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

HIV Infections Clinical Trial

Official title:

A Phase IA Single Dose Pharmacokinetics and Safety Study of the Oral Antiviral Compound, 9-[2-(Bispivaloyloxymethyl)Phosphonylmethoxyethyl]Adenine (Bis-POM PMEA) (Adefovir Dipivoxil) in Children With HIV-1 Infection

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00000843
• Other study ID #: ACTG 310
• Status: Completed
• Phase: Phase 1
• First received: November 2, 1999
• Last updated: June 23, 2005

Study information

• Verified date: April 1998
• Source: National Institute of Allergy and Infectious Diseases (NIAID)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 24
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A to 17 Years

Eligibility

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.

Study Design

Endpoint Classification: Pharmacokinetics Study, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• HIV Infections

Intervention

Drug:
• Adefovir dipivoxil

Locations

Country	Name	City	State
Puerto Rico	Univ of Puerto Rico / Univ Children's Hosp AIDS	San Juan
United States	Johns Hopkins Hosp - Pediatric	Baltimore	Maryland
United States	Children's Hosp of Boston	Boston	Massachusetts
United States	Chicago Children's Memorial Hosp	Chicago	Illinois
United States	Univ of Florida Health Science Ctr / Pediatrics	Jacksonville	Florida
United States	Saint Jude Children's Research Hosp of Memphis	Memphis	Tennessee
United States	Vanderbilt Univ Med Ctr	Nashville	Tennessee
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	UCSF / Moffitt Hosp - Pediatric	San Francisco	California

Sponsors (1)

Lead Sponsor	Collaborator
National Institute of Allergy and Infectious Diseases (NIAID)

Countries where clinical trial is conducted

United States,  Puerto Rico, 

References & Publications (1)

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