A Randomized Comparative Pharmacokinetic Study of Oral Ganciclovir After Treatment With Intravenous Ganciclovir for Cytomegalovirus Gastrointestinal Disease in AIDS Patients
Glutamic acid hydrochloride
+ Ganciclovir
Infections transmises par le sang+30
+ Maladies génito-urinaires
+ Maladies Génitales
Étude thérapeutique
Résumé
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.
Protocole
Cette section fournit des détails sur le plan de l'étude, y compris la manière dont l'étude est conçue et ce qu'elle évalue.24 participants à inclure
Nombre total de participants que l'essai clinique vise à recruter.Traitement
Éligibilité
Les chercheurs recherchent des patients correspondant à une certaine description appelée critères d'éligibilité : état de santé général ou traitements antérieurs du patient.Tout sexe
Le sexe biologique des participants éligibles à s'inscrire.À partir de 13 ans
Tranche d'âge des participants éligibles à participer.Volontaires sains non autorisés
Indique si les individus en bonne santé et ne présentant pas la condition étudiée peuvent participer.Conditions
Pathologie
Critères
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.
Centres d'étude
Ce sont les hôpitaux, cliniques ou centres de recherche où l'essai est conduit. Vous pouvez trouver le site le plus proche de vous ainsi que son statut.Cette étude comporte 5 sites
Ucsf Aids Crs
San Francisco, United StatesWashington U CRS
St Louis, United StatesNY Univ. HIV/AIDS CRS
New York, United States