Clinical trial NCT00000805: 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
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Cytomegalovirus Infections
HIV Infections
Keywords: Ganciclovir
Cytomegalovirus Infections
Acquired Immunodeficiency Syndrome
Lead sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Sponsor class: NIH
First posted: 2001-08-31
Enrollment: 32
Sex: ALL
Minimum age (years): 14
Maximum age (years): 20
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility criteria: 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.

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Childrens Hosp. LA - Dept. of Ped., Div. of Clinical Immunology & Allergy
state: California
city: Los Angeles
country: United States
facility: Usc La Nichd Crs
state: California
city: Los Angeles
country: United States
facility: UCLA-Los Angeles/Brazil AIDS Consortium (LABAC) CRS
state: California
city: Oakland
country: United States
facility: Children's Hosp. & Research Ctr. Oakland, Ped. Clinical Research Ctr. & Research Lab.
state: California
city: San Diego
country: United States
facility: UCSD Maternal, Child, and Adolescent HIV CRS
state: California
city: Torrance
country: United States
facility: Harbor - UCLA Med. Ctr. - Dept. of Peds., Div. of Infectious Diseases
state: California
city: Aurora
country: United States
facility: Univ. of Colorado Denver NICHD CRS
state: Colorado
city: Miami
country: United States
facility: Univ. of Miami Ped. Perinatal HIV/AIDS CRS
state: Florida
city: Chicago
country: United States
facility: Chicago Children's CRS
state: Illinois
city: New Orleans
country: United States
facility: Tulane/LSU Maternal/Child CRS
state: Louisiana
city: Boston
country: United States
facility: HMS - Children's Hosp. Boston, Div. of Infectious Diseases
state: Massachusetts
city: Boston
country: United States
facility: BMC, Div. of Ped Infectious Diseases
state: Massachusetts
city: Paterson
country: United States
facility: St. Joseph's Hosp. & Med. Ctr. of New Jersey
state: New Jersey
city: New York
country: United States
facility: Columbia IMPAACT CRS
state: New York
city: New York
country: United States
facility: Incarnation Children's Ctr.
state: New York
city: New York
country: United States
facility: NYU Med. Ctr., Dept. of Medicine
state: New York
city: Philadelphia
country: United States
facility: St. Christopher's Hosp. for Children
state: Pennsylvania
city: Seattle
country: United States
facility: UW School of Medicine - CHRMC
state: Washington
city: San Juan
country: Puerto Rico
facility: Univ. of Puerto Rico Ped. HIV/AIDS Research Program CRS
Study officials:
name: Frenkel L
role: STUDY_CHAIR
name: Dankner W
role: STUDY_CHAIR
References:
citation: 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)
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)
citation: 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. doi: 10.1086/317600. Epub 2000 Nov 8.