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Population Pharmacokinetics of Antiretroviral in Children (POPARV)

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ClinicalTrials.gov Identifier: NCT03194165
Recruitment Status : Recruiting
First Posted : June 21, 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 antiretroviral drugs in a pediatric population.

The interest of these models is multiple :

  • describe the pharmacokinetics of these drugs in children and explain the inter-individual variability of concentrations through covariates such as weight, age, sex, smoking status, co-treatments and bilirubin;
  • 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
Minor Patient Treated by One or More Antiretroviral and for Which a Blood Test Has Been Performed Biological: Dolutegravir Biological: Raltegravir Biological: Rilpivirine Biological: Nevirapine Biological: Atazanavir Biological: Darunavir Biological: Ritonavir

Detailed Description:

HIV (Human Immunodeficiency Virus) affects 36.7 million people worldwide. Major advances have been made in the discovery of antiretroviral therapy, significantly improving the lives of patients. Although these treatments have been studied and validated in adults, ethical and technical difficulties are hampering research in the pediatric population. However, it is important to know the administration patterns in children, as during its development, multiple physiological changes affect the pharmacokinetics as well as pharmacodynamics of drugs. As a result, the child can not be considered as a small adult and it is not possible to adjust the dosage by taking into account only his weight, age or body surface area.

In France, monitoring of HIV-infected children includes quantification of viral load and may also include pharmacological therapeutic monitoring. In fact, blood samples in children are taken to verify compliance is correct and their plasma concentrations are considered to be effective. Many data are thus generated and not exploited. However, a population pharmacokinetic method would allow us to understand the variability of concentrations existing between these children.

Demographic factors (age, sex, weight, smoking status, etc.) and clinical (bilirubinemia, viral load, genetics, co-treatments, etc.) can be included as covariates to explain inter-individual variability. This method of study is interesting in pediatrics because it has the advantage of being able to include many patients with little sampling per subject. The data used are generally plasma concentrations obtained as a result of sampling performed as part of the therapeutic follow-up of patients.

In clinical practice, the pharmacokinetic model allows to simulate doses and frequencies of administration but also to predict drug interactions. Indeed, patients infected with HIV are often poly-medicated, which represents a risk of drug interactions, especially since many molecules are inducing / inhibiting cytochromes P450.

The main goal is to develop population pharmacokinetic models for antiretroviral drugs in children.

The interest of these models is multiple:

  • describe the pharmacokinetics of these drugs in children and explain the inter-individual variability of concentrations through covariates such as weight, age, sex, smoking status, co-treatments and bilirubin;
  • 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 antiretroviral drugs, accounting for the strength of interactions between them during multiple therapies.
  • Link antiretroviral concentrations to the effects of treatment (decreased viral load) : pharmacokinetic-pharmacodynamic study with concentration / efficacy and concentration / toxicity relationships.
  • The evaluation of preexisting models in the literature and the comparison of our 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 antiretroviral molecule(s) and whose blood dosage of the drug(s) as part of their therapeutic follow-up is available


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Study Type : Observational
Estimated Enrollment : 700 participants
Observational Model: Cohort
Time Perspective: Retrospective
Official Title: Population Pharmacokinetics of Antiretroviral in Children
Actual Study Start Date : June 16, 2017
Estimated Primary Completion Date : June 2019
Estimated Study Completion Date : June 2019

Group/Cohort Intervention/treatment
antiretroviral dosage
titration of Dolutegravir, Raltegravir, Rilpivirine, Nevirapine, Atazanavir, Darunavir, Ritonavir
Biological: Dolutegravir
Dosage

Biological: Raltegravir
Dosage

Biological: Rilpivirine
Dosage

Biological: Nevirapine
Dosage

Biological: Atazanavir
Dosage

Biological: Darunavir
Dosage

Biological: Ritonavir
Dosage




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 : weight, age, sex, smoking status, co-treatments and bilirubin



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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 antiretroviral and for which a blood test has been performed
Criteria

Inclusion Criteria:

  • Children from 0 to 18 years;
  • Treatment with one antiretroviral drug (s) studied (dolutegravir, raltégravir, rilpivirine, nevirapine, atazanavir, darunavir, ritonavir));
  • 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:

  • Concentration too low below the limit of quantification (indicating an absence of medication
  • 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): NCT03194165


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

Locations
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France
Cochin Hospital Recruiting
Paris, France, 75014
Contact: Jean-Marc TRELUYER, MD, PhD    +33 1 58 41 28 84    jean-marc.treluyer@aphp.fr   
Principal Investigator: Jean-Marc TRELUYER, MD, PhD         
Sponsors and Collaborators
Assistance Publique - Hôpitaux de Paris
Investigators
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Principal Investigator: Jean-Marc TRELUYER Assistance Publique - Hôpitaux de Paris

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Responsible Party: Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier: NCT03194165     History of Changes
Other Study ID Numbers: NI17010HLJ
First Posted: June 21, 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

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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:
antiretroviral
children
pharmacokinetics
Additional relevant MeSH terms:
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Ritonavir
Darunavir
Atazanavir Sulfate
Raltegravir Potassium
Dolutegravir
Nevirapine
Rilpivirine
Anti-Retroviral Agents
HIV Protease Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-HIV Agents
Antiviral Agents
Anti-Infective Agents
Cytochrome P-450 CYP3A Inhibitors
Cytochrome P-450 Enzyme Inhibitors
HIV Integrase Inhibitors
Integrase Inhibitors
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors
Cytochrome P-450 CYP3A Inducers
Cytochrome P-450 Enzyme Inducers