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The Anti-HIV Effects of Saquinavir Soft Gelatin Capsules Versus Indinavir in Patients Who Have Used Saquinavir Hard Gelatin Capsules for One Year
This study has been completed.
Sponsored by: National Institute of Allergy and Infectious Diseases (NIAID)
Information provided by: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT00000848
  Purpose

To determine, in HIV-infected patients, whether switching to a new soft gelatin capsule formulation of saquinavir or to indinavir following prolonged use of the original hard capsule formulation of saquinavir results in an acute decrease in plasma HIV RNA.

Resistance to anti-HIV agents occurs with increasing duration of use. In vitro studies have shown that cross-resistance occurs among protease inhibitors, although no clinical trials have been conducted to examine antiretroviral activity with sequential use of protease inhibitors or to determine whether saquinavir resistance can be overcome with higher concentrations of the drug.


Condition Intervention Phase
HIV Infections
Drug: Indinavir sulfate
Drug: Saquinavir
Phase II

MedlinePlus related topics: AIDS
Drug Information available for: Saquinavir Saquinavir mesylate Indinavir Indinavir Sulfate Gelatin
U.S. FDA Resources
Study Type: Interventional
Study Design: Treatment
Official Title: The Antiviral Effect of Switching From Hard Capsule Saquinavir (SQVhc) to the Soft Gelatin Capsule of Saquinavir (SQVsc) Versus Switching to Indinavir (IDV) After 1 Year of Saquinavir Use

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

Estimated Enrollment: 144
Detailed Description:

Resistance to anti-HIV agents occurs with increasing duration of use. In vitro studies have shown that cross-resistance occurs among protease inhibitors, although no clinical trials have been conducted to examine antiretroviral activity with sequential use of protease inhibitors or to determine whether saquinavir resistance can be overcome with higher concentrations of the drug.

Patients who are currently receiving hard capsule saquinavir are randomized to continue receiving hard capsule saquinavir or to switch to soft gelatin capsule saquinavir or indinavir. At week 8, patients receiving the hard capsule formulation will switch to open-label indinavir for weeks 8-24. Patients on the other two arms will remain on their assigned regimen for the entire 24 weeks unless they have no virologic response by week 8, in which case they will be crossed-over to open-label therapy with the alternative drug (i.e., either soft gelatin capsule saquinavir or indinavir).

AS PER AMENDMENT 12/23/96: Viral RNA from weeks 16 and 24 will be assayed in batch after week 24. Patients who exhibit an antiviral response based on this assay will be allowed to continue their current drug assignment for a total of 12 months.

AS PER AMENDMENT 5/7/97: Based on an interim analysis performed after 72 patients had completed 8 weeks of therapy, the study was closed as of March 7, 1997. Patients currently enrolled may stop their participation in the trial and seek other anti-retroviral therapies or may continue on study. Patients on hard capsule saquinavir who remain on study will be switched to indinavir at 8 weeks. Patients on soft gel capsule saquinavir may switch immediately to indinavir or, when results of HIV RNA and CD4 cell counts are available, may choose to switch to indinavir or remain on soft gel capsule saquinavir. Patients receiving indinavir will continue that agent. Follow-up for all patients will end on 7/4/97.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria

Concurrent Medication:

Required:

  • PCP prophylaxis if CD4 count <= 200 cells/mm3.

Allowed:

  • Intralesional therapy for KS.
  • Vitamins.
  • Nucleoside RT inhibitors, provided regimen remains stable for first 8 weeks of study.

Concurrent Treatment:

Allowed:

  • Acupuncture.
  • Visualization techniques.

Patients must have:

  • HIV infection.
  • Prior hard capsule saquinavir at 1800 mg/day for more than 1 year.

Prior Medication:

Allowed:

  • Prior saquinavir.
  • Prior antiretrovirals, excluding protease inhibitors other than saquinavir.

Exclusion Criteria

Co-existing Condition:

Patients with the following symptoms or conditions are excluded:

  • Psychological condition or medical instability that would interfere with study evaluation or procedures.

AS PER AMENDMENT 5/7/97:

  • Active tuberculosis.

Concurrent Medication:

Excluded:

  • Protease inhibitors other than study drugs.
  • Non-nucleoside RT inhibitors.
  • Interferon.
  • Interleukins.
  • GM-CSF.
  • HIV vaccines.
  • Systemic cytotoxic chemotherapy.
  • Investigational drugs other than study medications.
  • Rifabutin.
  • Rifampin.
  • Midazolam.
  • Triazolam.
  • Ketoconazole.
  • Delavirdine.
  • Cisapride.
  • Terfenadine.
  • Astemizole.

