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A Phase II Double-Blind Study of Delavirdine Mesylate ( U-90152 ) in Combination With Zidovudine ( AZT ) and/or Didanosine ( ddI ) Versus AZT and ddI Combination Therapy
This study has been completed.
First Received: November 2, 1999   Last Updated: July 11, 2008   History of Changes
Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Information provided by: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT00000803
  Purpose

To determine the safety and anti-HIV activity of delavirdine mesylate ( U-90152 ) in combination with zidovudine ( AZT ) and/or didanosine ( ddI ) versus AZT/ddI combination.

U-90152 has demonstrated anti-HIV activity. Since the combination of this drug with either AZT or ddI has synergistic inhibitory activity against HIV-1 in vitro, and triple therapy appears to have greater inhibitory activity against HIV-1 in vitro than dual therapy, the use of U-90152 in combination with AZT and/or ddI may improve the benefits of these drugs in persons with HIV disease.


Condition Intervention Phase
HIV Infections
Drug: Delavirdine mesylate
Drug: Zidovudine
Drug: Didanosine
Phase II

Study Type: Interventional
Study Design: Treatment, Double-Blind, Safety Study
Official Title: A Phase II Double-Blind Study of Delavirdine Mesylate ( U-90152 ) in Combination With Zidovudine ( AZT ) and/or Didanosine ( ddI ) Versus AZT and ddI Combination Therapy

Resource links provided by NLM:


Further study details as provided by National Institute of Allergy and Infectious Diseases (NIAID):

Estimated Enrollment: 471
Detailed Description:

U-90152 has demonstrated anti-HIV activity. Since the combination of this drug with either AZT or ddI has synergistic inhibitory activity against HIV-1 in vitro, and triple therapy appears to have greater inhibitory activity against HIV-1 in vitro than dual therapy, the use of U-90152 in combination with AZT and/or ddI may improve the benefits of these drugs in persons with HIV disease.

Patients are randomized to receive U-90152/AZT/ddI, U-90152/AZT, U-90152/ddI, or AZT/ddI for 48 weeks.

  Eligibility

Ages Eligible for Study:   13 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria

Concurrent Medication:

Required:

  • PCP prophylaxis for patients with CD4 count <= 200 cells/mm3.

Allowed:

  • Topical antifungal agents.
  • Oral ketoconazole, fluconazole, and itraconazole for candidiasis or disseminated fungal infections.
  • Isoniazid, ethambutol, pyrazinamide, clofazimine, ciprofloxacin, and clarithromycin for acute or maintenance therapy for mycobacterial disease (also clarithromycin for MAC prophylaxis).
  • Acute or maintenance therapy for toxoplasmosis.
  • Acute or maintenance therapy with acyclovir (no more than 1000 mg/day) for herpes simplex virus infection.
  • rEPO and rG-CSF.
  • Antibiotics for bacterial infections (except rifampin and rifabutin).
  • Antipyretics, analgesics, nonsteroidal anti-inflammatory agents, antiemetics, and methadone.

Concurrent Treatment:

Allowed for cutaneous Kaposi's sarcoma:

  • Localized radiation therapy.
  • Limited intralesional therapy.

Patients must have:

  • HIV infection.
  • CD4 count 100 - 500 cells/mm3.
  • Prior cumulative monotherapy of <= 6 months (may have taken either AZT or ddI, but not both) OR no prior antiretroviral therapy.

Exclusion Criteria

Co-existing Condition:

Patients with the following symptoms or conditions are excluded:

  • Malignancy (other than basal or squamous cell carcinoma of the skin, Stage 1 or 2 cervical intraepithelial neoplasia, or minimal Kaposi's sarcoma).
  • Considered to be unlikely to comply with study requirements.

Concurrent Medication:

Excluded:

  • Antiretroviral therapies and biologic response modifiers (except for study medications, rEPO, and rG-CSF).
  • Rifampin.
  • Rifabutin.
  • Terfenadine.
  • Astemizole.
  • Loratadine.
  • Quinidine.
  • Digitoxin.
  • Systemic corticosteroids for more than 21 consecutive days.
  • Foscarnet.
  • Systemic cytotoxic chemotherapy for a malignancy.

Patients with the following prior conditions are excluded:

  • History of intolerance to AZT at <= 600 mg/day or ddI at <= 400 mg/day or discontinuation of either drug for toxicity.
  • History of intolerance to trifluoperazine or piperazine citrate (per amendment).
  • History of pancreatitis.
  • History of grade 2 or worse peripheral neuropathy.
  • Unexplained temperature >= 38.5 C on any 7 days within the past 30 days.
  • Chronic diarrhea on any 15 days during the past 30 days.

