Authors :
Presenting Author: Brian Moseley, MD – UCB Pharma, Morrisville, NC, USA
First Author: Yushi Inoue, – NHO Shizuoka Institute of Epilepsy and Neurological Disorders, Shizuoka, Japan
Somsak Tiamkao, MD – Khon Kaen University, Srinagarind Hospital, Khon Kaen, Thailand; Dong Zhou, MD – West China Hospital of Sichuan University, Sichuan, China; Leonor Cabral-Lim, MD – Department of Neurosciences, College of Medicine, Philippine General Hospital, University of the Philippines Manila, The Health Sciences Center, Manila, Philippines; Kheng Seang Lim, MD – Division of Neurology, Department of Medicine, Universiti Malaya, Kuala Lumpur, Malaysia; Shih Hui Lim, MD – Singapore General Hospital, Singapore; Jing-Jane Tsai, MD – Department of Neurology, National Cheng Kung University Hospital, Tainan, Taiwan; Lin Wang, MD – UCB Pharma, Shanghai, China; Weiwei Sun, MD – UCB Pharma, Shanghai, China; Yoshinobu Hayakawa, MPharma – UCB Pharma, Tokyo, Japan; Hiroshi Sasamoto – UCB Pharma, Tokyo, Japan; Tomonobu Sano – UCB Pharma, Tokyo, Japan; Carrie McClung, MS – UCB Pharma, Morrisville, NC, USA; Almasa Bass, PharmD – UCB Pharma, Morrisville, NC, USA
Rationale:
Efficacy and tolerability of adjunctive brivaracetam (BRV) in patients with focal onset seizures were established in Phase 3 trials in predominantly White/Caucasian populations. EP0083 was performed to assess adjunctive BRV in Asian patients.
Methods:
Phase 3, randomized, double-blind, placebo (PBO)-controlled trial (EP0083; NCT03083665) evaluating BRV 50mg and 200mg in patients (≥ 16-80 years; from Thailand, Japan, China, Philippines, Malaysia, Singapore and Taiwan) with focal onset seizures with/without secondary generalization despite current treatment with 1/2 concomitant antiseizure medications (ASMs). Following an 8-week baseline, patients were randomized 1:1:1 to PBO, 50mg, or 200mg BRV and entered a 12-week treatment period. Efficacy outcomes included percent reduction in focal onset seizure frequency per 28-days (primary) and 50% responder rate for focal onset seizure frequency (secondary) during the treatment period. Primary safety variables were incidences of treatment-emergent adverse events (TEAEs), TEAEs leading to discontinuation, and serious TEAEs.
Results:
Of 449 randomized patients, 448 (mean [SD] age: 34.5 [13.0] years; 53.8% female) received ≥ 1 dose of trial medication (PBO/BRV 50mg/BRV 200mg: n=149/151/148) and were included in the Safety Set (SS). 425/449 (94.7%) patients completed the trial (PBO/BRV 50mg/BRV 200mg: 92.6/96.7/94.6%; n=149/152/148). The Full Analysis Set (FAS) included 446 patients (PBO/BRV 50mg/BRV 200mg: n=147/151/148) with post-baseline seizure data. Mean (SD) duration of epilepsy was 16.6 (12.2) years.
Overall, 231 (51.8%), 144 (32.3%) and 71 (15.9%) patients had 0-1, 2-4, and ≥ 5 previous ASMs (discontinued prior to trial entry), respectively. 117 (26.2%) patients had previous levetiracetam use. Median baseline focal seizure frequency/28 days was 9.8, 9.0, and 7.8 in the PBO, BRV 50mg, and 200mg groups, respectively. Percent reduction over PBO in 28-day adjusted focal seizure frequency was 24.6% (p=0.0004) with BRV 50mg and 33.3% (p < 0.0001) with 200mg
(
Figure). 50% responder rate was 19.0%, 41.1%, and 49.3% with PBO, BRV 50mg and 200mg respectively (p < 0.0001 vs PBO for both BRV groups). Incidence of TEAEs was similar in patients on PBO (58.4%), BRV 50mg (57.0%) and 200mg (60.1%;
Table). 4.7%, 2.6% and 3.4% of patients on PBO, BRV 50mg and 200mg, respectively, discontinued due to TEAEs; and 0.7%, 1.3% and 2.7% reported serious TEAEs. In patients on BRV, the most common TEAEs were somnolence (50/200mg: 9.9/18.9%) and dizziness (11.3/14.2%).
Conclusions:
Adjunctive BRV was efficacious and well tolerated in Asian patients with focal onset seizures. Percent reduction in focal seizure frequency/28-days was significantly greater for BRV 50 and 200mg than PBO. Incidences of TEAEs, TEAEs leading to discontinuation, and serious TEAEs were similar between treatment groups. No unexpected TEAEs occurred. Efficacy/safety profiles were consistent with BRV trials in predominantly White/Caucasian populations, suggesting BRV is effective and well tolerated in Asian populations.
Funding:
UCB Pharma-sponsored