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

This study has been completed.
Sponsor:
Collaborator:
Schering-Plough
Information provided by:
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT00000677
First received: November 2, 1999
Last updated: June 23, 2005
Last verified: December 1994
  Purpose

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 Intervention Phase
Meningitis, Cryptococcal
HIV Infections
Drug: SCH 39304
Phase 1

Study Type: Interventional
Study Design: Masking: Open Label
Primary Purpose: Treatment
Official Title: SCH 39304 as Therapy for Acute Cryptococcal Meningitis in HIV-Infected Patients Followed by Maintenance Therapy

Resource links provided by NLM:


Further study details as provided by National Institute of Allergy and Infectious Diseases (NIAID):

Estimated Enrollment: 50
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.

  Eligibility

Ages Eligible for Study:   13 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00000677

  Hide Study Locations
Locations
United States, Alabama
Birmingham Veterans Administration Med Ctr
Birmingham, Alabama, United States, 35233
United States, California
Dr Robert Larsen
Los Angeles, California, United States, 90033
Univ of California / San Diego Treatment Ctr
San Diego, California, United States, 921036325
San Francisco AIDS Clinic / San Francisco Gen Hosp
San Francisco, California, United States, 941102859
United States, District of Columbia
George Washington Univ Med Ctr
Washington, District of Columbia, United States, 20037
United States, Georgia
Emory Univ School of Medicine
Atlanta, Georgia, United States, 30303
Med College of Georgia
Augusta, Georgia, United States, 30912
United States, Illinois
Rush Presbyterian - Saint Luke's Med Ctr
Chicago, Illinois, United States, 60612
United States, Indiana
Indiana Univ Hosp
Indianapolis, Indiana, United States, 462025250
United States, Louisiana
Tulane Univ School of Medicine
New Orleans, Louisiana, United States, 70112
United States, Massachusetts
Univ Hosp
Boston, Massachusetts, United States, 02118
United States, Missouri
St Louis Regional Hosp / St Louis Regional Med Ctr
St Louis, Missouri, United States, 63112
United States, New York
Bronx Veterans Administration / Mount Sinai Hosp
Bronx, New York, United States, 10468
Erie County Med Ctr
Buffalo, New York, United States, 14215
Mount Sinai Med Ctr
New York, New York, United States, 10029
Beth Israel Med Ctr
New York, New York, United States, 10003
Univ of Rochester Medical Center
Rochester, New York, United States, 14642
United States, North Carolina
Univ of North Carolina
Chapel Hill, North Carolina, United States, 275997215
Duke Univ Med Ctr
Durham, North Carolina, United States, 27710
United States, Ohio
Holmes Hosp / Univ of Cincinnati Med Ctr
Cincinnati, Ohio, United States, 452670405
Univ Hosp of Cleveland / Case Western Reserve Univ
Cleveland, Ohio, United States, 44106
Ohio State Univ Med Ctr
Columbus, Ohio, United States, 43210
United States, Pennsylvania
Buckley Braffman Stern Med Associates
Philadelphia, Pennsylvania, United States, 19107
United States, South Carolina
Julio Arroyo
West Columbia, South Carolina, United States, 29169
United States, Texas
Houston Veterans Administration Med Ctr
Houston, Texas, United States, 77030
Univ TX Health Science Ctr
Houston, Texas, United States, 77030
Audie L Murphy Veterans Administration Hosp
San Antonio, Texas, United States, 78284
United States, Virginia
Richmond AIDS Consortium
Richmond, Virginia, United States, 23219
Sponsors and Collaborators
Schering-Plough
Investigators
Study Chair: WG Powderly
  More Information

Publications:
ClinicalTrials.gov Identifier: NCT00000677     History of Changes
Other Study ID Numbers: ACTG 125, C89-258
Study First Received: November 2, 1999
Last Updated: June 23, 2005
Health Authority: United States: Federal Government

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
Sch 39304
AIDS-Related Opportunistic Infections
Meningitis
Cryptococcosis
Drug Evaluation
Antifungal Agents
Acquired Immunodeficiency Syndrome

Additional relevant MeSH terms:
HIV Infections
Acquired Immunodeficiency Syndrome
Meningitis
Meningitis, Cryptococcal
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Slow Virus Diseases
Central Nervous System Infections
Central Nervous System Diseases
Nervous System Diseases
Meningitis, Fungal
Central Nervous System Fungal Infections
Mycoses
Cryptococcosis
Sch 39304
Antifungal Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on August 26, 2014