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

NCT ID: NCT00000768

Last Updated: 2021-11-04

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 24 participants
• Study Classification: INTERVENTIONAL
• Study Completion Date: 1998-08-31

Brief Summary

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.

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.

Conditions

Colitis; HIV Infections

Keywords

Intestinal Absorption; Ganciclovir; Drug Therapy, Combination; Cytomegalovirus Infections; Colitis; Administration, Oral; Acquired Immunodeficiency Syndrome; Biological Availability; Glutamic Acid

Study Design

• Allocation Method: RANDOMIZED
• Primary Study Purpose: TREATMENT

Interventions

Glutamic acid hydrochloride

Intervention Type: DRUG

Ganciclovir

Intervention Type: DRUG

Eligibility 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.

• Minimum Eligible Age: 13 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Hoffmann-La Roche

INDUSTRY

Sponsor Role: collaborator

National Institute of Allergy and Infectious Diseases (NIAID)

NIH

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Jacobson M

Role: STUDY_CHAIR

Dieterich D

Role: STUDY_CHAIR

Kotler D

Role: STUDY_CHAIR

Laine L

Role: STUDY_CHAIR

Kumar P

Role: STUDY_CHAIR

Locations

Alabama Therapeutics CRS

Birmingham, Alabama, United States

Ucsf Aids Crs

San Francisco, California, United States

Washington U CRS

St Louis, Missouri, United States

NY Univ. HIV/AIDS CRS

New York, New York, United States

Univ. of Cincinnati CRS

Cincinnati, Ohio, United States

Countries

United States

References

Dieterich DT, Kotler DP, Busch DF, Crumpacker C, Du Mond C, Dearmand B, Buhles W. Ganciclovir treatment of cytomegalovirus colitis in AIDS: a randomized, double-blind, placebo-controlled multicenter study. J Infect Dis. 1993 Feb;167(2):278-82. doi: 10.1093/infdis/167.2.278.

Reference Type: BACKGROUND

PMID: 8380610 (View on PubMed)

Other Identifiers

11158

Identifier Type: REGISTRY

Identifier Source: secondary_id

ACTG 183

Identifier Type: -

Identifier Source: org_study_id