Clinical trial NCT00977756: IMPAACT P1058A: Pharmacokinetic Effects of New Antiretroviral Drugs on Children, Adolescents and Young Adults
Official title: IMPAACT P1058A: Intensive Pharmacokinetic Studies of New Classes of Antiretroviral Drug Combinations in Children, Adolescents and Young Adults
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: HIV Infections
Keywords: Treatment
Children
Integrase Inhibitors
Entry Inhibitors
Treatment Experienced
Lead sponsor: International Maternal Pediatric Adolescent AIDS Clinical Trials Group
Sponsor class: NETWORK
Collaborators: name: National Institute of Allergy and Infectious Diseases (NIAID)
First posted: 2009-09-16
Enrollment: 168
Sex: ALL
Minimum age (years): 6
Maximum age (years): 21
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
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.

Brief 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.

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 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

Primary outcomes:
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
timeFrame: Measured at baseline and 1, 2, 4, 6, 8, and 12 hours after dosing
measure: Steady state PK of etravirine administered to older children, adolescents and young adults
timeFrame: Measured at baseline and 1, 2, 4, 6, 8, and 12 hours after dosing
measure: Steady state PK of maraviroc administered in combination with atazanavir/ritonavir or lopinavir/ritonavir to older children, adolescents and young adults
timeFrame: Measured at baseline and 1, 2, 4, 6, 8, and 12 hours after dosing
measure: 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
timeFrame: Measured at baseline and 1, 2, 4, 6, 8, and 12 hours after dosing
Secondary outcomes:
measure: Relationship between Tanner stage and the PK of the regimens of interest in children and adolescents
timeFrame: Measured at baseline and 1, 2, 4, 6, 8, and 12 hours after dosing
measure: Relationships between the PK parameters and polymorphisms that may affect the antiretrovirals (ARVs) of interest in older children, adolescents and young adults
timeFrame: Measured at baseline and 1, 2, 4, 6, 8, and 12 hours after dosing
measure: Adverse events associated with the ARVs of interest
timeFrame: Measured throughout
measure: Steady state PK of darunavir/ritonavir administered to older children, adolescents and young adults
timeFrame: Measured at baseline and 1, 2, 4, 6, 8, and 12 hours after dosing
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Univ. of Alabama Birmingham NICHD CRS (5096)
state: Alabama
city: Long Beach
country: United States
facility: Miller Children's Hospital Long Beach, CA NICHD CRS (5093)
state: California
city: Los Angeles
country: United States
facility: Usc La Nichd Crs (5048)
state: California
city: San Diego
country: United States
facility: UCSD Mother, Child & Adolescent HIV Program(4601)
state: California
city: San Francisco,
country: United States
facility: Univ. of California San Francisco NICHD CRS (5091)
state: California
city: Torrance
country: United States
facility: Harbor (UCLA) Medical Center NICHD CRS (5045)
state: California
city: Torrance
country: United States
facility: Harbor Univeristy of California, Los Angeles (UCLA) Medical Center (603)
state: California
city: Denver
country: United States
facility: Childrens Hospital (U. Colorado, Denver) NICHD CRS (5052)
state: Colorado
city: Washington
country: United States
facility: Children's National Medical Center (5015)
state: District of Columbia
city: Fort Lauderdale
country: United States
facility: South Florida CDC Ft Lauderdale NICHD CRS (5055)
state: Florida
city: Miami
country: United States
facility: University of Miami Pediatric Perinatal HIV/AIDS CRS (4201)
state: Florida
city: Tampa
country: United States
facility: University of South Florida Tampa (5018)
state: Florida
city: Chicago
country: United States
facility: Rush University Cook County (5083)
state: Illinois
city: Chicago
country: United States
facility: Chicago Children's CRS (4001)
state: Illinois
city: Baltimore
country: United States
facility: University of Maryland NICHD CRS (5094)
state: Maryland
city: Baltimore
country: United States
facility: Johns Hopkins University NICHD CRS (5092)
state: Maryland
city: Boston
country: United States
facility: Children's Hospital of Boston NICHD CRS (5009)
state: Massachusetts
city: Boston
country: United States
facility: Boston Medical Center Ped. HIV Program NICHD CRS (5011)
state: Massachusetts
city: Worcester
country: United States
facility: WNE Maternal Pediatric Adolescent AIDS CRS (7301)
state: Massachusetts
city: Newark
country: United States
facility: New Jersey Medical School (NJ) (2802)
state: New Jersey
city: Bronx
country: United States
facility: Bronx-Lebanon Hospital (6901)
state: New York
city: Bronx
country: United States
facility: Jacobi Medical Center Bronx (5013)
state: New York
city: New York
country: United States
facility: New York University NY (5012)
state: New York
city: New York
country: United States
facility: Metropolitan Hospital (5003)
state: New York
city: New York
country: United States
facility: Columbia IMPAACT CRS (4101)
state: New York
city: Stony Brook
country: United States
facility: SUNY Stony Brook NICHD CRS (5040)
state: New York
city: Durham
country: United States
facility: Duke University Medical Center (DUMC) (4701)
state: North Carolina
city: Philadelphia
country: United States
facility: The Children's Hosp. of Philadelphia IMPAACT CRS (6701)
state: Pennsylvania
city: Memphis
country: United States
facility: St. Jude/UTHSC CRS (6501)
state: Tennessee
city: Houston
country: United States
facility: Texas Children's Hosp. CRS (3801)
state: Texas
city: Seattle
country: United States
facility: Harborview Medical Center NICHD CRS (5027)
state: Washington
city: Seattle
country: United States
facility: Univ of Washington Children's Hospital Seattle (5017)
state: Washington
city: Seattle
country: United States
facility: University of Washington NICHD CRS (5029)
state: Washington
city: San Juan
country: Puerto Rico
facility: San Juan City Hosp. PR NICHD CRS (5031)
city: San Juan
country: Puerto Rico
facility: University of Puerto Rico Pediatric HIV/AIDS Research (6601)
Study officials:
affiliation: University of Alabama at Birmingham
name: Jennifer R. King, PharmD
role: STUDY_CHAIR
affiliation: Northwestern University Feinberg School of Medicine
name: Ram Yogev, MD
role: STUDY_CHAIR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.