Safety and Pharmacokinetic Study of Fixed Dose Combination of Zidovudine, Lamivudine, and Nevirapine in HIV-Infected Children in Thailand

A Phase I/II Comparative Pharmacokinetic Study of the Fixed-Dose Combination (FDC) of Zidovudine (ZDV), Lamivudine (3TC), and Nevirapine (NVP) as GPO-Vir Z30 Pediatric Tablets Versus the Individual Liquid Formulations in HIV-Infected Children Greater Than or Equal to Five Months and Less Than 13 Years of Age in Thailand

In 2005, there were 50,620 HIV-infected children living in Thailand. Current anti-HIV regimens, comprised of individual pills for each drug, frequently lead to missed doses. To properly control their infection, regimens that are tolerable and effective in children and without pill burden are necessary. The primary purpose of this study is to evaluate the safety and bioavailability of GPO-VIR Z30, a combination fixed dose tablet containing zidovudine (ZDV), lamivudine (3TC), and nevirapine (NVP), in HIV-infected children in Thailand.

An important factor affecting the therapeutic response to ARVs is adherence. A common reason for poor adherence is high pill burden. A combination fixed dose drug approach appears to be an effective strategy to improve adherence and therapeutic response. In this study, investigators will compare the bioavailability and safety of GPO-VIR Z30, a combination fixed dose drug, with the liquid formulations of ZDV,3TC, and NVP, in children.

This study will last approximately 8 weeks. Participants will be randomly assigned to one of two arms. Participants in Arm 1 will receive GPO-VIR Z30 for 2 weeks before receiving liquid formulations of ZDV, 3TC, and NVP for the following 2 weeks. Participants in Arm 2 will receive liquid formulations of ZDV, 3TC, and NVP for 2 weeks before receiving GPO-VIR Z30 for the following 2 weeks.

This study will consist of 4 study visits after screening. Visits will occur at study entry and on Days 14, 28, and 56. Medical history and a physical exam will occur at all visits. A pregnancy test will occur for females at all visits. Pharmacokinetic tests, involving hospitalization for the 12 hour procedure, will occur on Days 14 and 28. Safety and adherence monitoring will occur by telephone on Days 7, 11 or 12, 13, 21, 25 or 26, 27, and 35. Home visits for directly observed therapy (DOT) may also occur.

Inclusion Criteria:

• Weigh between 6 and 30 kilograms
• HIV infected
• Receiving HAART regimen of NVP and 2 NRTIs. More information on this criterion can be found in the protocol.
• Agree to use two appropriate forms of contraception. More information on this criterion can be found in the protocol.
• Ability to swallow study drugs
• Willing to be hospitalized for 12-hour intensive PK study
• Agree to use two appropriate forms of contraception. More information on this criterion can be found in the protocol.
• Parent or legal guardian able and willing to provide written informed consent

Exclusion Criteria:

• Certain abnormal laboratory values. More information on this criterion can be found in the protocol.
• Vomiting or diarrhea (greater than Grade 2) within 30 days prior to study entry
• History of immunologic failure. More information on this criterion can be found in the protocol.
• Current treatment for an acute serious bacterial, viral, or opportunistic infection
• History of dose-limiting toxicity requiring treatment discontinuation of any of the study drugs
• Hypersensitivity to study drugs
• Surgical or medical problem affecting gastrointestinal motility or absorption or liver function
• Treatment with experimental drugs within 30 days prior to study entry
• Acute hepatitis
• Chemotherapy for active malignancy
• Any clinically significant diseases or findings during the screening medical history or physical examination that, in the opinion of the investigator, may interfere with the study
• Pregnant