The Safety and Effectiveness of Adefovir Dipivoxil in HIV-Infected Children

NCT ID: NCT00000843

Last Updated: 2005-06-24

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 24 participants
• Study Classification: INTERVENTIONAL

Brief Summary

To evaluate the single-dose pharmacokinetic profile and acute toxicity of bis-POM PMEA ( adefovir dipivoxil ) in HIV-1 infected children, and to determine whether age-related differences exist. To ascertain dosages that may be suitable for a multiple-dose evaluation in this patient population.

Although the oral bioavailability of PMEA ( adefovir ) is low, the prodrug bis-POM PMEA has resulted in increased bioavailability in adult patients in clinical trials. However, the safety and pharmacokinetic patterns of drugs in infants often differ from those of adults and the direction of the variation is not predictable. This study will assess these parameters of bis-POM PMEA in children.

Detailed Description

Although the oral bioavailability of PMEA ( adefovir ) is low, the prodrug bis-POM PMEA has resulted in increased bioavailability in adult patients in clinical trials. However, the safety and pharmacokinetic patterns of drugs in infants often differ from those of adults and the direction of the variation is not predictable. This study will assess these parameters of bis-POM PMEA in children.

Patients are stratified by age, and separate cohorts from each age group receive 1 of 2 single doses of bis-POM PMEA. The lower dose is given to patients ages 3 months through 17 years; if toxicity is acceptable, the other cohort in this age range receives the higher dose. At this point, accrual of infants < 3 months old may begin at the lower dose, followed by accrual of this age group at the higher dose if toxicity is acceptable. Serum drug concentrations are monitored up to 8 hours post dose.

AS PER AMENDMENT 5/2/97: Based on data from both the low- and high-dose cohorts of the older age group (>= 3 months to < 18 years), the younger age group (<3 months) will be started at the high-dose.

Conditions

HIV Infections

Study Design

• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Interventions

Adefovir dipivoxil

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

Patients must have:

• Asymptomatic or mildly symptomatic HIV infection, with no worse than grade 1 toxicity for any symptoms.
• Consent of parent or guardian.

Prior Medication:

Allowed:

• IV gammaglobulin and aerosolized pentamidine for PCP prophylaxis.
• Antiretrovirals if discontinued by 72 hr prior to study entry.

Exclusion Criteria

Co-existing Condition:

Patients with the following symptoms or conditions are excluded:

• Acute or chronic infections that require treatment during study.

Concurrent Medication:

Excluded:

• Antiretrovirals other than study drug.
• Other investigational agents.
• Immunomodulators.
• HIV-1 vaccines.
• Glucocorticoids.
• Drugs with potential for adverse interaction with study drug or that would interfere with quantitation of study drug in serum or plasma.
• TMP / SMX and dapsone.

PER AMENDMENT 8/23/96:

• Drugs which may affect renal excretion:
• Probenecid, Acyclovir, Ganciclovir, Foscarnet, Amphotericin B and Pentamidine.

Prior Medication:

Excluded within 72 hr prior to study entry:

• Antiretrovirals other than study drug.
• Other investigational agents.
• Immunomodulators.
• HIV-1 vaccines.
• Glucocorticoids.
• Drugs with potential for adverse interaction with study drug or that would interfere with quantitation of study drug in serum or plasma.
• TMP / SMX and dapsone.

PER AMENDMENT 8/23/96:

• Drugs which may affect renal excretion:
• Probenecid, Acyclovir, Ganciclovir, Foscarnet, Amphotericin B and Pentamidine.

• Minimum Eligible Age: 1 Day
• Maximum Eligible Age: 17 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Institute of Allergy and Infectious Diseases (NIAID)

NIH

Sponsor Role: lead

Principal Investigators

Hughes W

Role: STUDY_CHAIR

Shenep J

Role: STUDY_CHAIR

Locations

UCSF / Moffitt Hosp - Pediatric

San Francisco, California, United States

Univ of Florida Health Science Ctr / Pediatrics

Jacksonville, Florida, United States

Chicago Children's Memorial Hosp

Chicago, Illinois, United States

Johns Hopkins Hosp - Pediatric

Baltimore, Maryland, United States

Children's Hosp of Boston

Boston, Massachusetts, United States

Children's Hosp of New Jersey / UMDNJ - New Jersey Med Schl

Newark, New Jersey, United States

Children's Hosp of Philadelphia

Philadelphia, Pennsylvania, United States

Saint Jude Children's Research Hosp of Memphis

Memphis, Tennessee, United States

Vanderbilt Univ Med Ctr

Nashville, Tennessee, United States

Univ of Puerto Rico / Univ Children's Hosp AIDS

San Juan, , Puerto Rico

Countries

United States; Puerto Rico

References

McKinney RE Jr. Ongoing and future trials of antiretroviral therapy in the pediatric AIDS clinical trials group (PACTG). Conf Retroviruses Opportunistic Infect. 1996 Jan 28-Feb 1;3rd:173

Reference Type: BACKGROUND

Other Identifiers

ACTG 310

Identifier Type: -

Identifier Source: org_study_id