IMPAACT P1058A: Pharmacokinetic Effects of New Antiretroviral Drugs on Children, Adolescents and Young Adults

NCT ID: NCT00977756

Last Updated: 2015-08-07

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

Total Enrollment

168 participants

Study Classification

OBSERVATIONAL

Study Start Date

2002-08-31

Study Completion Date

2014-03-31

Brief Summary

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This study will examine drug and body interactions in children receiving anti-HIV treatment regimens using new medications. Drug regimens to be examined will feature the medications raltegravir (RAL), maraviroc (MVC), and etravirine (ETV). These drugs will not be provided through the study.

Detailed Description

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Antiretroviral (ARV) medication regimens for children, adolescents and young adults are often prescribed based on drug resistance because of previous treatment history. In order to find an effective regimen, clinicians must often turn to newer drugs before they have been fully tested in adolescent or pediatric clinical trials. One of the first steps in testing these drugs is to assess the drug pharmacokinetics (PK), or interaction between drugs and body. This study, a follow-on protocol to the International Maternal Pediatric Adolescent AIDS Clinical Trials Group (IMPAACT) P1058 study, will test children, adolescents and young adults who have already been prescribed treatment regimens with new drugs. The study will examine the PK of medication combinations featuring raltegravir, a new drug in the new ARV class of entry inhibitors (EIs); maraviroc, a new drug in the new class of fusion inhibitors (FIs); and etravirine, a new drug in the class of non-nucleoside reverse transcriptase inhibitors (NNRTIs). Older medications may also be used to complete these regimens.

Participation in this study will last between 1 and 7 weeks and involve at least two clinic visits. The first is a screening and entry visit at which a medical history will be taken and a physical exam and blood test will be completed. The second visit will measure PK of the medications. During this visit, participants will complete the same measures as before-medical history, physical exam, blood test-and then be given a dose of their anti-HIV medication regimen. After receiving the medications, participants will be monitored and give blood samples after 1, 2, 4, 6, 8, and 12 hours. For Groups G, H, I, J, K and L an intensive 12-hour PK study will be scheduled after at least 30 days on the combination of interest. For all Groups, the intensive 12-hour PK study should be performed within 35 days (5 weeks) of screening/entry evaluations. Medications will not be provided through this study.

Results of the 12-hour medication monitoring tests will be delivered to participants' physicians within 6 weeks. If, based on these results, a physician decides to change the dosage of a participant's medication, that participant may be asked to complete a second PK visit. Participants must have received the revised dose for at least 14 days before the PK study can be repeated.

Conditions

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HIV Infections

Study Design

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Observational Model Type

COHORT

Study Time Perspective

PROSPECTIVE

Study Groups

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Group G

Participants will receive a medication regimen including RAL + ATV + RTV.

Raltegravir (RAL)

Intervention Type DRUG

400 mg twice daily (BID)

Atazanavir (ATV)

Intervention Type DRUG

300 mg daily

Ritonavir (RTV)

Intervention Type DRUG

100 mg daily, dosing by weight in Group I

Group H

Participants will receive a medication regimen including RAL + TDF.

Raltegravir (RAL)

Intervention Type DRUG

400 mg twice daily (BID)

Tenofovir (TDF)

Intervention Type DRUG

300 mg daily

Group I

Participants will receive a medication regimen including ETV + DRV + RTV.

Ritonavir (RTV)

Intervention Type DRUG

100 mg daily, dosing by weight in Group I

Etravirine (ETV)

Intervention Type DRUG

200 mg BID

Darunavir (DRV)

Intervention Type DRUG

Dosing by weight

Group J

Participants will receive a medication regimen including MVC + ATV + RTV.

Atazanavir (ATV)

Intervention Type DRUG

300 mg daily

Ritonavir (RTV)

Intervention Type DRUG

100 mg daily, dosing by weight in Group I

Maraviroc (MVC)

Intervention Type DRUG

150 mg BID in groups J and K; 600 mg BID in group L

Group K

Participants will receive a medication regimen including MVC + LPV + RTV.

Ritonavir (RTV)

Intervention Type DRUG

100 mg daily, dosing by weight in Group I

Maraviroc (MVC)

Intervention Type DRUG

150 mg BID in groups J and K; 600 mg BID in group L

Lopinavir/ritonavir (LPV/r)

Intervention Type DRUG

Coformulation of 400 mg lopinavir and 100 mg ritonavir, taken twice daily

Group L

Participants will receive a medication regimen including MVC + RAL + ETV.

