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A Phase I Pharmacokinetic and Tolerance Study of 28-Day Regimens of Oral Ganciclovir

Primary Purpose

Cytomegalovirus Retinitis, HIV Infections

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Ganciclovir
Sponsored by
National Institute of Allergy and Infectious Diseases (NIAID)
About
Eligibility
Locations
Outcomes
Full info

About this trial

This is an interventional treatment trial for Cytomegalovirus Retinitis focused on measuring Retinitis, AIDS-Related Opportunistic Infections, Ganciclovir, Cytomegalovirus Infections, Acquired Immunodeficiency Syndrome

Eligibility Criteria

13 Years - 60 Years (Child, Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria Concurrent Medication: Allowed: Topical acyclovir. There are two groups of patients. Group A must have: Confirmation of HIV infection by HIV antibody testing, p24 antigen, or culture of HIV. A positive urine culture for cytomegalovirus (CMV) within 4 weeks of study entry. Not received prior ganciclovir therapy. Group B must have: A diagnosis of AIDS by CDC criteria. CMV retinitis diagnosed on funduscopic evaluation by an ophthalmologist. Completed 4 weeks of intravenous ganciclovir with an improvement or stabilization of retinitis. The course of therapy should include a minimum of 24 days total of intravenous ganciclovir. Patients in both groups must understand the nature of the study, agree to the tests required in the protocol, and must understand and sign an informed consent form approved by the appropriate Institutional Review Board (IRB) and by Syntex. Required: Group B: 4 weeks of intravenous ganciclovir which should include a minimum of 24 days total of intravenous ganciclovir. Exclusion Criteria Co-existing Condition: Patients with the following are excluded: Macular involvement due to cytomegalovirus (CMV) retinitis in both eyes. Active CMV retinitis in which there is progression. Presence of diarrhea or other clinically significant or uncontrolled gastrointestinal disease including persistent nausea and/or abdominal pain. Diarrhea is defined as > 3 unformed stools/day. Dementia or decreased mentation or other encephalopathic signs and symptoms which would interfere with the ability of the patient to follow the protocol, to take assigned dose regimen reliably, and to keep a daily record on a calendar. Significant CMV disease of other organs, including CMV gastroenteritis or CMV pneumonia. Concurrent Medication: Excluded: Any investigational drug. Acyclovir not specifically allowed. Any other nucleoside analog. Zidovudine (AZT). Probenecid. Aspirin. Patients with the following are excluded: Macular involvement due to cytomegalovirus (CMV) retinitis in both eyes. Active CMV retinitis in which there is progression. CMV end organ disease. Presence of diarrhea or other clinically significant or uncontrolled gastrointestinal disease including persistent nausea and/or abdominal pain. Diarrhea is defined as > 3 unformed stools/day. Dementia or decreased mentation or other encephalopathic signs and symptoms which would interfere with the ability of the patient to follow the protocol, to take assigned dose regimen reliably, and to keep a daily record on a calendar. Significant CMV disease of other organs, including CMV gastroenteritis or CMV pneumonia. Prior Medication: Excluded within 4 days of study entry: Antimetabolite. Interferon. Other nucleoside analog including zidovudine (AZT). Excluded for Group A: Ganciclovir or other anti-cytomegalovirus therapy.

Sites / Locations

  • Univ of California / San Diego Treatment Ctr
  • San Francisco AIDS Clinic / San Francisco Gen Hosp
  • Davies Med Ctr
  • Mount Zion Med Ctr
  • Cornell Univ Med Ctr

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

First Posted
November 2, 1999
Last Updated
October 26, 2021
Sponsor
National Institute of Allergy and Infectious Diseases (NIAID)
Collaborators
Hoffmann-La Roche
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1. Study Identification

Unique Protocol Identification Number
NCT00000668
Brief Title
A Phase I Pharmacokinetic and Tolerance Study of 28-Day Regimens of Oral Ganciclovir
Official Title
A Phase I Pharmacokinetic and Tolerance Study of 28-Day Regimens of Oral Ganciclovir
Study Type
Interventional

2. Study Status

Record Verification Date
October 2021
Overall Recruitment Status
Completed
Study Start Date
undefined (undefined)
Primary Completion Date
undefined (undefined)
Study Completion Date
February 1995 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
National Institute of Allergy and Infectious Diseases (NIAID)
Collaborators
Hoffmann-La Roche

4. Oversight

5. Study Description

Brief Summary
To determine the pharmacokinetics (blood levels) of three dose treatment plans of oral ganciclovir during a 28-day dosing period. Other purposes of the study are to determine in a population of HIV seropositive persons with cytomegalovirus (CMV) viremia, the safety, tolerance, and patient acceptability of oral ganciclovir given for 28 days, to collect preliminary laboratory evidence for antiviral activity and effectiveness of three dose regimens of oral ganciclovir based on blood and urine cultures of CMV, and to relate antiviral activity to dosage and to serum ganciclovir levels. CMV retinitis is an important sight-threatening opportunistic infection which affects about 10 to 15 percent of people with AIDS. A previous study has shown that treatment with ganciclovir resulted in a significant delay in time to first retinitis progression compared to untreated controls. More studies are warranted to evaluate effects at different doses.
Detailed Description
CMV retinitis is an important sight-threatening opportunistic infection which affects about 10 to 15 percent of people with AIDS. A previous study has shown that treatment with ganciclovir resulted in a significant delay in time to first retinitis progression compared to untreated controls. More studies are warranted to evaluate effects at different doses. In group A, 36 HIV seropositive patients with CMV viruria receive a single dose of intravenous ganciclovir followed by one of three oral dose regimens for 28 days. Twelve individuals are treated at each dose level. In group B, 12 patients with AIDS and CMV retinitis receive oral ganciclovir therapy. These 12 patients must have received an induction course of intravenous ganciclovir for 4 weeks prior to study entry and must have stable CMV retinitis. Measurements for both groups include pharmacokinetics, safety, and tolerance (history, physical examination, hematology, and serum chemistry), and CMV blood and urine cultures. In addition, there are weekly ophthalmologic evaluations for individuals in the group B study.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Cytomegalovirus Retinitis, HIV Infections
Keywords
Retinitis, AIDS-Related Opportunistic Infections, Ganciclovir, Cytomegalovirus Infections, Acquired Immunodeficiency Syndrome

