Abstracts

To assess the pharmacodynamics and tolerability of seletracetam (UCB 44212) single doses, a 2-pyrrolidinone derivative, in photosensitive patients. Seletracetam is an investigational new drug structurally related to levetiracetam (LEV) with a higher affinity and similar high selectivity towards the specific SV2A binding site. LEV and brivaracetam have shown to be effective in this POP model before., A placebo-controlled, single blind, single period study, conducted in photosensitive patients with epilepsy, aged 18-60 years, taking no more than 2 other concomitant antiepileptic drugs (AEDs). During a 3 day period (with possible extension to 5 days) patients underwent standardized intermittent photic stimulation (IPS) to define the standard photosensitive range (SPR) at fixed time points. After the 1st day with placebo, single oral doses of seletracetam were given on the 2nd day, starting at 10 mg in a group of patients and testing subsequently lower or higher doses depending on the results of the previous group. Doses tested were 0.5, 1, 2, 4, 10, and 20 mg. SPR was the main parameter to identify the lowest single dose of seletracetam producing maximal decrease or suppression of the IPS evoked photoparoxysmal EEG response (PPR) comparing the SPRs before and after intake of seletracetam. Plasma seletracetam was monitored up to 72 hours post-dose. Descriptive statistics were used., 28 patients (23 F, 5 M) completed the study. One was excluded from the per protocol analysis due to emesis. 9 patients returned for a 2nd dosing 1-6 months later, providing a total of 36 individual exposures. Overall, 53% (19/36) patients showed a complete suppression of the epileptiform EEG response after seletracetam intake and 36% (13/36) showed an important decrease in SPR. The maximum SPR decrease from time-matched placebo was dose related and appeared to reach its maximal level at 10 mg. The pharmacokinetic and side-effect profile was similar to that in healthy volunteers. 18 patients (64%) reported 42 adverse events during the study (5 after placebo and 37 after seletracetam), without specific association with dose. Somnolence (32%), dizziness (21%), headache (14%), feeling drunk (7%) were reported following seletracetam, compared to [lt]5% following placebo., Seletracetam was effective in reducing or even abolishing the photoparoxysmal EEG response in photosensitive patients with epilepsy. Maximal suppression was achieved at relatively low doses of 10 and 20 mg. Seletracetam is more potent in this model, compared to both LEV and brivaracetam., (Supported by UCB funded.)