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).

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.)

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.