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

• Status: Completed
• Trial end date: 1996-01-01
• Target enrollment: 0
• Participant gender: All

Summary

PRIMARY: To study the safety and tolerance of delavirdine mesylate ( U-90152 ) monotherapy. To compare the anti-HIV activity of three blood concentration levels of this agent with nucleoside analog monotherapy, either zidovudine ( AZT ) or didanosine ( ddI ), based on the reduction of HIV viral burden.

SECONDARY: To use pharmacokinetic parameters to assess the relationship between daily drug exposure and antiviral activity and toxicity of the U-90152, AZT, and ddI monotherapy. To assess anti-HIV activity using other disease markers.

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.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
• Treatments: Delavirdine; Didanosine; Zidovudine

Criteria

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.