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

Abstract

Introduction

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.

Methods

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.

Results

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.

Conclusion

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.

Trial Registration

ClinicalTrials.gov NCT03083665.

Graphical Abstract

Supplementary Information

The online version contains supplementary material available at 10.1007/s12325-025-03357-7.

Plain Language Summary

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.

Supplementary Information

The online version contains supplementary material available at 10.1007/s12325-025-03357-7.

Key Summary Points

Why carry out this study?

In adults with focal-onset seizures (FOS) recruited in Phase 3 trials predominantly in the US and European Union, most central nervous system-related treatment-emergent adverse events (TEAEs) occurred early in the course of brivaracetam treatment and then diminished over time (Meador KJ et al. Epilepsy Behav 2020)

The objective of this analysis was to assess the time course of TEAEs in adult Asian patients (in Thailand, Japan, China, Philippines, Malaysia, Singapore, and Taiwan) with FOS during adjunctive brivaracetam treatment

What was learned from the study?

Adjunctive brivaracetam had a favorable tolerability profile in Asian adults with FOS when initiated at a potentially therapeutic dose without titration (even at an initial dose of 200 mg/day)

TEAEs were generally mild and the incidence of drug-related TEAEs (including somnolence and dizziness) was highest during the first week of adjunctive brivaracetam treatment, abating thereafter

These data could help inform treatment decisions and patient monitoring as they provide further information on the tolerability profile of brivaracetam when initiated at a therapeutic dose

Digital Features

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Introduction

Treatment-emergent adverse events (TEAEs) are usually reported for the full treatment period in a clinical trial, including titration and maintenance [1]. Assessing TEAEs in the early and late phases of antiseizure medication (ASM) treatment may help guide patient expectations and clinician monitoring [1]. Drug-related central nervous system (CNS) TEAEs such as somnolence, fatigue, and dizziness are common with ASM treatment and can affect drug tolerability and quality of life [1, 2].

Brivaracetam (BRV) is an ASM with high and selective affinity for synaptic vesicle protein 2A (SV2A) in the brain, which is a known molecular target for ASM action [3, 4]. BRV was identified in a large drug discovery program to develop ASMs with greater binding affinity and selectivity to SV2A than levetiracetam [5]. BRV rapidly crosses the blood-brain barrier and can be started at a therapeutic dose without titration [6]. BRV has been approved in the US [7], the European Union [8], and several other regions globally, including Hong Kong, the Republic of Korea, Taiwan, and Japan [9–11].

Analyses of previous data from three pooled Phase 3 international clinical trials in adults aged ≥ 16 years with focal-onset seizures (FOS) who initiated BRV at a therapeutic dose (50, 100, or 200 mg/day) from day 1 (without titration) indicated that most of the drug-related TEAEs associated with the CNS were reported early during treatment with BRV and decreased over time [1]. The design of these Phase 3 clinical trials of BRV allowed the assessment of habituation of adverse events at the initial dose over time, unaffected by dose titration [1]. These international trials recruited patients predominantly from non-Asian populations [12].

Due to genetic factors, the Asian population can be more vulnerable to adverse drug events compared with European and North American populations, particularly Asian patients with the HLA-B*1502 variant who are more susceptible to severe cutaneous adverse drug reactions [13].

A Phase 3 clinical trial (EP0083, NCT03083665) showed that adjunctive BRV was well tolerated and efficacious in adult Asian patients with FOS (in China, Japan, Malaysia, Philippines, Singapore, Taiwan, and Thailand) [9]. A post hoc analysis of this trial was undertaken to assess the time course of TEAEs in adult Asian patients with FOS during adjunctive BRV treatment.

