A Phase I Pharmacokinetic and Tolerance Study of 28-Day Regimens of Oral Ganciclovir

Inclusion Criteria

Concurrent Medication:

Allowed:

• Topical acyclovir.

There are two groups of patients. Group A must have:

• Confirmation of HIV infection by HIV antibody testing, p24 antigen, or culture of HIV.
• A positive urine culture for cytomegalovirus (CMV) within 4 weeks of study entry.
• Not received prior ganciclovir therapy.

Group B must have:

• A diagnosis of AIDS by CDC criteria.
• CMV retinitis diagnosed on funduscopic evaluation by an ophthalmologist.
• Completed 4 weeks of intravenous ganciclovir with an improvement or stabilization of retinitis. The course of therapy should include a minimum of 24 days total of intravenous ganciclovir.
• Patients in both groups must understand the nature of the study, agree to the tests required in the protocol, and must understand and sign an informed consent form approved by the appropriate Institutional Review Board (IRB) and by Syntex.

Required:

Group B:

• 4 weeks of intravenous ganciclovir which should include a minimum of 24 days total of intravenous ganciclovir.

Exclusion Criteria

Co-existing Condition:

Patients with the following are excluded:

• Macular involvement due to cytomegalovirus (CMV) retinitis in both eyes.
• Active CMV retinitis in which there is progression.
• Presence of diarrhea or other clinically significant or uncontrolled gastrointestinal disease including persistent nausea and/or abdominal pain. Diarrhea is defined as > 3 unformed stools/day.
• Dementia or decreased mentation or other encephalopathic signs and symptoms which would interfere with the ability of the patient to follow the protocol, to take assigned dose regimen reliably, and to keep a daily record on a calendar.
• Significant CMV disease of other organs, including CMV gastroenteritis or CMV pneumonia.

Concurrent Medication:

Excluded:

• Any investigational drug.
• Acyclovir not specifically allowed.
• Any other nucleoside analog.
• Zidovudine (AZT).
• Probenecid.
• Aspirin.

Patients with the following are excluded:

• Macular involvement due to cytomegalovirus (CMV) retinitis in both eyes.
• Active CMV retinitis in which there is progression.
• CMV end organ disease.
• Presence of diarrhea or other clinically significant or uncontrolled gastrointestinal disease including persistent nausea and/or abdominal pain. Diarrhea is defined as > 3 unformed stools/day.
• Dementia or decreased mentation or other encephalopathic signs and symptoms which would interfere with the ability of the patient to follow the protocol, to take assigned dose regimen reliably, and to keep a daily record on a calendar.
• Significant CMV disease of other organs, including CMV gastroenteritis or CMV pneumonia.

Prior Medication:

Excluded within 4 days of study entry:

• Antimetabolite.
• Interferon.
• Other nucleoside analog including zidovudine (AZT).

Excluded for Group A:

• Ganciclovir or other anti-cytomegalovirus therapy.

History of severe allergic reactions to study medication Currently pregnant or breastfeeding Recent participation in another clinical trial within the last 30 days Presence of uncontrolled medical conditions that could affect safety