A Study of Multiple Doses of Vesnarinone in Advanced HIV Disease

A Phase I Safety and Tolerability Study of Four Doses of OPC-8212 (Vesnarinone) in Advanced HIV Disease

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.

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).