Official Title: “Double Blind Placebo Controlled Study of Fluconazole (UK-49,858) for Maintenance Treatment of Cryptococcal Meningitis in Patients With Acquired Immunodeficiency Syndrome”

To compare the safety and effectiveness of fluconazole with that of placebo as maintenance treatment for preventing the relapse of cryptococcal meningitis in patients with AIDS.

Study Type: Interventional

Study Design: Treatment, Double-Blind

Intervention(s) in this Clinical Trial

• Drug: Fluconazole

Inclusion Criteria

Concurrent Medication:

Allowed:

• Antiviral therapy (e.g., zidovudine).
• Prophylaxis (including aerosolized pentamidine) for Pneumocystis carinii pneumonia (PCP).

Concurrent Treatment:

Allowed:

• Radiation therapy for mucocutaneous Kaposi's sarcoma.
• Patients must be oriented to person, place, and time and able to give written informed consent.
• Patients must have had an acute episode of cryptococcal meningitis that was documented by recovery and identification of cryptococcus from lumbar cerebrospinal fluid (CSF) culture within 4 months of study entry.
• Adequate therapy will consist of 6 - 16 weeks of treatment with amphotericin B alone, amphotericin B + oral flucytosine, or a period of the combination followed by amphotericin alone. Adequate regimens will include:
• A minimum total amphotericin B dose of 2 grams as monotherapy.
• 6 weeks of flucytosine at 150 mg/kg/day (or levels of 20 to 100 mcg/ml demonstrated) plus amphotericin B at an average daily dose of at least 0.3 mg/kg/day or to a total dose of 1 gram.
• After a shorter period of the combination amphotericin/flucytosine therapy, an additional Y grams of amphotericin B monotherapy will make therapy adequate where Y = 2 gm-(X weeks combination therapy / 3 weeks).
• For example, a patient who received 3 weeks of combination followed by amphotericin alone would need an additional 2 gm - 3 weeks/3 weeks = 1 gm of amphotericin B.
• Patients need not be receiving amphotericin B at the time of randomization but must begin study maintenance therapy within 3 weeks of cessation of primary amphotericin B therapy.

Prior Medication:

Allowed:

• Antiviral therapy (e.g., zidovudine (AZT)).
• Prophylaxis (including aerosolized pentamidine) for Pneumocystis carinii pneumonia (PCP).

Exclusion Criteria

Co-existing Condition:

Patients with the following are excluded:

• Clinical evidence of acute or chronic meningitis based upon any etiology other than cryptococcosis.
• History of allergy or intolerance of imidazoles, azoles, or amphotericin B.
• Moderate or severe liver disease.

Concurrent Medication:

Excluded:

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

Concurrent Treatment:

Excluded:

• Lymphocyte replacement.

Patients with the following are excluded:

• Clinical evidence of acute or chronic meningitis based upon any etiology other than cryptococcosis.
• History of allergy or intolerance of imidazoles, azoles, or amphotericin B.
• Moderate or severe liver disease defined by specific lab values.
• Inability to take oral medications reliably.

Prior Medication:

Excluded:

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

Prior Treatment:

Excluded:

• Lymphocyte replacement.

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: Pfizer

Information obtained from ClinicalTrials.gov on September 05, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00002294

Study ID Number: 012A

ClinicalTrials.gov Identifier: NCT00002294

Health Authority: United States: Food and Drug Administration