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Population Pharmacokinetics of Antiepileptic in Pediatrics (EPIPOP)

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ClinicalTrials.gov Identifier: NCT03196466
Recruitment Status : Recruiting
First Posted : June 22, 2017
Last Update Posted : December 21, 2017
Sponsor:
Information provided by (Responsible Party):
Assistance Publique - Hôpitaux de Paris

Brief 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 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.

Condition or disease Intervention/treatment
Epilepsy Biological: Valproic acid Biological: carbamazepine Biological: phenobarbital Biological: phenytoin Biological: levetiracetam Biological: lamotrigine Biological: topiramate Biological: oxcarbazepine Biological: stiripentol Biological: clobazam

Detailed 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 and clobazam. 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 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


Study Type : Observational
Estimated Enrollment : 1000 participants
Observational Model: Cohort
Time Perspective: Retrospective
Official Title: Population Pharmacokinetics of Antiepileptic in Pediatrics
Actual Study Start Date : June 19, 2017
Estimated Primary Completion Date : June 2019
Estimated Study Completion Date : June 2019

Resource links provided by the National Library of Medicine


Group/Cohort Intervention/treatment
antiepileptics titration
Titration of valproic acid, carbamazepine, phenobarbital, phenytoin, levetiracetam, lamotrigine, topiramate, oxcarbazepine, stiripentol and clobazam
Biological: Valproic acid
titration

Biological: carbamazepine
titration

Biological: phenobarbital
titration

Biological: phenytoin
titration

Biological: levetiracetam
titration

Biological: lamotrigine
titration

Biological: topiramate
titration

Biological: oxcarbazepine
titration

Biological: stiripentol
titration

Biological: clobazam
titration




Primary Outcome Measures :
  1. Volume of distribution [ Time Frame: through study completion, an average of 2 years ]
  2. Absorption constant [ Time Frame: through study completion, an average of 2 years ]
  3. Clearance [ Time Frame: through study completion, an average of 2 years ]

Secondary Outcome Measures :
  1. Composite measure of the inter-individual variability [ Time Frame: through study completion, an average of 2 years ]
    Covariates of inter-individual variability : age, weight, Co-treatments and renal function



Information from the National Library of Medicine

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Ages Eligible for Study:   up to 18 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
Minor patient treated by one or more antiepileptics and for which a blood test has been performed
Criteria

Inclusion Criteria:

  • Children from 0 to 18 years of age with epilepsy;
  • Treatment with one or more antiepileptic drug (s) studied (valproic acid, carbamazepine, phenobarbital, phenytoin, levetiracetam, lamotrigine, topiramate, oxcarbazepine, stiripentol and clobazam);
  • Blood dosage of the drug (s) as part of their therapeutic follow-up in the Pharmacology laboratory of the Cochin hospital between 2007 and 2017

Exclusion Criteria:

  • patient with missing data on time of last drug taking, time of collection, co-treatments and / or dose administered;
  • patient with doubt about compliance

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03196466


Contacts
Contact: Jean-Marc TRELUYER, MD, PhD 01 58 41 28 84 jean-marc.treluyer@aphp.fr
Contact: Elodie HENRY, Master +33 1 44 49 56 66 elodie.henry@aphp.fr

Locations
France
AP-HP Cochin Recruiting
Paris, France, 75014
Contact: Jean-Marc Treluyer, M.D., PhD    + 00 1 58 41 28 85    jean-marc.treluyer@parisdescartes.fr   
Sponsors and Collaborators
Assistance Publique - Hôpitaux de Paris
Investigators
Principal Investigator: Jean-Marc TRELUYER, MD, PhD Assistance Publique - Hôpitaux de Paris

Responsible Party: Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier: NCT03196466     History of Changes
Other Study ID Numbers: NI17009HLJ
First Posted: June 22, 2017    Key Record Dates
Last Update Posted: December 21, 2017
Last Verified: December 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Assistance Publique - Hôpitaux de Paris:
antiepileptics
pharmacokinetics
children

Additional relevant MeSH terms:
Phenytoin
Topiramate
Etiracetam
Lamotrigine
Oxcarbazepine
Clobazam
Stiripentol
Valproic Acid
Carbamazepine
Anticonvulsants
Phenobarbital
Neuroprotective Agents
Protective Agents
Physiological Effects of Drugs
Anti-Obesity Agents
Nootropic Agents
Calcium Channel Blockers
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Excitatory Amino Acid Antagonists
Excitatory Amino Acid Agents
Neurotransmitter Agents
Voltage-Gated Sodium Channel Blockers
Sodium Channel Blockers
Enzyme Inhibitors
GABA Agents
Antimanic Agents
Tranquilizing Agents
Central Nervous System Depressants
Psychotropic Drugs