A Study of Saquinavir and Zalcitabine, Used Alone and Together, in the Treatment of Advanced HIV Infection in Patients Who Stopped Taking or Who Cannot Take Zidovudine

A Randomized, Double-Blind, Multicenter, Parallel Study of Ro 31-8959 (Saquinavir; HIV Proteinase Inhibitor) Alone, HIVID (Dideoxycytidine; Zalcitabine, ddC) Alone, and Both in Combination, as Treatment for Advanced HIV Infection (CD4 50-300 Cells/mm3) in Patients Discontinuing or Unable to Take Retrovir (Zidovudine; AZT) Therapy

To compare the safety, tolerance, and efficacy of saquinavir mesylate (Ro 31-8959) alone, zalcitabine (dideoxycytidine; ddC) alone, and both in combination, in patients discontinuing or unable to take zidovudine (AZT).

Study Overview

• Status: Completed
• Conditions: HIV Infections
• Intervention / Treatment: Drug: Zalcitabine; Drug: Saquinavir

Detailed Description

Patients are randomized to one of three treatment regimens: ddC alone, Ro 31-8959 alone, and ddC plus Ro 31-8959. Treatment continues for at least 48 weeks. Patients are stratified by baseline CD4 count. (Per 09/26/94 amendment, a fourth arm, lower dose Ro 31-8959 plus ddC, was discontinued.)

• Study Type: Interventional
• Enrollment: 900
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Alberta
    • Calgary, Alberta, Canada
      • Southern Alberta HIV Clinic
  • Ontario
    • Hamilton, Ontario, Canada
      • McMaster Univ Med Ctr
    • Toronto, Ontario, Canada
      • Sunnybrook Health Science Ctr
  • Quebec
    • Montreal, Quebec, Canada
      • Montreal Gen Hosp
    • Montreal, Quebec, Canada
      • Clinique Medicale L'Actuele
• Puerto Rico
  • San Juan, Puerto Rico, 009275800
    • San Juan Veterans Administration Med Ctr
• United States
  • California
    • Harbor City, California, United States, 90710
      • Kaiser Foundation Hosp
    • La Jolla, California, United States, 920930679
      • UCSD
    • Los Angeles, California, United States, 90095
      • CARE Ctr / UCLA Med Ctr
    • Los Angeles, California, United States, 900121973
      • UCLA School of Medicine
    • Sacramento, California, United States, 95817
      • UCD
    • San Francisco, California, United States, 94121
      • San Francisco Veterans Administration Med Ctr
    • San Francisco, California, United States, 94110
      • UCSF - San Francisco Gen Hosp
    • San Francisco, California, United States, 94115
      • Mount Zion Med Ctr / UCSF
    • San Francisco, California, United States, 94114
      • Davies Med Ctr / c/o HIV Institute
    • Sherman Oaks, California, United States, 91403
      • Pacific Oaks Med Group / Rsch & Scientific Investigation
    • Sunnyvale, California, United States, 94086
      • Sunnyvale Med Clinic
    • Torrance, California, United States, 90505
      • Harbor - UCLA Med Ctr
  • District of Columbia
    • Washington, District of Columbia, United States, 20422
      • Veterans Administration Med Ctr
  • Florida
    • Miami, Florida, United States, 33125
      • Miami Veterans Administration Med Ctr
    • Miami, Florida, United States, 33136
      • Univ of Miami Dept of Medicine
    • Miami Beach, Florida, United States, 33140
      • Stratogen of South Florida
  • Georgia
    • Atlanta, Georgia, United States, 30308
      • AIDS Research Consortium of Atlanta
    • Atlanta, Georgia, United States, 30327
      • West Paces Clinical Research Incoporated
  • Illinois
    • Chicago, Illinois, United States, 60612
      • Rush Presbyterian - Saint Luke's Med Ctr
  • Kansas
    • Wichita, Kansas, United States, 67214
      • Univ of Kansas School of Medicine
  • Louisiana
    • New Orleans, Louisiana, United States, 70112
      • Tulane Univ Med School
  • Massachusetts
    • Boston, Massachusetts, United States, 02111
      • New England Med Ctr
    • Boston, Massachusetts, United States, 02215
      • New England Deaconess Hosp
    • Boston, Massachusetts, United States, 02114
      • Massachusetts Gen Hosp / Harvard Med School
  • Michigan
    • Detroit, Michigan, United States, 48201
      • Harper Hosp
  • Missouri
    • St. Louis, Missouri, United States, 63108
      • Washington Univ School of Medicine
  • New Jersey
    • Camden, New Jersey, United States, 08103
      • UMDNJ - New Jersey Med School / Cooper Hosp
    • Newark, New Jersey, United States, 08103
      • UMDNJ - New Jersy Med School
  • New York
    • Albany, New York, United States, 12208
      • Albany Med College
    • New York, New York, United States, 10003
      • Beth Israel Med Ctr
    • New York, New York, United States, 10011
      • Saint Vincent's Hosp and Med Ctr
    • New York, New York, United States, 10032
      • Harkness Pavilion
  • Ohio
    • Columbus, Ohio, United States, 43210
      • Ohio State Univ Hosp
  • Oregon
    • Portland, Oregon, United States, 97201
      • Oregon Health Sciences Univ
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Thomas Jefferson Med College
    • Philadelphia, Pennsylvania, United States, 19146
      • Graduate Hosp / Tuttleman Cancer Ctr
  • Tennessee
    • Memphis, Tennessee, United States, 38163
      • Univ of Tennessee
  • Texas
    • Dallas, Texas, United States, 75219
      • Oaklawn Physicians Group
    • Galveston, Texas, United States, 775550882
      • Univ TX Galveston Med Branch
    • Houston, Texas, United States, 77005
      • Baylor College of Medicine
  • Washington
    • Seattle, Washington, United States, 98104
      • Univ of Washington / Harborview Med Ctr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria

