A Comparison of SCH 56592 and Fluconazole in the Treatment of Oropharyngeal Candidiasis (OPC) in HIV-Positive Patients

A Multicenter, Randomized, Double-Blind, Phase II Study to Evaluate the Safety, Tolerance and Efficacy of Multiple Doses of SCH 56592 Versus Fluconazole in the Treatment of Oropharyngeal Candidiasis (OPC) in HIV-Positive Patients

The purpose of this study is to compare the safety and effectiveness of SCH 56592 with that of fluconazole in the treatment of OPC (a fungal infection of the throat) in HIV-positive patients.

This is a randomized, multicenter, double-blind study consisting of 5 arms (4 dose levels of SCH 56592 vs fluconazole) in the treatment of oropharyngeal candidiasis (OPC) in HIV-positive patients.

Inclusion Criteria

Patients must have:

• Documented HIV seropositivity (by Western blot or other approved confirmatory test) prior to enrollment.
• Pseudomembranous oropharyngeal candidiasis.
• Fungal stain or KOH consistent with Candida species, confirmed by a positive mycologic culture.
• Ability to swallow study medication.

Exclusion Criteria

Co-existing Condition:

Patients with any of the following symptoms and conditions are excluded:

• Medical condition requiring use of prohibited drugs.
• Primary HIV seroconversion-related mucosal candidiasis.
• Systemic candidiasis.
• All forms of OPC other than pseudomembranous (unless accompanied by pseudomembranous OPC).
• Documented or suspected fungal esophagitis in patients with symptoms of esophagitis.
• EKG with prolonged QTc interval or clinically-significant abnormalities.

Concurrent Medication:

Excluded:

• Systemic antifungals (IV or oral).
• Topical oral antifungals, e.g., Nystatin, Mycelex, etc.
• Medications known to interact with azoles and that may lead to life-threatening side effects:
• terfenadine, astemizole, cisapride, ebastine, triazolam, midazolam.
• Medications known to lower the serum concentration/efficacy of azole antifungals:
• rifampin, carbamazepine, phenytoin, rifabutin, barbiturates, isoniazid, H2 blockers.
• Cytokines (except erythropoietin), interferon, or lymphocyte replacement therapy unless patient already taking these agents for at least 30 days prior to enrollment.
• Protease inhibitors, starting for the first time, 30 days prior to study enrollment.
• Cytotoxic therapy for cancer.
• Oral or intravenous corticosteroids at supraphysiologic doses (prednisone 10 mg/day or greater; hydrocortisone 40 mg/day or greater; dexamethasone 2 mg/day or greater.

Patients with any of the following prior conditions are excluded:

• Prior enrollment in this study.
• Less than 3 months life expectancy.
• History of hypersensitivity to azole antifungals.
• History of failed therapy with fluconazole 100 mg/day for 2 weeks in the last 3 months.

Prior Medication:

Excluded (wash-outs for medications):

• Systemic antifungals (IV, oral) within 14 days prior to enrollment.
• Topical oral antifungals within 1 day prior to enrollment.
• Oral or intravenous corticosteroids at supraphysiologic doses within 10 days prior to enrollment.
• Astemizole within 10 days prior to enrollment.
• Drugs known to lower the serum concentration/efficacy of azole antifungals within 30 days prior to enrollment.
• Investigational drug (unlicensed new chemical entity) use within 30 days prior to enrollment.

Current known drug abuse, in the opinion of the lead investigator, that would interfere with the subject's participation in the study.