A Randomized Comparative Pharmacokinetic Study of Oral Ganciclovir After Treatment With Intravenous Ganciclovir for Cytomegalovirus Gastrointestinal Disease in AIDS Patients

October 27, 2021 updated by: National Institute of Allergy and Infectious Diseases (NIAID)

To determine the oral bioavailability of three dose levels of oral ganciclovir given with and without glutamic acid hydrochloride in patients with cytomegalovirus (CMV) GI disease, and to compare the bioavailability of these regimens to that of standard intravenous (IV) ganciclovir.

Long-term ganciclovir maintenance therapy has been recommended for CMV colitis or esophagitis following induction treatment. Oral ganciclovir is a likely candidate for maintenance because of its possible therapeutic value and ease of administration, but an optimum dose has not been determined. Since oral ganciclovir has a low bioavailability and is more soluble in an acid pH environment, the addition of glutamic acid hydrochloride may enhance gastrointestinal absorption of this drug.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Long-term ganciclovir maintenance therapy has been recommended for CMV colitis or esophagitis following induction treatment. Oral ganciclovir is a likely candidate for maintenance because of its possible therapeutic value and ease of administration, but an optimum dose has not been determined. Since oral ganciclovir has a low bioavailability and is more soluble in an acid pH environment, the addition of glutamic acid hydrochloride may enhance gastrointestinal absorption of this drug.

All patients receive an induction regimen of IV ganciclovir administered twice daily for 21 to 42 (Per Amendment 3/4/95) days. A permanent venous catheter is implanted for the induction therapy. If clinically improved following induction, patients are then randomized to receive one of three doses of oral ganciclovir, given first without and then with oral glutamic acid hydrochloride, every 8 hours until they reach a steady state. PER AMENDMENT 3/14/95: After subjects have reached steady state with oral ganciclovir and glutamic acid hydrochloride then PK samples will be taken. Subjects will continue the dosing regimen they were assigned to (glutamic acid hydrochloride will be added if it resulted in at least 33% increased bioavailability) for up to 12 months or until relapse of CMV GI disease is documented. Subjects will be followed at monthly intervals for safety evaluation and for evidence of CMV GI relapse. Subjects who have clinical symptoms of relapse will undergo repeat endoscopy or colonoscopy to document the relapse.

Study Type

Interventional

Enrollment

24

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Alabama
      • Birmingham, Alabama, United States, 35294
        • Alabama Therapeutics CRS
    • California
      • San Francisco, California, United States
        • Ucsf Aids Crs
    • Missouri
      • Saint Louis, Missouri, United States
        • Washington U CRS
    • New York
      • New York, New York, United States, 10016
        • NY Univ. HIV/AIDS CRS
    • Ohio
      • Cincinnati, Ohio, United States, 45267
        • Univ. of Cincinnati CRS

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

13 years and older (ADULT, OLDER_ADULT, CHILD)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria

Concurrent Medication:

Recommended:

  • PCP prophylaxis.

Allowed:

  • Antiretroviral therapy during induction and pharmacokinetic part of study, provided patient remains on the same antiretroviral therapy for the duration of the study.
  • Chemotherapy for Kaposi's sarcoma, provided patient is hematologically stable for at least 30 days prior to study entry.
  • Recombinant human erythropoietin.
  • GM-CSF and G-CSF.
  • Other medications necessary for patient's welfare, at the physician's discretion.

Patients must have:

  • HIV infection.
  • Biopsy-proven cytomegalovirus (CMV) colitis.
  • Life expectancy of at least 3 months.
  • No active AIDS-defining opportunistic infection requiring therapy that is known to cause nephrotoxicity or myelosuppression.

NOTE:

  • Kaposi's sarcoma is permitted if patients are hematologically stable for at least 30 days prior to study entry.

Exclusion Criteria

Co-existing Condition:

Patients with the following symptoms or conditions are excluded:

  • Other etiologies for diarrhea identified at study entry.

PER AMENDMENT 3/14/95:

  • For subjects who have diarrhea - no other etiologies for diarrhea identified within 6 weeks of enrollment.
  • Known hypersensitivity to study drugs.
  • CMV retinitis.

Concurrent Medication:

Excluded:

  • Acyclovir or probenecid (PER AMENDMENT 3/14/95).
  • Immunomodulators.
  • Biologic response modifiers (other than GM-CSF or G-CSF).
  • Investigational agents, with the exception of treatment IND drugs.
  • Antacids.
  • H2 blockers.
  • Proton pump inhibitors.
  • Foscarnet during induction and pharmacokinetic part of study.
  • Intravenous CMV retinitis maintenance therapy (including ganciclovir) during pharmacokinetic part of study.
  • Nephrotoxic agents.

Prior Medication:

Excluded within 14 days prior to study entry:

  • Immunomodulators.
  • Biologic response modifiers (other than GM-CSF or G-CSF).
  • Investigational agents, with the exception of treatment IND drugs.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

National Institute of Allergy and Infectious Diseases (NIAID)

Collaborators

Hoffmann-La Roche

Investigators

  • Study Chair: Dieterich D
  • Study Chair: Kotler D
  • Study Chair: Laine L
  • Study Chair: Kumar P

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Completion (ACTUAL)

August 1, 1998

Study Registration Dates

First Submitted

November 2, 1999

First Submitted That Met QC Criteria

August 30, 2001

First Posted (ESTIMATE)

August 31, 2001

Study Record Updates

Last Update Posted (ACTUAL)

November 4, 2021

Last Update Submitted That Met QC Criteria

October 27, 2021

Last Verified

October 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ACTG 183
  • 11158 (DAIDS ES Registry Number)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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