Methods

Trial Design

EP0083 (ClinicalTrials.gov, NCT03083665) was a Phase 3, randomized, double-blind, placebo (PBO)-controlled trial that evaluated two doses of BRV (50 mg and 200 mg daily) as adjunctive therapy in adult Asian patients with FOS. Detailed methodology of this trial has been published previously [9] and is summarized here. Patients were eligible if they were aged ≥ 16 to 80 years with FOS with or without secondary generalization (focal to bilateral tonic–clonic seizures); had ≥ 8 FOS during the 8-week baseline period, with ≥ 2 FOS during each 4-week interval of the baseline period; had ≥ 2 FOS per month during the 3 months before screening; and had uncontrolled seizures with current treatment with one or two ASMs at screening that were at a stable or optimal dose for ≥ 4 weeks before visit 1 and remained stable throughout the trial.

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, followed by a 4-week down-titration period and 2-week trial drug-free period in those not continuing treatment, or followed by a 2-week transition period in patients continuing treatment in a long-term follow-up trial or managed access program. BRV was initiated without titration and was administered orally twice daily in equally divided doses.

The trial protocol, amendments, and patient informed consent were reviewed by a national, regional, or Independent Ethics Committee or Institutional Review Board. This trial was conducted in accordance with the current version of the applicable regulatory requirements, Japan’s Good Clinical Practice requirements, the International Council for Harmonisation-Good Clinical Practice requirements, the ethical principles originating in the principles of the Declaration of Helsinki, and the local laws of the countries involved. Patients provided informed consent or had a legally authorized representative sign the informed consent on their behalf before completing any trial-related procedures.

Post Hoc Analysis

This post hoc analysis was conducted with data from patients in the Safety Set, which included all patients randomized to a treatment arm who received ≥ 1 dose of trial drug. The incidence and prevalence of the following outcomes were assessed overall and by week of treatment during the 12-week evaluation period: TEAEs, drug-related TEAEs, and drug-related somnolence and dizziness (which were the most common drug-related TEAEs reported in ≥ 5% of patients receiving BRV overall [50 and 200 mg/day] during the 12-week evaluation period).

TEAEs were defined as any untoward medical occurrence in a patient administered the trial drug, regardless of whether they had a causal relationship with the drug. TEAEs were considered drug-related if the relationship to trial drug was specified as related as assessed by the investigator, or TEAEs for which the relationship was not specified. The intensity of TEAEs was assessed as mild, moderate, or severe. Severe intensity was assumed for any TEAEs for which the intensity was not specified. Adverse events were coded using the Medical Dictionary for Regulatory Activities, version 18.1.

Incidence was defined as the proportion of patients with TEAEs with onset during the specified week of treatment. Prevalence was defined as the proportion of patients with TEAEs with onset or that were ongoing during the specified week of treatment. For all tolerability analyses by week, the number of patients present in the trial during the corresponding week was used as the denominator. The incidence of discontinuations due to TEAEs was assessed overall and by week of treatment. The times to onset of drug-related somnolence and dizziness were also assessed, as well as the incidence by number of concomitant ASMs at trial entry (1 or 2). Changes in the incidence and prevalence of TEAEs across time were assessed comparing the first week (week 1) to each week for weeks 2–12 for the BRV 50 mg/day and BRV 200 mg/day group separately to determine whether the changes were statistically significant across time. For the comparisons of TEAEs over time (i.e., across the 12-week treatment period), p-values were computed using the Generalized Estimating Equations for Repeated Measures method and the GENMOD SAS® procedure. The model incorporated the seizure frequency per patient for the specific treatment week and treatment weeks as explanatory variables and the incidence/prevalence of the TEAEs as the dependent or response variable. All p-values could only be interpreted in an exploratory manner, i.e., were nominal. Because the incidence of drug-related TEAEs during weeks 6–12 was zero for either the BRV 50 mg/day or BRV 200 mg/day group and the model has the assumption of having non-zero values, to avoid non-convergence of the model, only weeks 1–5 were considered for statistical comparisons of the incidence of drug-related TEAEs. Statistical analyses were performed using SAS® version 9.4.

