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

NCT ID: NCT00000848

Last Updated: 2021-11-04

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

144 participants

Study Classification

INTERVENTIONAL

Study Completion Date

1998-10-31

Brief Summary

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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

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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.

Conditions

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HIV Infections

Keywords

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Administration, Oral Acquired Immunodeficiency Syndrome AIDS-Related Complex Antiviral Agents HIV Protease Inhibitors Biological Markers Indinavir Viremia RNA, Viral Saquinavir

Study Design

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Primary Study Purpose

TREATMENT

Interventions

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Indinavir sulfate

Intervention Type DRUG

Saquinavir

Intervention Type DRUG

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Institute of Allergy and Infectious Diseases (NIAID)

NIH

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Para MF

Role: STUDY_CHAIR

Collier A

Role: STUDY_CHAIR

Coombs R

Role: STUDY_CHAIR

Locations

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Stanford CRS

Palo Alto, California, United States

Site Status

Ucsf Aids Crs

San Francisco, California, United States

Site Status

Harbor-UCLA Med. Ctr. CRS

Torrance, California, United States

Site Status

University of Colorado Hospital CRS

Aurora, Colorado, United States

Site Status

Univ. of Miami AIDS CRS

Miami, Florida, United States

Site Status

Northwestern University CRS

Chicago, Illinois, United States

Site Status

Rush Univ. Med. Ctr. ACTG CRS

Chicago, Illinois, United States

Site Status

Massachusetts General Hospital ACTG CRS

Boston, Massachusetts, United States

Site Status

Washington U CRS

St Louis, Missouri, United States

Site Status

St. Louis ConnectCare, Infectious Diseases Clinic

St Louis, Missouri, United States

Site Status

SUNY - Buffalo, Erie County Medical Ctr.

Buffalo, New York, United States

Site Status

Beth Israel Med. Ctr. (Mt. Sinai)

New York, New York, United States

Site Status

NY Univ. HIV/AIDS CRS

New York, New York, United States

Site Status

Univ. of Rochester ACTG CRS

Rochester, New York, United States

Site Status

The Ohio State Univ. AIDS CRS

Columbus, Ohio, United States

Site Status

University of Washington AIDS CRS

Seattle, Washington, United States

Site Status

Countries

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United States

References

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Saquinavir update. Treat Rev. 1997 Aug;(No 25):6.

Reference Type BACKGROUND
PMID: 11364616 (View on PubMed)

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

Reference Type BACKGROUND
PMID: 11364285 (View on PubMed)

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

Reference Type BACKGROUND
PMID: 11364275 (View on PubMed)

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)

Reference Type BACKGROUND

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.

Reference Type BACKGROUND
PMID: 10882582 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 10950766 (View on PubMed)

Other Identifiers

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11305

Identifier Type: REGISTRY

Identifier Source: secondary_id

ACTG 333

Identifier Type: -

Identifier Source: org_study_id