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

Primary Purpose

HIV Infections

Status

Completed

Phase

Phase 1

Locations

Thailand

Study Type

Interventional

Intervention

GPO-Vir Z30 tablet

Lamivudine

Nevirapine

Zidovudine

About this trial

This is an interventional treatment trial for HIV Infections focused on measuring Treatment Experienced

Eligibility Criteria

5 Months - 12 Years (Child)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Prapokklao Hosp. CRS
Siriraj Hospital Mahidol University CRS
Chiang Mai University Pediatrics-Obstetrics CRS
Chonburi Hosp. CRS

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Arm Label

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

Safety and comparative bioavailability measured by concentration difference between the GPO-Vir Z30 and standard liquid regimens

Therapeutic adequacy of NVP measured by treatment-specific concentration distributions

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

Full Information

NCT ID

NCT00672412

First Posted

May 2, 2008

Last Updated

November 3, 2021

Sponsor

National Institute of Allergy and Infectious Diseases (NIAID)

Collaborators

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

1. Study Identification

Unique Protocol Identification Number

NCT00672412

Brief Title

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

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

Study Type

Interventional

2. Study Status

Record Verification Date

September 2012

Overall Recruitment Status

Completed

Study Start Date

October 2008 (undefined)

Primary Completion Date

January 2010 (Actual)

Study Completion Date

January 2010 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

National Institute of Allergy and Infectious Diseases (NIAID)

Collaborators

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

4. Oversight

5. Study Description

Brief Summary

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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

HIV Infections

Keywords

Treatment Experienced

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1, Phase 2

Interventional Study Model

Crossover Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

42 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Arm Type

Experimental

Arm Description

Arm Title

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

GPO-Vir Z30 tablet

Intervention Description

Tablet consisting of ZDV 30 mg/3TC 15 mg/NVP 28 mg taken orally twice daily

Intervention Type

Drug

Intervention Name(s)

Lamivudine

Other Intervention Name(s)

3TC, Epivir

Intervention Description

Oral suspension containing 10 mg 3TC in each mL. Dosage depends on weight.

Intervention Type

Drug

Intervention Name(s)

Nevirapine

Other Intervention Name(s)

NVP, Viramune

Intervention Description

Oral solution containing 10 mg NVP in each mL. Dosage depends on weight.

Intervention Type

Drug

Intervention Name(s)

Zidovudine

Other Intervention Name(s)

ZDV, Retrovir

Intervention Description

Oral solution containing 10 mg ZDV in each mL. Dosage depends on weight.

Primary Outcome Measure Information:

Title

Safety and comparative bioavailability measured by concentration difference between the GPO-Vir Z30 and standard liquid regimens

Time Frame

Throughout study

Title

Therapeutic adequacy of NVP measured by treatment-specific concentration distributions

Time Frame

Throughout study

Secondary Outcome Measure Information:

Title

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

10. Eligibility

Sex

All

Minimum Age & Unit of Time

5 Months

Maximum Age & Unit of Time

12 Years

Accepts Healthy Volunteers

Eligibility 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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Kulkanya Chokephaibulkit, MD

Organizational Affiliation

Siriraj Hospital

Official's Role

Study Chair

First Name & Middle Initial & Last Name & Degree

Nirum Vanprapar, MD

Organizational Affiliation

Siriraj Hospital

Official's Role

Study Chair

First Name & Middle Initial & Last Name & Degree

Ram Yogev, MD

Organizational Affiliation

CMRC Children's Memorial Hospital

Official's Role

Study Chair

Facility Information:

Facility Name

Prapokklao Hosp. CRS

City

Muang District

State/Province

Chantaburi

ZIP/Postal Code

22000

Country

Thailand

Facility Name

Siriraj Hospital Mahidol University CRS

City

Bangkok

State/Province

Ratchathewi

Country

Thailand

Facility Name

Chiang Mai University Pediatrics-Obstetrics CRS

City

Chiang Mai

ZIP/Postal Code

50200

Country

Thailand

Facility Name

Chonburi Hosp. CRS

City

Chonburi

Country

Thailand

12. IPD Sharing Statement

Citations:

PubMed Identifier

17375626

Citation

Kiertiburanakul S, Khongnorasat S, Rattanasiri S, Sungkanuparph S. Efficacy of a generic fixed-dose combination of stavudine, lamivudine and nevirapine (GPO-VIR) in Thai HIV-infected patients. J Med Assoc Thai. 2007 Feb;90(2):237-43.

Results Reference

background

PubMed Identifier

17375627

Citation

Manosuthi W, Kiertiburanakul S, Chaovavanich A, Sungkanuparph S. Plasma nevirapine levels and 24-week efficacy of a fixed-dose combination of stavudine, lamivudine and nevirapine (GPO-VIR) among Thai HIV-infected patients. J Med Assoc Thai. 2007 Feb;90(2):244-50.

Results Reference

background

Learn more about this trial

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

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