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HIV InfectionsPhase 1/2NCT00260078

Blood Levels of Anti-HIV Drugs Used in Combination Regimens in HIV Infected Children

A Phase 1/2 study testing Atazanavir, Darunavir and Efavirenz in people with HIV Infections, run by National Institute of Allergy and Infectious Diseases (NIAID) at 23 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

Limited data exist about combination anti-HIV treatment regimens in children, including how those drugs are cleared by the body in children. The purpose of this study is to measure the blood levels of the following combinations of anti-HIV drugs in HIV infected chilren: tenofovir disoproxil fumurate (TDF) and… Read more about this study

Who is it for?
Ages 8 to 17 years
Conditions the study is for
HIV Infections
What is being tested?
Atazanavir, Darunavir and Efavirenz
Could I receive a placebo?
No, everyone receives an active treatment
How many people
75 participants
Where
23 sitesin 2 countries
Study dates
Feb 2006to Apr 2009
Phase
Phase 1/2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 8 to 17 years
  • All sexes
  • No healthy volunteers
  • Child

Who may be able to join

  • HIV infected
  • Currently receiving or about to initiate one of the following anti-HIV regimens: TDF with EFV or NVP, TDF and DRV/r with or without EFV, or TDF with ATV/r with or without EFV
  • Body surface area at least 0.85 m2
  • Parent or guardian willing and able to provide signed informed consent
  • Willing to use acceptable forms of contraception

Who cannot join

  • Liver disease that may affect the metabolism of study drugs
  • Certain abnormal laboratory values
  • Require certain medications
  • Treatment with any anti-HIV or nonantiretroviral drug that could interact with drugs under PK study in the 14 days prior to study entry
  • Any clinical or laboratory toxicity of Grade 4 or higher at screening. More information on this criterion can be found in the protocol.
  • Pregnant or breastfeeding

Trial locations and contacts

23 sites in 2 countries.

23 sites in 2 countries

United States21 sites
  • Usc La Nichd Crs

    Alhambra, California, 91803

  • Univ. of Maryland Baltimore NICHD CRS

    Baltimore, Maryland, 21201

  • Johns Hopkins Univ. Baltimore NICHD CRS

    Baltimore, Maryland, 21287

  • Children's Hosp. of Boston NICHD CRS

    Boston, Massachusetts, 02115

  • SUNY Downstate Med. Ctr., Children's Hosp. at Downstate NICHD CRS

    Brooklyn, New York, 11203

  • Rush Univ. Cook County Hosp. Chicago NICHD CRS

    Chicago, Illinois, 60612

  • Ann & Robert H. Lurie Children's Hospital of Chicago (LCH) CRS

    Chicago, Illinois, 60614-3393

  • Children's Hospital of Michigan NICHD CRS

    Detroit, Michigan, 48201

  • DUMC Ped. CRS

    Durham, North Carolina, 27710

  • Connecticut Children's Med. Ctr.

    Hartford, Connecticut, 06106

  • University of California, UC San Diego CRS

    La Jolla, California, 92093-0672

  • Miller Children's Hosp. Long Beach CA NICHD CRS

    Long Beach, California, 90806

  • St. Jude Children's Research Hospital CRS

    Memphis, Tennessee, 38105-3678

  • Pediatric Perinatal HIV Clinical Trials Unit CRS

    Miami, Florida, 33136

  • Nyu Ny Nichd Crs

    New York, New York, 10016

  • Rutgers - New Jersey Medical School CRS

    Newark, New Jersey, 07103

  • Seattle Children's Hospital CRS

    Seattle, Washington, 98105

  • Baystate Health, Baystate Med. Ctr.

    Springfield, Massachusetts, 01199

  • Jacobi Med. Ctr. Bronx NICHD CRS

    The Bronx, New York, 10461

  • Harbor UCLA Medical Ctr. NICHD CRS

    Torrance, California, 90502

  • WNE Maternal Pediatric Adolescent AIDS CRS

    Worcester, Massachusetts, 01605

Other trials in United States

Puerto Rico2 sites
  • University of Puerto Rico Pediatric HIV/AIDS Research Program CRS

    San Juan, 00935

  • San Juan City Hosp. PR NICHD CRS

    San Juan, 00936

Other trials in Puerto Rico

About this study

Official title: Intensive Pharmacokinetic Studies of Antiretroviral Drug Combinations in Children

Limited data exist about combination anti-HIV treatment regimens in children, including how those drugs are cleared by the body in children. The purpose of this study is to measure the blood levels of the following combinations of anti-HIV drugs in HIV infected chilren: tenofovir disoproxil fumurate (TDF) and efavirenz (EFV) or nevirapine (NVP); TDF and darunavir (DRV) with or without EFV; and TDF and ritonavir (RTV) with or without EFV.

Read the detailed description

Because all of the available non-nucleoside reverse transcriptase inhibitors (NNRTIs) and protease inhibitors (PIs) are metabolized by and affect hepatic cytochrome enzymes, combinations of two or more of these drugs produce complex pharmacokinetic (PK) interactions. However, little data exist regarding PK of anti-HIV drug combinations in the pediatric population. The purpose of this study is to assess steady-state PK of the following anti-HIV regimens: TDF and EFV or NVP; TDF and DRV with or without EFV; and TDF and RTV with or without EFV. In addition, this study will evaluate how age, length of treatment, adverse effects, and genes affect children's response to different anti-HIV combinations.

