Eslicarbazepine Acetate Dose and ADRs Across Weight Groups Examined
Individual TEAE did not increase with higher modal daily dose of eslicarbazepine acetate in pediatric patients with focal seizures.
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NEW ORLEANS — Incidence of overall or individual treatment-emergent adverse events (TEAE) did not increase with higher modal daily dose of eslicarbazepine acetate in pediatric patients with focal seizures. Analyses of Study 208 (Part 1; ClinicalTrials.gov Identifier: NCT01527513) and Study 305 (Part 1; ClinicalTrials.gov Identifier: NCT00988156) were presented at the 72nd Annual Meeting of the American Epilepsy Society, held November 30–December 4, 2018.
Study 208 was a phase 2, 12-week, randomized, double-blind, placebo-controlled trial evaluated once-daily eslicarbazepine acetate as adjunctive therapy in children aged 6 to 16 years with focal seizures refractory to prior 1-2 antiepileptic drug (AED) therapy.
Study 305 was a phase 3, 18-week, randomized, double-blind, placebo-controlled study evaluating once-daily eslicarbazepine acetate as adjunctive therapy in children aged 2 to 18 years with focal seizure refractory to prior 1-2 AED therapy.
Pooled data of patients aged 4-17 years (N=362) were analyzed for occurrences of investigator-reported TEAEs based on modal daily eslicarbazepine acetate dose category (below low, low, high, and above high) and weight group (11-21 kg, 22-31 kg, 32-38 kg, and >38 kg).
The majority of the safety population were Caucasian (eslicarbazepine acetate: 97%; placebo 94%) and median age was 11 years in the eslicarbazepine acetate group and 10 years in the placebo group. Data showed a higher overall TEAE incidence with eslicarbazepine acetate vs placebo across all weight groups.
Incidence of TEAEs was lower with the above high eslicarbazepine acetate dose compared with placebo across all weight groups (11-21 kg: 2% vs 18%; 22-31 kg: 8% vs 22%; 32-38 kg: 8% vs 18%; >38 kg: 0% vs 47%).
"There was no clear relationship between patient weight and the overall incidence of TEAEs in any modal [eslicarbazepine acetate] dosing category," added lead author Jesus E Pina-Garza, from Centennial Children's Hospital, TriStar Children's Specialists, Nashville, TN.
Regarding individual TEAE incidence across weight groups, study authors did not find a dose-response in any weight group for the 6 most commonly reported events associated with eslicarbazepine acetate: headache, somnolence, vomiting, nasopharyngitis, pyrexia, and focal seizure.
Researchers concluded that "when assessing tolerability according to modal daily [eslicarbazepine acetate] dose category in four groups of children (aged 4-17 years, with focal seizures) defined by patient weight, neither overall TEAE incidence, nor incidences of the most common individual TEAEs, increased with increasing modal daily dose."
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Pina-Garza JE, Wolf SM, McGoldrick P, et al. Relationship betweeen adverse event incidence and eslicarbazepine acetate (esl) dose across weight groups in clinical trials of adjunctive esl in children. Presented at: AES 2018; November 30-December 4, 2018; New Orleans, LA. Poster 2.239.