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

HIV Infections Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00977756
• Other study ID #: IMPAACT P1058A
• Secondary ID: U01AI068632
• Status: Completed
• Phase: N/A
• First received: September 15, 2009
• Last updated: August 5, 2015
• Start date: August 2002
• Est. completion date: March 2014

Study information

• Verified date: August 2015
• Source: International Maternal Pediatric Adolescent AIDS Clinical Trials Group
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Observational

Clinical 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 168
• Est. completion date: March 2014
• Est. primary completion date: March 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 6 Years to 21 Years

Eligibility

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

Study Design

Observational Model: Cohort, Time Perspective: Prospective

Related Conditions & MeSH terms

• HIV Infections

Intervention

Drug:
• Raltegravir (RAL)
400 mg twice daily (BID)
• Atazanavir (ATV)
300 mg daily
• Ritonavir (RTV)
100 mg daily, dosing by weight in Group I
• Tenofovir (TDF)
300 mg daily
• Etravirine (ETV)
200 mg BID
• Darunavir (DRV)
Dosing by weight
• Maraviroc (MVC)
150 mg BID in groups J and K; 600 mg BID in group L
• Lopinavir/ritonavir (LPV/r)
Coformulation of 400 mg lopinavir and 100 mg ritonavir, taken twice daily

Locations

Country	Name	City	State
Puerto Rico	San Juan City Hosp. PR NICHD CRS (5031)	San Juan
Puerto Rico	University of Puerto Rico Pediatric HIV/AIDS Research (6601)	San Juan
United States	Johns Hopkins University NICHD CRS (5092)	Baltimore	Maryland
United States	University of Maryland NICHD CRS (5094)	Baltimore	Maryland
United States	Univ. of Alabama Birmingham NICHD CRS (5096)	Birmingham	Alabama
United States	Boston Medical Center Ped. HIV Program NICHD CRS (5011)	Boston	Massachusetts
United States	Children's Hospital of Boston NICHD CRS (5009)	Boston	Massachusetts
United States	Bronx-Lebanon Hospital (6901)	Bronx	New York
United States	Jacobi Medical Center Bronx (5013)	Bronx	New York
United States	Chicago Children's CRS (4001)	Chicago	Illinois
United States	Rush University Cook County (5083)	Chicago	Illinois
United States	Childrens Hospital (U. Colorado, Denver) NICHD CRS (5052)	Denver	Colorado
United States	Duke University Medical Center (DUMC) (4701)	Durham	North Carolina
United States	South Florida CDC Ft Lauderdale NICHD CRS (5055)	Fort Lauderdale	Florida
United States	Texas Children's Hosp. CRS (3801)	Houston	Texas
United States	Miller Children's Hospital Long Beach, CA NICHD CRS (5093)	Long Beach	California
United States	Usc La Nichd Crs (5048)	Los Angeles	California
United States	St. Jude/UTHSC CRS (6501)	Memphis	Tennessee
United States	University of Miami Pediatric Perinatal HIV/AIDS CRS (4201)	Miami	Florida
United States	Columbia IMPAACT CRS (4101)	New York	New York
United States	Metropolitan Hospital (5003)	New York	New York
United States	New York University NY (5012)	New York	New York
United States	New Jersey Medical School (NJ) (2802)	Newark	New Jersey
United States	The Children's Hosp. of Philadelphia IMPAACT CRS (6701)	Philadelphia	Pennsylvania
United States	UCSD Mother, Child & Adolescent HIV Program(4601)	San Diego	California
United States	Univ. of California San Francisco NICHD CRS (5091)	San Francisco,	California
United States	Harborview Medical Center NICHD CRS (5027)	Seattle	Washington
United States	Univ of Washington Children's Hospital Seattle (5017)	Seattle	Washington
United States	University of Washington NICHD CRS (5029)	Seattle	Washington
United States	SUNY Stony Brook NICHD CRS (5040)	Stony Brook	New York
United States	University of South Florida Tampa (5018)	Tampa	Florida
United States	Harbor (UCLA) Medical Center NICHD CRS (5045)	Torrance	California
United States	Harbor Univeristy of California, Los Angeles (UCLA) Medical Center (603)	Torrance	California
United States	Children's National Medical Center (5015)	Washington	District of Columbia
United States	WNE Maternal Pediatric Adolescent AIDS CRS (7301)	Worcester	Massachusetts

Sponsors (2)

Lead Sponsor	Collaborator
International Maternal Pediatric Adolescent AIDS Clinical Trials Group	National Institute of Allergy and Infectious Diseases (NIAID)

Countries where clinical trial is conducted

United States,  Puerto Rico, 

References & Publications (3)

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. — View 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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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 at baseline and 1, 2, 4, 6, 8, and 12 hours after dosing	No
Primary	Steady state PK of etravirine administered to older children, adolescents and young adults		Measured at baseline and 1, 2, 4, 6, 8, and 12 hours after dosing	No
Primary	Steady state PK of maraviroc administered in combination with atazanavir/ritonavir or lopinavir/ritonavir to older children, adolescents and young adults		Measured at baseline and 1, 2, 4, 6, 8, and 12 hours after dosing	No
Primary	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 at baseline and 1, 2, 4, 6, 8, and 12 hours after dosing	No
Secondary	Relationship between Tanner stage and the PK of the regimens of interest in children and adolescents		Measured at baseline and 1, 2, 4, 6, 8, and 12 hours after dosing	No
Secondary	Relationships between the PK parameters and polymorphisms that may affect the antiretrovirals (ARVs) of interest in older children, adolescents and young adults		Measured at baseline and 1, 2, 4, 6, 8, and 12 hours after dosing	No
Secondary	Adverse events associated with the ARVs of interest		Measured throughout	Yes
Secondary	Steady state PK of darunavir/ritonavir administered to older children, adolescents and young adults		Measured at baseline and 1, 2, 4, 6, 8, and 12 hours after dosing	No