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Masking
None (Open Label)
Enrollment
48 (false)

8. Arms, Groups, and Interventions

Intervention Type
Drug
Intervention Name(s)
Ganciclovir

10. Eligibility

Sex
All
Minimum Age & Unit of Time
13 Years
Maximum Age & Unit of Time
60 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria Concurrent Medication: Allowed: Topical acyclovir. There are two groups of patients. Group A must have: Confirmation of HIV infection by HIV antibody testing, p24 antigen, or culture of HIV. A positive urine culture for cytomegalovirus (CMV) within 4 weeks of study entry. Not received prior ganciclovir therapy. Group B must have: A diagnosis of AIDS by CDC criteria. CMV retinitis diagnosed on funduscopic evaluation by an ophthalmologist. Completed 4 weeks of intravenous ganciclovir with an improvement or stabilization of retinitis. The course of therapy should include a minimum of 24 days total of intravenous ganciclovir. Patients in both groups must understand the nature of the study, agree to the tests required in the protocol, and must understand and sign an informed consent form approved by the appropriate Institutional Review Board (IRB) and by Syntex. Required: Group B: 4 weeks of intravenous ganciclovir which should include a minimum of 24 days total of intravenous ganciclovir. Exclusion Criteria Co-existing Condition: Patients with the following are excluded: Macular involvement due to cytomegalovirus (CMV) retinitis in both eyes. Active CMV retinitis in which there is progression. Presence of diarrhea or other clinically significant or uncontrolled gastrointestinal disease including persistent nausea and/or abdominal pain. Diarrhea is defined as > 3 unformed stools/day. Dementia or decreased mentation or other encephalopathic signs and symptoms which would interfere with the ability of the patient to follow the protocol, to take assigned dose regimen reliably, and to keep a daily record on a calendar. Significant CMV disease of other organs, including CMV gastroenteritis or CMV pneumonia. Concurrent Medication: Excluded: Any investigational drug. Acyclovir not specifically allowed. Any other nucleoside analog. Zidovudine (AZT). Probenecid. Aspirin. Patients with the following are excluded: Macular involvement due to cytomegalovirus (CMV) retinitis in both eyes. Active CMV retinitis in which there is progression. CMV end organ disease. Presence of diarrhea or other clinically significant or uncontrolled gastrointestinal disease including persistent nausea and/or abdominal pain. Diarrhea is defined as > 3 unformed stools/day. Dementia or decreased mentation or other encephalopathic signs and symptoms which would interfere with the ability of the patient to follow the protocol, to take assigned dose regimen reliably, and to keep a daily record on a calendar. Significant CMV disease of other organs, including CMV gastroenteritis or CMV pneumonia. Prior Medication: Excluded within 4 days of study entry: Antimetabolite. Interferon. Other nucleoside analog including zidovudine (AZT). Excluded for Group A: Ganciclovir or other anti-cytomegalovirus therapy.
Facility Information:
Facility Name
Univ of California / San Diego Treatment Ctr
City
San Diego
State/Province
California
ZIP/Postal Code
921036325
Country
United States
Facility Name
San Francisco AIDS Clinic / San Francisco Gen Hosp
City
San Francisco
State/Province
California
ZIP/Postal Code
941102859
Country
United States
Facility Name
Davies Med Ctr
City
San Francisco
State/Province
California
ZIP/Postal Code
94114
Country
United States
Facility Name
Mount Zion Med Ctr
City
San Francisco
State/Province
California
ZIP/Postal Code
94115
Country
United States
Facility Name
Cornell Univ Med Ctr
City
New York
State/Province
New York
ZIP/Postal Code
10021
Country
United States

12. IPD Sharing Statement

Citations:
Citation
Spector SA, et al. Pharmacokinetic, safety and antiviral profile of oral ganciclovir in HIV-infected persons (ACTG 127). Natl Conf Hum Retroviruses Relat Infect (1st). 1993 Dec 12-16:154
Results Reference
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PubMed Identifier
7769276
Citation
Spector SA, Busch DF, Follansbee S, Squires K, Lalezari JP, Jacobson MA, Connor JD, Jung D, Shadman A, Mastre B, et al. Pharmacokinetic, safety, and antiviral profiles of oral ganciclovir in persons infected with human immunodeficiency virus: a phase I/II study. AIDS Clinical Trials Group, and Cytomegalovirus Cooperative Study Group. J Infect Dis. 1995 Jun;171(6):1431-7. doi: 10.1093/infdis/171.6.1431.
Results Reference
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A Phase I Pharmacokinetic and Tolerance Study of 28-Day Regimens of Oral Ganciclovir

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