Results

Baseline Characteristics

Overall, 448 patients received ≥ 1 dose of trial drug and were included in the Safety Set, with 149 patients receiving PBO, 151 receiving BRV 50 mg/day, and 148 receiving BRV 200 mg/day [9]. Overall in the Safety Set, patients’ mean age was 34.5 years, and 241 (53.8%) were female (Table S1) [9]. In patients taking PBO, BRV 50 mg/day, and BRV 200 mg/day, the median baseline FOS frequency per 28 days was 10.00, 8.98, and 7.82, respectively. For patients randomized to PBO, BRV 50 mg/day, and BRV 200 mg/day, 77 (51.7%), 77 (51.0%), and 80 (54.1%) had 0–1 previous ASMs, respectively (previous ASMs were ASMs taken and discontinued before trial entry). In patients randomized to PBO, BRV 50 mg/day, and BRV 200 mg/day, 67 (45.0%), 50 (33.1%), and 49 (33.1%) patients were taking one concomitant ASM at trial entry, respectively, and 82 (55.0%), 101 (66.9%), and 99 (66.9%) were taking two concomitant ASMs at trial entry, respectively (Table S1).

TEAEs

The overall incidence of TEAEs was similar across treatment arms (BRV 50 mg/day, 53.6%; BRV 200 mg/day, 58.1%; PBO, 53.7%; Fig. 1a [14]). Most of the TEAEs were mild in intensity. The incidence of TEAEs with PBO was 20.1% in week 1 and 10.8% in week 2. The incidence of TEAEs was highest during the first week of adjunctive BRV treatment (31.1% receiving BRV 50 mg/day; 35.8% receiving BRV 200 mg/day) and decreased substantially by week 2 (11.3% and 12.3%, respectively) (weeks 2–12 vs. week 1: all p values < 0.05; Fig. 2a). The prevalence of TEAEs was generally stable during the first 12 weeks of treatment in patients on 50 and 200 mg/day BRV (week 1 vs. weeks 2–12: all p values > 0.05). The prevalence of TEAEs ranged from 20.1% (week 1) to 31.9% (week 8) with PBO, 27.0% (weeks 10 and 11) to 35.3% (week 3) with BRV 50 mg/day, and 31.9% (week 11) to 40.3% (weeks 4 and 5) with BRV 200 mg/day (Fig. 2b).

Fig. 1.

Overall incidence of (a) TEAEs, (b) drug-related TEAEs, (c) drug-related somnolence, and (d) drug-related dizziness by intensity during the 12-week treatment period (Safety Set). BRV brivaracetam, PBO placebo, TEAE treatment-emergent adverse event. Panels a and b reproduced with modifications from Fig. 1 of Usui et al. [14], licensed under CC BY

Fig. 2.

(a) Incidence^a and (b) prevalence^b of TEAEs by week of treatment (Safety Set). The denominators are patients with exposure during the specified week. TEAEs commencing no earlier than week 13 are excluded. BRV brivaracetam, PBO placebo, TEAE treatment-emergent adverse event. ^aProportion of patients with TEAEs with onset during the specified week of treatment. ^bProportion of patients with TEAEs with onset or that were ongoing during the specified week of treatment

Discontinuations due to TEAEs

Patients discontinuing BRV due to TEAEs (1.3% for BRV 50 mg/day; 2.7% for BRV 200 mg/day) discontinued during the first 5 weeks of BRV treatment (Table S2). For patients receiving PBO, discontinuations due to TEAEs (3.4%) occurred between weeks 1 and 8 of treatment (Table S2).

Drug-Related TEAEs

The overall incidence of drug-related TEAEs was 18.1% in patients receiving PBO, 24.5% in those on BRV 50 mg/day, and 39.2% in those receiving BRV 200 mg/day (Fig. 1b). No patients receiving PBO or BRV reported severe drug-related TEAEs. The incidence of moderate drug-related TEAEs was 2.7% in patients on PBO, 2.0% in patients on BRV 50 mg/day, and 6.1% in patients on BRV 200 mg/day (Fig. 1b).