Prior Medication:

Excluded:

  • Prior foscarnet as induction or maintenance therapy.
  • Prior U-90152.
  • Prior ddC or d4T.
  • Prior AZT/ddI in combination or taken separately at different times.
  • Prior non-nucleoside reverse transcriptase inhibitors (nevirapine, atevirdine, etc.).
  • Prior protease inhibitors (although patients from ACTG 282 are eligible).
  • HIV-1 vaccine within the past 21 days.
  • Acute treatment for a serious infection or for any opportunistic infection within the past 14 days.

Excluded within the past 30 days:

  • Interferon or interleukin.
  • Rifampin.
  • Rifabutin.
  • Terfenadine.
  • Astemizole.
  • Loratadine.
  • Recombinant EPO or G-CSF.
  • Hydroxyurea.
  • SPV-30.
  • Any other investigational drug.

Active drug or alcohol use.

  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00000803

  Hide Study Locations
Locations
United States, Alabama
Univ of Alabama at Birmingham
Birmingham, Alabama, United States, 35294
United States, California
Univ of California / San Diego Treatment Ctr
San Diego, California, United States, 921036325
VA Hosp at San Diego / Pediatrics
San Diego, California, United States, 92161
Stanford at Kaiser / Kaiser Permanente Med Ctr
San Francisco, California, United States, 94115
Univ of Southern California / LA County USC Med Ctr
Los Angeles, California, United States, 900331079
Stanford Univ Med Ctr
Stanford, California, United States, 943055107
Summitt Med Ctr / San Francisco Gen Hosp
Oakland, California, United States, 94609
San Francisco Gen Hosp
San Francisco, California, United States, 941102859
Olive View Med Ctr
Sylmar, California, United States, 91342
USC Univ Hosp & Ambulatory Hlth Care Ctr / USC Med Ctr
Los Angeles, California, United States, 900334508
United States, Colorado
Denver Dept of Health and Hosps
Denver, Colorado, United States, 80262
Kaiser Permanente Franklin Med Ctr
Denver, Colorado, United States, 80262
Rose Med Ctr
Denver, Colorado, United States, 80262
United States, Connecticut
Yale Univ / New Haven
New Haven, Connecticut, United States, 065102483
United States, District of Columbia
Howard Univ
Washington, District of Columbia, United States, 20059
George Washington Univ / Hershey Med Ctr
Washington, District of Columbia, United States, 20037
United States, Florida
Univ of Miami School of Medicine
Miami, Florida, United States, 331361013
United States, Hawaii
Queens Med Ctr
Honolulu, Hawaii, United States, 96816
Univ of Hawaii
Honolulu, Hawaii, United States, 96816
United States, Indiana
Indiana Univ Hosp
Indianapolis, Indiana, United States, 462025250
Methodist Hosp of Indiana / Life Care Clinic
Indianapolis, Indiana, United States, 46202
United States, Louisiana
Tulane Univ / Charity Hosp of New Orleans
New Orleans, Louisiana, United States, 701122699
United States, Maryland
Johns Hopkins Hosp
Baltimore, Maryland, United States, 21287
State of MD Div of Corrections / Johns Hopkins Univ Hosp
Baltimore, Maryland, United States, 212052196
United States, Massachusetts
Harvard (Massachusetts Gen Hosp)
Boston, Massachusetts, United States, 02114
Beth Israel Deaconess Med Ctr
Boston, Massachusetts, United States, 02215
Beth Israel Deaconess - West Campus
Boston, Massachusetts, United States, 02215
Boston Med Ctr
Boston, Massachusetts, United States, 02118
Worcester Memorial Hosp / Med Ctr of Cntrl MA-Memorial
Worcester, Massachusetts, United States, 01605
United States, Minnesota
Univ of Minnesota
Minneapolis, Minnesota, United States, 55455
United States, Missouri
St Louis Regional Hosp / St Louis Regional Med Ctr
St Louis, Missouri, United States, 63112
United States, New York
Montefiore Family Health Ctr / Bronx Municipal Hosp
Bronx, New York, United States, 10461
SUNY / State Univ of New York
Syracuse, New York, United States, 13210
Univ of Rochester Medical Center
Rochester, New York, United States, 14642
Mem Sloan - Kettering Cancer Ctr
New York, New York, United States, 10021
Bellevue Hosp / New York Univ Med Ctr
New York, New York, United States, 10016
Mount Sinai Med Ctr
New York, New York, United States, 10029
Jack Weiler Hosp / Bronx Municipal Hosp
Bronx, New York, United States, 10465
Cornell Univ Med Ctr
New York, New York, United States, 10021
Bronx Municipal Hosp Ctr/Jacobi Med Ctr
Bronx, New York, United States, 10461
North Central Bronx Hosp / Bronx Municipal Hosp
Bronx, New York, United States, 10467
Bronx Veterans Administration / Mount Sinai Hosp
Bronx, New York, United States, 10468
SUNY / Erie County Med Ctr at Buffalo
Buffalo, New York, United States, 14215
Beth Israel Med Ctr
New York, New York, United States, 10003
City Hosp Ctr at Elmhurst / Mount Sinai Hosp
Elmhurst, New York, United States, 11373
SUNY / Health Sciences Ctr at Brooklyn
Brooklyn, New York, United States, 112032098
North Shore Univ Hosp
Manhasset, New York, United States, 11030
Montefiore Med Ctr / Bronx Municipal Hosp
Bronx, New York, United States, 10467
Comprehensive Health Care Ctr / Bronx Municipal Hosp
Bronx, New York, United States, 10461
Columbia Presbyterian Med Ctr
New York, New York, United States, 100323784
Adirondack Med Ctr at Saranac Lake
Albany, New York, United States, 122083479
Mid - Hudson Care Ctr
Albany, New York, United States, 122083479
Albany Med College / Division of HIV Medicine A158
Albany, New York, United States, 122083479
Harlem Hosp Ctr
New York, New York, United States, 10037
Montefiore Adolescent AIDS Prog / Bronx Municipal Hosp
Bronx, New York, United States, 10461
United States, Ohio
Case Western Reserve Univ
Cleveland, Ohio, United States, 44106
Univ of Cincinnati
Cincinnati, Ohio, United States, 452670405
Ohio State Univ Hosp Clinic
Columbus, Ohio, United States, 432101228
United States, Pennsylvania
Thomas Jefferson Univ Hosp
Philadelphia, Pennsylvania, United States, 191075098
United States, South Carolina
Julio Arroyo
West Columbia, South Carolina, United States, 29169
United States, Texas
Univ of Texas Galveston
Galveston, Texas, United States, 775550435
United States, Washington
Univ of Washington
Seattle, Washington, United States, 981224304
United States, Wisconsin
Youngstown Hemophilia Ctr / Great Lakes Hemophilia Fdn
Wauwatosa, Wisconsin, United States, 53213
Puerto Rico
Univ of Puerto Rico
San Juan, Puerto Rico, 009365067
Sponsors and Collaborators
Investigators
Study Chair: Friedland G
Study Chair: Fischl MA
Study Chair: Pollard R
  More Information

