Randomized, Phase I/II, Dose-Ranging, Open-Label Trial of the Anti-HIV Activity of Delavirdine Mesylate (DLV; U-90,152S)

Data suggest that bisheteroarylpiperazines (BHAPs) such as delavirdine mesylate are potent and safe anti-HIV agents and may have different biological behavior than other currently available non-nucleoside RT inhibitors.

Patients are randomized to receive U-90152 at one of three doses (treatment arms I through III) or either AZT or ddI (treatment arm IV). Patients on arm IV who are AZT-naive receive AZT; those who are AZT-experienced receive ddI. Treatment continues for 24 weeks.

PER 12/22/94 AMENDMENT: All patients receiving U-90152 have the same starting dose, to attain one of three target trough levels.

Inclusion criteria

Concurrent Medication:

Allowed:

• PCP prophylaxis.
• Topical antifungal agents, clotrimazole troches, nystatin oral suspension, topical ketoconazole, and oral fluconazole.
• Acyclovir (<= 1000 mg/day) as maintenance therapy for herpes simplex virus.
• Recombinant erythropoietin and G-CSF.
• Antibiotics for bacterial infections, unless specifically excluded.
• Symptomatic treatment such as antipyretics, analgesics, nonsteroidal anti-inflammatory agents, and antiemetics.
• Antacids.

Patients must have:

• HIV-1 infection.
• CD4 count 200 - 500 cells/mm3.
• Either no prior antiretroviral therapy or discontinued AZT monotherapy 3 or more weeks prior to study entry.

NOTE:

• Half of patients should be antiretroviral naive.

Prior Medication:

Allowed:

• Prior AZT.

Exclusion criteria

Co-existing Condition:

Patients with the following symptoms or conditions are excluded:

• Malignancy other than minimal Kaposi's sarcoma.

Concurrent Medication:

Excluded:

• Rifabutin.
• Rifampin.
• Terfenadine.
• Astemizole.
• Loratadine.
• Trifluoperazine.
• Piperazine citrate.
• Any acute or chronic therapy for CMV, MAC, toxoplasmosis, or disseminated fungal infection.
• Non-study antiretroviral therapies, interferons, biologic response modifiers, and HIV vaccines.
• Systemic corticosteroids for more than 21 consecutive days.
• Foscarnet.
• Systemic cytotoxic chemotherapy for a malignancy.

Patients with the following prior conditions are excluded:

• History of pancreatitis (in patients who received prior AZT).
• History of grade 2 or worse peripheral neuropathy (in patients who received prior AZT).
• History of hypersensitivity to BHAP compounds (e.g., trifluoperazine - Stelazine, piperazine citrate - Antepar).

Prior Medication:

Excluded within 30 days prior to study entry:

• Any investigational medication.
• Interferon.
• Interleukin.
• Rifabutin.
• Rifampin.
• Terfenadine.
• Astemizole.
• Loratadine.
• Trifluoperazine.
• Piperazine citrate.

Excluded at any time:

• Prior ddI, ddC, d4T, or 3TC.
• Prior foscarnet.
• Prior BHAP compound or other non-nucleoside RT inhibitor.

Active substance abuse interfering with compliance.