Temporal Profile of Treatment-Emergent Adverse Events in Adult Asian Patients with Focal-Onset Seizures During Adjunctive Brivaracetam Treatment: Post Hoc Analysis of a Phase 3, Randomized Trial

We assessed the time course of treatment-emergent adverse events (TEAEs) in adult Asian patients (in Thailand, Japan, China, Philippines, Malaysia, Singapore, and Taiwan) with focal-onset seizures (FOS) during adjunctive brivaracetam (BRV) treatment. Post hoc analysis of EP0083/NCT03083665, a Phase 3, randomized, double-blind, placebo (PBO)-controlled trial that evaluated BRV 50 and 200 mg/day 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. Overall, 448 patients (mean age 34.5 years; 53.8% female) received ≥ 1 dose of trial medication (PBO/BRV 50 mg/BRV 200 mg: n = 149/151/148 [Safety Set]). The overall incidence of TEAEs was similar across treatment arms (53.6−58.1%), and most TEAEs were mild in intensity (45.0−48.3%). Patients discontinuing BRV because of TEAEs (1.3% BRV 50 mg; 2.7% BRV 200 mg) discontinued during the first 5 weeks of treatment (for PBO, discontinuations due to TEAEs [3.4%] took place between weeks 1−8). The incidence of drug-related TEAEs was 18.1% in patients receiving PBO, 24.5% in those on BRV 50 mg/day, and 39.2% for BRV 200 mg/day; however, most were of mild intensity and did not lead to BRV discontinuation. The incidence of TEAEs and drug-related TEAEs was highest during the first week of adjunctive BRV treatment and decreased thereafter. The onset of drug-related somnolence and dizziness occurred mainly during the first week of treatment. In Asian adults with FOS, most drug-related TEAEs were mild in intensity, indicating that adjunctive BRV had a favorable tolerability profile when initiated at a potentially therapeutic dose without titration. The incidence of drug-related TEAEs including somnolence and dizziness was highest during the first week of adjunctive BRV treatment, abating thereafter. These tolerability data could help inform patient monitoring and treatment decisions when prescribing BRV. ClinicalTrials.gov NCT03083665. Brivaracetam is an antiseizure medication used to treat patients with focal-onset seizures, which is a type of seizure commonly experienced by people with epilepsy. During treatment with antiseizure medications, people can have side effects. It is useful to understand when side effects such as somnolence (drowsiness) or dizziness occur when taking a new medication. In the trial reported here, we looked at the time at which any side effects, particularly somnolence or dizziness, occur when Asian people with epilepsy (recruited in Thailand, Japan, China, Philippines, Malaysia, Singapore, and Taiwan) received brivaracetam treatment and how quickly these side effects go away. The results show that most of the side effects were mild, including those that the doctor who treated them considered to be related to the medication. The side effects most frequently occurred in the first week of treatment and then decreased over time; during this time, people with epilepsy continued to receive treatment with brivaracetam. These findings show that brivaracetam was well tolerated in adult Asian patients. Drug-related somnolence or dizziness started within the first 3 weeks of brivaracetam treatment and subsequently decreased over time. The results from this trial provide important information for doctors and healthcare providers monitoring patients and help in making decisions on treatment approaches.