Raltegravir (RAL)

Intervention Type DRUG

400 mg twice daily (BID)

Etravirine (ETV)

Intervention Type DRUG

200 mg BID

Maraviroc (MVC)

Intervention Type DRUG

150 mg BID in groups J and K; 600 mg BID in group L

Arm M

Participants will receive a medication regimen of DRV

No interventions assigned to this group

Arm N

Participants will receive a medication regimen of DRV

No interventions assigned to this group

Arm O

Participants will receive a medication regimen of unboosted ATV

No interventions assigned to this group

Arm P

Participants will receive a medication regimen of RPV

No interventions assigned to this group

Arm Q

Participants will receive a medication regimen of RPV

No interventions assigned to this group

Interventions

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Raltegravir (RAL)

400 mg twice daily (BID)

Intervention Type DRUG

Atazanavir (ATV)

300 mg daily

Intervention Type DRUG

Ritonavir (RTV)

100 mg daily, dosing by weight in Group I

Intervention Type DRUG

Tenofovir (TDF)

300 mg daily

Intervention Type DRUG

Etravirine (ETV)

200 mg BID

Intervention Type DRUG

Darunavir (DRV)

Dosing by weight

Intervention Type DRUG

Maraviroc (MVC)

150 mg BID in groups J and K; 600 mg BID in group L

Intervention Type DRUG

Lopinavir/ritonavir (LPV/r)

Coformulation of 400 mg lopinavir and 100 mg ritonavir, taken twice daily

Intervention Type DRUG

Other Intervention Names

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Isentress Reyataz Norvir Viread Intelence Prezista Selzentry Kaletra

Eligibility Criteria

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Inclusion Criteria

* Certain laboratory values received within 5 weeks of the date of the screening or entry evaluations
* HIV infected
* Stable on the specified antiretroviral (ARV) regimen for 30 days prior to screening and entry. ARVs will not be provided through this protocol.
* Prescribed one of the regimens described in the study details by clinician on the basis of clinical need (although the availability of drug levels may have been a factor in clinical decision-making). The decision to initiate the regimen must have been solely that of the prescribing physician.
* On the ARV combination of interest for at least 14 days and within 5 weeks (35 days) of the date of screening results
* Body surface area (BSA) of at least 0.85 m2
* Participants in P1058 Version 1.0 and Version 2.0 who have switched to a regimen specified in the entry criteria are eligible for P1058A.
* Any licensed formulation that achieves these dosages, but without including a disallowed drug, may be used.
* Participants who have enrolled in P1058A (Groups G-L) and who subsequently switch to a different regimen specified in the entry criteria are eligible to re-register to a subsequent step of P1058A (re-consent required)
* Females must agree to use two reliable methods of contraception, one of which must be a barrier method, while taking study medications and for 6 weeks after study testing
* Documentation of presence of an R5-tropic virus at the start of treatment with maraviroc (MVC)

Exclusion Criteria

* Pregnant or breastfeeding
* Hemoglobin level less than 8.5 g/dL
* Clinical evidence of pancreatitis as defined by moderate clinical symptoms
* Treatment with any anti-HIV or non-ARV drug that could interact with drugs under pharmacokinetic (PK) study in the 14 days prior to study entry
* Known allergy, sensitivity, or hypersensitivity to components of two or more study-specified drugs or their formulation
Minimum Eligible Age

6 Years

Maximum Eligible Age

21 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Institute of Allergy and Infectious Diseases (NIAID)

NIH

Sponsor Role collaborator

International Maternal Pediatric Adolescent AIDS Clinical Trials Group

NETWORK

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Jennifer R. King, PharmD

Role: STUDY_CHAIR

University of Alabama at Birmingham

Ram Yogev, MD

Role: STUDY_CHAIR

Northwestern University Feinberg School of Medicine

Locations

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Univ. of Alabama Birmingham NICHD CRS (5096)

Birmingham, Alabama, United States

Site Status

Miller Children's Hospital Long Beach, CA NICHD CRS (5093)

Long Beach, California, United States

Site Status

Usc La Nichd Crs (5048)

Los Angeles, California, United States

Site Status

UCSD Mother, Child & Adolescent HIV Program(4601)

San Diego, California, United States

Site Status

Univ. of California San Francisco NICHD CRS (5091)

San Francisco, California, United States

Site Status

Harbor (UCLA) Medical Center NICHD CRS (5045)

Torrance, California, United States

Site Status

Harbor Univeristy of California, Los Angeles (UCLA) Medical Center (603)

Torrance, California, United States

Site Status

Childrens Hospital (U. Colorado, Denver) NICHD CRS (5052)

Denver, Colorado, United States

Site Status

Children's National Medical Center (5015)

Washington D.C., District of Columbia, United States

Site Status

South Florida CDC Ft Lauderdale NICHD CRS (5055)