This study will last between 1 and 7 weeks. Participants in this study will be grouped based on the treatment regimen they are receiving or about to initiate. There are three groups in this study. Group D participants will receive TDF and EFV or NVP; Group E participants will receive TDF and DRV with or without EFV; and Group F participants will receive TDF and RTV with or without EFV. The inclusion of EFV or NVP will be dependent on each participant's prescribed regimen. Participants within each group will be stratified by age and how long they have been receiving their anti-HIV regimens. Antiretrovirals will not be provided by this study.

Most participants will have two study visits. The first visit will occur at study entry. Medical history, a physical exam, and blood collection will occur. The second visit will occur within 35 days of study entry and will take approximately 24 hours. Blood collection for PK studies, a physical exam, and medical history will be done at this visit. Urine collection will occur at all visits for female participants.

Participants will undergo PK testing at least 14 days after initiating their study regimens. Participants will be given a dose of their anti-HIV medications with food. A blood sample will be taken before dosing. Blood samples will also be taken at 1, 2, 4, 6, 8, 12, and 24 hours after dosing. Participants in Groups E and F may need to repeat PK testing within 6 weeks of initial PK testing at the discretion of the investigator.

Conditions
HIV Infections
Being tested
Atazanavir, Darunavir, Efavirenz, Nevirapine, Ritonavir
Keywords
Treatment Experienced, Pharmacokinetics, PK
Medical subject headings
HIV Infections

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • AtazanavirDrug

    Also called ATV

    200 mg to 400 mg orally daily

  • DarunavirDrug

    Also called DRV

    300 mg or 600 mg orally twice daily

  • EfavirenzDrug

    Also called EFV

    Dosage dependent on participant

  • NevirapineDrug

    Also called NVP

    Dosage dependent on participant

  • RitonavirDrug

    Also called RTV

    50 mg or 100 mg orally twice daily

  • Tenofovir disoproxil fumarateDrug

    Also called TDF

    300 mg orally daily

  • Pharmacokinetic StudyProcedure or surgery

    Also called PK Study

    Intensive PK study will occur at least once. This will require a 24-hour inpatient visit.

Study groups in NCT00260078
Study groupRoleWhat they receive
DExperimentalTDF and EFV or NVP throughout study
Receives: Drug: Efavirenz; Drug: Nevirapine; Drug: Tenofovir disoproxil fumarate; Procedure: Pharmacokinetic Study
EExperimentalTDF and DRV with or without EFV throughout study
Receives: Drug: Darunavir; Drug: Efavirenz; Drug: Ritonavir; Drug: Tenofovir disoproxil fumarate; Procedure: Pharmacokinetic Study
FExperimentalTDF and ATV and RTV with or without EFV throughout study
Receives: Drug: Atazanavir; Drug: Efavirenz; Drug: Ritonavir; Drug: Tenofovir disoproxil fumarate; Procedure: Pharmacokinetic Study

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Predosage concentration (C0 and C12) and area under the concentration-time curve (AUC)

    Measured: Over the dosing interval

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted1 Dec 2005 (estimated)
  2. Study startFeb 2006
  3. Primary completionApr 2009
  4. Study completionApr 2009

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
75 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00260078
Sponsor's protocol ID
P1058
Other IDs
PACTG 1058, IMPAACT P1058, 10050
Status last verified
Jul 2016
First submitted
29 Nov 2005
Last updated
9 Nov 2021
Results posted
No
Data monitoring committee
Yes

Publications

  • Kiser JJ, Fletcher CV, Flynn PM, Cunningham CK, Wilson CM, Kapogiannis BG, Major-Wilson H, Viani RM, Liu NX, Muenz LR, Harris DR, Havens PL; Adolescent Trials Network for HIV/AIDS Interventions. Pharmacokinetics of antiretroviral regimens containing tenofovir disoproxil fumarate and atazanavir-ritonavir in adolescents and young adults with human immunodeficiency virus infection. Antimicrob Agents Chemother. 2008 Feb;52(2):631-7. doi: 10.1128/AAC.00761-07. Epub 2007 Nov 19.

    PubMed 18025112
  • Hazra R, Gafni RI, Maldarelli F, Balis FM, Tullio AN, DeCarlo E, Worrell CJ, Steinberg SM, Flaherty J, Yale K, Kearney BP, Zeichner SL. Tenofovir disoproxil fumarate and an optimized background regimen of antiretroviral agents as salvage therapy for pediatric HIV infection. Pediatrics. 2005 Dec;116(6):e846-54. doi: 10.1542/peds.2005-0975. Epub 2005 Nov 15.

    PubMed 16291735

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Atazanavir, Darunavir and Efavirenz in people with HIV Infections, run by National Institute of Allergy and Infectious Diseases (NIAID) at 23 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 9 Nov 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 23 sites in United States, Puerto Rico. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Predosage concentration (C0 and C12) and area under the concentration-time curve (AUC) (time frame: Over the dosing interval). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00260078, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Nov 2021.

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