Pharmacokinetics of Once Daily Darunavir/Ritonavir in HIV-infected Children

Human Immunodeficiency Virus Clinical Trial

— DAPHNE  

Official title:

Once Daily Darunavir/Ritonavir in HIV-infected Children 6-12 Years Old: a Pharmacokinetic Validation of Model Based Dosing Recommendations

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02285478
• Other study ID #: UMCN-AKF 13.03
• Status: Completed
• Start date: March 2015
• Est. completion date: July 2016

Study information

• Verified date: December 2020
• Source: Radboud University
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Darunavir/ritonavir is one of the preferred antiretroviral agents as part of combination antiretroviral therapy for treatment of HIV-infected adults according to international guidelines. For children 3-12 years old, FDA has approved once daily dosing of darunavir/ritonavir. Dosing recommendations for children 6-12 years old have been approved based on a modelling and simulation procedure by the company.

This pharmacokinetic study is designed to validate the proposed dosing recommendation for once daily darunavir/ritonavir in HIV-infected children aged 6-12 years old.

Description:

The EMA and FDA recommended weight band dosing for once daily DRV/r dosing in children 3 -12 years of age has been derived from pharmacokinetic modelling. Results from population pharmacokinetic modelling and simulation in these children predict similar DRV plasma exposures compared to treatment-naïve adults, but has not been formally studied in the target population. Although no clinical trial was conducted to collect exposure-safety data, the predicted exposures from the once daily dosing is supported by exposures observed in a paediatric clinical trial where twice-daily dosing was administered. To validate the weight band based dosing recommendations, we want to evaluate the pharmacokinetics of DRV/r administered once daily, using DRV tablets, in HIV-infected children.

Darunavir/ritonavir is one of the preferred antiretroviral agents as part of combination antiretroviral therapy for treatment of HIV-infected adults according to international guidelines. For children 3-12 years old, FDA has approved once daily dosing of darunavir/ritonavir. Dosing recommendations for children 6-12 years old have been approved based on a modelling and simulation procedure by the company.

This pharmacokinetic study is designed to validate the proposed dosing recommendation for once daily darunavir/ritonavir in HIV-infected children aged 6-12 years old.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 12
• Est. completion date: July 2016
• Est. primary completion date: July 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 6 Years to 12 Years

Eligibility

Inclusion Criteria:

1. Parents/carers are able and willing to sign the informed consent form prior to screening evaluations

2. Subject is HIV infected

3. Subject is at least 6 and less than 12 years at day of screening

4. Subject has a body weight of at least 15kg

5. Subject is able to swallow tablets

6. Subject has an undetectable viral load (<50 copies/mL) for the last 6 months prior to screening (at least 2 measurements)

7. ART regimen consists of darunavir/ritonavir and 2 NRTIs

Exclusion Criteria:

1. Inability to understand the nature and extent of the trial and the procedures required

2. Documented history of sensitivity/idiosyncrasy to darunavir or ritonavir medicinal products or its excipients

3. Relevant history or current condition that might interfere with drug absorption, distribution, metabolism or excretion

4. Abnormal renal or liver function (grade 3 or above)

5. Participation in a drug trial within 60 days prior to the first dose

6. Hemoglobin < 10 g/dL (6.0 mmol/L)

7. Children who have previously failed virologically on a PI containing regimen (where virological failure is defined as two successive HIV-1 RNA results >1,000 c/mL more than 24 weeks after starting cART, i.e. changes for toxicity or convenience are not counted as failure)

8. Acute illness

9. Receiving concomitant therapy except for prophylaxis for opportunistic infections; some treatments may be allowed, but must first be discussed with the principal investigator or project manager.

Related Conditions & MeSH terms

• Acquired Immunodeficiency Syndrome
• Children
• HIV Infections
• Human Immunodeficiency Virus

Locations

Country	Name	City	State
Netherlands	Radboud University Medical Center	Nijmegen

Sponsors (4)

Lead Sponsor	Collaborator
Radboud University	Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA), Erasmus Medical Center, UMC Utrecht

Country where clinical trial is conducted

Netherlands, 

References & Publications (1)

Bastiaans DET, Geelen SPM, Visser EG, van der Flier M, Vermont CL, Colbers APH, Roukens M, Burger DM, van Rossum AMC; Dutch Paediatric HIV Study Group. Pharmacokinetics, Short-term Safety and Efficacy of the Approved Once-daily Darunavir/Ritonavir Dosing — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The exposure of darunavir, compared to the target exposure (AUC0-24) in adults		24 hours