Drug Levels of Tablet and Liquid Forms of Lamivudine, Nevirapine, and Stavudine in HIV Infected Thai Children

This study has been completed.
Sponsor:
Collaborators:
International Maternal Pediatric Adolescent AIDS Clinical Trials Group
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT00312091
First received: April 5, 2006
Last updated: September 10, 2012
Last verified: September 2012
  Purpose

The purpose of this study is to compare the blood levels, absorption, and breakdown of lamivudine (3TC), nevirapine (NVP), and stavudine (d4T) in a fixed-dose tablet to that of the individual liquid formulations of the same anti-HIV drugs in HIV infected Thai children.


Condition Intervention Phase
HIV Infections
Drug: Lamivudine, nevirapine, and stavudine fixed-dose tablet
Drug: Lamivudine
Drug: Nevirapine
Drug: Stavudine
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Bio-availability 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 Stavudine (d4T), Lamivudine (3TC), and Nevirapine (NVP) as GPO-VIR Pediatric Chewable Tablets Versus the Individual Liquid Formulations in HIV Infected Children 6 Months and Older to Less Than 13 Years of Age in Thailand

Resource links provided by NLM:


Further study details as provided by National Institute of Allergy and Infectious Diseases (NIAID):

Primary Outcome Measures:
  • Comparative bioavailability [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
  • therapeutic adequacy [ Time Frame: Throughout study ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Drug absorption from standard pharmacokinetic (PK) analyses [ Time Frame: Throughout study ] [ Designated as safety issue: No ]

Enrollment: 44
Study Start Date: December 2006
Study Completion Date: September 2008
Primary Completion Date: September 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: A, Stage 1
Tablet containing d4T, 3TC, and NVP taken orally twice daily for the first 4 weeks, then liquid formulations of d4T, 3TC, and NVP taken orally twice daily for the final 4 weeks
Drug: Lamivudine, nevirapine, and stavudine fixed-dose tablet
7 mg d4T, 30 mg 3TC, 50 mg NVP tablet
Other Names:
  • GPO-Vir
  • d4T/3TC/NVP
Drug: Lamivudine
Dosage dependent on weight. More information on this criterion can be found in the protocol.
Drug: Nevirapine
Dosage dependent on weight. More information on this criterion can be found in the protocol.
Drug: Stavudine
Dosage dependent on weight. More information on this criterion can be found in the protocol.
Experimental: A, Stage 2
Tablet containing d4T, 3TC, and NVP taken orally twice daily for 4 weeks, then liquid formulations of d4T, 3TC, and NVP taken orally twice daily for 4 weeks
Drug: Lamivudine, nevirapine, and stavudine fixed-dose tablet
7 mg d4T, 30 mg 3TC, 50 mg NVP tablet
Other Names:
  • GPO-Vir
  • d4T/3TC/NVP
Drug: Lamivudine
Dosage dependent on weight. More information on this criterion can be found in the protocol.
Drug: Nevirapine
Dosage dependent on weight. More information on this criterion can be found in the protocol.
Drug: Stavudine
Dosage dependent on weight. More information on this criterion can be found in the protocol.
Experimental: B, Stage 1
Liquid formulations of d4T, 3TC, and NVP taken orally twice daily for 2 weeks, then tablet containing d4T, 3TC, and NVP taken orally twice daily for 2 weeks
Drug: Lamivudine, nevirapine, and stavudine fixed-dose tablet
7 mg d4T, 30 mg 3TC, 50 mg NVP tablet
Other Names:
  • GPO-Vir
  • d4T/3TC/NVP
Drug: Lamivudine
Dosage dependent on weight. More information on this criterion can be found in the protocol.
Drug: Nevirapine
Dosage dependent on weight. More information on this criterion can be found in the protocol.
Drug: Stavudine
Dosage dependent on weight. More information on this criterion can be found in the protocol.
Experimental: B, Stage 2
Liquid formulations of d4T, 3TC, and NVP taken orally twice daily for 4 weeks, then tablet containing d4T, 3TC, and NVP taken orally twice daily for 4 weeks
Drug: Lamivudine, nevirapine, and stavudine fixed-dose tablet
7 mg d4T, 30 mg 3TC, 50 mg NVP tablet
Other Names:
  • GPO-Vir
  • d4T/3TC/NVP
Drug: Lamivudine
Dosage dependent on weight. More information on this criterion can be found in the protocol.
Drug: Nevirapine
Dosage dependent on weight. More information on this criterion can be found in the protocol.
Drug: Stavudine
Dosage dependent on weight. More information on this criterion can be found in the protocol.

Detailed Description:

The Thai Ministry of Public Health strives to provide the HIV infected people of Thailand with affordable antiretrovirals (ARVs). A fixed-dose combination tablet of 3TC, NVP, and d4T is recommended as first-line treatment in HIV infected adults in Thailand. There has been no similar product developed for children for several reasons: pediatric dosing is based on age, weight, or body surface area; developmental changes may influence the bioavailability and pharmacokinetics (PK) of ARVs; and medication adherence may also be a problem. The purpose of this study is to gather bioavailability and PK data in children taking a fixed-dose tablet of 3TC, NVP, and d4T. This information will then be compared to the bioavailability and PK of the individual liquid formulations of these ARVs.

This study has two stages. Stage 1 will last a minimum of 4 weeks; Stage 2 will last a minimum of 8 weeks. In Stage 1, patients will be randomly assigned to one of two arms. Arm A will receive the fixed-dose tablet twice daily for 2 weeks, then switch to the individual liquid formulations twice daily for 2 weeks. Arm B will receive the individual liquid formulations twice daily for 2 weeks, then switch to the fixed-dose tablet twice daily for 2 weeks. To encourage medication adherence, study staff will make home visits and phone calls to each patient's parent or guardian the first week of each treatment regimen. Medical history, a physical exam, and urine collection will occur on Days 11 and 25. Also on Days 11 and 25, patients will be admitted to the hospital to ensure 100% medication adherence and to provide blood for PK studies.

Stage 1 patients are not eligible for Stage 2. In Stage 2, patients will be stratified by body weight, then randomly assigned to one of two arms. Arm A will receive the fixed-dose tablet twice daily for 4 weeks, then switch to the individual liquid formulations twice daily for 4 weeks. Arm B will receive the individual liquid formulations twice daily for 4 weeks, then switch to the fixed-dose tablet twice daily for 4 weeks. To encourage medication adherence, study staff will make home visits and phone calls to each patient's parent or guardian the first week of each treatment regimen. Medical history, documentation of direct observation of therapy (DOT), a physical exam, and urine collection will occur on Days 25 and 53. Also on Days 25 and 53, patients will be admitted to the hospital to ensure 100% medication adherence and to provide blood for PK studies.

  Eligibility

Ages Eligible for Study:   6 Months to 13 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria for Stages 1 and 2:

  • HIV infected
  • On a highly active antiretroviral regimen (HAART) including NVP and 2 nucleoside reverse transcriptase inhibitors and receiving a maintenance of NVP for at least 4 weeks prior to study entry and taking the current recommended oral dose every 12 hours
  • Willing to swallow or chew study drugs
  • Willing to be hospitalized for the 12 hour PK studies
  • Willing to use acceptable forms of contraception
  • Parent or guardian willing to provide informed consent

Inclusion Criteria for Stage 1:

  • Between 12 to 30 kg (26.5 to 66.1 lbs)

Inclusion Criteria for Stage 2:

  • Between 6 to 30 kg (13.2 to 66.1 lbs)

Exclusion Criteria:

  • Certain abnormal laboratory values
  • Require certain medications
  • Grade 2 or greater vomiting within 30 days prior to study entry
  • Grade 2 or greater diarrhea within 30 days prior to study entry
  • History of immunological failure (CD4 percentage decrease of more than 30% within a 6-month period for children 6 years or younger OR CD4 cell count decrease of more than 30% within a 6-month period for children older than 6 years)
  • Current treatment for acute serious bacterial, viral, or opportunistic infection
  • History of dose-limiting toxicity requiring treatment discontinuation of any of the study drugs
  • Known hypersensitivity to any of the study drugs
  • Current surgical or medical problem affecting gastrointestinal motility or absorption (e.g., ileus, ulcerative colitis) or liver function
  • Treatment with immune modulators or myelosuppressive, neurotoxic, pancreatotoxic, hepatotoxic, or cytotoxic drugs within 30 days prior to study entry. Patients who have received therapeutic vaccines are not excluded.
  • Treatment with experimental drugs within 30 days of study entry
  • Acute inflammation of the liver
  • Chemotherapy for active cancer
  • Any clinically significant diseases other than HIV infection or clinically significant findings that, in the investigator's opinion, may interfere with the study
  • Inability to provide a reliable means of contact (e.g., telephone number)
  • Pregnancy
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00312091

Locations
Thailand
Siriraj Hospital Mahidol University CRS
Bangkok, Ratchathewi, Thailand, 10700
Queen Sirikit National Institute of Child Health, Pediatric Infectious Unit
Bangkok, Ratchathewi, Thailand, 10400
Chiang Mai University Pediatrics-Obstetrics CRS
Chiang Mai, Thailand, 50200
Chonburi Hosp. CRS
Chonburri, Thailand, 20000 TH
Sponsors and Collaborators
International Maternal Pediatric Adolescent AIDS Clinical Trials Group
Investigators
Study Chair: Nirun Vanprapar, MD Pediatric Infectious Unit, Department of Pediatrics, Siriraj Hopstial, Mahidol University
  More Information

Additional Information:
Publications:
Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT00312091     History of Changes
Other Study ID Numbers: P1056, 10139, PACTG P1056, IMPAACT P1056
Study First Received: April 5, 2006
Last Updated: September 10, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
Pharmacokinetics
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
Nevirapine
Stavudine
Lamivudine
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antimetabolites

ClinicalTrials.gov processed this record on July 29, 2014