Back to resultsThe Anti-HIV Effects of Saquinavir Soft Gelatin Capsules Versus Indinavir in Patients Who Have Used Saquinavir Hard Gelatin Capsules for One Year
Primary Purpose
HIV Infections
Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Indinavir sulfate
Saquinavir
Sponsored by
About this trial
This is an interventional treatment trial for HIV Infections focused on measuring Administration, Oral, Acquired Immunodeficiency Syndrome, AIDS-Related Complex, Antiviral Agents, HIV Protease Inhibitors, Biological Markers, Indinavir, Viremia, RNA, Viral, Saquinavir
Eligibility 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.
Sites / Locations
- Stanford CRS
- Ucsf Aids Crs
- Harbor-UCLA Med. Ctr. CRS
- University of Colorado Hospital CRS
- Univ. of Miami AIDS CRS
- Northwestern University CRS
- Rush Univ. Med. Ctr. ACTG CRS
- Massachusetts General Hospital ACTG CRS
- Washington U CRS
- St. Louis ConnectCare, Infectious Diseases Clinic
- SUNY - Buffalo, Erie County Medical Ctr.
- Beth Israel Med. Ctr. (Mt. Sinai)
- NY Univ. HIV/AIDS CRS
- Univ. of Rochester ACTG CRS
- The Ohio State Univ. AIDS CRS
- University of Washington AIDS CRS
Outcomes
Primary Outcome Measures
Secondary Outcome Measures
Full Information
NCT ID
NCT00000848
First Posted
November 2, 1999
Last Updated
October 27, 2021
Sponsor
National Institute of Allergy and Infectious Diseases (NIAID)
1. Study Identification
Unique Protocol Identification Number
NCT00000848
Brief Title
The Anti-HIV Effects of Saquinavir Soft Gelatin Capsules Versus Indinavir in Patients Who Have Used Saquinavir Hard Gelatin Capsules for One Year
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
Study Type
Interventional
2. Study Status
Record Verification Date
October 2021
Overall Recruitment Status
Completed
Study Start Date
undefined (undefined)
Primary Completion Date
undefined (undefined)
Study Completion Date
October 1998 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
National Institute of Allergy and Infectious Diseases (NIAID)
4. Oversight
5. Study Description
Brief Summary
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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
HIV Infections
Keywords
Administration, Oral, Acquired Immunodeficiency Syndrome, AIDS-Related Complex, Antiviral Agents, HIV Protease Inhibitors, Biological Markers, Indinavir, Viremia, RNA, Viral, Saquinavir
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Enrollment
144 (Anticipated)
8. Arms, Groups, and Interventions
Intervention Type
Drug
Intervention Name(s)
Indinavir sulfate
Intervention Type
Drug
Intervention Name(s)
Saquinavir
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Para MF
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Collier A
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Coombs R
Official's Role
Study Chair
Facility Information:
Facility Name
Stanford CRS
City
Palo Alto
State/Province
California
ZIP/Postal Code
94304
Country
United States
Facility Name
Ucsf Aids Crs
City
San Francisco
State/Province
California
ZIP/Postal Code
94110
Country
United States
Facility Name
Harbor-UCLA Med. Ctr. CRS
City
Torrance
State/Province
California
ZIP/Postal Code
90502
Country
United States
Facility Name
University of Colorado Hospital CRS
City
Aurora
State/Province
Colorado
ZIP/Postal Code
80045
Country
United States
Facility Name
Univ. of Miami AIDS CRS
City
Miami
State/Province
Florida
ZIP/Postal Code
33136
Country
United States
Facility Name
Northwestern University CRS
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60611
Country
United States
Facility Name
Rush Univ. Med. Ctr. ACTG CRS
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60612
Country
United States
Facility Name
Massachusetts General Hospital ACTG CRS
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States
Facility Name
Washington U CRS
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Facility Name
St. Louis ConnectCare, Infectious Diseases Clinic
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63112
Country
United States
Facility Name
SUNY - Buffalo, Erie County Medical Ctr.
City
Buffalo
State/Province
New York
ZIP/Postal Code
14260
Country
United States
Facility Name
Beth Israel Med. Ctr. (Mt. Sinai)
City
New York
State/Province
New York
ZIP/Postal Code
10003
Country
United States
Facility Name
NY Univ. HIV/AIDS CRS
City
New York
State/Province
New York
ZIP/Postal Code
10016
Country
United States
Facility Name
Univ. of Rochester ACTG CRS
City
Rochester
State/Province
New York
ZIP/Postal Code
14642
Country
United States
Facility Name
The Ohio State Univ. AIDS CRS
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43210
Country
United States
Facility Name
University of Washington AIDS CRS
City
Seattle
State/Province
Washington
ZIP/Postal Code
98104
Country
United States
12. IPD Sharing Statement
Citations:
PubMed Identifier
11364616
Citation
Saquinavir update. Treat Rev. 1997 Aug;(No 25):6.
Results Reference
background
PubMed Identifier
11364285
Citation
Saquinavir switch study stopped. Treat Rev. 1997 Apr;(No 24):6.
Results Reference
background
PubMed Identifier
11364275
Citation
Gilden D. Spring cleaning in trial land. GMHC Treat Issues. 1997 Mar;11(3):4-7.
Results Reference
background
Citation
Para MF, Coombs R, Collier A, Glidden D, Bassett R, Duff F, Boucher C, Leavitt RY, Condra J, Pettinelli C. Relationship of baseline genotype to RNA response in ACTG 333 after switching from long term saquinavir (SQVhc) to indinavir (IDV) or saquinavir soft gelatin capsule (SQVsgc). Conf Retroviruses Opportunistic Infect. 1998 Feb 1-5;5th:175 (abstract no 511)
Results Reference
background
PubMed Identifier
10882582
Citation
Sevin AD, DeGruttola V, Nijhuis M, Schapiro JM, Foulkes AS, Para MF, Boucher CA. Methods for investigation of the relationship between drug-susceptibility phenotype and human immunodeficiency virus type 1 genotype with applications to AIDS clinical trials group 333. J Infect Dis. 2000 Jul;182(1):59-67. doi: 10.1086/315673. Epub 2000 Jul 6.
Results Reference
background
PubMed Identifier
10950766
Citation
Para MF, Glidden DV, Coombs RW, Collier AC, Condra JH, Craig C, Bassett R, Leavitt R, Snyder S, McAuliffe V, Boucher C. Baseline human immunodeficiency virus type 1 phenotype, genotype, and RNA response after switching from long-term hard-capsule saquinavir to indinavir or soft-gel-capsule saquinavir in AIDS clinical trials group protocol 333. J Infect Dis. 2000 Sep;182(3):733-43. doi: 10.1086/315769. Epub 2000 Aug 14.
Results Reference
background
Learn more about this trial
The Anti-HIV Effects of Saquinavir Soft Gelatin Capsules Versus Indinavir in Patients Who Have Used Saquinavir Hard Gelatin Capsules for One Year
We'll reach out to this number within 24 hrs