Abstracts

The purpose of this trial was to assess the safety profile of an intravenous (IV) formulation of the antiepileptic drug (AED) levetiracetam (LEV) when substituted for the same oral dose. This new formulation has been developed for patients for whom oral administration is temporarily not feasible. Bioequivalence between oral and IV formulations has previously been demonstrated. A multicenter, open-label, single-arm trial was conducted to evaluate the safety and tolerability of IV LEV (1000-3000 mg/day). Patients taking oral LEV as adjunctive therapy were switched to the equivalent IV dosage (mg-by-mg substitution, without washout period). 1 to 3 LEV ampoules (500 mg/5mL) were injected into a 100 mL pouch of 0.9% sterile saline solution. 15-minute infusions were administered twice daily on 4 consecutive days. Standard safety assessments (adverse events [AEs], vital signs), physical and neurological examinations, and measurement of LEV and other AED plasma concentrations, were performed repeatedly. On Day 1 and Day 4, two 12-lead electrocardiograms (ECGs) were performed (pre-dose and at the end of the morning infusion). On Day 5 patients were switched back to their oral LEV dosage. In addition, seizure occurrences were recorded in diaries. 25 adults with partial-onset seizures (12 males; 13 females) were included and completed all study visits. Mean age was 40.8[plusmn]10.6 years, age at onset of epilepsy ranging from 0 to 46 years. AEs, mostly mild or moderate, were consistent with the known AE profile of LEV. Eleven subjects (44%) experienced at least one treatment-emergent AE. The most frequently reported AEs were headache (n=5) and fatigue (n=3). No serious AEs or deaths occurred, no clinically relevant changes in vital signs or ECG parameters were noted, and clinical laboratory parameters remained stable. No temporal relationship between IV infusion and onset of AEs was observed, and no local reaction occurred at the infusion site. Moreover, no seizure worsening was reported during the clinical trial period, or the brief follow-up. The IV LEV formulation appears to be well tolerated and may constitute a useful treatment alternative for patients with partial-onset seizures temporarily unable to take the drug orally. (Supported by funds from UCB.)