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

NCT00977756 | Completed

• 2 other identifiers: IMPAACT P1058AU01AI068632
• Study Type: observational
• Target: 168
• Locations: 2 countries
• Sites: 35

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.

Conditions

HIV Infections

Keywords

Treatment; Children; Integrase Inhibitors; Entry Inhibitors; Treatment Experienced

Outcome Measures

Primary Outcomes (4)

• 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

• 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

• 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

• 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

Secondary Outcomes (4)

• 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

• 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

• Adverse events associated with the ARVs of interest

  Measured throughout

• 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

Study Arms (11)

Group G

Participants will receive a medication regimen including RAL + ATV + RTV.

Drug: Raltegravir (RAL); Drug: Atazanavir (ATV); Drug: Ritonavir (RTV)

Group H

Participants will receive a medication regimen including RAL + TDF.

Drug: Raltegravir (RAL); Drug: Tenofovir (TDF)

Group I

Participants will receive a medication regimen including ETV + DRV + RTV.

Drug: Ritonavir (RTV); Drug: Etravirine (ETV); Drug: Darunavir (DRV)

Group J

Participants will receive a medication regimen including MVC + ATV + RTV.

Drug: Atazanavir (ATV); Drug: Ritonavir (RTV); Drug: Maraviroc (MVC)

Group K

Participants will receive a medication regimen including MVC + LPV + RTV.

Drug: Ritonavir (RTV); Drug: Maraviroc (MVC); Drug: Lopinavir/ritonavir (LPV/r)

Group L

Participants will receive a medication regimen including MVC + RAL + ETV.

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

Interventions

Raltegravir (RAL) DRUG

400 mg twice daily (BID)

Also known as: Isentress

Group G; Group H; Group L

Atazanavir (ATV) DRUG

300 mg daily

Also known as: Reyataz

Group G; Group J

Ritonavir (RTV) DRUG

100 mg daily, dosing by weight in Group I

Also known as: Norvir

Group G; Group I; Group J; Group K

Tenofovir (TDF) DRUG

300 mg daily

Also known as: Viread

Group H

Etravirine (ETV) DRUG

200 mg BID

Also known as: Intelence

Group I; Group L

Darunavir (DRV) DRUG

Dosing by weight

Also known as: Prezista

Group I

Maraviroc (MVC) DRUG

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

Also known as: Selzentry

Group J; Group K; Group L

Lopinavir/ritonavir (LPV/r) DRUG

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

Also known as: Kaletra

Group K

Eligibility Criteria

• Age: 6 Years - 21 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)
• 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.

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• International Maternal Pediatric Adolescent AIDS Clinical Trials Group: lead
• National Institute of Allergy and Infectious Diseases (NIAID): collaborator

Study Sites (35)

Univ. of Alabama Birmingham NICHD CRS (5096)

Birmingham, Alabama, 35294, United States

Location

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

Long Beach, California, 90806, United States

Location

Usc La Nichd Crs (5048)

Los Angeles, California, 90033, United States

Location

UCSD Mother, Child & Adolescent HIV Program(4601)

San Diego, California, 92103, United States

Location

Univ. of California San Francisco NICHD CRS (5091)

San Francisco, California, 94117, United States

Location

Harbor (UCLA) Medical Center NICHD CRS (5045)

Torrance, California, 90509, United States

Location

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

Torrance, California, 90509, United States

Location

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

Denver, Colorado, 80218-1088, United States

Location

Children's National Medical Center (5015)

Washington D.C., District of Columbia, 20010, United States

Location

South Florida CDC Ft Lauderdale NICHD CRS (5055)

Fort Lauderdale, Florida, 33316, United States

Location

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

Miami, Florida, 33136, United States

Location

University of South Florida Tampa (5018)

Tampa, Florida, 33620, United States

Location

Rush University Cook County (5083)

Chicago, Illinois, 60612, United States

Location

Chicago Children's CRS (4001)

Chicago, Illinois, 60614, United States

Location

University of Maryland NICHD CRS (5094)

Baltimore, Maryland, 21201, United States

Location

Johns Hopkins University NICHD CRS (5092)

Baltimore, Maryland, 21287, United States

Location

Children's Hospital of Boston NICHD CRS (5009)

Boston, Massachusetts, 02115, United States

Location

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

Boston, Massachusetts, 02118, United States

Location

WNE Maternal Pediatric Adolescent AIDS CRS (7301)

Worcester, Massachusetts, 01605, United States

Location

New Jersey Medical School (NJ) (2802)

Newark, New Jersey, 07103, United States

Location

New York University NY (5012)

New York, New York, 10016, United States

Location

Metropolitan Hospital (5003)

New York, New York, 10029, United States

Location

Columbia IMPAACT CRS (4101)

New York, New York, 10032, United States

Location

SUNY Stony Brook NICHD CRS (5040)

Stony Brook, New York, 11794, United States

Location

Bronx-Lebanon Hospital (6901)

The Bronx, New York, 10457, United States

Location

Jacobi Medical Center Bronx (5013)

The Bronx, New York, 10461, United States

Location

Duke University Medical Center (DUMC) (4701)

Durham, North Carolina, 27710, United States

Location

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

Philadelphia, Pennsylvania, 19104, United States

Location

St. Jude/UTHSC CRS (6501)

Memphis, Tennessee, 38105, United States

Location

Texas Children's Hosp. CRS (3801)

Houston, Texas, 77030, United States

Location

Harborview Medical Center NICHD CRS (5027)

Seattle, Washington, 98105, United States

Location

Univ of Washington Children's Hospital Seattle (5017)

Seattle, Washington, 98105, United States

Location

University of Washington NICHD CRS (5029)

Seattle, Washington, 98105, United States

Location

San Juan City Hosp. PR NICHD CRS (5031)

San Juan, 00927, Puerto Rico

Location

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

San Juan, 00936-5067, Puerto Rico

Location

Related Publications (4)

• 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.

  PMID: 9572665 BACKGROUND

• 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.

  PMID: 18838589 BACKGROUND

• 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.

  PMID: 18625763 BACKGROUND

• 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.

  PMID: 27583590 DERIVED

Biospecimen

Retention: SAMPLES WITH DNA

Blood samples

MeSH Terms

Conditions

HIV Infections

Interventions

Raltegravir Potassium; Atazanavir Sulfate; Ritonavir; Tenofovir; etravirine; Darunavir; Maraviroc; Lopinavir; lopinavir-ritonavir drug combination

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Intervention Hierarchy (Ancestors)

Pyrrolidinones; Pyrrolidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyridines; Oligopeptides; Peptides; Amino Acids, Peptides, and Proteins; Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Organophosphonates; Organophosphorus Compounds; Adenine; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Sulfonamides; Amides; Carbamates; Acids, Acyclic; Carboxylic Acids; Sulfones; Furans; Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Triazoles; Pyrimidinones; Pyrimidines

Study Officials

• Jennifer R. King, PharmD

  University of Alabama at Birmingham

  STUDY CHAIR

• Ram Yogev, MD

  Northwestern University Feinberg School of Medicine

  STUDY CHAIR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 15, 2009
• First Posted: September 16, 2009
• Study Start: August 1, 2002
• Primary Completion: March 1, 2014
• Study Completion: March 1, 2014
• Last Updated: August 7, 2015

Record last verified: 2015-08

Locations

US (33); PR (2)