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

Sponsor

National Institute of Allergy and Infectious Diseases (NIAID) (NIH)

Overall Status

Completed

CT.gov ID

NCT00000768

Collaborator

Hoffmann-La Roche (Industry)

Enrollment

Locations

4.8

Patients Per Site

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Colitis HIV Infections	Drug: Glutamic acid hydrochloride Drug: Ganciclovir	Phase 1

Detailed Description

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 Design

Study Type:

Interventional

Allocation:

Randomized

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

Actual Study Completion Date :

Aug 1, 1998

Outcome Measures

Primary Outcome Measures

Eligibility Criteria

Criteria

Ages Eligible for Study:

13 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria

Concurrent Medication:

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

Locations

	Site	City	State	Country	Postal Code
1	Alabama Therapeutics CRS	Birmingham	Alabama	United States	35294
2	Ucsf Aids Crs	San Francisco	California	United States
3	Washington U CRS	Saint Louis	Missouri	United States
4	NY Univ. HIV/AIDS CRS	New York	New York	United States	10016
5	Univ. of Cincinnati CRS	Cincinnati	Ohio	United States	45267