A Study of Fluconazole in the Treatment of Cryptococcal Meningitis in Patients Who Have Not Had Success With Amphotericin B

Multi-Center Evaluation of Fluconazole (UK-49,858) as Treatment for Acute Cryptococcal Meningitis in Patients Who Have Failed to Respond or Have Experienced Unacceptable Toxicity During Treatment With Amphotericin B

To evaluate the safety and effectiveness of fluconazole as treatment for acute cryptococcal meningitis in patients who have had an unsatisfactory response to or have experienced unacceptable toxicity with amphotericin B.

Inclusion Criteria

Concurrent Medication:

Allowed:

• Immunosuppressant therapy.
• Antiviral therapy such as zidovudine.
• Prophylaxis for Pneumocystis carinii pneumonia.
• Aerosolized pentamidine.

Concurrent Treatment:

Allowed:

• Radiation therapy for mucocutaneous Kaposi's sarcoma.

Not previously treated for acute cryptococcal meningitis and not eligible for Pfizer Central Research, protocol #159.

• Patients must have a baseline cerebrospinal fluid (CSF) culture-positive for Cryptococcus neoformans.
• Written informed consent must be obtained for each patient, either from the patient himself or from the patient's legal guardian.
• Each individual patient must be approved by Pfizer Central Research prior to study entry.

Prior Medication:

Allowed:

• Immunosuppressant therapy.
• Antiviral therapy such as zidovudine.
• Prophylaxis for Pneumocystis carinii pneumonia.
• Aerosolized pentamidine.

Exclusion Criteria

Co-existing Condition:

Patients with the following are excluded:

• Evidence of acute or chronic meningitis based upon any etiology other than cryptococcosis.
• History of allergy to or intolerance of imidazoles or azoles.
• Moderate or severe liver disease.

Concurrent Treatment:

Excluded:

• Lymphocyte replacement.

Patients with the following are excluded:

• Evidence of acute or chronic meningitis based upon any etiology other than cryptococcosis.
• History of allergy to or intolerance of imidazoles or azoles.
• Moderate or severe liver disease.
• Satisfactory response to amphotericin B and have received a total amphotericin B dose of 15 mg/kg or more since CSF culture documentation of the current episode of acute cryptococcal meningitis.
• Life expectancy of < 2 weeks.

Prior Medication:

Excluded:

• Coumadin-type anticoagulants.
• Oral hypoglycemics.
• Barbiturates.
• Phenytoin.
• Immunostimulants.
• Investigational drugs or approved (licensed) drugs for investigational indications.

Prior Treatment:

Excluded:

• Lymphocyte replacement.