The Anti-HIV Effects of Saquinavir Soft Gelatin Capsules Versus Indinavir in Patients Who Have Used Saquinavir Hard Gelatin Capsules for One Year
Information source: National Institute of Allergy and Infectious Diseases (NIAID)
Information obtained from ClinicalTrials.gov on June 20, 2008
Link to the current ClinicalTrials.gov record.
Condition(s) targeted: HIV Infections
Intervention: Indinavir sulfate (Drug); Saquinavir (Drug)
Phase: Phase 2
Status: Completed
Sponsored by: National Institute of Allergy and Infectious Diseases (NIAID) Official(s) and/or principal investigator(s):
Para MF, Study Chair
Collier A, Study Chair
Coombs R, Study Chair
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.
Clinical Details
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 design: Treatment
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
Minimum age: 18 Years.
Maximum age: N/A.
Gender(s): Both.
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.
Locations and Contacts
Stanford at Kaiser / Kaiser Permanente Med Ctr, San Francisco, California 94115, United States
San Francisco Gen Hosp, San Francisco, California 941102859, United States
Stanford Univ Med Ctr, Stanford, California 943055107, United States
Children's Hosp of Oakland, Oakland, California 946091809, United States
Univ of Colorado Health Sciences Ctr, Denver, Colorado 80262, United States
Univ of Miami School of Medicine, Miami, Florida 331361013, United States
Northwestern Univ Med School, Chicago, Illinois 60611, United States
Rush Presbyterian - Saint Luke's Med Ctr, Chicago, Illinois 60612, United States
Tulane Univ School of Medicine, New Orleans, Louisiana 70112, United States
Harvard (Massachusetts Gen Hosp), Boston, Massachusetts 02114, United States
St Louis Regional Hosp / St Louis Regional Med Ctr, St. Louis, Missouri 63112, United States
St Vincent's Hosp / Mem Sloan-Kettering Cancer Ctr, New York, New York 10021, United States
Univ of Rochester Medical Center, Rochester, New York 14642, United States
Bellevue Hosp / New York Univ Med Ctr, New York, New York 10016, United States
SUNY / Erie County Med Ctr at Buffalo, Buffalo, New York 14215, United States
Beth Israel Med Ctr, New York, New York 10003, United States
Ohio State Univ Hosp Clinic, Columbus, Ohio 432101228, United States
Julio Arroyo, West Columbia, South Carolina 29169, United States
Univ of Texas Galveston, Galveston, Texas 775550435, United States
Univ of Washington, Seattle, Washington 981224304, United States
Additional Information
Click here for more information about Saquinavir Click here for more information about Indinavir sulfate
Related publications: [No authors listed] Saquinavir update. Treat Rev. 1997 Aug;(No 25):6. No abstract available. [No authors listed] Saquinavir switch study stopped. Treat Rev. 1997 Apr;(No 24):6. No abstract available. Gilden D. Spring cleaning in trial land. GMHC Treat Issues. 1997 Mar;11(3):4-7. No abstract available. 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) 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. 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.
Last updated: June 23, 2005
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