Abstracts

To assess the pharmacodynamics and the tolerability of single doses of the new AED ucb 34714a 2-pyrrolidinone derivative, in photosensitive subjects. This new drug exhibits a high, selective interaction with the brain-specific levetiracetam (LEV) binding site. LEV has shown to be effective in this POP model before. A placebo-controlled, single blind, single period study was conducted in 19 photosensitive subjects (15 females) between 18- 60 yrs of age, taking one or two concomitant AEDs (VPA, LTG, PHT, GBP and LEV) or none (3). During a three day period, subjects underwent standardized intermittent photic stimulation (IPS) to define the Standard Photosensitive Range (SPR) per patient at fixed time points. After the first day with placebo, single oral dosages of ucb 34714 were given, starting with 80 mg and subsequent lowering of the dose per 4 patients. The SPR was the main parameter to identify the lowest single oral dose of ucb 34714 producing maximal diminution or suppression of the IPS evoked photoparoxysmal EEG response (PPR) comparing the SPRs before and after intake of ucb 34714. Pharmacokinetic parameters of ucb 34714 were computed from the blood samples collected up to 72 hours post-dose.
Profile Of Mood State (POMS) and Addiction Research Center Inventory short form questionnaire (ARCI-49) were administered to investigate possible effects on mood.Descriptive statistics were used. A total of 18 patients were evaluable: important SPR changes (100%) or complete abolishment (14/18, 78%) of the PPRs were observed after ucb 34714 intake (doses tested and effective: 80, 40, 20 and 10 mg). No relationship between the pharmacodynamics of the drug (expressed as SPR change and duration of response) and the dose or the exposure to the drug (expressed as AUC or Cmax) was found. The 80 mg dose appeared more efficient (time to maximal response and duration of response). The pharmacokinetic and side-effect profile was similar to that in healthy volunteers. Twelve subjects reported 20 mild to moderate AEs (4/ 20 after placebo). Dizziness (5), dry mouth (1) and nausea (1) were reported exclusively in the verum period. A small increase in sedation (ARCI-49) was noticed 3 hrs after administration of 80 mg of ucb 34714. The POMS did not show any change. All the single doses (10, 20, 40, and 80 mg) of ucb 34714 were effective in reducing or even abolishing (78%) the photoparoxysmal EEG response in photosensitive subjects. Eighty mg of ucb 34714 was however the most efficient dosage. Compared to levetiracetam, the efficacy of ucb 34714 in this model is more potent. (Supported by UCB Pharma BV)