The Anti-HIV Effects of Saquinavir Soft Gelatin Capsules Versus Indinavir in Patients Who Have Used Saquinavir Hard Gelatin Capsules for One Year

HIV Infections Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00000848
• Other study ID #: ACTG 333
• Secondary ID: 11305
• Status: Completed
• Phase: Phase 2
• Est. completion date: October 1998

Study information

• Verified date: October 2021
• Source: National Institute of Allergy and Infectious Diseases (NIAID)
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 144
• Est. completion date: October 1998
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• HIV Infections

Intervention

Drug:
• Indinavir sulfate

• Saquinavir

Locations

Country	Name	City	State
United States	University of Colorado Hospital CRS	Aurora	Colorado
United States	Massachusetts General Hospital ACTG CRS	Boston	Massachusetts
United States	SUNY - Buffalo, Erie County Medical Ctr.	Buffalo	New York
United States	Northwestern University CRS	Chicago	Illinois
United States	Rush Univ. Med. Ctr. ACTG CRS	Chicago	Illinois
United States	The Ohio State Univ. AIDS CRS	Columbus	Ohio
United States	Univ. of Miami AIDS CRS	Miami	Florida
United States	Beth Israel Med. Ctr. (Mt. Sinai)	New York	New York
United States	NY Univ. HIV/AIDS CRS	New York	New York
United States	Stanford CRS	Palo Alto	California
United States	Univ. of Rochester ACTG CRS	Rochester	New York
United States	St. Louis ConnectCare, Infectious Diseases Clinic	Saint Louis	Missouri
United States	Washington U CRS	Saint Louis	Missouri
United States	Ucsf Aids Crs	San Francisco	California
United States	University of Washington AIDS CRS	Seattle	Washington
United States	Harbor-UCLA Med. Ctr. CRS	Torrance	California

Sponsors (1)

Lead Sponsor	Collaborator
National Institute of Allergy and Infectious Diseases (NIAID)

Country where clinical trial is conducted

United States, 

References & Publications (6)

Gilden D. Spring cleaning in trial land. GMHC Treat Issues. 1997 Mar;11(3):4-7. — View 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)

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. Epub 2000 Aug 14. — View Citation

Saquinavir switch study stopped. Treat Rev. 1997 Apr;(No 24):6. — View Citation

Saquinavir update. Treat Rev. 1997 Aug;(No 25):6. — View 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. Epub 2000 Jul 6. — View Citation