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

Purpose

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.

Condition	Intervention
HIV Infections	Drug: Raltegravir (RAL) Drug: Atazanavir (ATV) Drug: Ritonavir (RTV) Drug: Tenofovir (TDF) Drug: Etravirine (ETV) Drug: Darunavir (DRV) Drug: Maraviroc (MVC) Drug: Lopinavir/ritonavir (LPV/r)


Study Type:	Observational
Study Design:	Observational Model: Cohort Time Perspective: Prospective
Official Title:	IMPAACT P1058A: Intensive Pharmacokinetic Studies of New Classes of Antiretroviral Drug Combinations in Children, Adolescents and Young Adults

Resource links provided by NLM:

MedlinePlus related topics: HIV/AIDS

Drug Information available for: Tenofovir Ritonavir Lopinavir Atazanavir Tenofovir Disoproxil Fumarate Darunavir Atazanavir sulfate Etravirine Maraviroc Raltegravir Darunavir ethanolate Raltegravir potassium

U.S. FDA Resources

Further study details as provided by International Maternal Pediatric Adolescent AIDS Clinical Trials Group:

Primary Outcome Measures:

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 ]

Secondary Outcome Measures:

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 ]

Biospecimen Retention: Samples With DNA

Blood samples


Enrollment:	168
Study Start Date:	August 2002
Study Completion Date:	March 2014
Primary Completion Date:	March 2014 (Final data collection date for primary outcome measure)

Groups/Cohorts	Assigned Interventions
Group G Participants will receive a medication regimen including RAL + ATV + RTV.	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
Group H Participants will receive a medication regimen including RAL + TDF.	Drug: Raltegravir (RAL) 400 mg twice daily (BID) Other Name: Isentress Drug: Tenofovir (TDF) 300 mg daily Other Name: Viread
Group I Participants will receive a medication regimen including ETV + DRV + RTV.	Drug: Ritonavir (RTV) 100 mg daily, dosing by weight in Group I Other Name: Norvir Drug: Etravirine (ETV) 200 mg BID Other Name: Intelence Drug: Darunavir (DRV) Dosing by weight Other Name: Prezista
Group J Participants will receive a medication regimen including MVC + ATV + RTV.	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: Maraviroc (MVC) 150 mg BID in groups J and K; 600 mg BID in group L Other Name: Selzentry
Group K Participants will receive a medication regimen including MVC + LPV + RTV.	Drug: Ritonavir (RTV) 100 mg daily, dosing by weight in Group I Other Name: Norvir 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 L Participants will receive a medication regimen including MVC + RAL + ETV.	Drug: Raltegravir (RAL) 400 mg twice daily (BID) Other Name: Isentress Drug: Etravirine (ETV) 200 mg BID Other Name: Intelence Drug: Maraviroc (MVC) 150 mg BID in groups J and K; 600 mg BID in group L Other Name: Selzentry
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

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.

Eligibility


Ages Eligible for Study:	6 Years to 21 Years (Child, Adult)
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No
Sampling Method:	Non-Probability Sample

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.

Criteria

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

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00977756

Show 35 Study Locations

Sponsors and Collaborators

International Maternal Pediatric Adolescent AIDS Clinical Trials Group

National Institute of Allergy and Infectious Diseases (NIAID)

Investigators


Study Chair:	Jennifer R. King, PharmD	University of Alabama at Birmingham
Study Chair:	Ram Yogev, MD	Northwestern University Feinberg School of Medicine

More Information

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. Erratum in: MMWR Morb Mortal Wkly Rep 1998 Apr 24;47(15):315.

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.

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.


Responsible Party:	International Maternal Pediatric Adolescent AIDS Clinical Trials Group
ClinicalTrials.gov Identifier:	NCT00977756 History of Changes
Other Study ID Numbers:	IMPAACT P1058A U01AI068632
Study First Received:	September 15, 2009
Last Updated:	August 5, 2015
Health Authority:	United States: Food and Drug Administration

Keywords provided by International Maternal Pediatric Adolescent AIDS Clinical Trials Group:


Treatment Children Integrase Inhibitors Entry Inhibitors Treatment Experienced

Additional relevant MeSH terms:


HIV Infections Lentivirus Infections Retroviridae Infections RNA Virus Infections Virus Diseases Sexually Transmitted Diseases, Viral Sexually Transmitted Diseases Immunologic Deficiency Syndromes Immune System Diseases Ritonavir Lopinavir Atazanavir Sulfate Darunavir Tenofovir Raltegravir Potassium	Maraviroc Etravirine HIV Protease Inhibitors Protease Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Anti-HIV Agents Anti-Retroviral Agents Antiviral Agents Anti-Infective Agents Cytochrome P-450 CYP3A Inhibitors Cytochrome P-450 Enzyme Inhibitors Reverse Transcriptase Inhibitors Nucleic Acid Synthesis Inhibitors HIV Integrase Inhibitors

ClinicalTrials.gov processed this record on September 23, 2016