Blood Levels of Abacavir in HIV Infected Adolescents

Abacavir Pharmacokinetics During Chronic Therapy in HIV-1 Infected Adolescents and Young Adults

The way abacavir (ABC) behaves in the body differs between children and adults, but little is known about ABC in adolescents. It is unclear if adult doses of ABC are appropriate for adolescents. The purpose of this study is to determine the blood levels of ABC in HIV infected adolescents who are on ABC-containing regimens.

Study Overview

• Status: Completed
• Conditions: HIV Infections
• Intervention / Treatment: Drug: Abacavir sulfate; Drug: Abacavir sulfate, lamivudine, and zidovudine

Detailed Description

ABC is approved for the treatment of HIV in adults and children, but it is unclear if currently recommended ABC doses are appropriate for adolescents. Previous data suggest ABC clearance in children is about twice that found in adults, but limited data exist on the pharmacokinetics of ABC in adolescents. This study will evaluate the 8-hour pharmacokinetics of ABC in HIV infected adolescents who are currently on ABC-containing treatment regimens.

There will be two groups in this study. Group 1 participants will be 13 to 17 years old. Group 2 participants will be 18 to 25 years old. All participants will receive a 300 mg dose of ABC as either a single-agent tablet or a combination tablet of ABC, lamivudine, and zidovudine (whichever they are currently taking). Participants will have a medical history assessment and a physical exam at screening and study entry. Participants will also be asked about adherence to their ABC-containing regimen at study entry. During the 8-hour drug level study, blood collection for pharmacokinetic analysis will occur prior to taking ABC, and at 0.5, 1, 2, 3, 4, 6, and 8 hours after taking ABC.

• Study Type: Interventional
• Enrollment: 30
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Puerto Rico
  • San Juan, Puerto Rico, 00936
    • San Juan City Hosp. PR NICHD CRS
• United States
  • California
    • Alhambra, California, United States, 91803
      • Usc La Nichd Crs
    • Los Angeles, California, United States, 90027
      • Children's Hospital of Los Angeles NICHD CRS
    • San Diego, California, United States, 92103
      • UCSD Mother-Child-Adolescent Program CRS
  • District of Columbia
    • Washington, District of Columbia, United States, 20010
      • Children's National Med. Ctr., ACTU
    • Washington, District of Columbia, United States, 20010
      • Children's National Med. Ctr. Washington DC NICHD CRS
  • Florida
    • Jacksonville, Florida, United States, 32209
      • Univ. of Florida Jacksonville NICHD CRS
    • Tampa, Florida, United States, 33606
      • USF - Tampa NICHD CRS
  • Georgia
    • Augusta, Georgia, United States, 30912
      • Med. College of Georgia School of Medicine, Dept. of Peds., Div. of Infectious Diseases
  • Illinois
    • Chicago, Illinois, United States, 60614
      • Chicago Children's CRS
  • Louisiana
    • New Orleans, Louisiana, United States, 70112
      • Tulane/LSU Maternal/Child CRS
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • HMS - Children's Hosp. Boston, Div. of Infectious Diseases
    • Springfield, Massachusetts, United States, 01199
      • Baystate Health, Baystate Med. Ctr.
  • Michigan
    • Detroit, Michigan, United States, 48201
      • Children's Hospital of Michigan NICHD CRS
  • New Jersey
    • New Brunswick, New Jersey, United States, 08901
      • UMDNJ - Robert Wood Johnson Med. School, Div. of Allergy, Immunology & Infectious Diseases
    • Newark, New Jersey, United States, 07103
      • Rutgers - New Jersey Medical School CRS
  • New York
    • Bronx, New York, United States, 10457
      • Bronx-Lebanon Hosp. IMPAACT CRS
    • New York, New York, United States, 10032
      • Columbia IMPAACT CRS
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • UNC at Chapel Hill School of Medicine - Dept. of Peds., Div. of Immunology & Infectious Diseases
  • Tennessee
    • Memphis, Tennessee, United States, 38105
      • St. Jude/UTHSC CRS

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 13 years to 25 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• HIV-1 infected
• CD4 count greater than 100 cells/mm3
• Viral load less than 100,000 copies/ml
• Have taken an abacavir-containing regimen for at least 8 weeks prior to study entry
• Weight more than 83 lbs (37.5 kg)
• Ability and willingness to swallow study medications
• Consent of parent or guardian, if applicable

Exclusion Criteria:

• Any Grade 3 or greater toxicity within 14 days prior to study entry
• Participation in PACTG P1018
• CDC Category C opportunistic infections or HIV-1 associated cancer requiring drug therapy at the time of study enrollment
• Treatment with immune modulators, including interleukin-2 or intravenous gamma globulin, within 30 days of study entry
• Received therapeutic vaccines or any HIV-1 vaccine given for primary prevention within 30 days of study entry
• Surgical or medical problem affecting gastrointestinal motility or absorption (e.g., ileus, ulcerative colitis) or liver function
• History of chronic alcohol use
• Any clinically significant disease other than HIV-1 infection that, in the investigator's opinion, would represent an increased risk for the participant or compromise the outcome of the study
• Chemotherapy for active cancer
• Pregnancy or breastfeeding

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Collaborators and Investigators

• Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
• Collaborators: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
• Investigators: Study Chair: John Rodman, PharmD, St. Jude's Children's Research Hospital

Publications and helpful links

General Publications

• Chittick GE, Gillotin C, McDowell JA, Lou Y, Edwards KD, Prince WT, Stein DS. Abacavir: absolute bioavailability, bioequivalence of three oral formulations, and effect of food. Pharmacotherapy. 1999 Aug;19(8):932-42. doi: 10.1592/phco.19.11.932.31568.
• Hughes W, McDowell JA, Shenep J, Flynn P, Kline MW, Yogev R, Symonds W, Lou Y, Hetherington S. Safety and single-dose pharmacokinetics of abacavir (1592U89) in human immunodeficiency virus type 1-infected children. Antimicrob Agents Chemother. 1999 Mar;43(3):609-15. doi: 10.1128/AAC.43.3.609.
• Kline MW, Blanchard S, Fletcher CV, Shenep JL, McKinney RE Jr, Brundage RC, Culnane M, Van Dyke RB, Dankner WM, Kovacs A, McDowell JA, Hetherington S. A phase I study of abacavir (1592U89) alone and in combination with other antiretroviral agents in infants and children with human immunodeficiency virus infection. AIDS Clinical Trials Group 330 Team. Pediatrics. 1999 Apr;103(4):e47. doi: 10.1542/peds.103.4.e47.

Study record dates

Study Major Dates

• Study Start: July 1, 2004
• Study Completion (Actual): December 1, 2004

Study Registration Dates

• First Submitted: July 16, 2004
• First Submitted That Met QC Criteria: July 16, 2004
• First Posted (Estimate): July 19, 2004

Study Record Updates

• Last Update Posted (Estimate): October 8, 2013
• Last Update Submitted That Met QC Criteria: October 4, 2013
• Last Verified: October 1, 2013

More Information

Terms related to this study

• Keywords: Treatment Experienced
• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; Immune System Diseases; HIV Infections; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Reverse Transcriptase Inhibitors; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Antimetabolites; Lamivudine; Zidovudine; Abacavir; Dideoxynucleosides
• Other Study ID Numbers: PACTG P1052; 10194 (Registry Identifier: DAIDS ES)