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.
Sponsor:
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT00000848
First received: November 2, 1999
Last updated: February 13, 2012
Last verified: February 2012
  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 2

Study Type: Interventional
Study Design: Primary Purpose: 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

Resource links provided by NLM:


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

Estimated Enrollment: 144
Study Completion Date: October 1998
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
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: NCT00000848

Locations
United States, California
Stanford CRS
Palo Alto, California, United States, 94304
Ucsf Aids Crs
San Francisco, California, United States, 94110
Harbor-UCLA Med. Ctr. CRS
Torrance, California, United States, 90502
United States, Colorado
University of Colorado Hospital CRS
Aurora, Colorado, United States, 80045
United States, Florida
Univ. of Miami AIDS CRS
Miami, Florida, United States, 33136
United States, Illinois
Northwestern University CRS
Chicago, Illinois, United States, 60611
Rush Univ. Med. Ctr. ACTG CRS
Chicago, Illinois, United States, 60612
United States, Massachusetts
Massachusetts General Hospital ACTG CRS
Boston, Massachusetts, United States, 02114
United States, Missouri
St. Louis ConnectCare, Infectious Diseases Clinic
St. Louis, Missouri, United States, 63112
Washington U CRS
St. Louis, Missouri, United States, 63110
United States, New York
SUNY - Buffalo, Erie County Medical Ctr.
Buffalo, New York, United States, 14260
NY Univ. HIV/AIDS CRS
New York, New York, United States, 10016
Beth Israel Med. Ctr. (Mt. Sinai)
New York, New York, United States, 10003
Univ. of Rochester ACTG CRS
Rochester, New York, United States, 14642
United States, Ohio
The Ohio State Univ. AIDS CRS
Columbus, Ohio, United States, 43210
United States, Washington
University of Washington AIDS CRS
Seattle, Washington, United States, 98104
Sponsors and Collaborators
Investigators
Study Chair: Para MF
Study Chair: Collier A
Study Chair: Coombs R
  More Information

Additional Information:
Publications:
Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT00000848     History of Changes
Other Study ID Numbers: ACTG 333, 11305
Study First Received: November 2, 1999
Last Updated: February 13, 2012
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

Additional relevant MeSH terms:
HIV Infections
Acquired Immunodeficiency Syndrome
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
Antiviral Agents
Indinavir
Saquinavir
HIV Protease Inhibitors
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-HIV Agents
Anti-Retroviral Agents

ClinicalTrials.gov processed this record on July 26, 2014