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

HIV Infections Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00002124
• Other study ID #: 228B
• Secondary ID: M/3331/0021
• Status: Completed
• Phase: Phase 3
• First received: November 2, 1999
• Last updated: June 23, 2005

Study information

• Verified date: July 1997
• Source: NIH AIDS Clinical Trials Information Service
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1250
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 14 Years and older

Eligibility

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.

Study Design

Endpoint Classification: Safety Study, Masking: Double-Blind, Primary Purpose: Treatment

Related Conditions & MeSH terms

• HIV Infections

Intervention

Drug:
• Delavirdine mesylate

• Lamivudine

• Zidovudine

Locations

Country	Name	City	State
Puerto Rico	UPR School of Medicine	San Juan
United States	Albany Med College	Albany	New York
United States	Univ of Michigan Hospitals and Health Ctrs	Ann Arbor	Michigan
United States	Infectious Disease Rsch Consortium of GA / SE Clin Resources	Atlanta	Georgia
United States	Central Texas Med Foundation	Austin	Texas
United States	Johns Hopkins Hosp	Baltimore	Maryland
United States	Univ of Maryland at Baltimore	Baltimore	Maryland
United States	East Bay AIDS Ctr	Berkeley	California
United States	Univ of Alabama at Birmingham	Birmingham	Alabama
United States	Boston City Hosp / FGH-1	Boston	Massachusetts
United States	Brigham and Women's Hosp	Boston	Massachusetts
United States	Massachusetts Gen Hosp	Boston	Massachusetts
United States	New England Deaconess Hosp	Boston	Massachusetts
United States	SUNY / Erie County Med Ctr at Buffalo	Buffalo	New York
United States	Med Ctr of Vermont Hosp	Burlington	Vermont
United States	Univ of North Carolina School of Medicine	Chapel Hill	North Carolina
United States	Med Univ of South Carolina	Charleston	South Carolina
United States	Carolinas Med Ctr	Charlotte	North Carolina
United States	Rush Presbyterian - Saint Luke's Med Ctr	Chicago	Illinois
United States	Univ of Illinois	Chicago	Illinois
United States	Univ of Cincinnati / Holmes Hosp	Cincinnati	Ohio
United States	Univ Hosp of Cleveland / Case Western Reserve Univ	Cleveland	Ohio
United States	Peachwood Med Ctr	Clovis	California
United States	Stratogen Health / Independent Research Nurses	Cranston	Rhode Island
United States	Dallas Veterans Administration Med Ctr	Dallas	Texas
United States	Univ Hosp / Univ of Colorado Health Sci Ctr	Denver	Colorado
United States	Harper Hosp	Detroit	Michigan
United States	Henry Ford Hosp	Detroit	Michigan
United States	Duke Univ Med Ctr	Durham	North Carolina
United States	Hampton Roads Med Specialists	Hampton	Virginia
United States	Pennsylvania State Univ / Hershey Med Ctr	Hershey	Pennsylvania
United States	Houston Veterans Administration Med Ctr	Houston	Texas
United States	Park Plaza Hosp	Houston	Texas
United States	Univ TX Health Science Ctr	Houston	Texas
United States	Indiana Univ Infectious Disease Research Clinic	Indianapolis	Indiana
United States	Univ of Iowa	Iowa City	Iowa
United States	Univ of Kansas School of Medicine / Univ Hosp	Kansas City	Kansas
United States	Univ of Missouri at Kansas City School of Medicine	Kansas City	Missouri
United States	Univ of Kentucky Med Ctr / Chandler Med Ctr	Lexington	Kentucky
United States	CARE Ctr / UCLA Med Ctr	Los Angeles	California
United States	Los Angeles County - USC Med Ctr	Los Angeles	California
United States	Los Angeles County / Health Research Assoc / Drew Med Ctr	Los Angeles	California
United States	Univ of Wisconsin	Madison	Wisconsin
United States	Univ of Tennessee	Memphis	Tennessee
United States	Univ of Miami School of Medicine	Miami	Florida
United States	Vanderbilt Univ	Nashville	Tennessee
United States	Jersey Shore Med Ctr	Neptune	New Jersey
United States	Tulane Univ Med School	New Orleans	Louisiana
United States	Beth Israel Med Ctr	New York	New York
United States	Community Research Initiative on AIDS	New York	New York
United States	Mount Sinai Med Ctr	New York	New York
United States	New York Hosp - Cornell Med Ctr	New York	New York
United States	Saint Vincent's Hosp and Med Ctr	New York	New York
United States	Highland Gen Hosp / San Francisco Gen Hosp	Oakland	California
United States	Univ of Oklahoma	Oklahoma City	Oklahoma
United States	Univ of Nebraska Med Ctr / HIV Clinic	Omaha	Nebraska
United States	UCI Med Ctr	Orange	California
United States	Caremark Inc	Palm Beach Gardens	Florida
United States	Buckley Braffman Stern Med Associates	Philadelphia	Pennsylvania
United States	Oncology and Hematology Association	Philadelphia	Pennsylvania
United States	Univ of Pennsylvania / HIV Clinic	Philadelphia	Pennsylvania
United States	Univ of Pittsburgh Med School	Pittsburgh	Pennsylvania
United States	AIDS Consultation Service / Maine Med Ctr	Portland	Maine
United States	Portland Veterans Adm Med Ctr / Rsch & Education Grp	Portland	Oregon
United States	AIDS Community Research Consortium	Redwood City	California
United States	Richmond AIDS Consortium	Richmond	Virginia
United States	Community Health Network	Rochester	New York
United States	Univ of Rochester Med Ctr	Rochester	New York
United States	UCD Med Ctr / AIDS and Related Disorders Clinic	Sacramento	California
United States	Audie L Murphy Veterans Administration Hosp	San Antonio	Texas
United States	St Lukes Medical Group	San Diego	California
United States	UCSD / Ctr for Special Immunology	San Diego	California
United States	Davies Med Ctr	San Francisco	California
United States	Saint Francis Mem Hosp	San Francisco	California
United States	ViRx Inc	San Francisco	California
United States	Univ of Washington	Seattle	Washington
United States	Baystate Med Ctr of Springfield	Springfield	Massachusetts
United States	Washington Univ	St. Louis	Missouri
United States	St Paul Ramsey Med Ctr / HIV Program Office	St. Paul	Minnesota
United States	SUNY / Health Sciences Ctr at Stony Brook	Stony Brook	New York
United States	Infectious Disease Research Institute Inc	Tampa	Florida
United States	Shared Med Research Foundation	Tarzana	California
United States	Harbor - UCLA Med Ctr	Torrance	California
United States	New York Med College / Westchester County Med Ctr	Valhalla	New York
United States	George Washington Univ Med Ctr	Washington	District of Columbia
United States	Georgetown Univ Med Ctr	Washington	District of Columbia
United States	Univ of Kansas School of Medicine	Wichita	Kansas
United States	Univ of Massachusetts Med Ctr	Worcester	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
Pharmacia and Upjohn

Countries where clinical trial is conducted

United States,  Puerto Rico,