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

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:
NCT00000768
First received: November 2, 1999
Last updated: March 30, 2012
Last verified: March 2012
  Purpose

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.


Condition Intervention Phase
Colitis
HIV Infections
Drug: Glutamic acid hydrochloride
Drug: Ganciclovir
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics Study
Primary Purpose: Treatment
Official Title: A Randomized Comparative Pharmacokinetic Study of Oral Ganciclovir After Treatment With Intravenous Ganciclovir for Cytomegalovirus Gastrointestinal Disease in AIDS Patients

Resource links provided by NLM:


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

Estimated Enrollment: 24
Study Completion Date: August 1998
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.

  Eligibility

Ages Eligible for Study:   13 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  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: NCT00000768

Locations
United States, Alabama
Alabama Therapeutics CRS
Birmingham, Alabama, United States, 35294
United States, California
Ucsf Aids Crs
San Francisco, California, United States
United States, Missouri
Washington U CRS
St. Louis, Missouri, United States
United States, New York
NY Univ. HIV/AIDS CRS
New York, New York, United States, 10016
United States, Ohio
Univ. of Cincinnati CRS
Cincinnati, Ohio, United States, 45267
Sponsors and Collaborators
Hoffmann-La Roche
Investigators
Study Chair: Jacobson M
Study Chair: Dieterich D
Study Chair: Kotler D
Study Chair: Laine L
Study Chair: Kumar P
  More Information

Additional Information:
Publications:
Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT00000768     History of Changes
Other Study ID Numbers: ACTG 183, 11158
Study First Received: November 2, 1999
Last Updated: March 30, 2012
Health Authority: United States: Federal Government

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
Intestinal Absorption
Ganciclovir
Drug Therapy, Combination
Cytomegalovirus Infections
Colitis
Administration, Oral
Acquired Immunodeficiency Syndrome
Biological Availability
Glutamic Acid

Additional relevant MeSH terms:
Acquired Immunodeficiency Syndrome
Colitis
Digestive System Diseases
Gastrointestinal Diseases
HIV Infections
Infection
Colonic Diseases
Gastroenteritis
Immune System Diseases
Immunologic Deficiency Syndromes
Intestinal Diseases
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Sexually Transmitted Diseases
Sexually Transmitted Diseases, Viral
Slow Virus Diseases
Virus Diseases
Ganciclovir
Anti-Infective Agents
Antiviral Agents
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on October 23, 2014