Abstracts

Lacosamide (LCM, SPM 927; formerly harkoseride) is a new chemical entity being developed as an oral and intravenous (iv) formulation for treatment of partial seizures and neuropathic pain. LCM has a favorable pharmacokinetic profile and when given orally twice daily (bid) has been shown to reduce seizure frequency in subjects. LCM solution for iv infusion (10mg/mL) is being developed as short-term replacement for oral LCM. Infusion of 200mg iv LCM over 30- or 60-minutes has been shown to be bioequivalent (C[sub]max, [/sub]AUC) to 200mg oral LCM. The objectives of SP757 were to investigate whether iv LCM was safe and well tolerated when given bid as short-term adjunctive therapy in subjects with partial seizures and to identify the appropriate infusion rate(s)., Subjects (n=101) receiving adjunctive, stable, bid dosing with oral LCM (200 to 600 mg/day) were progressively studied in 3 cohorts: 30-min infusion (n=40); 15-min infusion (n=41); 10-min infusion (n=20). A fourth cohort (15-min infusion, n=60) was recently completed and those data are under review. Subjects were administered iv LCM bid for 2-5 days. Treatment duration was at the discretion of the investigator and subject. After trial completion subjects resumed treatment with oral LCM. Safety was evaluated through reported adverse events (AEs); 12-lead electrocardiogram (ECG) and vital sign data collection; and clinical laboratory data. Seizure data were collected in a diary. A Data Monitoring Committee reviewed safety data from each completed cohort prior to initiation of subsequent cohorts., All subjects were administered 2 days of iv LCM bid; 47 (77%) of subjects from the 15- and 10-min infusion groups were dosed for 3-5 days. A total of 16% of subjects took 200mg/day, 48% of subjects took 300-400mg/day and 36% of subjects took 500-600mg/day LCM. Dizziness was the most commonly reported AE; frequency ranged from 5% in the 15- and 10-min groups to 8% in the 30-min infusion group. Infusion site related AEs were infrequently reported and did not result in discontinuation of iv LCM. Mean vital sign results remained stable during and following iv LCM infusion. Seizure patterns for individual subjects did not appear to change during the trial period., In this trial, lacosamide solution for intravenous infusion (administered over 10, 15, or 30 minutes) was successfully used as short-term replacement for oral lacosamide in subjects with partial seizures., (Supported by Schwarz Biosciences, Inc.)