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

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)
Information provided by:	National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:	NCT00672412

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 I Phase II

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:

Genetics Home Reference related topics: complement factor I deficiency

MedlinePlus related topics: HIV/AIDS

Drug Information available for: Zidovudine Nevirapine Lamivudine

U.S. FDA Resources

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 ]

Estimated Enrollment:	48
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

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

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

Locations

Thailand
Prapokklao Hospital
Muang District, Chantaburi, Thailand, 22000

Sponsors and Collaborators

National Institute of Allergy and Infectious Diseases (NIAID)

International Maternal Pediatric Adolescent AIDS Clinical Trials Group

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

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:

Click here for more information about lamivudine This link exits the ClinicalTrials.gov site

Click here for more information about nevirapine This link exits the ClinicalTrials.gov site

Click here for more information about zidovudine This link exits the ClinicalTrials.gov site

Publications:

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.

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.

Responsible Party:	Rona Siskind, DAIDS
ClinicalTrials.gov Identifier:	NCT00672412 History of Changes
Other Study ID Numbers:	IMPAACT P1069
Study First Received:	May 2, 2008
Last Updated:	April 15, 2011
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:

HIV Infections
Acquired Immunodeficiency Syndrome
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Slow Virus Diseases
Zidovudine
Nevirapine

Lamivudine
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Anti-HIV Agents

ClinicalTrials.gov processed this record on February 09, 2012