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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.

ClinicalTrials.gov Identifier: NCT00260078

Recruitment Status : Completed

First Posted : December 1, 2005

Last Update Posted : July 28, 2016

Sponsor:

Collaborator:

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Information provided by (Responsible Party):

National Institute of Allergy and Infectious Diseases (NIAID)

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
HIV Infections	Drug: Atazanavir Drug: Darunavir Drug: Efavirenz Drug: Nevirapine Drug: Ritonavir Drug: Tenofovir disoproxil fumarate Procedure: Pharmacokinetic Study	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 (Clinical Trial)
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 :	February 2006
Actual Primary Completion Date :	April 2009
Actual Study Completion Date :	April 2009

Resource links provided by the National Library of Medicine

MedlinePlus related topics: HIV/AIDS

U.S. FDA Resources

Arms and Interventions

Arm	Intervention/treatment
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

Outcome Measures

Primary Outcome Measures :

Predosage concentration (C0 and C12) and area under the concentration-time curve (AUC) [ Time Frame: Over the dosing interval ]

Eligibility Criteria

Information from the National Library of Medicine

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, Learn About Clinical Studies.


Ages Eligible for Study:	8 Years to 17 Years (Child)
Sexes Eligible for Study:	All
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): 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
Rush Univ. Cook County Hosp. Chicago NICHD CRS
Chicago, Illinois, United States, 60612
Ann & Robert H. Lurie Children's Hospital of Chicago (LCH) CRS
Chicago, Illinois, United States, 60614-3393
United States, Maryland
Univ. of Maryland Baltimore NICHD CRS
Baltimore, Maryland, United States, 21201
Johns Hopkins Univ. Baltimore NICHD CRS
Baltimore, Maryland, United States, 21287
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
University of Puerto Rico Pediatric HIV/AIDS Research Program CRS
San Juan, Puerto Rico, 00935
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

More Information

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. Epub 2007 Nov 19.

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. Epub 2005 Nov 15.


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 ( Registry Identifier: DAIDS-ES )
First Posted:	December 1, 2005 Key Record Dates
Last Update Posted:	July 28, 2016
Last Verified:	July 2016

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):


Treatment Experienced Pharmacokinetics PK

Additional relevant MeSH terms:


HIV Infections Lentivirus Infections Retroviridae Infections RNA Virus Infections Virus Diseases Sexually Transmitted Diseases, Viral Sexually Transmitted Diseases Immunologic Deficiency Syndromes Immune System Diseases Ritonavir Darunavir Atazanavir Sulfate Tenofovir Nevirapine Efavirenz	HIV Protease Inhibitors Protease Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Anti-HIV Agents Anti-Retroviral Agents Antiviral Agents Anti-Infective Agents Cytochrome P-450 CYP3A Inhibitors Cytochrome P-450 Enzyme Inhibitors Reverse Transcriptase Inhibitors Nucleic Acid Synthesis Inhibitors Cytochrome P-450 CYP2C9 Inhibitors Cytochrome P-450 CYP2C19 Inhibitors Cytochrome P-450 CYP2B6 Inducers

HIV Infections
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Ritonavir
Darunavir
Atazanavir Sulfate
Tenofovir
Nevirapine
Efavirenz

HIV Protease Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Cytochrome P-450 CYP3A Inhibitors
Cytochrome P-450 Enzyme Inhibitors
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors
Cytochrome P-450 CYP2C9 Inhibitors
Cytochrome P-450 CYP2C19 Inhibitors
Cytochrome P-450 CYP2B6 Inducers

To Top