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

NCT ID: NCT00260078

Last Updated: 2021-11-09

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1/PHASE2

Total Enrollment

75 participants

Study Classification

INTERVENTIONAL

Study Start Date

2006-02-28

Study Completion Date

2009-04-30

Brief Summary

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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.

Detailed Description

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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

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HIV Infections

Keywords

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Treatment Experienced Pharmacokinetics PK

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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D

TDF and EFV or NVP throughout study

Group Type EXPERIMENTAL

Efavirenz

Intervention Type DRUG

Dosage dependent on participant

Nevirapine

Intervention Type DRUG

Dosage dependent on participant

Tenofovir disoproxil fumarate

Intervention Type DRUG

300 mg orally daily

Pharmacokinetic Study

Intervention Type PROCEDURE

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

E

TDF and DRV with or without EFV throughout study

Group Type EXPERIMENTAL

Darunavir

Intervention Type DRUG

300 mg or 600 mg orally twice daily

Efavirenz

Intervention Type DRUG

Dosage dependent on participant

Ritonavir

Intervention Type DRUG

50 mg or 100 mg orally twice daily

Tenofovir disoproxil fumarate

Intervention Type DRUG

300 mg orally daily

Pharmacokinetic Study

Intervention Type PROCEDURE

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

F

TDF and ATV and RTV with or without EFV throughout study

Group Type EXPERIMENTAL

Atazanavir

Intervention Type DRUG

200 mg to 400 mg orally daily

Efavirenz

Intervention Type DRUG

Dosage dependent on participant

Ritonavir

Intervention Type DRUG

50 mg or 100 mg orally twice daily

Tenofovir disoproxil fumarate

Intervention Type DRUG

300 mg orally daily

Pharmacokinetic Study

Intervention Type PROCEDURE

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

Interventions

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Atazanavir

200 mg to 400 mg orally daily

Intervention Type DRUG

Darunavir

300 mg or 600 mg orally twice daily

Intervention Type DRUG

Efavirenz

Dosage dependent on participant

Intervention Type DRUG

Nevirapine

Dosage dependent on participant

Intervention Type DRUG

Ritonavir

50 mg or 100 mg orally twice daily

Intervention Type DRUG

Tenofovir disoproxil fumarate

300 mg orally daily

Intervention Type DRUG

Pharmacokinetic Study

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

Intervention Type PROCEDURE

Other Intervention Names

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ATV DRV EFV NVP RTV TDF PK Study

Eligibility Criteria

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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
Minimum Eligible Age

8 Years

Maximum Eligible Age

17 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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

NIH

Sponsor Role collaborator

National Institute of Allergy and Infectious Diseases (NIAID)

NIH

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Jennifer King, PharmD

Role: STUDY_CHAIR

Department of Pharmacology and Toxicology, University of Alabama at Birmingham

Ram Yogev, MD

Role: STUDY_CHAIR

Section of Pediatrics and Maternal HIV Infection, Children's Memorial Hospital, Northwestern University Medical School

Locations

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Usc La Nichd Crs

Alhambra, California, United States

Site Status

University of California, UC San Diego CRS

La Jolla, California, United States

Site Status

Miller Children's Hosp. Long Beach CA NICHD CRS

Long Beach, California, United States

Site Status

Harbor UCLA Medical Ctr. NICHD CRS

Torrance, California, United States

Site Status

Connecticut Children's Med. Ctr.

Hartford, Connecticut, United States

Site Status

Pediatric Perinatal HIV Clinical Trials Unit CRS

Miami, Florida, United States

Site Status

Rush Univ. Cook County Hosp. Chicago NICHD CRS

Chicago, Illinois, United States

Site Status

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

Chicago, Illinois, United States

Site Status

Univ. of Maryland Baltimore NICHD CRS

Baltimore, Maryland, United States

Site Status

Johns Hopkins Univ. Baltimore NICHD CRS

Baltimore, Maryland, United States

Site Status

Children's Hosp. of Boston NICHD CRS

Boston, Massachusetts, United States

Site Status

Baystate Health, Baystate Med. Ctr.

Springfield, Massachusetts, United States

Site Status

WNE Maternal Pediatric Adolescent AIDS CRS

Worcester, Massachusetts, United States

Site Status

Children's Hospital of Michigan NICHD CRS

Detroit, Michigan, United States

Site Status

Rutgers - New Jersey Medical School CRS

Newark, New Jersey, United States

Site Status

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

Brooklyn, New York, United States

Site Status

Nyu Ny Nichd Crs

New York, New York, United States

Site Status

Jacobi Med. Ctr. Bronx NICHD CRS

The Bronx, New York, United States

Site Status

DUMC Ped. CRS

Durham, North Carolina, United States

Site Status

St. Jude Children's Research Hospital CRS

Memphis, Tennessee, United States

Site Status

Seattle Children's Hospital CRS

Seattle, Washington, United States

Site Status

University of Puerto Rico Pediatric HIV/AIDS Research Program CRS

San Juan, , Puerto Rico

Site Status

San Juan City Hosp. PR NICHD CRS

San Juan, , Puerto Rico

Site Status

Countries

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United States Puerto Rico

References

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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.

Reference Type BACKGROUND
PMID: 18025112 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 16291735 (View on PubMed)

Other Identifiers

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PACTG 1058

Identifier Type: -

Identifier Source: secondary_id

IMPAACT P1058

Identifier Type: -

Identifier Source: secondary_id

10050

Identifier Type: REGISTRY

Identifier Source: secondary_id

P1058

Identifier Type: -

Identifier Source: org_study_id