A Double-Blind, Randomized, Dose Response Study of Three Doses of Delavirdine Mesylate (U-90152S) in Combination With Zidovudine (ZDV) Versus ZDV Alone in HIV-1 Infected Individuals With CD4 Counts of 200-500mm3

Study Overview
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Brief Summary
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PART I: To evaluate the safety, tolerance, efficacy, and pharmacokinetics of three fixed doses of delavirdine mesylate (DLV) in combination with zidovudine (AZT) versus AZT alone in HIV-positive patients. PART II: To evaluate the safety, tolerance, efficacy, and pharmacokinetics of ZDV plus 3TC with or without DLV versus ZDV plus DLV in HIV-positive patients.

Detailed Description
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PART I: Patients are originally randomized to receive ZDV plus DLV (DLV at 1 of 3 doses) or ZDV plus placebo. AS PER AMENDMENT 3/7/96: PART II: Patients are rerandomized from PART I. Arm I: ZDV plus 3TC plus placebo. Arm II: ZDV plus 3TC plus DLV. Arm III: ZDV plus DLV (DLV at a higher dose than in the original protocol). Arm IV: ZDV plus DLV (no change from original; same treatment as Arm III). AS PER AMENDMENT 1/24/97: Approximately 450 more patients will be enrolled in one of these 3 revised arms on PART II. Half of these new patients will be anti-retroviral naive and half will be anti-retroviral experienced.

Official Title
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A Double-Blind, Randomized, Dose Response Study of Three Doses of Delavirdine Mesylate (U-90152S) in Combination With Zidovudine (ZDV) Versus ZDV Alone in HIV-1 Infected Individuals With CD4 Counts of 200-500mm3

Conditions
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HIV Infections

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


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria Patients must have: HIV-1 seropositivity. CD4 count 200-500 cells/mm3. No active or acute (onset within the past month) opportunistic infections such as active cryptococcosis, pneumocystis carinii, herpes zoster, histoplasmosis, or cytomegalovirus (CMV). Consent of parent or guardian if less than 18 years of age. Understanding of potential risk to fetus related to study participation. Acceptable medical history, physical exam, EKG, and chest x-ray during screening. NOTE: Patients with cutaneous Kaposi's sarcoma requiring no systemic therapy are permitted. PER AMENDMENT 3/7/96: ZDV therapy for 0-6 months prior to study entry. (Part II) Prior Medication: Allowed: Prior AZT (no more than 6 months total). Exclusion Criteria Co-existing Condition: Patients with the following symptoms or conditions are excluded: Active tuberculosis that is sensitive to rifampin. Inability to swallow numerous tablets. Clinically significant active or acute medical problems, including progressive multifocal leukoencephalopathy, lymphoma, or malignancy requiring systemic therapy. Clinically significant hypersensitivity to piperazine-type drugs (e.g., Antepar and Stelazine). Grade 2 or worse baseline organ function. NOTE: Hemophiliacs with grade 2 bilirubin, alkaline phosphatase, SGOT, or SGPT will be considered if these values have been stable over the past year. NOTE: Patients with suspected Gilbert's syndrome will be considered if bilirubin is grade 2 or better. Patients with the following prior conditions are excluded: History of pancreatitis within the past 2 years. History of clinically significant nervous system or muscle disease, seizure disorder, AIDS dementia, or psychiatric disorder that would preclude study compliance. History of grade 2 or worse peripheral neuropathy. Intolerance to AZT in previously treated patients. Prior Medication: Excluded: More than 6 months total of prior AZT. Any prior ddC, d4T, 3TC, or ddI. Prior non-nucleoside reverse transcriptase inhibitors, including L-drugs, nevirapine, TIBO, HEPT, delavirdine, atevirdine, and alpha-APA. Other investigational antiretroviral medications (including foscarnet) or immunomodulators (including all interferons) within 21 days prior to initial study drug dose. Prior prophylactic or therapeutic HIV-1 gp120 or 160 vaccines. Rifampin, rifabutin, astemizole, loratadine, or terfenadine within 21 days prior to initial study drug dose. Any unapproved investigational medication for any indication within 21 days prior to initial study drug dose. Any enzyme-inducing drugs known to affect cytochrome P450 3A, (e.g., ketoconazole, fluconazole, isoniazid, itraconazole, etc.) within 21 days prior to initial study drug dose. Active substance abuse.

Ages Eligible for Study
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Minimum Age: 14 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
Masking: Double


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: Delavirdine mesylate|nan|
|Drug: Lamivudine|nan|
|Drug: Zidovudine|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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Drug Therapy, Combination, Acquired Immunodeficiency Syndrome, AIDS-Related Complex, Antiviral Agents, Zidovudine