A multicenter Phase II randomized, placebo-controlled single-blind trial with the SV2A ligand seletracetam in photosensitive epilepsy patients.

The objective of this study was to evaluate the effect of seletracetam (SEL), a potent modulator of synaptic vesicle glycoprotein 2A (SV2A), in patients with photoparoxysmal EEG response (PPR) to intermittent photic stimulation (IPS) as proof-of-principle of efficacy in patients with epilepsy. In this multicenter, single-blind Phase II study, adults with photosensitive epilepsy, with/without concomitant antiseizure medication therapy, underwent IPS under 3 eye conditions (at eye closure, eyes closed and eyes open) after a single oral dose of placebo (day - 1) or SEL (day 1; 0.5, 1, 2, 4, 10, or 20 mg).

Brivaracetam exposure-response predictions in pediatric patients from age 1 month: Extrapolation of levetiracetam adult-pediatric scaling to brivaracetam.

Background: An adult population pharmacokinetic/pharmacodynamic (PK/PD) model for the antiseizure medication (ASM) brivaracetam (BRV) was previously extended to children aged 4-16 years by using a pediatric BRV population PK model. Effects were scaled using information from a combined adult-pediatric PK/PD model of a related ASM, levetiracetam (LEV).

Objective: To scale an existing adult population PK/PD model for BRV to children aged 1 month to < 4 years using information from a combined adult-pediatric PK/PD model for LEV, and to predict the effective dose of BRV in children aged 1 month to < 4 years using the adult BRV PK/PD model modified for the basal seizure rate in children.

Pharmacokinetics, Safety, and Tolerability of Brivaracetam in Healthy Elderly Participants.

The pharmacokinetics, metabolism, safety, and tolerability of the antiseizure medication brivaracetam (BRV) were characterized in 16 healthy elderly participants (8 men/8 women) aged 65-78 years who received a single 200-mg oral dose of BRV on day 1, followed by 200 mg twice daily from day 3 until day 12. BRV and three metabolites were determined in plasma and urine. Adverse events, vital signs, electrocardiograms, laboratory tests, general and neurological examinations, and psychometric rating scales were recorded at regular intervals.

Drug characteristics derived from kinetic modeling: combined C-UCB-J human PET imaging with levetiracetam and brivaracetam occupancy of SV2A.

Background: Antiepileptic drugs, levetiracetam (LEV) and brivaracetam (BRV), bind to synaptic vesicle glycoprotein 2A (SV2A). In their anti-seizure activity, speed of brain entry may be an important factor. BRV showed faster entry into the human and non-human primate brain, based on more rapid displacement of SV2A tracer C-UCB-J.

Bioavailability, safety and tolerability of intravenous brivaracetam in healthy Japanese participants.

We characterised the bioavailability, safety, and tolerability of brivaracetam 100 mg intravenous bolus and 15-min infusion versus oral reference tablet in 24 healthy Japanese participants.In this randomised, open-label, three-period crossover study, participants received three 100 mg single doses of brivaracetam, intravenous bolus, infusion, and oral tablets. Maximum plasma concentration (C), area under the plasma concentration-time curve from time zero to the time of last quantifiable concentration (AUC), and area under the plasma concentration-time curve extrapolated to infinity (AUC), were compared using analysis of variance following logarithmic transformation.