Drug Levels of Tablet and Liquid Forms of Lamivudine, Nevirapine, and Stavudine in HIV Infected Thai Children
Condition: HIV Infections
MeSH terms: HIV Infections
Study type: Interventional
Phase: Phase 1/Phase 2

Summary: 
      The purpose of this study is to compare the blood levels, absorption, and breakdown of
      lamivudine (3TC), nevirapine (NVP), and stavudine (d4T) in a fixed-dose tablet to that of the
      individual liquid formulations of the same anti-HIV drugs in HIV infected Thai children.
    

Detailed description: 
      The Thai Ministry of Public Health strives to provide the HIV infected people of Thailand
      with affordable antiretrovirals (ARVs). A fixed-dose combination tablet of 3TC, NVP, and d4T
      is recommended as first-line treatment in HIV infected adults in Thailand. There has been no
      similar product developed for children for several reasons: pediatric dosing is based on age,
      weight, or body surface area; developmental changes may influence the bioavailability and
      pharmacokinetics (PK) of ARVs; and medication adherence may also be a problem. The purpose of
      this study is to gather bioavailability and PK data in children taking a fixed-dose tablet of
      3TC, NVP, and d4T. This information will then be compared to the bioavailability and PK of
      the individual liquid formulations of these ARVs.

      This study has two stages. Stage 1 will last a minimum of 4 weeks; Stage 2 will last a
      minimum of 8 weeks. In Stage 1, patients will be randomly assigned to one of two arms. Arm A
      will receive the fixed-dose tablet twice daily for 2 weeks, then switch to the individual
      liquid formulations twice daily for 2 weeks. Arm B will receive the individual liquid
      formulations twice daily for 2 weeks, then switch to the fixed-dose tablet twice daily for 2
      weeks. To encourage medication adherence, study staff will make home visits and phone calls
      to each patient's parent or guardian the first week of each treatment regimen. Medical
      history, a physical exam, and urine collection will occur on Days 11 and 25. Also on Days 11
      and 25, patients will be admitted to the hospital to ensure 100% medication adherence and to
      provide blood for PK studies.

      Stage 1 patients are not eligible for Stage 2. In Stage 2, patients will be stratified by
      body weight, then randomly assigned to one of two arms. Arm A will receive the fixed-dose
      tablet twice daily for 4 weeks, then switch to the individual liquid formulations twice daily
      for 4 weeks. Arm B will receive the individual liquid formulations twice daily for 4 weeks,
      then switch to the fixed-dose tablet twice daily for 4 weeks. To encourage medication
      adherence, study staff will make home visits and phone calls to each patient's parent or
      guardian the first week of each treatment regimen. Medical history, documentation of direct
      observation of therapy (DOT), a physical exam, and urine collection will occur on Days 25 and
      53. Also on Days 25 and 53, patients will be admitted to the hospital to ensure 100%
      medication adherence and to provide blood for PK studies.
    

Intervention name(s): Lamivudine, nevirapine, and stavudine fixed-dose tablet; Lamivudine; Nevirapine; Stavudine
Intervention type(s): Drug; Drug; Drug; Drug
Intervention description(s): 7 mg d4T, 30 mg 3TC, 50 mg NVP tablet; Dosage dependent on weight. More information on this criterion can be found in the protocol.; Dosage dependent on weight. More information on this criterion can be found in the protocol.; Dosage dependent on weight. More information on this criterion can be found in the protocol.
Other intervention name(s): GPO-Vir; d4T/3TC/NVP
Intervention MeSH terms: Lamivudine; Nevirapine; Stavudine
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Pharmacokinetics; Treatment Experienced