A Study of Multiple Doses of Vesnarinone in Advanced HIV Disease

Fourteen patients per dose level receive vesnarinone at 1 of 4 doses for 12 weeks. At least seven patients at a given dose level must have completed 4 weeks of treatment before dose is escalated in subsequent patients.

Inclusion criteria

Concurrent Medication:

Allowed:

• Chemoprophylaxis for Pneumocystis carinii, candida, mycobacteria, and other opportunistic infections.
• Acyclovir for up to 14 days for acute herpes outbreaks.

Patients must have:

• Documented HIV infection.
• CD4 count 50 - 300 cells/mm3.
• No active opportunistic infections.
• No fever, diarrhea, or Herpes zoster.

Exclusion criteria

Co-existing Condition:

Patients with the following symptoms or conditions are excluded:

• Clinically significant current cardiac disease, including patients who exhibit long QTC syndrome on EKG screening and who have an abnormal cardiothoracic ratio on chest x-ray at baseline.
• Active malignancy (other than cutaneous Kaposi's sarcoma or cutaneous basal cell carcinoma or in situ carcinoma of the cervix).

Concurrent Medication:

Excluded:

• Antiretroviral agents, including ddI, ddC, AZT, and d4T.
• Immunosuppressive agents.
• Investigational HIV drugs/therapies including vaccines.
• Interferon or other immunomodulating agents.
• Corticosteroids (other than topical).
• Hematopoietins.
• Megestrol acetate.
• Agents known to cause neutropenia.
• Trimethoprim/sulfamethoxazole in excess of 160 mg trimethoprim and 800 mg sulfamethoxazole thrice weekly.
• Cytotoxic chemotherapy.

Concurrent Treatment:

Excluded:

• Radiation therapy.

Patients with the following prior conditions are excluded:

• Prior history of cardiac disease.
• History of agranulocytosis or severe (grade 3 or worse) drug-induced neutropenia or documented abnormalities in granulocyte function.

Prior Medication:

Excluded:

• AZT, ddI, ddC, d4T, or other nucleoside analog antiretroviral therapy within 14 days prior to study entry.
• Prior cytotoxic chemotherapy.
• Acyclovir for herpes prophylaxis within 48 hours prior to study entry.

Prior Treatment:

Excluded within 30 days prior to study entry:

• Erythropoietin, transfusion, or blood product use.
• Radiation therapy (including electron beam irradiation). Active use of illicit drugs (specifically cocaine, amyl nitrate, heroin, and other cardioactive agents).