Abstracts

Rationale: To assess safety and tolerability of adjunctive brivaracetam (BRV) in two studies of pediatric patients with epilepsy aged ≥1 month and  < 17 years.  Methods: Study N01263 (NCT00422422) was a Phase IIa open-label study of adjunctive BRV in patients aged ≥1 month– <16 years with various seizure syndromes. The study comprised a 1-week baseline followed by a 3-week evaluation period, during which the BRV dose was increased each week: 0.4, 0.8, and 1.6 mg/kg bid for patients ≥8 years, and 0.5, 1.0, and 2.0 mg/kg bid for patients <8 years. After the evaluation period, patients could convert to a long-term follow-up (LTFU) study (N01266; NCT01364597) or down-titrate. Study N01266, a Phase III open-label study, enrolled new patients aged ≥4– <17 years with focal seizures, and those opting to continue from study N01263. Directly-enrolled patients started at 1 mg/kg/day bid and were up-titrated over 3 weeks to 1–5 mg/kg/day bid (maximum 200 mg/day). Patients >50 kg were dosed as adults (50–200 mg/day). LTFU patients continued at the same dose as in the previous study. Data from the two studies were pooled. Treatment-emergent adverse events (TEAEs) are reported for the subgroup with focal seizures. Results: Of 219 patients in the pooled analysis, 168 had focal seizures. Among these patients, 10 received BRV in N01263 but did not enter N01266, 40 continued from N01263 to N01266, and 118 were direct enrollers to N01266. For the pediatric pool (n=219), mean (range) age was 7.7 (0–16) years, 54.8% male, 70.3% white, and 29.7%, 39.3%, and 31.1% had previously taken 0–1, 2–4, and ≥5 antiepileptic drugs, respectively. Total exposure to BRV was 399.5 patient-years; 166, 146, 93, 50, 33, and three patients taking BRV for ≥6, ≥12, ≥24, ≥36, ≥48, and ≥60 months, respectively. In patients with focal seizures, 157/168 (93.5%) reported ≥1 TEAE; most frequently reported TEAEs (≥20%) were nasopharyngitis, pyrexia, and convulsion (Table 1). Drug-related TEAEs were reported by 66/168 (39.3%) of patients, most frequently (≥5%) decreased appetite and somnolence (Table 2). Serious TEAEs were reported by 39/168 (23.2%) patients, and drug-related serious TEAEs by 3/168 (1.8%). Severe TEAEs were reported by 19/168 (11.3%), and discontinuation due to TEAEs by 15/168 (8.9%). Two patients (1.2%) died due to pneumonia/septic shock and circulatory collapse; neither death was considered to be related to study medication. Conclusions: In this pooled analysis from two open-label studies, infants and children aged ≥1 month– < 17 years with focal seizures were exposed to adjunctive BRV for up to 60 months. TEAEs were reported by the majority of patients (93.5%), with 39.3% reporting drug-related TEAEs, and 8.9% discontinuing due to TEAEs. BRV was generally well tolerated in this pediatric population with the most common drug-related TEAEs being decreased appetite and somnolence. Funding: Studies supported by UCB Pharma