Abstracts

Seletracetam (UCB 44212) is an investigational new drug structurally related to levetiracetam with a higher affinity and similar high selectivity towards the specific SV2A binding site. The anticipated pharmacologically active dose in humans is around 15 mg based on animal models of epilepsy., Single and multiple rising dose studies of seletracetam were performed in a randomized, double-blind, placebo controlled manner. Healthy male volunteers were enrolled. For the single administration, 3 alternating panels of 9 subjects received the following doses: 2, 4, 10, 20, 50, 100, 200, 400, and 600 mg (6 active : 3 placebo). Food effect was assessed in an additional group of 8 subjects. For the multiple dose administration, 3 different panels of 12 subjects (9 active : 3 placebo) received 20, 60 and 200 mg twice daily during 2 weeks. CNS effects were explored with psychomotor tests, rating scales and neurological assessments., The maximum single dose of 600 mg and the maximum repeated dose of 400 mg/day were well tolerated. During multiple dosing, treatment-emergent adverse events (AEs) occurred in 44%, 89%, 78% and 100% of subjects receiving placebo, 20, 60 and 200 mg b.i.d., respectively. The most frequent were dizziness, drowsiness, euphoria and feeling drunk. Most appeared shortly after first dosing, were of mild or moderate intensity, and lasted for less than 12 hours. In most subjects, the AEs did not reappear when given the next dose. AE severity was mild to moderate. There were no serious AEs and no changes in laboratory, vital signs, ECGs or neurological examinations. Seletracetam pharmacokinetics were linear, dose-proportional and time invariant, with a plasma half-life of 8 hours. Co-administration with a high fat meal resulted in reduced absorption rate and no change in AUC., The maximum tolerated dose of seletracetam was [gt]600 mg after single dose and [gt]400 mg/day after 2 weeks of repeated dosing. Its favorable pharmacokinetics and good tolerability, with AEs limited to mild to moderate CNS effects at initial dosing, are encouraging for the continued clinical development of this new antiepileptic drug., (Supported by UCB funded.)