Safety and Tolerability of Adjunctive Brivaracetam in Pediatric Patients?
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ABSTRACT:
SUBMITTER: Liu E
PROVIDER: S-EPMC6682562 | biostudies-literature | 2019 Aug
REPOSITORIES: biostudies-literature
Publications
Safety and Tolerability of Adjunctive Brivaracetam in Pediatric Patients < 16 Years with Epilepsy: An Open-Label Trial.
Liu Edwin E Dilley Deanne D McDonough Belinda B Stockis Armel A Daniels Tony T
Paediatric drugs 20190801 4
<h4>Objective</h4>This trial evaluated the short-term safety and tolerability, steady-state pharmacokinetics, and preliminary efficacy of brivaracetam oral solution in children aged 1 month to < 16 years with epilepsy.<h4>Methods</h4>This was a phase IIa, open-label, single-arm, fixed three-step dose escalation trial of 3-weeks duration (N01263; NCT00422422). Patients were taking one to three concomitant antiepileptic drugs. Brivaracetam oral solution dosage, in two divided daily doses, was incr ...[more]
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Project description:PurposeThe aims of the study were to develop a population pharmacokinetic model of orally administered brivaracetam in paediatric patients and to provide dosing suggestions.MethodsAnalysis included 600 brivaracetam plasma concentrations from a phase 2a study (NCT00422422; N01263) in 96 paediatric patients with epilepsy aged 1 month to 16 years, taking one to three concomitant antiepileptic drugs (AEDs). Pharmacokinetic analysis was performed using non-linear mixed effects modelling, and a stepwise covariate search was used to determine factors influencing brivaracetam clearance. Simulations were performed to investigate dosing regimens.ResultsThe final model consisted of first-order absorption, single compartment distribution and first-order elimination components with allometric scaling of clearance and volume using lean body weight and fixed allometric exponents. Co-administration with phenobarbital or carbamazepine was associated with a 29% (95%CI 17%/39%) and 32% (22%/42%) decrease in exposure, respectively. Co-administration with valproate was associated with an 11% (1%/23%) increase in exposure. Simulations demonstrated that the majority of children were predicted to have an exposure similar to that in adults, using an age-independent dosing regimen of 2.0 mg/kg bid with a maximum of 100 mg bid for body weight >50 kg.ConclusionsA paediatric dose adaptation of 2.0 mg/kg twice daily with a maximum of 100 mg twice daily for body weight >50 kg is predicted to ensure steady-state plasma concentrations in the same range as in adult patients receiving 100 mg twice daily (highest recommended dose). Data suggest no need to change brivaracetam dosing when used concomitantly with carbamazepine, phenobarbital or valproate.
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