy data on levetiracetam in the real-world setting of community-based practice. METHODS: This was a phase IV prospective, open-label, multicenter, community-based trial. A total of 1030 patients (intent-to-treat (ITT) population) at least 16 years old (mean, 42.2 years) with partial-onset seizures were enrolled by over 300 investigators. Patients whose partial-onset seizures were inadequately controlled on their current medications had levetiracetam 500 mg bid added to their regimens. The levetiracetam dose was increased by 500 mg bid at the end of weeks 2 and 4 to a maximum dose of 1500 mg bid, unless the patient had been seizure-free during the preceding 2-week period. The dose was then to remain the same for 12 weeks. The main outcome measures were reduction in seizure frequency, global evaluation scale (GES), and adverse events. RESULTS: During the 16 weeks of the trial, 57.9% (542/936) experienced at least a 50% reduction in the frequency of partial-onset seizures, 40.1% (375/936) experienced at least a 75% reduction, and 20% (187/936) demonstrated a 100% seizure reduction. During the last 6 weeks of the study, 66.7% (500/750) experienced at least a 50% reduction in the frequency of partial seizures, 52.4% (393/750) experienced at least a 75% reduction, and 42.1% (316/750) demonstrated a 100% seizure reduction. On the investigator-completed clinical impression rating (GES), 74.3% (734/988) of patients were considered improved, with 37% of patients showing marked improvement. The most common adverse events were somnolence, dizziness, asthenia, and headache; these events were predominantly mild-to-moderate in nature. CONCLUSIONS: These results provide further evidence regarding the efficacy and safety of levetiracetam as adjunctive treatment for partial-onset seizures.