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

This study has been completed.
Sponsor:
Collaborator:
Hoffmann-La Roche
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT00000668
First received: November 2, 1999
Last updated: March 15, 2012
Last verified: March 2012
  Purpose

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.


Condition Intervention Phase
Cytomegalovirus Retinitis
HIV Infections
Drug: Ganciclovir
Phase 1

Study Type: Interventional
Study Design: Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I Pharmacokinetic and Tolerance Study of 28-Day Regimens of Oral Ganciclovir

Resource links provided by NLM:


Further study details as provided by National Institute of Allergy and Infectious Diseases (NIAID):

Estimated Enrollment: 48
Study Completion Date: February 1995
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.

  Eligibility

Ages Eligible for Study:   13 Years to 60 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00000668

Locations
United States, California
Univ of California / San Diego Treatment Ctr
San Diego, California, United States, 921036325
San Francisco AIDS Clinic / San Francisco Gen Hosp
San Francisco, California, United States, 941102859
Mount Zion Med Ctr
San Francisco, California, United States, 94115
Davies Med Ctr
San Francisco, California, United States, 94114
United States, New York
Cornell Univ Med Ctr
New York, New York, United States, 10021
Sponsors and Collaborators
Hoffmann-La Roche
  More Information

Additional Information:
Publications:
Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT00000668     History of Changes
Other Study ID Numbers: ACTG 127, ICM 1505, FDA 37A, RS-21592, 11102
Study First Received: November 2, 1999
Last Updated: March 15, 2012
Health Authority: United States: Federal Government

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
Retinitis
AIDS-Related Opportunistic Infections
Ganciclovir
Cytomegalovirus Infections
Acquired Immunodeficiency Syndrome

Additional relevant MeSH terms:
HIV Infections
Acquired Immunodeficiency Syndrome
Retinitis
Cytomegalovirus Retinitis
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Slow Virus Diseases
Retinal Diseases
Eye Diseases
Cytomegalovirus Infections
Herpesviridae Infections
DNA Virus Infections
Eye Infections, Viral
Eye Infections
Ganciclovir
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on July 13, 2014