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

November 3, 2021 updated by: National Institute of Allergy and Infectious Diseases (NIAID)

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

42

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Thailand
      • Chiang Mai, Thailand, 50200
        • Chiang Mai University Pediatrics-Obstetrics CRS
      • Chonburi, Thailand
        • Chonburi Hosp. CRS
    • Chantaburi
      • Muang District, Chantaburi, Thailand, 22000
        • Prapokklao Hosp. CRS
    • Ratchathewi
      • Bangkok, Ratchathewi, Thailand
        • Siriraj Hospital Mahidol University CRS

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

5 months to 12 years (Child)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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:
  • Viramune
  • NVP
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:
  • Viramune
  • NVP
Drug: Zidovudine
Oral solution containing 10 mg ZDV in each mL. Dosage depends on weight.
Other Names:
  • ZDV
  • Retrovir

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Safety and comparative bioavailability measured by concentration difference between the GPO-Vir Z30 and standard liquid regimens
Time Frame: Throughout study
Throughout study
Therapeutic adequacy of NVP measured by treatment-specific concentration distributions
Time Frame: Throughout study
Throughout study

Secondary Outcome Measures

Outcome Measure
Time Frame
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
Throughout study

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

National Institute of Allergy and Infectious Diseases (NIAID)

Collaborators

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
International Maternal Pediatric Adolescent AIDS Clinical Trials Group

Investigators

  • Study Chair: Kulkanya Chokephaibulkit, MD, Siriraj Hospital
  • Study Chair: Nirum Vanprapar, MD, Siriraj Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

October 1, 2008

Primary Completion (Actual)

January 1, 2010

Study Completion (Actual)

January 1, 2010

Study Registration Dates

First Submitted

May 2, 2008

First Submitted That Met QC Criteria

May 2, 2008

First Posted (Estimate)

May 6, 2008

Study Record Updates

Last Update Posted (Actual)

November 9, 2021

Last Update Submitted That Met QC Criteria

November 3, 2021

Last Verified

September 1, 2012

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • P1069
  • 10620 (DAIDS ES)
  • IMPAACT P1069

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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