Fort Lauderdale, Florida, United States

Site Status

University of Miami Pediatric Perinatal HIV/AIDS CRS (4201)

Miami, Florida, United States

Site Status

University of South Florida Tampa (5018)

Tampa, Florida, United States

Site Status

Rush University Cook County (5083)

Chicago, Illinois, United States

Site Status

Chicago Children's CRS (4001)

Chicago, Illinois, United States

Site Status

University of Maryland NICHD CRS (5094)

Baltimore, Maryland, United States

Site Status

Johns Hopkins University NICHD CRS (5092)

Baltimore, Maryland, United States

Site Status

Children's Hospital of Boston NICHD CRS (5009)

Boston, Massachusetts, United States

Site Status

Boston Medical Center Ped. HIV Program NICHD CRS (5011)

Boston, Massachusetts, United States

Site Status

WNE Maternal Pediatric Adolescent AIDS CRS (7301)

Worcester, Massachusetts, United States

Site Status

New Jersey Medical School (NJ) (2802)

Newark, New Jersey, United States

Site Status

New York University NY (5012)

New York, New York, United States

Site Status

Metropolitan Hospital (5003)

New York, New York, United States

Site Status

Columbia IMPAACT CRS (4101)

New York, New York, United States

Site Status

SUNY Stony Brook NICHD CRS (5040)

Stony Brook, New York, United States

Site Status

Bronx-Lebanon Hospital (6901)

The Bronx, New York, United States

Site Status

Jacobi Medical Center Bronx (5013)

The Bronx, New York, United States

Site Status

Duke University Medical Center (DUMC) (4701)

Durham, North Carolina, United States

Site Status

The Children's Hosp. of Philadelphia IMPAACT CRS (6701)

Philadelphia, Pennsylvania, United States

Site Status

St. Jude/UTHSC CRS (6501)

Memphis, Tennessee, United States

Site Status

Texas Children's Hosp. CRS (3801)

Houston, Texas, United States

Site Status

Harborview Medical Center NICHD CRS (5027)

Seattle, Washington, United States

Site Status

Univ of Washington Children's Hospital Seattle (5017)

Seattle, Washington, United States

Site Status

University of Washington NICHD CRS (5029)

Seattle, Washington, United States

Site Status

San Juan City Hosp. PR NICHD CRS (5031)

San Juan, , Puerto Rico

Site Status

University of Puerto Rico Pediatric HIV/AIDS Research (6601)

San Juan, , Puerto Rico

Site Status

Countries

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United States Puerto Rico

References

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Guidelines for the use of antiretroviral agents in pediatric HIV infection. Center for Disease Control and Prevention. MMWR Recomm Rep. 1998 Apr 17;47(RR-4):1-43.

Reference Type BACKGROUND
PMID: 9572665 (View on PubMed)

Iwamoto M, Wenning LA, Petry AS, Laethem M, De Smet M, Kost JT, Breidinger SA, Mangin EC, Azrolan N, Greenberg HE, Haazen W, Stone JA, Gottesdiener KM, Wagner JA. Minimal effects of ritonavir and efavirenz on the pharmacokinetics of raltegravir. Antimicrob Agents Chemother. 2008 Dec;52(12):4338-43. doi: 10.1128/AAC.01543-07. Epub 2008 Oct 6.

Reference Type BACKGROUND
PMID: 18838589 (View on PubMed)

Wenning LA, Friedman EJ, Kost JT, Breidinger SA, Stek JE, Lasseter KC, Gottesdiener KM, Chen J, Teppler H, Wagner JA, Stone JA, Iwamoto M. Lack of a significant drug interaction between raltegravir and tenofovir. Antimicrob Agents Chemother. 2008 Sep;52(9):3253-8. doi: 10.1128/AAC.00005-08. Epub 2008 Jul 14.

Reference Type BACKGROUND
PMID: 18625763 (View on PubMed)

Cressey TR, Hazra R, Wiznia A, Foca M, Jean-Philippe P, Graham B, King JR, Britto P, Carey VJ, Acosta EP, Yogev R; IMPAACT P1058A Team. Pharmacokinetics of Unboosted Atazanavir in Treatment-experienced HIV-infected Children, Adolescents and Young Adults. Pediatr Infect Dis J. 2016 Dec;35(12):1333-1335. doi: 10.1097/INF.0000000000001320.

Reference Type DERIVED
PMID: 27583590 (View on PubMed)

Other Identifiers

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U01AI068632

Identifier Type: NIH

Identifier Source: secondary_id

View Link

IMPAACT P1058A

Identifier Type: -

Identifier Source: org_study_id

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