The Safety and Effectiveness of U-90152 in HIV-1 Infected Patients Who Take Zidovudine

Open-Label Escalating Multiple-Dose Study of the Safety, Tolerance, and Pharmacokinetics of Oral U-90152 in HIV-1 Infected Males and Females With CD4 Counts of 200 - 500 Cells/mm3 Who Are Maintained on a Stable Dose of Zidovudine (AZT)

To evaluate the pharmacokinetics, safety, and tolerance of delavirdine mesylate ( U-90152 ) after multiple doses given orally to asymptomatic HIV-1 positive patients who are maintained on a stable dose of zidovudine ( AZT ). To investigate the optimum dose regimen of U-90152 that gives average trough concentrations > 1 micromolar in combination with standard AZT therapy, and to examine drug interactions between the two drugs. To establish the MTD of U-90152 in HIV-1 positive patients on stable AZT therapy. To investigate comparative pharmacokinetics between HIV-1 positive men and women.

Study Overview

• Status: Completed
• Conditions: HIV Infections
• Intervention / Treatment: Drug: Zidovudine; Drug: Delavirdine mesylate

• Study Type: Interventional
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Michigan
    • Kalamazoo, Michigan, United States, 490074949
      • Bronson Methodist Hosp / Upjohn Research Clinic

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria

Concurrent Medication:

Allowed:

• Inhaled pentamidine following completion of the inpatient pharmacokinetic portion of the study.

Patients must have:

• HIV-1 infection.
• CD4 count 200 - 500 cells/mm3.
• Maintenance on AZT for at least 6 weeks.
• No active opportunistic infections.
• Ability to swallow numerous tablets without difficulty.
• Ability to have blood samples drawn.

Exclusion Criteria

Co-existing Condition:

Patients with the following symptoms or conditions are excluded:

• Acute medical problems, including opportunistic infections (such as active cryptococcosis, pneumocystis carinii, herpes zoster, histoplasmosis, CMV) and nonopportunistic diseases (liver and renal disease, orthostatic hypotension, hypertension, progressive multifocal leukoencephalopathy, lymphoma, Kaposi's sarcoma, or other malignancy).
• Clinically significant hypersensitivity to piperazine type drugs (Antepar, Stelazine, and U-87201E).
• Negative EMIT drug screen or equivalent for drugs of abuse.

Concurrent Medication:

Excluded:

• Antiretroviral agents other than AZT.
• Primary or secondary prophylactic medications for opportunistic infections (inhaled pentamidine is permitted following completion of the inpatient pharmacokinetic portion of the study).

Patients with the following prior conditions are excluded:

• History of clinically significant nervous system or muscle disease, seizure disorder, AIDS dementia, or psychotic disorder that might impair study compliance.
• History of clinically significant cardiovascular, renal, hepatic, cardiac, pulmonary, endocrine, hematologic, vascular, or collagen disease.

Prior Medication:

Excluded:

• Prior U-87201E or other non-nucleoside reverse transcriptase inhibitors (nevirapine, TIBO, L-drugs, and HEPT).
• Antiretroviral agents (other than AZT) or immunomodulating agents within 15 days prior to study entry.
• Primary prophylactic drugs within 15 days prior to study entry.
• Any known enzyme-inducing drug or any enzyme-inhibiting agents, such as ketoconazole, fluconazole, rifampin, isoniazid, and cimetidine, within 15 days prior to study entry.
• Any investigational medication within 15 days prior to study entry. Unwilling to comply with safer sex practices. Active substance abuse. Alcohol consumption during the inpatient pharmacokinetic portion of the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Masking: None (Open Label)

Collaborators and Investigators

• Sponsor: Pharmacia and Upjohn

Publications and helpful links

General Publications

• Batts DH, Freimuth WW, Cox SR, Peel BG, Hanover CK, Wathen LK, Staton BA. Open-label escalating multiple-dose study of the safety,tolerance, and pharmacokinetics of oral U-90152S (delavirdine, DLV) in HIV-1 infected males and females with CD4 counts of 200 to 500/mm3, who are maintained on a stable dose of AZT. Natl Conf Hum Retroviruses Relat Infect (1st). 1993 Dec 12-16:158

Study record dates

Study Registration Dates

• First Submitted: November 2, 1999
• First Submitted That Met QC Criteria: August 30, 2001
• First Posted (Estimate): August 31, 2001

Study Record Updates

• Last Update Posted (Estimate): June 24, 2005
• Last Update Submitted That Met QC Criteria: June 23, 2005
• Last Verified: April 1, 1994

More Information

Terms related to this study

• Keywords: Antiviral Agents; Drug Interactions; Zidovudine
• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; Immune System Diseases; HIV Infections; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Reverse Transcriptase Inhibitors; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Antimetabolites; Zidovudine; Delavirdine
• Other Study ID Numbers: 125A; M/3331/0003