To validate FDA-approved dosing recommendation for once daily darunavir/ritonavir in children 6-12 years old

Phase 1

Conditions: HIV infected children treated with darunavir
MedDRA version: 19.0Level: LLTClassification code 10068341Term: HIV-1 infectionSystem Organ Class: 10021881 - Infections and infestations
MedDRA version: 19.0Level: PTClassification code 10020161Term: HIV infectionSystem Organ Class: 10021881 - Infections and infestations
Therapeutic area: Diseases [C] - Virus Diseases [C02]

Registration Number: EUCTR2014-001111-39-NL

Lead Sponsor: Radboud University Nijmegen Medical Center

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: Not specified

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
Are the trial subjects under 18? yes
Number of subjects for this age range: 12
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range 0
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range 0

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.

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To validate FDA-approved dosing recommendation for once daily DRV/r in children 6-12 years old. This will be done by evaluating the pharmacokinetics of DRV/r given once daily (according to FDA dosing guideline) to children from 6 – 12 years;Secondary Objective: •To determine whether adequate exposure to DRV is attained when DRV/r is dosed once daily when compared to twice daily in children aged 6-12 years.<br>•To determine the safety of DRV/r once daily in children 6 – 12 years of age.<br>•Child and carers acceptability of once-daily DRV compared to alternative treatment regime at day of PK assessment.<br>;Primary end point(s): Area under the curve over one dosing interval (24 hours) of darunavir;Timepoint(s) of evaluation of this end point: Day of PK assessment (day 1)

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): 1. Comparison target exposure in adults (geometric mean AUC0-24: 89.7 mg*h/L)<br>2. Explore, quantify and describe the occurrence of side effects of darunavir once daily<br>3. Explore acceptability of once-daily darunavir.;Timepoint(s) of evaluation of this end point: Day of PK assessment (day 1)