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

Sponsor
National Institute of Allergy and Infectious Diseases (NIAID) (NIH)
Overall Status
Completed
CT.gov ID
NCT00260078
Collaborator
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) (NIH)
75
Enrollment
23
Locations
3
Arms
37.9
Duration (Months)
3.3
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

Brief 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 efavirenz (EFV) or nevirapine (NVP); TDF and darunavir (DRV) with or without EFV; and TDF and ritonavir (RTV) with or without EFV.

Condition or Disease Intervention/Treatment Phase
Phase 1/Phase 2

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.

Study Design

Study Type:
Interventional
Actual Enrollment :
75 participants
Allocation:
Non-Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Intensive Pharmacokinetic Studies of Antiretroviral Drug Combinations in Children
Study Start Date :
Feb 1, 2006
Actual Primary Completion Date :
Apr 1, 2009
Actual Study Completion Date :
Apr 1, 2009

Arms and Interventions

Arm Intervention/Treatment
Experimental: D

TDF and EFV or NVP throughout study

Drug: Efavirenz
Dosage dependent on participant
Other Names:
  • EFV

    • Drug: Nevirapine
    Dosage dependent on participant
    Other Names:
  • NVP

    • Drug: Tenofovir disoproxil fumarate
    300 mg orally daily
    Other Names:
  • TDF

    • Procedure: Pharmacokinetic Study
    Intensive PK study will occur at least once. This will require a 24-hour inpatient visit.
    Other Names:
  • PK Study

    		•
    Experimental: E

    TDF and DRV with or without EFV throughout study

    Drug: Darunavir
    300 mg or 600 mg orally twice daily
    Other Names:
  • DRV

    • Drug: Efavirenz
    Dosage dependent on participant
    Other Names:
  • EFV

    • Drug: Ritonavir
    50 mg or 100 mg orally twice daily
    Other Names:
  • RTV

    • Drug: Tenofovir disoproxil fumarate
    300 mg orally daily
    Other Names:
  • TDF

    • Procedure: Pharmacokinetic Study
    Intensive PK study will occur at least once. This will require a 24-hour inpatient visit.
    Other Names:
  • PK Study

    		•
    Experimental: F

    TDF and ATV and RTV with or without EFV throughout study

    Drug: Atazanavir
    200 mg to 400 mg orally daily
    Other Names:
  • ATV

    • Drug: Efavirenz
    Dosage dependent on participant
    Other Names:
  • EFV

    • Drug: Ritonavir
    50 mg or 100 mg orally twice daily
    Other Names:
  • RTV

    • Drug: Tenofovir disoproxil fumarate
    300 mg orally daily
    Other Names:
  • TDF

    • Procedure: Pharmacokinetic Study
    Intensive PK study will occur at least once. This will require a 24-hour inpatient visit.
    Other Names:
  • PK Study

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Predosage concentration (C0 and C12) and area under the concentration-time curve (AUC) [Over the dosing interval]

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    8 Years to 17 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No

    Note: The original Groups A, B, and C have been removed, and Groups D, E, and F have been added per protocol amendment dated 11/16/07.

    Inclusion Criteria:

    • 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

    Exclusion Criteria:

    • 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

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Usc La Nichd Crs Alhambra California United States 91803
    2 University of California, UC San Diego CRS La Jolla California United States 92093-0672
    3 Miller Children's Hosp. Long Beach CA NICHD CRS Long Beach California United States 90806
    4 Harbor UCLA Medical Ctr. NICHD CRS Torrance California United States 90502
    5 Connecticut Children's Med. Ctr. Hartford Connecticut United States 06106
    6 Pediatric Perinatal HIV Clinical Trials Unit CRS Miami Florida United States 33136
    7 Rush Univ. Cook County Hosp. Chicago NICHD CRS Chicago Illinois United States 60612
    8 Ann & Robert H. Lurie Children's Hospital of Chicago (LCH) CRS Chicago Illinois United States 60614-3393
    9 Univ. of Maryland Baltimore NICHD CRS Baltimore Maryland United States 21201
    10 Johns Hopkins Univ. Baltimore NICHD CRS Baltimore Maryland United States 21287
    11 Children's Hosp. of Boston NICHD CRS Boston Massachusetts United States 02115
    12 Baystate Health, Baystate Med. Ctr. Springfield Massachusetts United States 01199
    13 WNE Maternal Pediatric Adolescent AIDS CRS Worcester Massachusetts United States 01605
    14 Children's Hospital of Michigan NICHD CRS Detroit Michigan United States 48201
    15 Rutgers - New Jersey Medical School CRS Newark New Jersey United States 07103
    16 Jacobi Med. Ctr. Bronx NICHD CRS Bronx New York United States 10461
    17 SUNY Downstate Med. Ctr., Children's Hosp. at Downstate NICHD CRS Brooklyn New York United States 11203
    18 Nyu Ny Nichd Crs New York New York United States 10016
    19 DUMC Ped. CRS Durham North Carolina United States 27710
    20 St. Jude Children's Research Hospital CRS Memphis Tennessee United States 38105-3678
    21 Seattle Children's Hospital CRS Seattle Washington United States 98105
    22 University of Puerto Rico Pediatric HIV/AIDS Research Program CRS San Juan Puerto Rico 00935
    23 San Juan City Hosp. PR NICHD CRS San Juan Puerto Rico 00936

    Sponsors and Collaborators

    • National Institute of Allergy and Infectious Diseases (NIAID)
    • Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

    Investigators

    • Study Chair: Jennifer King, PharmD, Department of Pharmacology and Toxicology, University of Alabama at Birmingham
    • Study Chair: Ram Yogev, MD, Section of Pediatrics and Maternal HIV Infection, Children's Memorial Hospital, Northwestern University Medical School

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    Responsible Party:
    National Institute of Allergy and Infectious Diseases (NIAID)
    ClinicalTrials.gov Identifier:
    NCT00260078
    Other Study ID Numbers:
    • P1058
    • PACTG 1058
    • IMPAACT P1058
    • 10050
    First Posted:
    Dec 1, 2005
    Last Update Posted:
    Nov 9, 2021
    Last Verified:
    Jul 1, 2016
    Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID)
    Treatment Experienced
    Pharmacokinetics
    PK
    Additional relevant MeSH terms:
    HIV Infections
    Ritonavir
    Atazanavir Sulfate
    Darunavir
    Tenofovir
    Nevirapine
    Efavirenz

    Study Results

    No Results Posted as of Nov 9, 2021