Abstracts

Rationale: To evaluate the safety and tolerability of the novel SV2A ligand brivaracetam (BRV, ucb 34714) in patients with refractory focal epilepsy.Methods: Studies N01114 and N01193 were double-blind, randomised, parallel-group, placebo-controlled dose-ranging studies in patients (age 16-65 yrs) with focal epilepsy experiencing ≥4 partial-onset seizures (with/without secondary generalisation) per 4 week baseline and uncontrolled on 1-2 antiepileptic drugs (AEDs). Patients were randomised to BRV 5, 20, 50 mg/day or placebo (PBO) (study N01193) and 50, 150 mg/day or PBO (study N01114), dosed BID. Treatment duration was 7 weeks (study N01193) and 10 weeks (study N01114). Safety and tolerability data (adverse events [AEs]), vital signs and selected laboratory examinations) were pooled and data distributed into 5 treatment groups for analysis (PBO, BRV <50 mg/day, BRV 50 mg/day, BRV 150 mg/day all BRV).Results: Patient numbers per treatment group were: PBO n=106, BRV <50 mg/day n=102, BRV 50 mg/day n=105, BRV 150 mg/day n=52 and all BRV n=259. BRV was very well tolerated at all doses tested. The retention rate in the BRV groups was high in both studies, between 92% and 98% of patients completing the study, compared with 91% and 92% in the PBO groups. The most frequent AEs with an incidence ≥5% in any group were nausea, vomiting, fatigue, nasopharyngitis, anorexia, convulsion, dizziness, headache, somnolence and insomnia. No difference in incidence >3% was observed between the pooled BRV and PBO groups for any of these AEs. A dose-response relationship was not observed for the majority of AEs in the studies analysed. Actual values and change from baseline were computed for haematology and biochemistry parameters, for the last measure in the treatment period. No medically significant changes were observed in any treatment group. Actual values and change from baseline were computed for orthostatic vital sign parameters (systolic and diastolic blood pressure and pulse rate). No medically significant orthostatic changes were observed in these analyses. Conclusions: Adjunctive BRV demonstrated a highly favourable safety and tolerability profile in a patient population suffering from refractory partial-onset seizures, uncontrolled despite treatment with 1-2 AEDs. No major differences between the BRV and PBO groups were found for AE incidence, laboratory parameters and vital signs. UCB S.A.Funded.