Clinical Trial Details
— Status: Recruiting
Administrative data
| NCT number |
NCT03196466 |
| Other study ID # |
NI17009HLJ |
| Secondary ID |
|
| Status |
Recruiting |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
June 19, 2017 |
| Est. completion date |
June 19, 2026 |
Study information
| Verified date |
June 2023 |
| Source |
Assistance Publique - Hôpitaux de Paris |
| Contact |
Jean-Marc TRELUYER, MD, PhD |
| Phone |
01 58 41 28 84 |
| Email |
jean-marc.treluyer[@]aphp.fr |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational
|
Clinical Trial Summary
The purpose of this study is to develop population pharmacokinetic models for antiepileptic
drugs in a pediatric population.
The interest of these models is multiple:
- describe the pharmacokinetics of these molecules in children and explain the
inter-individual variability of concentrations through covariates such as weight, age,
co-treatments, genetic polymorphisms and renal function;
- estimate maximum, minimum and exposure concentrations from the individual
pharmacokinetic parameters for each patient;
- propose adaptations of doses for certain classes of children (according to age, weight
etc.) and individualize the doses.
Description:
Epilepsy affects about 1% of the population, with a peak incidence in childhood, and
persistent seizures on antiepileptic therapy in approximately 30% of patients. Over the past
two decades, many antiepileptic molecules have emerged, raising the question of their optimal
use, especially in pediatrics, where pharmacokinetics and pharmacodynamics are different from
adults and largely influenced by age and development.
The pharmacokinetics of antiepileptics have been little studied in pediatric populations. In
children, it is important to know if a maturational effect (of age) has to be taken into
account in addition to the physiological effect (of the weight) to adapt the doses. Moreover,
these molecules are often used in combination and lot of enzyme interactions make their use
delicate. All of these factors explain the existence of significant inter-individual
variability in the pediatric population.
The implication of the demographic and medicinal factors mentioned above, as well as the
balance of efficacy / undesirable effects, justify the interest of a pharmacological
monitoring of these drugs in a pediatric population. The use of population pharmacokinetics
is particularly interesting in children because it requires only a small number of samples
per patient and can be used to describe the predominant inter-individual variability in this
population.
The main goal is to develop population pharmacokinetic models for the following antiepileptic
drugs in children: valproic acid, carbamazepine, phenobarbital, phenytoin, levetiracetam,
lamotrigine, topiramate, oxcarbazepine, stiripentol, clobazam, brivaracétam, felbamate,
lacosamide, rufinamide, gabapentine, pregabaline, sultiame, tiagabine, vigabatrine,
mesuximide, primidone, perampanel, ethosuximide, zonisamide and cannabidiol. The interest of
these models is multiple:
- describe the pharmacokinetics of these molecules in children and explain the
interindividual variability of concentrations through covariates such as weight, age,
co-treatments, genetic polymorphisms and renal function;
- estimate maximum, minimum and exposure concentrations from the individual
pharmacokinetic parameters for each patient;
- propose adaptations of doses for certain classes of children (according to age, weight
etc.) and individualize the doses.
The secondary objectives of this work are:
- Build models jointly with several antiepileptic drugs, accounting for the strength of
interactions between them during multiple therapies.
- Link antiepileptic concentrations to the effects of treatment (reduction or cessation of
seizures): pharmacokinetic-pharmacodynamic study with concentration / efficacy and
concentration / toxicity relationships.
- The evaluation of preexisting models in the literature and the comparison of the data
with the results of these models (external validation).
Pharmaco-statistical analysis will be carried out on the retrospective data of patients
treated with one or more antiepileptic molecule (s) and whose blood dosage of the drug(s) as
part of their therapeutic follow-up is available. The study of genetic polymorphisms will be
carried out from available blood samples, collected and stored as part of therapeutic
follow-up of patients.
