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

  Show 28 Study Locations
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 April 23, 2014