Efficacy, safety, and tolerability of adjunctive brivaracetam in adult Asian patients with uncontrolled focal-onset seizures: A phase III randomized, double-blind, placebo-controlled trial

Objective: The objective was to assess the efficacy and safety of adjunctive brivaracetam (BRV) with concomitant use of lamotrigine (LTG) or topiramate (TPM) in patients with uncontrolled focal seizures. Methods: Data were pooled from three randomized, placebo-controlled Phase III studies (NCT00490035/N01252, NCT00464269/N01253, NCT01261325/N01358) of adults with focal (partial-onset) seizures. Patients taking concomitant levetiracetam were excluded from the efficacy populations, but included in the safety populations. This post-hoc analysis reports data from patients taking BRV in the approved therapeutic range (50-200 mg/day) concomitantly with LTG or TPM. Results: The number of patients in each of the three BRV dosage groups was small, particularly for the TPM subgroup. Mean percent reduction over placebo in baseline-adjusted focal seizure frequency/28 days for BRV 50, 100, and 200 mg/day was 8.7, 5.3, and 8.9 in the LTG subgroup (n = 220), and 8.4, 21.3, and - 4.2 in the TPM subgroup (n = 122). The >= 50% responder rate with concomitant LTG or TPM with BRV 50, 100, and 200 mg/day or placebo was LTG: 28.1%, 36.1%, 34.1%, and 29.1%; and TPM: 14.3%, 44.4%, 25.0%, and 17.5%. There were numerically >= 50%, >= 75%, >= 90%, and 100% responder rates for patients taking BRV >= 50 mg/day compared with placebo in both subgroups. In the LTG and TPM safety populations (n = 245 versus n = 125), treatment-emergent adverse events (TEAEs) were reported with LTG 68.7% versus 68.4%, and TPM 65.6% versus 57.8% (BRV >= 50 mg/day versus placebo). Discontinuations due to TEAEs versus placebo were LTG 7.3% versus 6.3% and TPM 8.2% versus 4.7%. The three most frequently reported TEAEs for both subgroups were somnolence, dizziness, and fatigue. Of these, the incidence of fatigue in the LTG population appeared to increase with dose. Significance: In this post-hoc pooled analysis, BRV administered with concomitant LTG or TPM reduced seizure frequency and was generally well tolerated for BRV doses of 50-200 mg/day.