A Randomized Comparative Pharmacokinetic Study of Oral Ganciclovir After Treatment With Intravenous Ganciclovir for Cytomegalovirus Gastrointestinal Disease in AIDS Patients
Information source: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov processed this data on August 20, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Colitis; HIV Infections
Intervention: Glutamic acid hydrochloride (Drug); Ganciclovir (Drug)
Phase: Phase 1
Status: Completed
Sponsored by: National Institute of Allergy and Infectious Diseases (NIAID) Official(s) and/or principal investigator(s): Jacobson M, Study Chair Dieterich D, Study Chair Kotler D, Study Chair Laine L, Study Chair Kumar P, Study Chair
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.
Clinical Details
Official title: A Randomized Comparative Pharmacokinetic Study of Oral Ganciclovir After Treatment With Intravenous Ganciclovir for Cytomegalovirus Gastrointestinal Disease in AIDS Patients
Study design: Allocation: Randomized, Endpoint Classification: Pharmacokinetics Study, Primary Purpose: Treatment
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
Minimum age: 13 Years.
Maximum age: N/A.
Gender(s): Both.
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.
Locations and Contacts
Alabama Therapeutics CRS, Birmingham, Alabama 35294, 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 10016, United States
Univ. of Cincinnati CRS, Cincinnati, Ohio 45267, United States
Additional Information
Related publications: 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.
Last updated: March 30, 2012
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