To evaluate the safety and tolerability of four doses of oral vesnarinone in patients with
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.
- Chemoprophylaxis for Pneumocystis carinii, candida, mycobacteria, and other
- 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.
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).
- 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).
- Megestrol acetate.
- Agents known to cause neutropenia.
- Trimethoprim/sulfamethoxazole in excess of 160 mg trimethoprim and 800 mg
sulfamethoxazole thrice weekly.
- Cytotoxic chemotherapy.
- 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.
- 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.
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).