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

HIV Infections Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00000677
• Other study ID #: ACTG 125
• Secondary ID: C89-258
• Status: Completed
• Phase: Phase 1
• First received: November 2, 1999
• Last updated: June 23, 2005

Study information

• Verified date: December 1994
• Source: National Institute of Allergy and Infectious Diseases (NIAID)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 50
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 13 Years and older

Eligibility

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.

Study Design

Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• HIV Infections
• Meningitis
• Meningitis, Cryptococcal

Intervention

Drug:
• SCH 39304

Locations

Country	Name	City	State
United States	Emory Univ School of Medicine	Atlanta	Georgia
United States	Med College of Georgia	Augusta	Georgia
United States	Birmingham Veterans Administration Med Ctr	Birmingham	Alabama
United States	Univ Hosp	Boston	Massachusetts
United States	Bronx Veterans Administration / Mount Sinai Hosp	Bronx	New York
United States	Erie County Med Ctr	Buffalo	New York
United States	Univ of North Carolina	Chapel Hill	North Carolina
United States	Rush Presbyterian - Saint Luke's Med Ctr	Chicago	Illinois
United States	Holmes Hosp / Univ of Cincinnati Med Ctr	Cincinnati	Ohio
United States	Univ Hosp of Cleveland / Case Western Reserve Univ	Cleveland	Ohio
United States	Ohio State Univ Med Ctr	Columbus	Ohio
United States	Duke Univ Med Ctr	Durham	North Carolina
United States	Houston Veterans Administration Med Ctr	Houston	Texas
United States	Univ TX Health Science Ctr	Houston	Texas
United States	Indiana Univ Hosp	Indianapolis	Indiana
United States	Dr Robert Larsen	Los Angeles	California
United States	Tulane Univ School of Medicine	New Orleans	Louisiana
United States	Beth Israel Med Ctr	New York	New York
United States	Mount Sinai Med Ctr	New York	New York
United States	Buckley Braffman Stern Med Associates	Philadelphia	Pennsylvania
United States	Richmond AIDS Consortium	Richmond	Virginia
United States	Univ of Rochester Medical Center	Rochester	New York
United States	Audie L Murphy Veterans Administration Hosp	San Antonio	Texas
United States	Univ of California / San Diego Treatment Ctr	San Diego	California
United States	San Francisco AIDS Clinic / San Francisco Gen Hosp	San Francisco	California
United States	St Louis Regional Hosp / St Louis Regional Med Ctr	St Louis	Missouri
United States	George Washington Univ Med Ctr	Washington	District of Columbia
United States	Julio Arroyo	West Columbia	South Carolina

Sponsors (2)

Lead Sponsor	Collaborator
National Institute of Allergy and Infectious Diseases (NIAID)	Schering-Plough

Country where clinical trial is conducted

United States, 

References & Publications (1)

Lee BL, Padula AM, Täuber 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. — View Citation