Safety and Pharmacokinetic Study of Fixed Dose Combination of Zidovudine, Lamivudine, and Nevirapine in HIV-Infected Children in Thailand
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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 |
- 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 ]
- 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:
Drug: Nevirapine
Oral solution containing 10 mg NVP in each mL. Dosage depends on weight.
Other Names:
Drug: Zidovudine
Oral solution containing 10 mg ZDV in each mL. Dosage depends on weight.
Other Names:
|
|
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:
Drug: Nevirapine
Oral solution containing 10 mg NVP in each mL. Dosage depends on weight.
Other Names:
Drug: Zidovudine
Oral solution containing 10 mg ZDV in each mL. Dosage depends on weight.
Other Names:
|
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 |
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 LocationsPlease refer to this study by its ClinicalTrials.gov identifier: NCT00672412
| 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 | |
| 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:
|
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 February 27, 2015