Most drug-related TEAEs had an onset during the first week of treatment, with an incidence of 6.0% in patients receiving PBO, 19.2% for BRV 50 mg/day, and 29.1% for BRV 200 mg/day (Fig. 3a). The incidence of drug-related TEAEs substantially decreased after the first week of BRV treatment (weeks 2–5 vs. week 1: all p values < 0.05), and no substantial differences between patients randomized to PBO, BRV 50 mg/day, or BRV 200 mg/day were observed between weeks 2 and 12 (Fig. 3a).

Fig. 3.

(a) Incidence^a and (b) prevalence^b of drug-related TEAEs by week of treatment (Safety Set). The denominators are patients with exposure during the specified week. TEAEs commencing no earlier than week 13 are excluded. BRV brivaracetam, PBO placebo, TEAE treatment-emergent adverse event. ^aProportion of patients with drug-related TEAEs with onset during the specified week of treatment. ^bProportion of patients with drug-related TEAEs with onset or that were ongoing during the specified week of treatment

The prevalence of drug-related TEAEs was generally stable in patients receiving PBO and decreased over time in patients receiving BRV 50 mg/day (p < 0.05 in weeks 2 and 6–12 vs. week 1) and 200 mg/day (p < 0.05 in weeks 2, 8, and 10–12 vs. week 1) (Fig. 3b). The prevalence of drug-related TEAEs was similar in patients receiving PBO and BRV 50 mg/day between weeks 6 and 12 of treatment. The prevalence of drug-related TEAEs over the 12-week treatment period ranged from 7.4 to 19.2% in patients receiving BRV 50 mg/day and from 17.7 to 29.1% for BRV 200 mg/day (Fig. 3b).

Drug-Related Somnolence

Overall, drug-related somnolence was reported by 41 (13.7%) patients receiving BRV overall (50 and 200 mg/day) during the 12-week evaluation period. The incidence of drug-related somnolence was 7.4% in patients receiving PBO, 9.3% in patients on BRV 50 mg/day, and 18.2% in patients on BRV 200 mg/day (Fig. 1c).

The onset of drug-related somnolence occurred mainly during week 1 of treatment (Fig. 4a). The incidence of drug-related somnolence during weeks 2 and 3 of treatment was similar in patients receiving BRV 50 and 200 mg/day and similar to the incidence with PBO. In patients randomized to BRV, no onset of drug-related somnolence was observed after week 3 of treatment (Fig. 4a).

Fig. 4.

(a) Incidence^a and (b) prevalence^b of drug-related somnolence by week of treatment (Safety Set). The denominators are patients with exposure during the specified week. TEAEs commencing no earlier than week 13 are excluded. BRV brivaracetam, PBO placebo, TEAE treatment-emergent adverse event. ^aProportion of patients with TEAEs with the preferred term somnolence with onset during the specified week of treatment. ^bProportion of patients with TEAEs with the preferred term somnolence with onset or that were ongoing during the specified week of treatment. Panel (a) reproduced with modifications from Fig. 2 of Usui et al. [14], licensed under CC BY

The prevalence of drug-related somnolence was generally stable in patients receiving PBO and decreased over time in patients receiving BRV 50 and 200 mg/day (Fig. 4b).

For patients receiving PBO (n = 11), BRV 50 mg/day (n = 14), and BRV 200 mg/day (n = 27), the median time from administration of the first dose to the first onset of drug-related somnolence was 9.0, 1.0, and 0 days, respectively (mean 17.6, 2.6, and 2.0 days, respectively). For patients receiving PBO, BRV 50 mg/day, and BRV 200 mg/day with drug-related somnolence, 8/11 (72.7%), 10/14 (71.4%), and 16/27 (59.3%) reported resolved outcomes during the 12-week evaluation period, respectively. Drug-related somnolence was mostly mild in intensity (Fig. 1c). During the 12-week evaluation period, one patient (0.7%) receiving BRV 200 mg/day discontinued because of somnolence during the first week of treatment (Table S2).

