Clinical trial NCT00002124: 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
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: HIV Infections
Keywords: Drug Therapy, Combination
Acquired Immunodeficiency Syndrome
AIDS-Related Complex
Antiviral Agents
Zidovudine
Lead sponsor: NIH AIDS Clinical Trials Information Service
Sponsor class: INDUSTRY
First posted: 2001-08-31
Enrollment: 1250
Sex: ALL
Minimum age (years): 14
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Primary purpose: TREATMENT

Brief 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.

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.

Eligibility criteria: 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.

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