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).

Condition	Treatment or Intervention	Phase
HIV Infections	Drug: Saquinavir  Drug: Zalcitabine	Phase II

Further Study Details: 

Expected Total Enrollment:  900

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.)

Ages Eligible for Study:  18 Years and above,  Genders Eligible for Study:  Both

Criteria

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.

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

Study ID Numbers:  229A; NV 14256B; NV 14256A
Record last reviewed:  February 1995
Last Updated:  October 13, 2004
Record first received:  November 2, 1999
ClinicalTrials.gov Identifier:  NCT00002333
Health Authority: United States: Food and Drug Administration
ClinicalTrials.gov processed this record on 2005-04-08