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

HIV Infections Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00000768
• Other study ID #: ACTG 183
• Secondary ID: 11158
• Status: Completed
• Phase: Phase 1
• Est. completion date: August 1998

Study information

• Verified date: October 2021
• Source: National Institute of Allergy and Infectious Diseases (NIAID)
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 24
• Est. completion date: August 1998
• Accepts healthy volunteers: No
• Gender: All
• Age group: 13 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Colitis
• Digestive System Diseases
• Gastrointestinal Diseases
• HIV Infections

Intervention

Drug:
• Glutamic acid hydrochloride

• Ganciclovir

Locations

Country	Name	City	State
United States	Alabama Therapeutics CRS	Birmingham	Alabama
United States	Univ. of Cincinnati CRS	Cincinnati	Ohio
United States	NY Univ. HIV/AIDS CRS	New York	New York
United States	Washington U CRS	Saint Louis	Missouri
United States	Ucsf Aids Crs	San Francisco	California

Sponsors (2)

Lead Sponsor	Collaborator
National Institute of Allergy and Infectious Diseases (NIAID)	Hoffmann-La Roche

Country where clinical trial is conducted

United States, 

References & Publications (1)

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. — View Citation