Atazanavir Used in Combination With Other Anti-HIV Drugs in HIV Infected Infants, Children, and Adolescents
The purpose of this study is to find a safe and tolerable dose of the protease inhibitor (PI) atazanavir (ATV), with or without a low-dose boost of the PI ritonavir (RTV), when taken with other anti-HIV drugs in HIV infected infants, children, and adolescents.
Advancements in anti-HIV drugs for HIV infected children and adolescents have been hard to make, in part because these patients often do not take the drugs as prescribed. ATV may be a better option because it is available in the form of powder which children and adolescents may be more willing to take regularly. Using a low dose of RTV as a boosting agent for ATV may also increase the chances of virologic response of highly active antiretroviral treatment (HAART)-experienced patients. This study will try to find safe and tolerable doses of ATV with or without low-dose RTV boost in infants, children, and adolescents. For this study, participants will be enrolled in the U.S. and South Africa.
Advancements in HAART for HIV-infected children and adolescents are hindered by patient nonadherence. The availability of a powder formulation and the once-daily dosing schedule make ATV an attractive agent for improved adherence in pediatric treatment regimens. This study is designed to provide pharmacokinetic (PK) data to guide dosing recommendations for ATV, when given concurrently with or without low-dose RTV boost, in infants, children, and adolescents. During the study, the safety and tolerance of ATV (with or without low-dose RTV) will be closely monitored, and virologic efficacy data will be obtained.
There are two parts to this study. Step I will take place in the U.S. and South Africa, and will be further divided into two sets of groups, Parts A and B. Part A participants will receive ATV only and Part B participants will receive ATV with low-dose RTV boost. All participant will receive ATV once a day with 2 other antiretroviral drugs (not provided by the study). In Part B only, participants will receive ATV with a low dose of RTV. Participants will be placed into 1 of 8 groups (Groups 1 to 4 for Part A; Groups 5 to 8 for Part B) with respect to age and study drug formulation. Participants in Groups 1 and 5 will be infants between ages 3 months and 1 day (91 days) and 2 years (less than or exactly 730 days) and will take ATV in powder form. Participants in Groups 2, 3, 6, and 7 will be children between 2 years and 1 day (731 days) old and 13 years old. Groups 2 and 6 will receive ATV in powder form, while Groups 3 and 7 will receive the capsule form. Patients in Groups 4 and 8 will be adolescents between 13 years and 1 day old up to 21 years old (not including the 22nd birthday) and will take ATV in capsule form. As of 01/02/2008 a new group, 5A has been opened for enrollment. Participants in Group 5A will be between 3 months and 6 months old and will take ATV in powder form plus a low dose RTV booster.
For each group, enrollment will start with five participants per group. All participants will be evaluated for PK and safety criteria, adjusting the dose of ATV until one is found that passes both sets of criteria. Then five additional participants will be enrolled, with enrollment continuing for each group once all participants within that group meet the PK criteria. For groups receiving RTV (Groups 5 to 8), additional criteria must be met for each dose of ATV studied. In addition to the PK and safety evaluations, 24-hour post-dose concentrations (Cmin) will be monitored in the first 10 participants enrolled for a dose of ATV before more participants can be enrolled and studied at that same dose. Clinic visits will be every 4 weeks through Week 48, then every 8 weeks until the last participant to enroll in the study has reached Week 96 of his/her treatment. If, after 56 weeks, a participant has a toxic reaction to a nucleoside/tide reverse transcriptase inhibitor (NRTI) in their medication regimen, the regimen may be changed to a different NRTI. At every visit, participants will undergo a complete medical history and physical exam, cardiac conduction evaluation, and urine and blood collection. Participants of childbearing age will have a pregnancy test performed at each visit.
Step II will be open only to South African participants of Step I who have responded to treatment by the end of Step I. All such participants will be given ATV in capsule form at the same dose they received at the end of Step I, as well as the other antiretrovirals they were receiving during Step I. Step II will continue until ATV is approved in South Africa and readily available by individual prescription, and participants will have a study visit every 12 weeks.
Allocation: Randomized, Endpoint Classification: Pharmacokinetics Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Univ of Alabama at Birmingham - Pediatric
Active, not recruiting
National Institute of Allergy and Infectious Diseases (NIAID)
Results (where available)
- Source: http://clinicaltrials.gov/show/NCT00006604
- Information obtained from ClinicalTrials.gov on July 15, 2010
Medical and Biotech [MESH] Definitions
An HIV protease inhibitor that works by interfering with the reproductive cycle of HIV.
Inflammation of brain parenchymal tissue as a result of viral infection. Encephalitis may occur as primary or secondary manifestation of TOGAVIRIDAE INFECTIONS; HERPESVIRIDAE INFECTIONS; ADENOVIRIDAE INFECTIONS; FLAVIVIRIDAE INFECTIONS; BUNYAVIRIDAE INFECTIONS; PICORNAVIRIDAE INFECTIONS; PARAMYXOVIRIDAE INFECTIONS; ORTHOMYXOVIRIDAE INFECTIONS; RETROVIRIDAE INFECTIONS; and ARENAVIRIDAE INFECTIONS.
Viral infections of the leptomeninges and subarachnoid space. TOGAVIRIDAE INFECTIONS; FLAVIVIRIDAE INFECTIONS; RUBELLA; BUNYAVIRIDAE INFECTIONS; ORBIVIRUS infections; PICORNAVIRIDAE INFECTIONS; ORTHOMYXOVIRIDAE INFECTIONS; RHABDOVIRIDAE INFECTIONS; ARENAVIRIDAE INFECTIONS; HERPESVIRIDAE INFECTIONS; ADENOVIRIDAE INFECTIONS; JC VIRUS infections; and RETROVIRIDAE INFECTIONS may cause this form of meningitis. Clinical manifestations include fever, headache, neck pain, vomiting, PHOTOPHOBIA, and signs of meningeal irritation. (From Joynt, Clinical Neurology, 1996, Ch26, pp1-3)
Infections with viruses of the family PARAMYXOVIRIDAE. This includes MORBILLIVIRUS INFECTIONS; RESPIROVIRUS INFECTIONS; PNEUMOVIRUS INFECTIONS; HENIPAVIRUS INFECTIONS; AVULAVIRUS INFECTIONS; and RUBULAVIRUS INFECTIONS.
Central Nervous System Infections
Pathogenic infections of the brain, spinal cord, and meninges. DNA VIRUS INFECTIONS; RNA VIRUS INFECTIONS; BACTERIAL INFECTIONS; MYCOPLASMA INFECTIONS; SPIROCHAETALES INFECTIONS; fungal infections; PROTOZOAN INFECTIONS; HELMINTHIASIS; and PRION DISEASES may involve the central nervous system as a primary or secondary process.
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