Study of Itraconazole in Patients With Advanced HIV Infection

Pharmacokinetics Study of Intravenous Itraconazole Followed by Oral Dosing at 200 Mg Twice Daily in Patients With Advanced HIV Infection

To demonstrate a dosage regimen for intravenous itraconazole that produces a plasma concentration range comparable to that obtained after currently used oral dosages of itraconazole oral solution; and to obtain preliminary safety data in patients with advanced HIV disease.

Patients will receive intravenous itraconazole solution twice daily for 2 days and then once daily for five additional days. Patients then randomized to receive twice-daily or once-daily itraconazole oral solution for an additional 28 days.

Inclusion Criteria

Concurrent Medication:

Allowed:

Antiretroviral therapy providing patient has already been on a stable, unchanged regimen for 8 weeks prior to study entry.

Patients must have:

• Documented HIV infection.
• CD4 lymphocyte count < 300 cells/mm3.
• No clinically significant abnormalities, elicited by history and physical examination.
• No clinically significant abnormalities in blood count, biochemical profile, or urinalysis within 2 weeks of study entry.
• Negative urine screening.
• No clinically significant abnormalities of electrocardiogram.

Prior Medication:

Allowed:

Antiretroviral therapy providing patient has been on a stable, unchanged regimen for 8 weeks prior to study entry.

Exclusion Criteria

Co-existing Condition:

Patients with the following symptoms and conditions are excluded:

• Acute opportunistic infection or other significant concurrent illness that would preclude participation for the required 36 days.
• Unable to swallow oral solution.
• Obesity greater than 25% of ideal body weight.

Concurrent Medication:

Excluded:

• Rifampin.
• Rifabutin.
• Phenobarbital.
• Phenytoin.
• Carbamazepine.
• Digoxin.
• Warfarin.
• Midazolam.
• Triazolam.
• Terfenadine.
• Astemizole.
• Cisapride.
• H2 blockers.
• Omeprazole.
• Continual antacids.
• Didanosine.
• Any medication known to affect absorption, metabolism or excretion of imidazole or azole compounds.

Patients with the following prior symptoms and conditions are excluded:

• Previous hypersensitivity to azole antifungals.
• History of surgical procedure that may interfere with absorption of itraconazole.
• History of significant blood loss in the previous 30 days.

Prior Medication:

Excluded:

Excluded within 15 days prior to study entry:

• Rifampin.
• Rifabutin.
• Phenobarbital.
• Phenytoin.
• Carbamazepine.
• Digoxin.
• Warfarin.
• Midazolam.
• Triazolam.

Excluded within 8 weeks prior to study entry:

• Change in antiretroviral therapy.

Risk Behavior:

Excluded:

Patients who chew tobacco or regularly smoke more than 10 cigarettes per day.