SCH 39304 as Therapy for Acute Cryptococcal Meningitis in HIV-Infected Patients Followed by Maintenance Therapy

Condition(s) targeted: Meningitis, Cryptococcal; HIV Infections

Intervention: SCH 39304 (Drug)

Phase: Phase 1

Status: Completed

Sponsored by: National Institute of Allergy and Infectious Diseases (NIAID)

Official(s) and/or principal investigator(s):
WG Powderly, Study Chair

To assess the safety and effectiveness of SCH 39304 as primary treatment of acute cryptococcal meningitis in HIV-infected patients. Safety and effectiveness of maintenance therapy following successful treatment of acute disease are also evaluated. Cryptococcal meningitis is a significant cause of illness and death in HIV-infected patients. Intravenous amphotericin B is effective for acute disease but relapse occurs in the majority of patients. Maintenance therapy is recommended but must be balanced against the multiple toxicities of the drugs used and the problems associated with the weekly administration of intravenous therapy. Treatments that are equally or more effective and less toxic than traditional methods are needed, especially oral therapy. SCH 39304 is an orally active antifungal drug that in animal studies is active against a wide range of systemic fungal infections including infections due to Cryptococcus. Features of SCH 39304 suggest that it might be of value in the treatment of cryptococcal meningitis.

Official title: SCH 39304 as Therapy for Acute Cryptococcal Meningitis in HIV-Infected Patients Followed by Maintenance Therapy

Study design: Treatment, Open Label

Detailed description: Cryptococcal meningitis is a significant cause of illness and death in HIV-infected patients. Intravenous amphotericin B is effective for acute disease but relapse occurs in the majority of patients. Maintenance therapy is recommended but must be balanced against the multiple toxicities of the drugs used and the problems associated with the weekly administration of intravenous therapy. Treatments that are equally or more effective and less toxic than traditional methods are needed, especially oral therapy. SCH 39304 is an orally active antifungal drug that in animal studies is active against a wide range of systemic fungal infections including infections due to Cryptococcus. Features of SCH 39304 suggest that it might be of value in the treatment of cryptococcal meningitis. HIV-infected patients with a diagnosis of acute cryptococcal meningitis, previously untreated or relapsed following a successfully treated acute episode, are enrolled in the study. SCH 39304 is administered orally once daily for 3 days followed by a lower dose once daily for 12 weeks. Patients who respond to primary therapy are randomized to receive SCH 39304 maintenance therapy at a higher dose once weekly or at the lower dose once daily for up to 12 months under this protocol.

Minimum age: 13 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

Inclusion Criteria Concurrent Medication: Allowed: Currently approved antiviral therapy. Maintenance therapy for cytomegalovirus retinitis or toxoplasmosis. Rifampin. Isoniazid. Dilantin or barbiturates if investigator agrees to rigorously monitor anticonvulsant drug levels. Coumarin-type anticoagulants if investigator agrees to rigorously monitor prothrombin time. Prophylactic treatment for Pneumocystis carinii pneumonia (PCP). Concurrent Treatment: Allowed: Local radiotherapy for mucocutaneous Kaposi's sarcoma. Prior Medication: Allowed: Amphotericin B, up to 1 mg/kg, during the previous 7 days. Patients must be HIV positive by 2 methodologies and have either primary cryptococcal meningitis with no prior anti-cryptococcal therapy or relapsed disease after prior therapy. Prior therapy for cryptococcal meningitis is limited to approved drugs. Written informed consent either from patient or patient's parent or legal guardian is required. Exclusion Criteria Co-existing Condition: Patients with the following conditions or symptoms are excluded: History of hypersensitivity to imidazole or azole compounds. Central nervous system disease. Acute opportunistic infection. Underlying conditions that in the opinion of the investigator could preclude assessment of response. Concurrent Medication: Excluded: Systemic antifungal drugs other than study drug. Any investigational drug other than treatment IND drugs. Oral hypoglycemic agents. Oral contraceptives. Cytotoxic chemotherapy. Patients with the following are excluded: Unable to take oral medications. Concurrent central nervous system disease which in opinion of investigator would interfere with assessment of response. Concurrent acute opportunistic infection requiring therapy (patients who develop an acute opportunistic infection after initiation of study medication may remain on study medication). Prior Medication: Excluded within 7 days of study entry: Amphotericin B, > 1 mg/kg.

Birmingham Veterans Administration Med Ctr, Birmingham, Alabama 35233, United States

Univ of California / San Diego Treatment Ctr, San Diego, California 921036325, United States

San Francisco AIDS Clinic / San Francisco Gen Hosp, San Francisco, California 941102859, United States

Dr Robert Larsen, Los Angeles, California 90033, United States

George Washington Univ Med Ctr, Washington, District of Columbia 20037, United States

Med College of Georgia, Augusta, Georgia 30912, United States

Emory Univ School of Medicine, Atlanta, Georgia 30303, United States

Rush Presbyterian - Saint Luke's Med Ctr, Chicago, Illinois 60612, United States

Indiana Univ Hosp, Indianapolis, Indiana 462025250, United States

Tulane Univ School of Medicine, New Orleans, Louisiana 70112, United States

Univ Hosp, Boston, Massachusetts 02118, United States

St Louis Regional Hosp / St Louis Regional Med Ctr, St. Louis, Missouri 63112, United States

Univ of Rochester Medical Center, Rochester, New York 14642, United States

Mount Sinai Med Ctr, New York, New York 10029, United States

Bronx Veterans Administration / Mount Sinai Hosp, Bronx, New York 10468, United States

Beth Israel Med Ctr, New York, New York 10003, United States

Erie County Med Ctr, Buffalo, New York 14215, United States

Univ of North Carolina, Chapel Hill, North Carolina 275997215, United States

Duke Univ Med Ctr, Durham, North Carolina 27710, United States

Holmes Hosp / Univ of Cincinnati Med Ctr, Cincinnati, Ohio 452670405, United States

Ohio State Univ Med Ctr, Columbus, Ohio 43210, United States

Univ Hosp of Cleveland / Case Western Reserve Univ, Cleveland, Ohio 44106, United States

Buckley Braffman Stern Med Associates, Philadelphia, Pennsylvania 19107, United States

Julio Arroyo, West Columbia, South Carolina 29169, United States

Audie L Murphy Veterans Administration Hosp, San Antonio, Texas 78284, United States

Houston Veterans Administration Med Ctr, Houston, Texas 77030, United States

Univ TX Health Science Ctr, Houston, Texas 77030, United States

Richmond AIDS Consortium, Richmond, Virginia 23219, United States

Related publications:

Lee BL, Padula AM, Tauber MG, Chambers HF, Sande MA. Oral SCH 39304 as primary, salvage, and maintenance therapy for cryptococcal meningitis in AIDS. J Acquir Immune Defic Syndr. 1992;5(6):600-4.

Last updated: June 23, 2005