Time Course of Treatment-emergent Adverse Events in Adult Asian Patients with Focal-onset Seizures During Adjunctive Brivaracetam Treatment: A Post Hoc Analysis of a Phase III, Randomized Trial
Abstract number :
3.408
Submission category :
7. Anti-seizure Medications / 7B. Clinical Trials
Year :
2024
Submission ID :
81
Source :
www.aesnet.org
Presentation date :
12/9/2024 12:00:00 AM
Published date :
Authors :
Presenting Author: Naotaka Usui, MD,PhD – NHO Shizuoka Institute of Epilepsy and Neurological Disorders
Dong Zhou, MD – West China Hospital, Sichuan University
Bing Qin, MD – The First Affiliated Hospital of Jinan University, Guangdong, China
Somsak Tiamkao, MD – Khon Kaen University, Srinagarind Hospital
Leonor Cabral-Lim, MD – Department of Neurosciences, College of Medicine, Philippine General Hospital, University of the Philippines Manila, The Health Sciences Center
Kheng Seang Lim, MD – Division of Neurology, Department of Medicine, Universiti Malaya
Shih-Hui Lim, MD – Singapore General Hospital
Jing-Jane Tsai, MD – Department of Neurology, National Cheng Kung University Hospital
Jun Watanabe, PhD – UCB Pharma, Tokyo, Japan
Weiwei Sun, M.Med – UCB Pharma, Shanghai, China
Najla Dickson, MD – UCB Pharma, Morrisville, NC, USA
Dimitrios Bourikas, PhD – UCB Pharma, Alimos, Greece
Brian Moseley, MD – UCB Pharma, Morrisville, NC, USA
Yushi Inoue, MD, PhD – NHO Shizuoka institute of epilepsy and neurological disorders
Rationale: In clinical trials, treatment-emergent adverse events (TEAEs) are usually reported for the full treatment period. Analysis of previous clinical trials data indicated that the majority of drug-related central nervous system TEAEs occurred early in the course of brivaracetam (BRV) treatment and then diminished over time (Meador et al. 2020; Epilepsy Behav.; Oct.111:107212). Here, we assess the time course of TEAEs in adult Asian patients with focal-onset seizures (FOS) during adjunctive BRV treatment.
Methods: A post hoc analysis of EP0083/NCT03083665; a phase III, randomized, double-blind, placebo (PBO)-controlled trial that evaluated two doses of BRV (50 mg and 200 mg daily) in adult Asian patients (≥ 16-80 years) with FOS. Following an 8-week prospective baseline, patients were randomized 1:1:1 to PBO, BRV 50 mg, or BRV 200 mg and entered a 12-week treatment period (Inoue et al. 2024; Epilepsia Open).
Results: Overall, 448 patients (mean [SD] age: 34.5 [13.0] years; 53.8% female) received ≥ 1 dose of trial medication (PBO/BRV50 mg/BRV200 mg: n=149/151/148; Safety Set). The overall incidence of TEAEs was similar across treatment arms and the incidence of drug-related TEAEs was numerically higher in patients on BRV 200 mg compared to those on PBO or BRV 50 mg (Figure 1). Most of the TEAEs were of mild intensity. The incidence of TEAEs and drug-related TEAEs was highest during the first week of adjunctive BRV treatment and decreased thereafter. Patients discontinuing BRV due to TEAEs (1.3% BRV 50 mg; 2.7% BRV 200 mg) generally discontinued during the first 5 weeks of BRV treatment (for PBO, discontinuations due to TEAEs [3.4%] were between week 1 and 8). For PBO, BRV 50 mg, and BRV 200 mg, the incidence of drug-related somnolence was 7.4%, 9.3%, and 18.2%, respectively, and the incidence of drug-related dizziness was 2.7%, 7.3%, and 10.8%, respectively. The onset of drug-related somnolence and dizziness occurred mainly during the first week of treatment (Figure 2). For patients on PBO, BRV 50 mg, and BRV 200 mg, respectively, 3/4 (75.0%), 10/11 (90.9%), and 15/16 (93.8%) patients with drug-related dizziness reported resolved outcome during the 12-week evaluation period; and 8/11 (72.7%), 10/14 (71.4%), and 16/27 (59.3%), respectively, with drug-related somnolence reported resolved outcome during the 12-week period. The prevalence of drug-related TEAEs including drug-related somnolence and dizziness decreased over time.
Conclusions: This post hoc analysis indicated that, in Asian adults with FOS, the majority of reported drug-related TEAEs were mild in intensity. Discontinuations due to TEAEs were numerically lower in patients on adjunctive BRV vs PBO and generally occurred during the first five weeks of treatment. The incidence of drug-related TEAEs including somnolence and dizziness was highest during the first week of adjunctive BRV treatment and abated thereafter. These tolerability data could help inform patient monitoring and treatment decisions.
Funding: UCB Pharma-sponsored
Anti-seizure Medications