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To evaluate long-term safety and tolerability of adjunctive brivaracetam (BRV) in children with epilepsy.This was an interim analysis (cut-off March 15, 2017) of pooled data from two open-label, single-arm, multicentre trials. N01263 (NCT00422422) was a 3-week trial of BRV 0.8-4 mg/kg/day in patients (1 month-16 years) with epilepsy. Patients who completed this trial could continue into a long-term follow-up trial (N01266, NCT01364597) which also directly enrolled patients (4-17 years) with focal seizures. After dose-escalation, patients received BRV 1-5 mg/kg/day (maximum 200 mg/day) during long-term evaluation. Data are reported for patients aged 4 to16 years with focal seizures.The safety set comprised 149 patients: 34 from the initial trial (26 entered long-term trial) and 115 directly enrolled into the long-term trial. At the cut-off, 90 patients were receiving BRV (total exposure: 299.4 patient-years). Treatment-emergent adverse events (TEAEs) were reported by 140/149 (94.0%) patients, most commonly (≥20%) nasopharyngitis (24.8%), pharyngitis (22.1%), convulsion (21.5%), and pyrexia (20.1%). TEAEs considered drug-related by the investigator were reported by 56/149 (37.6%) patients, most commonly somnolence (6.0%). Two patients died; neither death was considered related to BRV. Mean changes from baseline in child behaviour rating scales were small; most patients remained in their baseline category.In this pooled analysis of two open-label trials including long-term data, adjunctive BRV was generally well tolerated in children aged 4 to16 years with focal seizures. These findings supported approval of BRV as a new therapy option for children aged ≥4 years with focal seizures.

Objective The objective of this analysis was to provide a comprehensive analysis of safety data for adjunctive brivaracetam (BRV), an antiepileptic drug (AED) of the racetam class, for treatment of focal seizures in patients with epilepsy. Methods Data were pooled from two phase II, placebo-controlled, double-blind, dose-ranging trials (N01114 [ ClinicalTrials.gov : NCT00175929 ], N01193 [ NCT00175825 ]) and three phase III, placebo-controlled, double-blind, 12-week trials (N01252 [ NCT00490035 ], N01253 [ NCT00464269 ], and N01358 [ NCT01261325 ]) in patients aged ≥ 16 years with focal seizures, as well as a phase III, placebo-controlled, double-blind, 16-week trial in patients aged ≥ 16 years with focal or generalized epilepsy (N01254 [ NCT00504881 ]). Data are presented for the approved therapeutic dose range of 50–200 mg/day. Data for BRV administered intravenously (25–150 mg doses) were pooled separately from one phase III trial (N01258 NCT01405508 ]) and two clinical pharmacology trials (N01256 [Part B] [UCB Pharma, data on file]; EP0007 [ NCT01796899 ]). Adverse events (AEs) of interest were summarized in relevant categories. Results The safety pool comprised 1957 patients: 1271 receiving adjunctive BRV and 686 receiving placebo. Overall, the incidence of treatment-emergent adverse events (TEAEs) was 66.9% with BRV versus 62.8% with placebo. The most frequently reported TEAEs with BRV (≥ 5% of patients) versus placebo were somnolence (13.3% vs. 7.9%), headache (10.5% vs. 11.5%), dizziness (10.0% vs. 7.0%), and fatigue (8.2% vs. 4.2%). Incidence of psychiatric disorder-related TEAEs was 11.3% with BRV versus 8.2% with placebo. Behavioral disorder-related TEAE incidence was low (4.0% with BRV vs. 2.5% with placebo). Irritability was reported in 2.7% of BRV-treated patients vs. 1.5% of patients receiving placebo; anger, aggression, and agitation were each reported by ≤ 1% of patients receiving BRV. Treatment-emergent adverse events potentially associated with psychosis were psychotic disorder (three patients on BRV vs. two patients on placebo), auditory hallucination, illusion, visual hallucination (one patient each on BRV), epileptic psychosis, and hallucination (one patient each on placebo). No additional safety concerns were identified in patients with intravenous (IV) BRV administration (n = 104). Conclusions These safety data for adjunctive BRV support its acceptable safety and tolerability profile.