A Randomized Comparative Pharmacokinetic Study of Oral Ganciclovir After Treatment With Intravenous Ganciclovir for Cytomegalovirus Gastrointestinal Disease in AIDS Patients
Glutamic acid hydrochloride
+ Ganciclovir
Blood-Borne Infections+30
+ Urogenital Diseases
+ Genital Diseases
Treatment Study
Summary
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.
Protocol
This section provides details of the study plan, including how the study is designed and what the study is measuring.24 patients to be enrolled
Total number of participants that the clinical trial aims to recruit.Treatment Study
Eligibility
Researchers look for people who fit a certain description, called eligibility criteria: person's general health condition or prior treatments.Any sex
Biological sex of participants that are eligible to enroll.Over 13 Years
Range of ages for which participants are eligible to join.Healthy volunteers not allowed
If individuals who are healthy and do not have the condition being studied can participate.Conditions
Pathology
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.
Study Centers
These are the hospitals, clinics, or research facilities where the trial is being conducted. You can find the location closest to you and its status.This study has 5 locations
Ucsf Aids Crs
San Francisco, United StatesWashington U CRS
St Louis, United StatesNY Univ. HIV/AIDS CRS
New York, United States