In patients receiving PBO, the incidence of drug-related somnolence was 1.5% in those receiving one concomitant ASM at trial entry and 12.2% in those on two concomitant ASMs at trial entry (Fig. S1a). The incidence of drug-related somnolence was generally similar in patients treated with BRV receiving one and two concomitant ASMs (BRV 50 mg/day, 10.0% and 8.9%, respectively; BRV 200 mg/day, 16.3% and 19.2%, respectively; Fig. S1a).

Drug-Related Dizziness

Overall, drug-related dizziness was reported by 27 (9.0%) patients receiving BRV overall (50 and 200 mg/day) during the 12-week evaluation period. The incidence of drug-related dizziness was 2.7%, 7.3%, and 10.8% in patients receiving PBO, BRV 50 mg/day, and BRV 200 mg/day, respectively (Fig. 1d). The onset of drug-related dizziness occurred mainly during the first week of treatment (Fig. 5). In patients randomized to BRV, no onset of drug-related dizziness was observed after week 3 of treatment. The prevalence of drug-related dizziness generally decreased over time in patients randomized to each treatment group and was similar in patients receiving PBO and BRV 50 mg/day between weeks 2 and 12 of treatment (Fig. 5).

Fig. 5.

(a) Incidence^a and (b) prevalence^b of drug-related dizziness by week of treatment (Safety Set). The denominators are patients with exposure during the specified week. TEAEs commencing no earlier than week 13 are excluded. BRV brivaracetam, PBO placebo, TEAE treatment-emergent adverse event. ^aProportion of patients with TEAEs with the preferred term dizziness with onset during the specified week of treatment. ^bProportion of patients with TEAEs with the preferred term dizziness with onset during the specified week of treatment. Panel a reproduced with modifications from Fig. 2 of Usui et al. [14], licensed under CC BY

For patients receiving PBO (n = 4), BRV 50 mg/day (n = 11), and BRV 200 mg/day (n = 16), the median time from administration of the first dose to the first onset of drug-related dizziness was 1.5, 0, and 0 days, respectively (mean 2.8, 1.6, and 0.3 days). For patients receiving PBO, BRV 50 mg/day, and BRV 200 mg/day, 3/4 (75.0%), 10/11 (90.9%), and 15/16 (93.8%) patients with drug-related dizziness reported resolved outcomes during the 12-week evaluation period, respectively. Drug-related dizziness was of mild intensity for most of the patients who experienced it (Fig. 1d). Three patients discontinued because of dizziness: one receiving PBO, one receiving BRV 50 mg/day, and one receiving BRV 200 mg/day (0.7% each); all discontinuing during the first week of treatment (Table S2).

The incidence of drug-related dizziness was similar in patients receiving one and two concomitant ASMs in all treatment arms (PBO, 3.0% and 2.4%, respectively; BRV 50 mg/day, 8.0% and 6.9%, respectively; BRV 200 mg/day, 10.2% and 11.1%, respectively; Fig. S1b).

Discussion

Knowing the time to occurrence of TEAEs is of great clinical importance for adapting treatment dosing and managing patients’ expectations. The results from this post hoc analysis of a Phase 3 trial indicated that in Asian adults with FOS (in Thailand, Japan, China, Philippines, Malaysia, Singapore, and Taiwan), most of the TEAEs and drug-related TEAEs (including drug-related somnolence and dizziness) were of mild intensity, did not lead to BRV discontinuation, and had the highest incidence during the first week of adjunctive BRV treatment, which then decreased substantially from week 1 to week 2.

