A Phase II Double-Blind Study of Two Doses of SC-49483 in Combination With Zidovudine (ZDV) Versus ZDV

• Status: Completed
• Trial end date: 1995-07-01
• Target enrollment: 0
• Participant gender: All

Summary

To determine the safety and anti-HIV activity of two doses of SC-49483 in combination with zidovudine (AZT) versus AZT alone. To determine the influences of viral phenotype on the anti-HIV activity of these treatment regimens.

SC-49483 has no inherent activity against HIV-1 but is converted in the intestinal wall to SC-48334, which has demonstrated anti-HIV activity. Since SC-49483 causes significantly less gastrointestinal toxicity than SC-48334, the combination of SC-49483 with AZT may improve the benefits of both drugs in patients with HIV infection.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
• Collaborators: G D Searle; Glaxo Wellcome
• Treatments: Zidovudine

Criteria

Inclusion Criteria

Concurrent Medication:

Required:

• PCP prophylaxis (trimethoprim/sulfamethoxazole, dapsone, or aerosolized pentamidine) in patients with CD4 count <= 200 cells/mm3.

Allowed:

• Topical antifungal agents, ketoconazole, fluconazole, and itraconazole for candidiasis or disseminated fungal infections, as medically indicated.

• Maintenance therapy for Mycobacteria disease with isoniazid, ethambutol, rifampin, pyrazinamide, clofazimine, ciprofloxacin, clarithromycin, or rifabutin.

• Maintenance therapy for toxoplasmosis with pyrimethamine, sulfadiazine, or clindamycin.

• Maintenance therapy for herpes simplex virus with acyclovir at <= 1000 mg/day.

• Recombinant erythropoietin and G-CSF, if indicated.

• Antibiotics for bacterial infections.

• Symptomatic treatment such as antipyretics, analgesics, nonsteroidal anti-inflammatory agents, and antiemetics.

Concurrent Treatment:

Allowed:

• Localized radiation therapy and limited intralesional therapy for cutaneous Kaposi's sarcoma.

Patients must have:

• Documented HIV infection.

• Per 07/19/94 amendment, one of the following:

• CD4 count 150 - 350 cells/mm3 within 60 days prior to study entry AND prior AZT for no more than 12 months cumulative (given with or without ddI or ddC).

• CD4 count 50 - 350 cells/mm3 within 60 days prior to study entry AND no prior antiretroviral therapy.

• MT-2 cell assay within 60 days prior to study entry.

NOTE:

• Minimal Kaposi's sarcoma is permitted.

Exclusion Criteria

Co-existing Condition:

Patients with the following condition are excluded:

• Malignancy other than minimal Kaposi's sarcoma.

Concurrent Medication:

Excluded:

• Antiretroviral therapies (other than study drug).

• Biologic response modifiers.

• Systemic corticosteroids for > 21 consecutive days.

• Foscarnet.

• Systemic cytotoxic chemotherapy for a malignancy.

Patients with the following prior conditions are excluded:

• History of cataracts.

• History of intolerance to AZT at <= 600 mg/day.

• Unexplained temperature >= 38.5 degrees C that persists for any 7 days within the 30 days prior to study entry.

• Chronic diarrhea (defined as >= 3 stools per day) that persists for any 15 days within the 30 days prior to study entry.

Prior Medication:

Excluded:

• More than 6 months (more than 12 months per 07/19/94 amendment) cumulative prior therapy with AZT.

• Prior induction or maintenance therapy with foscarnet.

• Any investigational drug within 30 days prior to study entry.

• Prior SC-49483 or SC-48334.

• Prior ddC, ddI, or stavudine (d4T) as monotherapy.

• Interferon or interleukin within 30 days prior to study entry.

• Prior non-nucleoside reverse transcriptase inhibitors (e.g., NVP, ATV).

• Systemic corticosteroids for > 21 consecutive days.

• Acute treatment for a serious infection or any opportunistic infection within 14 days prior to study entry.

• Prior combination therapy with AZT, ddI, and/or ddC within 30 days prior to study entry.