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HIV InfectionsNCT00977756

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

An observational study of HIV Infections, run by International Maternal Pediatric Adolescent AIDS Clinical Trials Group at 35 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

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. Read more about this study

Who is it for?
Ages 6 to 21 years
Conditions the study is for
HIV Infections
What is being tested?
Raltegravir (RAL), Atazanavir (ATV) and Ritonavir (RTV)
How many people
168 participants
Where
35 sitesin 2 countries
Study dates
Aug 2002to Mar 2014
Phase
Observational
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 6 to 21 years
  • All sexes
  • No healthy volunteers
  • Child, Adult

Study population: HIV infected children, adolescents and young adults who are receiving a regimen of antiretroviral drugs prescribed by their physician that includes one of the target combinations.

Who may be able to join

  • 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
Show all 11Show fewer
  • 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)

Who cannot join

  • 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

Trial locations and contacts

35 sites in 2 countries.

35 sites in 2 countries

United States33 sites

  • University of Maryland NICHD CRS (5094)

    Baltimore, Maryland, 21201

  • Johns Hopkins University NICHD CRS (5092)

    Baltimore, Maryland, 21287

  • Univ. of Alabama Birmingham NICHD CRS (5096)

    Birmingham, Alabama, 35294

  • Children's Hospital of Boston NICHD CRS (5009)

    Boston, Massachusetts, 02115

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

    Boston, Massachusetts, 02118

  • Rush University Cook County (5083)

    Chicago, Illinois, 60612

  • Chicago Children's CRS (4001)

    Chicago, Illinois, 60614

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

    Denver, Colorado, 80218-1088

  • Duke University Medical Center (DUMC) (4701)

    Durham, North Carolina, 27710

  • South Florida CDC Ft Lauderdale NICHD CRS (5055)

    Fort Lauderdale, Florida, 33316

  • Texas Children's Hosp. CRS (3801)

    Houston, Texas, 77030

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

    Long Beach, California, 90806

  • Usc La Nichd Crs (5048)

    Los Angeles, California, 90033

  • St. Jude/UTHSC CRS (6501)

    Memphis, Tennessee, 38105

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

    Miami, Florida, 33136

  • New York University NY (5012)

    New York, New York, 10016

  • Metropolitan Hospital (5003)

    New York, New York, 10029

  • Columbia IMPAACT CRS (4101)

    New York, New York, 10032

  • New Jersey Medical School (NJ) (2802)

    Newark, New Jersey, 07103

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

    Philadelphia, Pennsylvania, 19104

  • UCSD Mother, Child & Adolescent HIV Program(4601)

    San Diego, California, 92103

  • Univ. of California San Francisco NICHD CRS (5091)

    San Francisco, California, 94117

  • Harborview Medical Center NICHD CRS (5027)

    Seattle, Washington, 98105

  • Univ of Washington Children's Hospital Seattle (5017)

    Seattle, Washington, 98105

  • University of Washington NICHD CRS (5029)

    Seattle, Washington, 98105

  • SUNY Stony Brook NICHD CRS (5040)

    Stony Brook, New York, 11794

  • University of South Florida Tampa (5018)

    Tampa, Florida, 33620

  • Bronx-Lebanon Hospital (6901)

    The Bronx, New York, 10457

  • Jacobi Medical Center Bronx (5013)

    The Bronx, New York, 10461

  • Harbor (UCLA) Medical Center NICHD CRS (5045)

    Torrance, California, 90509

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

    Torrance, California, 90509

  • Children's National Medical Center (5015)

    Washington D.C., District of Columbia, 20010

  • WNE Maternal Pediatric Adolescent AIDS CRS (7301)

    Worcester, Massachusetts, 01605

Other trials in United States

Puerto Rico2 sites

  • San Juan City Hosp. PR NICHD CRS (5031)

    San Juan, 00927

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

    San Juan, 00936-5067

Other trials in Puerto Rico

About this study

Official title: IMPAACT P1058A: Intensive Pharmacokinetic Studies of New Classes of Antiretroviral Drug Combinations in Children, Adolescents and Young Adults

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.