The overall rate of discontinuation due to TEAEs in patients receiving PBO, BRV 50 mg/day, and BRV 200 mg/day was low (3.4%, 1.3%, and 2.7%, respectively), supporting the good tolerability profile of BRV initiated at therapeutic doses from day 1. Discontinuation of BRV due to TEAEs occurred during the first 5 weeks after treatment initiation, indicating that patients who will not be able to tolerate BRV could be identified early after BRV initiation, independent of the dose of BRV that was initiated. Only one patient receiving BRV 200 mg/day discontinued because of somnolence, and three patients (one receiving PBO, one receiving BRV 50 mg/day, and one receiving BRV 200 mg/day) discontinued because of dizziness; all discontinuations due to somnolence or dizziness occurred during the first week of BRV treatment.

The most common drug-related TEAEs during adjunctive BRV treatment were somnolence and dizziness. For patients receiving adjunctive BRV, the onset of drug-related somnolence and dizziness occurred mainly during the first week of treatment, and no onset was observed after week 3. In this analysis, the incidence of drug-related somnolence and dizziness had a similar pattern to that observed in a previous analysis of drug-related CNS effects, with the highest incidence observed during the first week of adjunctive BRV treatment [1]. In this analysis in Asian patients with FOS, the overall tolerability profile of BRV was consistent with previous findings in a predominantly non-Asian patient population from the Phase 3 clinical trials of BRV, and as reported in the labeling [7, 8, 12, 15–17]. The prevalence of drug-related somnolence and dizziness decreased over time. Patients in this trial continued to receive the same dose of BRV that they started at randomization (i.e., in EP0083 no dosage decreases were allowed, only discontinuation due to TEAEs). Therefore, these TEAEs resolved in many patients without any BRV dosage adjustments. In patients receiving BRV, the incidence of drug-related somnolence and dizziness was generally similar in patients receiving one and two concomitant ASMs.

In this trial, BRV was initiated at target dose without titration, which allowed the assessment of whether and how much adaptation and improvement in TEAEs occurred over time, which could not be as easily assessed in clinical trials with dose titration. This contrasts with ASMs that require titrations (some up to 10–11 weeks). For those drugs requiring titration, there is the potential for TEAEs reported with lower doses to either worsen or reappear (if previously resolved) when the dose is increased as part of the titration. The results from this analysis show that when BRV is initiated at target dose without titration in Asian adults with FOS (in Thailand, Japan, China, Philippines, Malaysia, Singapore, and Taiwan), TEAEs and drug-related TEAEs occurred early and substantially habituated over several weeks; this can help inform patient expectations after initiating BRV (i.e., that new adverse events are less likely to arise later on, unless a new ASM is added or the BRV dose is altered). The clinician can also more quickly determine whether a patient is tolerating BRV or not and, if needed, adapt the treatment regimen within a short time frame after BRV initiation.

These data should be interpreted with caution because this was a post hoc analysis of prior data that had not been powered for these comparisons, and outcomes were exploratory. In addition, the trial only had a short evaluation period of 12 weeks. Future prospective studies could provide further useful information on the time course and progression of TEAEs in adult Asian patients with FOS receiving ASM therapy.

Conclusion

This post hoc analysis indicated that in Asian adults with FOS (in Thailand, Japan, China, Philippines, Malaysia, Singapore, and Taiwan), adjunctive BRV had a favorable tolerability profile when initiated at a therapeutic dose without titration (even at an initial dose of 200 mg/day). Most TEAEs and drug-related TEAEs were mild in intensity. Discontinuations due to TEAEs were similar in patients receiving adjunctive BRV compared with PBO and occurred during the first 5 weeks of BRV treatment. The incidence of drug-related TEAEs, including somnolence and dizziness, was highest during the first week of adjunctive BRV treatment and substantially decreased by week 2. Additionally, no new-onset drug-related somnolence or dizziness was reported in patients on BRV after 3 weeks of treatment. These data provide further information on the tolerability profile of BRV when initiated at a therapeutic dose and could help inform patient monitoring and treatment decisions and manage patient and caregiver treatment expectations.

Supplementary Information

Below is the link to the electronic supplementary material.