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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
International Maternal Pediatric Adolescent AIDS Clinical Trials Group
ClinicalTrials.gov Identifier:
NCT00977756
First received: September 15, 2009
Last updated: March 20, 2014
Last verified: March 2014

September 15, 2009
March 20, 2014
August 2002
December 2015   (final data collection date for 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 ] [ Designated as safety issue: No ]
  • Steady state PK of etravirine administered to older children, adolescents and young adults [ Time Frame: Measured at baseline and 1, 2, 4, 6, 8, and 12 hours after dosing ] [ Designated as safety issue: No ]
  • Steady state PK of maraviroc administered in combination with atazanavir/ritonavir or lopinavir/ritonavir to older children, adolescents and young adults [ Time Frame: Measured at baseline and 1, 2, 4, 6, 8, and 12 hours after dosing ] [ Designated as safety issue: No ]
  • 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 [ Time Frame: Measured at baseline and 1, 2, 4, 6, 8, and 12 hours after dosing ] [ Designated as safety issue: No ]
  • Steady state pharmacokinetics 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 ] [ Designated as safety issue: No ]
  • Steady state pharmacokinetics of etravirine administered to older children, adolescents and young adults [ Time Frame: Measured at baseline and 1, 2, 4, 6, 8, and 12 hours after dosing ] [ Designated as safety issue: No ]
  • Steady state pharmacokinetics of maraviroc administered in combination with atazanavir/ritonavir or lopinavir/ritonavir to older children, adolescents and young adults [ Time Frame: Measured at baseline and 1, 2, 4, 6, 8, and 12 hours after dosing ] [ Designated as safety issue: No ]
  • Steady state pharmacokinetics of maraviroc (600 mg BID) given in combination with raltegravir and etravirine (a PI sparing regimen) to older children, adolescents and young adults [ Time Frame: Measured at baseline and 1, 2, 4, 6, 8, and 12 hours after dosing ] [ Designated as safety issue: No ]
Complete list of historical versions of study NCT00977756 on ClinicalTrials.gov Archive Site
  • Relationship between Tanner stage and the PK of the regimens of interest in children and adolescents [ Time Frame: Measured at baseline and 1, 2, 4, 6, 8, and 12 hours after dosing ] [ Designated as safety issue: No ]
  • Relationships between the PK parameters and polymorphisms that may affect the antiretrovirals (ARVs) of interest in older children, adolescents and young adults [ Time Frame: Measured at baseline and 1, 2, 4, 6, 8, and 12 hours after dosing ] [ Designated as safety issue: No ]
  • Adverse events associated with the ARVs of interest [ Time Frame: Measured throughout ] [ Designated as safety issue: Yes ]
  • Steady state PK of darunavir/ritonavir administered to older children, adolescents and young adults [ Time Frame: Measured at baseline and 1, 2, 4, 6, 8, and 12 hours after dosing ] [ Designated as safety issue: No ]
  • Relationship between Tanner stage and the pharmacokinetics of the regimens of interest in children and adolescents [ Time Frame: Measured at baseline and 1, 2, 4, 6, 8, and 12 hours after dosing ] [ Designated as safety issue: No ]
  • Relationships between the pharmacokinetic parameters and polymorphisms that may affect the antiretrovirals of interest in older children, adolescents and young adults [ Time Frame: Measured at baseline and 1, 2, 4, 6, 8, and 12 hours after dosing ] [ Designated as safety issue: No ]
  • Adverse events associated with the antiretrovirals of interest [ Time Frame: Measured throughout ] [ Designated as safety issue: Yes ]
  • Steady state pharmacokinetics of darunavir/ritonavir administered to older children, adolescents and young adults [ Time Frame: Measured at baseline and 1, 2, 4, 6, 8, and 12 hours after dosing ] [ Designated as safety issue: No ]
Not Provided
Not Provided
 
Pharmacokinetic Effects of New Antiretroviral Drugs on Children, Adolescents and Young Adults
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.

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.

Observational
Observational Model: Cohort
Time Perspective: Prospective
Not Provided
Retention:   Samples With DNA
Description:

Blood samples

Non-Probability Sample

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.

HIV Infections
  • Drug: Raltegravir (RAL)
    400 mg twice daily (BID)
    Other Name: Isentress
  • Drug: Atazanavir (ATV)
    300 mg daily
    Other Name: Reyataz
  • Drug: Ritonavir (RTV)
    100 mg daily, dosing by weight in Group I
    Other Name: Norvir
  • Drug: Tenofovir (TDF)
    300 mg daily
    Other Name: Viread
  • Drug: Etravirine (ETV)
    200 mg BID
    Other Name: Intelence
  • Drug: Darunavir (DRV)
    Dosing by weight
    Other Name: Prezista
  • Drug: Maraviroc (MVC)
    150 mg BID in groups J and K; 600 mg BID in group L
    Other Name: Selzentry
  • Drug: Lopinavir/ritonavir (LPV/r)
    Coformulation of 400 mg lopinavir and 100 mg ritonavir, taken twice daily
    Other Name: Kaletra
  • Group G
    Participants will receive a medication regimen including RAL + ATV + RTV.
    Interventions:
    • Drug: Raltegravir (RAL)
    • Drug: Atazanavir (ATV)
    • Drug: Ritonavir (RTV)
  • Group H
    Participants will receive a medication regimen including RAL + TDF.
    Interventions:
    • Drug: Raltegravir (RAL)
    • Drug: Tenofovir (TDF)
  • Group I
    Participants will receive a medication regimen including ETV + DRV + RTV.
    Interventions:
    • Drug: Ritonavir (RTV)
    • Drug: Etravirine (ETV)
    • Drug: Darunavir (DRV)
  • Group J
    Participants will receive a medication regimen including MVC + ATV + RTV.
    Interventions:
    • Drug: Atazanavir (ATV)
    • Drug: Ritonavir (RTV)
    • Drug: Maraviroc (MVC)
  • Group K
    Participants will receive a medication regimen including MVC + LPV + RTV.
    Interventions:
    • Drug: Ritonavir (RTV)
    • Drug: Maraviroc (MVC)
    • Drug: Lopinavir/ritonavir (LPV/r)
  • Group L
    Participants will receive a medication regimen including MVC + RAL + ETV.
    Interventions:
    • Drug: Raltegravir (RAL)
    • Drug: Etravirine (ETV)
    • Drug: Maraviroc (MVC)
  • Arm M
    Participants will receive a medication regimen of DRV
  • Arm N
    Participants will receive a medication regimen of DRV
  • Arm O
    Participants will receive a medication regimen of unboosted ATV
  • Arm P
    Participants will receive a medication regimen of RPV
  • Arm Q
    Participants will receive a medication regimen of RPV

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
200
May 2016
December 2015   (final data collection date for primary outcome measure)

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
Both
6 Years to 21 Years
No
Contact information is only displayed when the study is recruiting subjects
United States,   Puerto Rico
 
NCT00977756
IMPAACT P1058A, U01AI068632
No
International Maternal Pediatric Adolescent AIDS Clinical Trials Group
International Maternal Pediatric Adolescent AIDS Clinical Trials Group
National Institute of Allergy and Infectious Diseases (NIAID)
Study Chair: Jennifer R. King, PharmD University of Alabama at Birmingham
Study Chair: Ram Yogev, MD Northwestern University Feinberg School of Medicine
International Maternal Pediatric Adolescent AIDS Clinical Trials Group
March 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP