HIV Infections
Conditions
Keywords
Pharmacokinetics, Treatment Experienced
Brief summary
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.
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.
Interventions
DRUGLamivudine, nevirapine, and stavudine fixed-dose tablet
7 mg d4T, 30 mg 3TC, 50 mg NVP tablet
DRUGLamivudine
Dosage dependent on weight. More information on this criterion can be found in the protocol.
DRUGNevirapine
Dosage dependent on weight. More information on this criterion can be found in the protocol.
DRUGStavudine
Dosage dependent on weight. More information on this criterion can be found in the protocol.
Sponsors
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
International Maternal Pediatric Adolescent AIDS Clinical Trials Group
National Institute of Allergy and Infectious Diseases (NIAID)
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
6 Months to 13 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Comparative bioavailability | Throughout study |
| therapeutic adequacy | Throughout study |
Secondary
| Measure | Time frame |
|---|---|
| Drug absorption from standard pharmacokinetic (PK) analyses | Throughout study |
Countries
Thailand
Outcome results
None listed