Concurrent Medication:

Allowed:

• G-CSF and erythropoietin.
• Prophylaxis or chronic suppression/maintenance therapy with dapsone, aerosolized pentamidine, isoniazid, rifampin, fluoroquinolones, pyrazinamide, ethambutol, fluconazole, itraconazole, acyclovir, clotrimazole, nystatin, trimethoprim/sulfamethoxazole, pyrimethamine, folic acid, sulfadiazine, clindamycin, and fansidar.

Concurrent Treatment:

Allowed:

• Limited localized radiation therapy to the skin.

Patients must have:

• Documented HIV infection.
• CD4 count 50 - 300 cells/mm3.
• Received prior AZT that has been discontinued at least 28 days prior to study entry.
• No active opportunistic infection requiring immediate treatment.

Exclusion Criteria

Co-existing Condition:

Patients with the following symptoms or conditions are excluded:

• Signs or symptoms of peripheral neuropathy.
• Malabsorption or inadequate oral intake (defined as unable to eat one or more meals daily because of chronic nausea, emesis, or abdominal/oral-esophageal discomfort.
• Malignancy, visceral Kaposi's sarcoma, or lymphoma requiring systemic chemotherapy and/or radiotherapy within the next 48 weeks.
• Any grade 3 or worse laboratory or clinical abnormality.
• Inability to comply with protocol requirements.

Concurrent Medication:

Excluded:

• Other antiretroviral drugs.
• Experimental drugs.
• Nephrotoxic or hepatotoxic drugs.
• Drugs likely to cause peripheral neuropathy.
• Antineoplastic agents.
• Biologic response modifiers.

Concurrent Treatment:

Excluded:

• Radiation therapy other than limited localized therapy to skin.

Patients with the following prior conditions are excluded:

• History of non-Hodgkin's lymphoma.
• Unexplained fever >= 38.5 C (101.5 F) persisting for 14 days or longer within the 28 days prior to study entry.
• Unexplained, chronic diarrhea (defined as 3 or more loose stools daily) persisting for 14 days or longer within the 28 days prior to study entry.
• History of grade 2 or worse peripheral neuropathy.

Prior Medication:

Excluded:

• Prior HIV proteinase inhibitor.
• Prior antiretroviral therapy other than AZT.
• Acute therapy for opportunistic infection within 14 days prior to study entry.

Prior Treatment:

Excluded:

• More than 3 units of blood in any 21-day period within 3 months prior to study entry.

Required:

• Prior AZT.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Masking: Double

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche

Publications and helpful links

General Publications

• Revicki D, Swartz C. Quality of life outcomes of saquinavir, zalcitabine and combination saquinavir-zalcitabine therapy for advanced HIV-infection. Conf Retroviruses Opportunistic Infect. 1997 Jan 22-26;4th:113 (abstract no 266)

Study record dates

Study Registration Dates

• First Submitted: November 2, 1999
• First Submitted That Met QC Criteria: August 30, 2001
• First Posted (Estimate): August 31, 2001

Study Record Updates

• Last Update Posted (Estimate): June 24, 2005
• Last Update Submitted That Met QC Criteria: June 23, 2005
• Last Verified: February 1, 1995

More Information

Terms related to this study

• Keywords: Drug Therapy, Combination; Acquired Immunodeficiency Syndrome; AIDS-Related Complex; HIV Protease Inhibitors; Zalcitabine; Saquinavir
• Additional Relevant MeSH Terms: Pathologic Processes; RNA Virus Infections; Virus Diseases; Blood-Borne Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; Immune System Diseases; Disease Attributes; Slow Virus Diseases; HIV Infections; Infections; Communicable Diseases; Acquired Immunodeficiency Syndrome; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Reverse Transcriptase Inhibitors; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Antimetabolites; Protease Inhibitors; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; HIV Protease Inhibitors; Viral Protease Inhibitors; Zalcitabine; Saquinavir
• Other Study ID Numbers: 229A; NV 14256B; NV 14256A