AS PER AMENDMENT 5/7/97:

  • Nevirapine.

Patients with the following prior conditions are excluded:

  • Unexplained fever > 38.5 C for any 7 days within 30 days prior to study entry.
  • Diarrhea persisting for 15 days within 30 days prior to study entry.

Prior Medication:

Excluded:

  • Any prior protease inhibitor other than saquinavir.

Excluded within the past 2 months.

  • Change in antiretroviral regimen.
  • Systemic chemotherapy for KS.

Excluded within the past month:

  • Non-nucleoside RT inhibitors.
  • Interferons.
  • Interleukins.
  • HIV vaccines.
  • Experimental therapies.

Excluded within the past 2 weeks:

  • Rifabutin.
  • Cisapride.
  • Terfenadine.
  • Astemizole.
  • Midazolam.
  • Triazolam.
  • Oral ketoconazole.
  • Delavirdine.
  • Acute therapy for infection or other medical illness.

Active substance abuse that would interfere with study evaluation or procedures.

  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00000848

Locations
United States, California
Stanford at Kaiser / Kaiser Permanente Med Ctr
San Francisco, California, United States, 94115
San Francisco Gen Hosp
San Francisco, California, United States, 941102859
Stanford Univ Med Ctr
Stanford, California, United States, 943055107
Children's Hosp of Oakland
Oakland, California, United States, 946091809
United States, Colorado
Univ of Colorado Health Sciences Ctr
Denver, Colorado, United States, 80262
United States, Florida
Univ of Miami School of Medicine
Miami, Florida, United States, 331361013
United States, Illinois
Northwestern Univ Med School
Chicago, Illinois, United States, 60611
Rush Presbyterian - Saint Luke's Med Ctr
Chicago, Illinois, United States, 60612
United States, Louisiana
Tulane Univ School of Medicine
New Orleans, Louisiana, United States, 70112
United States, Massachusetts
Harvard (Massachusetts Gen Hosp)
Boston, Massachusetts, United States, 02114
United States, Missouri
St Louis Regional Hosp / St Louis Regional Med Ctr
St Louis, Missouri, United States, 63112
United States, New York
St Vincent's Hosp / Mem Sloan-Kettering Cancer Ctr
New York, New York, United States, 10021
Univ of Rochester Medical Center
Rochester, New York, United States, 14642
Bellevue Hosp / New York Univ Med Ctr
New York, New York, United States, 10016
SUNY / Erie County Med Ctr at Buffalo
Buffalo, New York, United States, 14215
Beth Israel Med Ctr
New York, New York, United States, 10003
United States, Ohio
Ohio State Univ Hosp Clinic
Columbus, Ohio, United States, 432101228
United States, South Carolina
Julio Arroyo
West Columbia, South Carolina, United States, 29169
United States, Texas
Univ of Texas Galveston
Galveston, Texas, United States, 775550435
United States, Washington
Univ of Washington
Seattle, Washington, United States, 981224304
Sponsors and Collaborators
Investigators
Study Chair: Para MF
Study Chair: Collier A
Study Chair: Coombs R
  More Information

Additional Information:
Publications:
Study ID Numbers: ACTG 333
Study First Received: November 2, 1999
Last Updated: July 29, 2008
ClinicalTrials.gov Identifier: NCT00000848  
Health Authority: United States: Federal Government

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
Administration, Oral
Acquired Immunodeficiency Syndrome
AIDS-Related Complex
Antiviral Agents
HIV Protease Inhibitors
Biological Markers
Indinavir
Viremia
RNA, Viral
Saquinavir

Study placed in the following topic categories:
Virus Diseases
Sexually Transmitted Diseases, Viral
Indinavir
Saquinavir
HIV Infections
Sexually Transmitted Diseases
Acquired Immunodeficiency Syndrome
AIDS-Related Complex
Viremia
Retroviridae Infections
Immunologic Deficiency Syndromes

Additional relevant MeSH terms:
Anti-Infective Agents
RNA Virus Infections
HIV Protease Inhibitors
Slow Virus Diseases
Anti-HIV Agents
Immune System Diseases
Molecular Mechanisms of Pharmacological Action
Enzyme Inhibitors
Infection
Antiviral Agents
Pharmacologic Actions
Protease Inhibitors
Anti-Retroviral Agents
Therapeutic Uses
Lentivirus Infections

ClinicalTrials.gov processed this record on February 12, 2009