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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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HIV Infections

Intervention / Treatment
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* Drug: Delavirdine mesylate
* Drug: Zidovudine
* Drug: Didanosine


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: Delavirdine mesylate|nan|
|Drug: Zidovudine|nan|
|Drug: Didanosine|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Didanosine, Acquired Immunodeficiency Syndrome, AIDS-Related Complex, Antiviral Agents, Zidovudine