Abstracts

Rationale:
Eslicarbazepine acetate (ESL) is a once-daily, oral antiseizure drug, which has shown to be safe and well-tolerated.1 We aim to evaluate and compare ESL safety profile, in paediatric patients (4-18 years-old) with focal-onset seizures, observed in clinical trials (CTs) versus the profile observed in post-marketing surveillance (PMS) data for a period of 3 years.
Method:
Data was collected from double-blind and open-label CTs: BIA-2093-208 (Part I-III), BIA-2093-305 (Part I-V) and PMS data was retrieved during the period from December 8th, 2016 to September 30th, 2019. Adverse events (AEs) were coded according to the Medical Dictionary for Regulatory Activities (MedDRA) and assessed by causality and seriousness. Two groups were created for the analysis: I (4-10 years old) and II (11-18 years old). Results  In the overall paediatric population, a total of 2158 AEs were reported in CTs (1105 from Group I and 1053 from Group II); 112 (5.2%) assessed as serious (64 from Group I and 48 from Group II). 1719 (79.7%) were considered not related to ESL and 439 (20.3%) related to ESL (272 possibly; 147 probably; 20 definitely). 264 AEs were reported during 3 years of PMS (72 from Group I and 192 from Group II), 84 (31.8%) considered serious (15 from Group I and 69 from Group II). Most of these (n=208; 78.8%) were considered related to ESL (196 possibly; 12 probably).   From CTs data (group I) the System Organ Class (SOC) Infections and Infestations was the most representative (36.9%), followed by SOC Nervous System Disorders (16.8%) and SOC Gastrointestinal Disorders (10.8%). Most frequently reported AEs: convulsion (n=79; 7.1%); nasopharyngitis (n=59; 5.3%) and vomiting (n=56; 5.1%). Most frequent drug related AEs: somnolence and diplopia (n=23; 2.1%); vomiting (n=22; 2.0%) and convulsion (n=19; 1.7%). From PMS (group I), SOC Nervous System Disorders was the most representative (20.8%), followed by SOC Injury, Poisoning and Procedural Complications (18.1%) and SOC Skin and Subcutaneous Tissue Disorders (16.7%). Most frequently reported AEs: seizure (n=7; 9.7%); rash (n=3; 4.2%) and somnolence, dermatitis allergic, hyponatraemia and aggression (n=2; 2.8%, each). From CTs data (group II) SOC Infections and Infestations was the most representative (24.9%), followed by SOC Nervous System Disorders (20.9%) and SOC Gastrointestinal Disorders (10.5%). Most frequently reported AEs: headache (n=71; 6.7%); pyrexia (n=45; 4.2%); nasopharyngitis (n=43; 4.1%) and convulsion (n=36; 3.4%). Most frequent related AEs: somnolence (n=24; 2.3%); diplopia (n=18; 1.7%) and dizziness (n=13; 1.2%). From PMS (group II), SOC Nervous System Disorders was the most representative (29.2%), followed by SOC Injury, Poisoning and Procedural Complications (17.8%) and SOC Psychiatric Disorders (14.1%). Most frequently reported AEs: seizure (n=24; 12.5%); hyponatraemia (n=7; 3.6%); dizziness (n=5; 2.6%) and rash (n=4; 2.1%).
Conclusion:
ESL was well tolerated, with no new safety signals identified during PMS, reinforcing the positive benefit-risk profile observed during the clinical development in paediatric population.
Funding:
:Bial – Portela & Cª, S.A., Coronado, Portugal