Safety and Pharmacokinetic Study of Fixed Dose Combination of Zidovudine, Lamivudine, and Nevirapine in HIV-Infected Children in Thailand
Information source: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: HIV Infections
Intervention: GPO-Vir Z30 tablet (Drug); Lamivudine (Drug); Nevirapine (Drug); Zidovudine (Drug)
Phase: Phase 1/Phase 2
Status: Completed
Sponsored by: National Institute of Allergy and Infectious Diseases (NIAID) Official(s) and/or principal investigator(s): Kulkanya Chokephaibulkit, MD, Study Chair, Affiliation: Siriraj Hospital, Mahidol University Nirum Vanprapar, MD, Study Chair, Affiliation: Siriraj Hospital, Mahidol University Ram Yogev, MD, Study Chair, Affiliation: CMRC Children's Memorial Hospital
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.
Clinical Details
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 design: Allocation: Randomized, Endpoint Classification: Pharmacokinetics Study, Intervention Model: Crossover Assignment, Masking: Open Label, Primary Purpose: Treatment
Primary outcome: Safety and comparative bioavailability measured by concentration difference between the GPO-Vir Z30 and standard liquid regimensTherapeutic adequacy of NVP measured by treatment-specific concentration distributions
Secondary outcome: 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
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
Minimum age: 5 Months.
Maximum age: 12 Years.
Gender(s): Both.
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
Locations and Contacts
Chiang Mai University Pediatrics-Obstetrics CRS, Chiang Mai 50200, Thailand
Chonburi Hosp. CRS, Chonburi, Thailand
Prapokklao Hosp. CRS, Muang District, Chantaburi 22000, Thailand
Siriraj Hospital Mahidol University CRS, Bangkok, Ratchathewi, Thailand
Additional Information
Click here for more information about lamivudine Click here for more information about nevirapine Click here for more information about zidovudine
Related 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.
Starting date: October 2008
Last updated: September 11, 2012
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