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

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT00260078
First received: November 29, 2005
Last updated: May 22, 2014
Last verified: May 2014
  Purpose

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 Intervention Phase
HIV Infections
Drug: Atazanavir
Drug: Darunavir
Drug: Efavirenz
Drug: Nevirapine
Drug: Ritonavir
Drug: Tenofovir disoproxil fumarate
Procedure: Pharmacokinetic Study
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Intensive Pharmacokinetic Studies of Antiretroviral Drug Combinations in Children

Resource links provided by NLM:


Further study details as provided by National Institute of Allergy and Infectious Diseases (NIAID):

Primary Outcome Measures:
  • Predosage concentration (C0 and C12) and area under the concentration-time curve (AUC) [ Time Frame: Over the dosing interval ] [ Designated as safety issue: Yes ]

Enrollment: 75
Study Start Date: February 2006
Study Completion Date: April 2009
Primary Completion Date: April 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: D
TDF and EFV or NVP throughout study
Drug: Efavirenz
Dosage dependent on participant
Other Name: EFV
Drug: Nevirapine
Dosage dependent on participant
Other Name: NVP
Drug: Tenofovir disoproxil fumarate
300 mg orally daily
Other Name: TDF
Procedure: Pharmacokinetic Study
Intensive PK study will occur at least once. This will require a 24-hour inpatient visit.
Other Name: PK Study
Experimental: E
TDF and DRV with or without EFV throughout study
Drug: Darunavir
300 mg or 600 mg orally twice daily
Other Name: DRV
Drug: Efavirenz
Dosage dependent on participant
Other Name: EFV
Drug: Ritonavir
50 mg or 100 mg orally twice daily
Other Name: RTV
Drug: Tenofovir disoproxil fumarate
300 mg orally daily
Other Name: TDF
Procedure: Pharmacokinetic Study
Intensive PK study will occur at least once. This will require a 24-hour inpatient visit.
Other Name: 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 Name: ATV
Drug: Efavirenz
Dosage dependent on participant
Other Name: EFV
Drug: Ritonavir
50 mg or 100 mg orally twice daily
Other Name: RTV
Drug: Tenofovir disoproxil fumarate
300 mg orally daily
Other Name: TDF
Procedure: Pharmacokinetic Study
Intensive PK study will occur at least once. This will require a 24-hour inpatient visit.
Other Name: PK Study

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.

  Eligibility

Ages Eligible for Study:   8 Years to 17 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00260078

Locations
United States, California
Usc La Nichd Crs
Alhambra, California, United States, 91803
University of California, UC San Diego CRS
La Jolla, California, United States, 92093-0672
Miller Children's Hosp. Long Beach CA NICHD CRS
Long Beach, California, United States, 90806
Harbor UCLA Medical Ctr. NICHD CRS
Torrance, California, United States, 90502
United States, Connecticut
Connecticut Children's Med. Ctr.
Hartford, Connecticut, United States, 06106
United States, Florida
Pediatric Perinatal HIV Clinical Trials Unit CRS
Miami, Florida, United States, 33136
United States, Illinois
Ann & Robert H. Lurie Children's Hospital of Chicago (LCH) CRS
Chicago, Illinois, United States, 60614-3393
Rush Univ. Cook County Hosp. Chicago NICHD CRS
Chicago, Illinois, United States, 60612
United States, Maryland
Johns Hopkins Univ. Baltimore NICHD CRS
Baltimore, Maryland, United States, 21287
Univ. of Maryland Baltimore NICHD CRS
Baltimore, Maryland, United States, 21201
United States, Massachusetts
Children's Hosp. of Boston NICHD CRS
Boston, Massachusetts, United States, 02115
Baystate Health, Baystate Med. Ctr.
Springfield, Massachusetts, United States, 01199
WNE Maternal Pediatric Adolescent AIDS CRS
Worcester, Massachusetts, United States, 01605
United States, Michigan
Children's Hospital of Michigan NICHD CRS
Detroit, Michigan, United States, 48201
United States, New Jersey
Rutgers - New Jersey Medical School CRS
Newark, New Jersey, United States, 07103
United States, New York
Jacobi Med. Ctr. Bronx NICHD CRS
Bronx, New York, United States, 10461
SUNY Downstate Med. Ctr., Children's Hosp. at Downstate NICHD CRS
Brooklyn, New York, United States, 11203
Nyu Ny Nichd Crs
New York, New York, United States, 10016
United States, North Carolina
DUMC Ped. CRS
Durham, North Carolina, United States, 27710
United States, Tennessee
St. Jude Children's Research Hospital CRS
Memphis, Tennessee, United States, 38105-3678
United States, Washington
Seattle Children's Hospital CRS
Seattle, Washington, United States, 98105
Puerto Rico
San Juan City Hosp. PR NICHD CRS
San Juan, Puerto Rico, 00936
University of Puerto Rico Pediatric HIV/AIDS Research Program CRS
San Juan, Puerto Rico, 00935
Sponsors and Collaborators
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
  More Information

Additional Information:
Publications:
Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT00260078     History of Changes
Other Study ID Numbers: P1058, PACTG 1058, IMPAACT P1058, 10050
Study First Received: November 29, 2005
Last Updated: May 22, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
Treatment Experienced
Pharmacokinetics
PK

Additional relevant MeSH terms:
HIV Infections
Acquired Immunodeficiency Syndrome
Anti-HIV Agents
HIV Protease Inhibitors
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Slow Virus Diseases
Nevirapine
Tenofovir
Tenofovir disoproxil
Efavirenz
Ritonavir
Atazanavir
Darunavir
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Protease Inhibitors

ClinicalTrials.gov processed this record on August 21, 2014