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

June 23, 2005 updated by: National Institute of Allergy and Infectious Diseases (NIAID)

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment

50

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

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

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

13 years and older (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Masking: None (Open Label)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

National Institute of Allergy and Infectious Diseases (NIAID)

Collaborators

Schering-Plough

Investigators

  • Study Chair: WG Powderly

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

First Submitted

November 2, 1999

First Submitted That Met QC Criteria

August 30, 2001

First Posted (Estimate)

August 31, 2001

Study Record Updates

Last Update Posted (Estimate)

June 24, 2005

Last Update Submitted That Met QC Criteria

June 23, 2005

Last Verified

December 1, 1994

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ACTG 125
  • C89-258

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on HIV Infections

Clinical Trials on SCH 39304

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Canada

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe