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

NCT ID: NCT00672412

Last Updated: 2021-11-09

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 42 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-10-31
• Study Completion Date: 2010-01-31

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.

Conditions

HIV Infections

Keywords

Treatment Experienced

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

GPO-Vir Z30 tablet

Intervention Type: DRUG

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

Lamivudine

Intervention Type: DRUG

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

Nevirapine

Intervention Type: DRUG

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

Zidovudine

Intervention Type: DRUG

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

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.

Group Type: EXPERIMENTAL

GPO-Vir Z30 tablet

Intervention Type: DRUG

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

Lamivudine

Intervention Type: DRUG

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

Nevirapine

Intervention Type: DRUG

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

Zidovudine

Intervention Type: DRUG

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

Interventions

GPO-Vir Z30 tablet

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

Intervention Type: DRUG

Lamivudine

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

Intervention Type: DRUG

Nevirapine

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

Intervention Type: DRUG

Zidovudine

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

Intervention Type: DRUG

Other Intervention Names

3TC; Epivir; NVP; Viramune; ZDV; Retrovir

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

• Minimum Eligible Age: 5 Months
• Maximum Eligible Age: 12 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

International Maternal Pediatric Adolescent AIDS Clinical Trials Group

NETWORK

Sponsor Role: collaborator

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

NIH

Sponsor Role: collaborator

National Institute of Allergy and Infectious Diseases (NIAID)

NIH

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Kulkanya Chokephaibulkit, MD

Role: STUDY_CHAIR

Siriraj Hospital

Nirum Vanprapar, MD

Role: STUDY_CHAIR

Siriraj Hospital

Ram Yogev, MD

Role: STUDY_CHAIR

CMRC Children's Memorial Hospital

Locations

Prapokklao Hosp. CRS

Muang District, Changwat Chanthaburi, Thailand

Siriraj Hospital Mahidol University CRS

Bangkok, Ratchathewi, Thailand

Chiang Mai University Pediatrics-Obstetrics CRS

Chiang Mai, , Thailand

Chonburi Hosp. CRS

Chon Buri, , Thailand

Countries

Thailand

References

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.

Reference Type: BACKGROUND

PMID: 17375626 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 17375627 (View on PubMed)

Other Identifiers

10620

Identifier Type: REGISTRY

Identifier Source: secondary_id

IMPAACT P1069

Identifier Type: -

Identifier Source: secondary_id

P1069

Identifier Type: -

Identifier Source: org_study_id