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

Sponsor

National Institute of Allergy and Infectious Diseases (NIAID) (NIH)

Overall Status

Completed

CT.gov ID

NCT00000677

Collaborator

Schering-Plough (Industry)

Enrollment

Locations

1.8

Patients Per Site

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
Meningitis, Cryptococcal HIV Infections	Drug: SCH 39304	Phase 1

Detailed Description

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.

Study Design

Study Type:

Interventional

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Outcome Measures

Primary Outcome Measures

Eligibility Criteria

Criteria

Ages Eligible for Study:

13 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Birmingham Veterans Administration Med Ctr	Birmingham	Alabama	United States	35233
2	Dr Robert Larsen	Los Angeles	California	United States	90033
3	Univ of California / San Diego Treatment Ctr	San Diego	California	United States	921036325
4	San Francisco AIDS Clinic / San Francisco Gen Hosp	San Francisco	California	United States	941102859
5	George Washington Univ Med Ctr	Washington	District of Columbia	United States	20037
6	Emory Univ School of Medicine	Atlanta	Georgia	United States	30303
7	Med College of Georgia	Augusta	Georgia	United States	30912
8	Rush Presbyterian - Saint Luke's Med Ctr	Chicago	Illinois	United States	60612
9	Indiana Univ Hosp	Indianapolis	Indiana	United States	462025250
10	Tulane Univ School of Medicine	New Orleans	Louisiana	United States	70112
11	Univ Hosp	Boston	Massachusetts	United States	02118
12	St Louis Regional Hosp / St Louis Regional Med Ctr	St Louis	Missouri	United States	63112
13	Bronx Veterans Administration / Mount Sinai Hosp	Bronx	New York	United States	10468
14	Erie County Med Ctr	Buffalo	New York	United States	14215
15	Beth Israel Med Ctr	New York	New York	United States	10003
16	Mount Sinai Med Ctr	New York	New York	United States	10029
17	Univ of Rochester Medical Center	Rochester	New York	United States	14642
18	Univ of North Carolina	Chapel Hill	North Carolina	United States	275997215
19	Duke Univ Med Ctr	Durham	North Carolina	United States	27710
20	Holmes Hosp / Univ of Cincinnati Med Ctr	Cincinnati	Ohio	United States	452670405
21	Univ Hosp of Cleveland / Case Western Reserve Univ	Cleveland	Ohio	United States	44106
22	Ohio State Univ Med Ctr	Columbus	Ohio	United States	43210
23	Buckley Braffman Stern Med Associates	Philadelphia	Pennsylvania	United States	19107
24	Julio Arroyo	West Columbia	South Carolina	United States	29169
25	Houston Veterans Administration Med Ctr	Houston	Texas	United States	77030
26	Univ TX Health Science Ctr	Houston	Texas	United States	77030
27	Audie L Murphy Veterans Administration Hosp	San Antonio	Texas	United States	78284
28	Richmond AIDS Consortium	Richmond	Virginia	United States	23219