A Pharmacokinetic and Tolerance Study of Oral Ganciclovir in HIV-Infected Children With Asymptomatic Cytomegalovirus Infection and Low CD4 Cell Counts or Quiescent Cytomegalovirus Disease

HIV Infections Clinical Trial

Official title:

A Pharmacokinetic and Tolerance Study of Oral Ganciclovir in HIV-Infected Children With Asymptomatic Cytomegalovirus Infection and Low CD4 Cell Counts or Quiescent Cytomegalovirus Disease

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00000805
• Other study ID #: ACTG 226
• Secondary ID: 11203
• Status: Completed
• Phase: Phase 1
• Est. completion date: March 1998

Study information

• Verified date: October 2021
• Source: National Institute of Allergy and Infectious Diseases (NIAID)
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

PRIMARY: To determine the pharmacokinetics, MTD, and long-term safety and tolerance of oral ganciclovir in HIV-infected infants, children, and adolescents.

SECONDARY: To evaluate the effect of oral ganciclovir on the virologic parameters of CMV.

Maintenance treatment with intravenous (IV) ganciclovir for cytomegalovirus retinitis in AIDS patients is now standard therapy, but daily IV therapy can be complicated by catheter infections and thrombosis. An oral regimen of ganciclovir has been administered safely in adult AIDS patients and may be of significant benefit to children and infants as well.

Description:

Maintenance treatment with intravenous (IV) ganciclovir for cytomegalovirus retinitis in AIDS patients is now standard therapy, but daily IV therapy can be complicated by catheter infections and thrombosis. An oral regimen of ganciclovir has been administered safely in adult AIDS patients and may be of significant benefit to children and infants as well.

Patients are assigned to 1 of 5 (PER AMENDMENT 10/24/95, was 4) oral (syrup or capsules) dose levels following a single intravenous dose of ganciclovir. Treatment continues for 72 (PER AMENDMENT 10/24/95, was 24 weeks) weeks after the last patient has been enrolled.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 32
• Est. completion date: March 1998
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 20 Years

Eligibility

Inclusion Criteria

Concurrent Medication:

PER AMENDMENT 10/24/95: Allowed:

• All antiretroviral agents and other medications except those listed under Exclusion - Concurrent Medications.

• Didanosine. However, patients receiving both drugs (didanosine and ganciclovir) should be monitored for toxicity.

• Amphotericin B is allowed but requires additional monitoring.

Patients must have:

• HIV infection.

• CMV infection.

• CD4 count < 150 cells/mm3 or < 15 percent AND/OR quiescent CMV disease.

• NO loss of sight from CMV retinitis.

• NO acute opportunistic infection.

• Life expectancy at least to study completion.

• Consent of parent or guardian.

NOTE:

• Infants < 6 months of age at enrollment must have been >= 36 weeks gestational age at birth.

NOTE:

• Patients may co-enroll in other ACTG protocols that do not involve the administration of disallowed medications.

Exclusion Criteria

Co-existing Condition:

Patients with the following symptoms or conditions are excluded:

• Loss of sight in one eye for any reason, with evidence of CMV retinitis in the other eye.

• Acute or chronic diarrhea that would affect absorption.

• Clinical or laboratory toxicities of grade 3 or worse.

Concurrent Medication:

Excluded:

• Foscarnet.

• Acyclovir.

• Interferon.

• Myelotoxic agents for malignancy or other condition.

• Other agents with anti-CMV activity. (NOTE:

Enrollment of patients on IVIG must be discussed with protocol chair.)

• Imipenem/cilastatin sodium.

Prior Medication:

Excluded within 30 days prior to study entry:

• G-CSF or GM-CSF.

Related Conditions & MeSH terms

• Communicable Diseases
• Cytomegalovirus Infections
• HIV Infections
• Infections

Intervention

Drug:
• Ganciclovir

Locations

Country	Name	City	State
Puerto Rico	Univ. of Puerto Rico Ped. HIV/AIDS Research Program CRS	San Juan
United States	Univ. of Colorado Denver NICHD CRS	Aurora	Colorado
United States	BMC, Div. of Ped Infectious Diseases	Boston	Massachusetts
United States	HMS - Children's Hosp. Boston, Div. of Infectious Diseases	Boston	Massachusetts
United States	Chicago Children's CRS	Chicago	Illinois
United States	Childrens Hosp. LA - Dept. of Ped., Div. of Clinical Immunology & Allergy	Los Angeles	California
United States	UCLA-Los Angeles/Brazil AIDS Consortium (LABAC) CRS	Los Angeles	California
United States	Usc La Nichd Crs	Los Angeles	California
United States	Univ. of Miami Ped. Perinatal HIV/AIDS CRS	Miami	Florida
United States	Tulane/LSU Maternal/Child CRS	New Orleans	Louisiana
United States	Columbia IMPAACT CRS	New York	New York
United States	Incarnation Children's Ctr.	New York	New York
United States	NYU Med. Ctr., Dept. of Medicine	New York	New York
United States	Children's Hosp. & Research Ctr. Oakland, Ped. Clinical Research Ctr. & Research Lab.	Oakland	California
United States	St. Joseph's Hosp. & Med. Ctr. of New Jersey	Paterson	New Jersey
United States	St. Christopher's Hosp. for Children	Philadelphia	Pennsylvania
United States	UCSD Maternal, Child, and Adolescent HIV CRS	San Diego	California
United States	UW School of Medicine - CHRMC	Seattle	Washington
United States	Harbor - UCLA Med. Ctr. - Dept. of Peds., Div. of Infectious Diseases	Torrance	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 (3)

Capparelli EV, Frenkel LM, Dankner W, Wei LJ, Xu J, Spector S, Connor J, Ballow A, Mohan K, Robinson C, Shaver A, Rich K, Thompson M, Read J, Wirkus C, Balsley J, Culnane M, Mcintosh K. Population pharmacokinetics of oral and intravenous ganciclovir (GCV) in HIV and CMV infected children. Program Abstr Intersci Conf Antimicrob Agents Chemother. 1996 Sep 15-18:10 (abstract no A51)

Frenkel LM, Capparelli EV, Dankner WM, Xu J, Smith IL, Ballow A, Culnane M, Read JS, Thompson M, Mohan KM, Shaver A, Robinson CA, Stempien MJ, Burchett SK, Melvin AJ, Borkowsky W, Petru A, Kovacs A, Yogev R, Goldsmith J, McFarland EJ, Spector SA. Oral ganciclovir in children: pharmacokinetics, safety, tolerance, and antiviral effects. The Pediatric AIDS Clinical Trials Group. J Infect Dis. 2000 Dec;182(6):1616-24. Epub 2000 Nov 8. — View Citation

Frenkel LM, Dankner W, Capparelli E, Wei LJ, Xu J, Spector S, Connor J, Ballow A, Mohan K, Robinson C, Shaver A, Rich K, Thompson M, Read J, Wirkus C, Balsley J, Culnane M, McIntosh K. A pharmacokinetic (PK) study of oral ganciclovir (GCV) in HIV- and cytomegalovirus (CMV)- infected children. Int Conf AIDS. 1996 Jul 7-12;11(2):31 (abstract no WeB550)