Read the detailed description

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
HIV Infections
Being tested
Raltegravir (RAL), Atazanavir (ATV), Ritonavir (RTV), Tenofovir (TDF), Etravirine (ETV)
Keywords
Treatment, Children, Integrase Inhibitors, Entry Inhibitors, Treatment Experienced
Medical subject headings
HIV Infections

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Raltegravir (RAL)Drug

    Also called Isentress

    400 mg twice daily (BID)

  • Atazanavir (ATV)Drug

    Also called Reyataz

    300 mg daily

  • Ritonavir (RTV)Drug

    Also called Norvir

    100 mg daily, dosing by weight in Group I

  • Tenofovir (TDF)Drug

    Also called Viread

    300 mg daily

  • Etravirine (ETV)Drug

    Also called Intelence

    200 mg BID

  • Darunavir (DRV)Drug

    Also called Prezista

    Dosing by weight

  • Maraviroc (MVC)Drug

    Also called Selzentry

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

  • Lopinavir/ritonavir (LPV/r)Drug

    Also called Kaletra

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

Study groups in NCT00977756
Study groupRoleWhat they receive
Group GParticipants will receive a medication regimen including RAL + ATV + RTV.
Receives: Drug: Raltegravir (RAL); Drug: Atazanavir (ATV); Drug: Ritonavir (RTV)
Group HParticipants will receive a medication regimen including RAL + TDF.
Receives: Drug: Raltegravir (RAL); Drug: Tenofovir (TDF)
Group IParticipants will receive a medication regimen including ETV + DRV + RTV.
Receives: Drug: Ritonavir (RTV); Drug: Etravirine (ETV); Drug: Darunavir (DRV)
Group JParticipants will receive a medication regimen including MVC + ATV + RTV.
Receives: Drug: Atazanavir (ATV); Drug: Ritonavir (RTV); Drug: Maraviroc (MVC)
Group KParticipants will receive a medication regimen including MVC + LPV + RTV.
Receives: Drug: Ritonavir (RTV); Drug: Maraviroc (MVC); Drug: Lopinavir/ritonavir (LPV/r)
Group LParticipants will receive a medication regimen including MVC + RAL + ETV.
Receives: Drug: Raltegravir (RAL); Drug: Etravirine (ETV); Drug: Maraviroc (MVC)
Arm MParticipants will receive a medication regimen of DRV
Arm NParticipants will receive a medication regimen of DRV
Arm OParticipants will receive a medication regimen of unboosted ATV
Arm PParticipants will receive a medication regimen of RPV
Arm QParticipants will receive a medication regimen of RPV

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Steady state pharmacokinetics (PK) of raltegravir administered in combination with atazanavir/ritonavir or tenofovir or maraviroc/etravirine to older children, adolescents and young adults

    Measured: Measured at baseline and 1, 2, 4, 6, 8, and 12 hours after dosing

  2. Steady state PK of etravirine administered to older children, adolescents and young adults

    Measured: Measured at baseline and 1, 2, 4, 6, 8, and 12 hours after dosing

  3. Steady state PK of maraviroc administered in combination with atazanavir/ritonavir or lopinavir/ritonavir to older children, adolescents and young adults

    Measured: Measured at baseline and 1, 2, 4, 6, 8, and 12 hours after dosing

  4. Steady state PK of maraviroc (600 mg twice daily [BID]) given in combination with raltegravir and etravirine (a protease inhibitor [PI]-sparing regimen) to older children, adolescents and young adults

    Measured: Measured at baseline and 1, 2, 4, 6, 8, and 12 hours after dosing

Secondary outcomes (4)

  1. Relationship between Tanner stage and the PK of the regimens of interest in children and adolescents

    Measured: Measured at baseline and 1, 2, 4, 6, 8, and 12 hours after dosing

  2. Relationships between the PK parameters and polymorphisms that may affect the antiretrovirals (ARVs) of interest in older children, adolescents and young adults

    Measured: Measured at baseline and 1, 2, 4, 6, 8, and 12 hours after dosing

  3. Adverse events associated with the ARVs of interest

    Measured: Measured throughout

  4. Steady state PK of darunavir/ritonavir administered to older children, adolescents and young adults

    Measured: Measured at baseline and 1, 2, 4, 6, 8, and 12 hours after dosing

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted16 Sep 2009 (estimated)
  2. Study startAug 2002
  3. Primary completionMar 2014
  4. Study completionMar 2014

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Observational
Observational model
Cohort
Time perspective
Prospective
Enrolment
168 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00977756
Sponsor's protocol ID
IMPAACT P1058A
Other IDs
U01AI068632
Status last verified
Aug 2015
First submitted
15 Sep 2009
Last updated
7 Aug 2015
Results posted
No
Data monitoring committee
No

Publications

  • 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.

    PubMed 9572665

  • 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.

    PubMed 18838589

  • 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.

    PubMed 18625763

  • 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.

    PubMed 27583590

Questions about this trial

What is this clinical trial studying?

An observational study of HIV Infections, run by International Maternal Pediatric Adolescent AIDS Clinical Trials Group at 35 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 11 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 7 Aug 2015. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 35 sites in United States, Puerto Rico. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Steady state pharmacokinetics (PK) of raltegravir administered in combination with atazanavir/ritonavir or tenofovir or maraviroc/etravirine to older children, adolescents and young adults (time frame: Measured at baseline and 1, 2, 4, 6, 8, and 12 hours after dosing). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00977756, which also lists 4 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Aug 2015.

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