Now Available for Public Comment: Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

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

This study has been completed.
Sponsor:
Collaborators:
International Maternal Pediatric Adolescent AIDS Clinical Trials Group
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT00672412
First received: May 2, 2008
Last updated: September 11, 2012
Last verified: September 2012
  Purpose

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.


Condition Intervention Phase
HIV Infections
Drug: GPO-Vir Z30 tablet
Drug: Lamivudine
Drug: Nevirapine
Drug: Zidovudine
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Crossover Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by National Institute of Allergy and Infectious Diseases (NIAID):

Primary Outcome Measures:
  • Safety and comparative bioavailability measured by concentration difference between the GPO-Vir Z30 and standard liquid regimens [ Time Frame: Throughout study ] [ Designated as safety issue: Yes ]
  • Therapeutic adequacy of NVP measured by treatment-specific concentration distributions [ Time Frame: Throughout study ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Comparisons in PK analyses between GPO-VIR Z30 and standard liquid regimens including pharmacokinetic parameters, adverse drug reactions, and the influence of SNPs on NVP pharmacokinetic parameters [ Time Frame: Throughout study ] [ Designated as safety issue: Yes ]

Enrollment: 42
Study Start Date: October 2008
Study Completion Date: January 2010
Primary Completion Date: January 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
Participants receive GPO-VIR Z30 tablets containing ZDV, 3TC, and NVP for the first 14 days of the study. On Day 15, participants receive liquid ZDV, 3TC, and NVP for the following 14 days of the study.
Drug: GPO-Vir Z30 tablet
Tablet consisting of ZDV 30 mg/3TC 15 mg/NVP 28 mg taken orally twice daily
Drug: Lamivudine
Oral suspension containing 10 mg 3TC in each mL. Dosage depends on weight.
Other Names:
  • 3TC
  • Epivir
Drug: Nevirapine
Oral solution containing 10 mg NVP in each mL. Dosage depends on weight.
Other Names:
  • NVP
  • Viramune
Drug: Zidovudine
Oral solution containing 10 mg ZDV in each mL. Dosage depends on weight.
Other Names:
  • ZDV
  • Retrovir
Experimental: 2
Participants receive liquid ZDV, 3TC, and NVP for the first 14 days of the study. On Day 15, participants receive GPO-VIR Z30 tablets containing ZDV, 3TC, and NVP for the following 14 days of the study.
Drug: GPO-Vir Z30 tablet
Tablet consisting of ZDV 30 mg/3TC 15 mg/NVP 28 mg taken orally twice daily
Drug: Lamivudine
Oral suspension containing 10 mg 3TC in each mL. Dosage depends on weight.
Other Names:
  • 3TC
  • Epivir
Drug: Nevirapine
Oral solution containing 10 mg NVP in each mL. Dosage depends on weight.
Other Names:
  • NVP
  • Viramune
Drug: Zidovudine
Oral solution containing 10 mg ZDV in each mL. Dosage depends on weight.
Other Names:
  • ZDV
  • Retrovir

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   5 Months to 12 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00672412

Locations
Thailand
Prapokklao Hosp. CRS
Muang District, Chantaburi, Thailand, 22000
Siriraj Hospital Mahidol University CRS
Bangkok, Ratchathewi, Thailand
Chiang Mai University Pediatrics-Obstetrics CRS
Chiang Mai, Thailand, 50200
Chonburi Hosp. CRS
Chonburi, Thailand
Sponsors and Collaborators
International Maternal Pediatric Adolescent AIDS Clinical Trials Group
Investigators
Study Chair: Kulkanya Chokephaibulkit, MD Siriraj Hospital, Mahidol University
Study Chair: Nirum Vanprapar, MD Siriraj Hospital, Mahidol University
Study Chair: Ram Yogev, MD CMRC Children's Memorial Hospital
  More Information

Additional Information:
Publications:
Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT00672412     History of Changes
Other Study ID Numbers: P1069, 10620, IMPAACT P1069
Study First Received: May 2, 2008
Last Updated: September 11, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
Treatment Experienced

Additional relevant MeSH terms:
Acquired Immunodeficiency Syndrome
HIV Infections
Immune System Diseases
Immunologic Deficiency Syndromes
Lentivirus Infections
RNA Virus Infections
Retroviridae Infections
Sexually Transmitted Diseases
Sexually Transmitted Diseases, Viral
Slow Virus Diseases
Virus Diseases
Lamivudine
Nevirapine
Zidovudine
Anti-HIV Agents
Anti-Infective Agents
Anti-Retroviral Agents
Antimetabolites
Antiviral Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Nucleic Acid Synthesis Inhibitors
Pharmacologic Actions
Reverse Transcriptase Inhibitors
Therapeutic Uses

ClinicalTrials.gov processed this record on November 25, 2014