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

Overview

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.

Study Type

  • Study Type: Interventional
  • Study Design
    • Primary Purpose: Treatment
    • Masking: Double

Detailed Description

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.

Interventions

  • Drug: Delavirdine mesylate
  • Drug: Lamivudine
  • Drug: Zidovudine

Participating in This Clinical Trial

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.

Gender Eligibility: All

Minimum Age: 14 Years

Maximum Age: N/A

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • Pharmacia and Upjohn

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