Blood Levels of Anti-HIV Drugs Used in Combination Regimens in HIV Infected Children
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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 |
- 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 |
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 LocationsPlease refer to this study by its ClinicalTrials.gov identifier: NCT00260078
| 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 | |
| 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: | December 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:
|
Tenofovir Tenofovir disoproxil Anti-HIV Agents Anti-Infective Agents Anti-Retroviral Agents Antiviral Agents |
Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Nucleic Acid Synthesis Inhibitors Pharmacologic Actions Reverse Transcriptase Inhibitors Therapeutic Uses |
ClinicalTrials.gov processed this record on March 01, 2015