Additional Information:
Publications:
Griffit B, Morse G, Demeter L, Bassett R, Hughes M, Friedland G. Relationship between delavirdine (DLV) plasma levels, HIV RNA responses and DLV resistance during combination therapy with zidovudine (ZDV), and didanosine (ddI). Int Conf AIDS. 1998;12:52 (abstract no 12206)
Freimuth WW, Chuang-Stein CJ, Greenwald CA, Wathen LK, Edge-Padbury BA, Cox SR, Daenzer CL, Wang Y, Carberry PA. Delavirdine (DLV) combined with zidovudine (ZDV) or didanosine (ddI) produces sustained reduction in viral burden and increases in CD4 count in early and advanced HIV-1 infection. Int Conf AIDS. 1996 Jul 7-12;11(1):22 (abstract no MoB295)
Nokta M, Turk P. Partial restoration of HIV specific neutralizing activity (NA) of HIV infected patients receiving antiretrovial therapy: DDI/delaviridine (DLV), AZT/DLV, DDI/AZT or DDI/AZT/DLV. Int Conf AIDS. 1998;12:516 (abstract no 31108)
Friedland GH, Pollard R, Griffith B, Hughes M, Morse G, Bassett R, Freimuth W, Demeter L, Connick E, Nevin T, Hirsch M, Fischl M. Efficacy and safety of delavirdine mesylate with zidovudine and didanosine compared with two-drug combinations of these agents in persons with HIV disease with CD4 counts of 100 to 500 cells/mm3 (ACTG 261). ACTG 261 Team. J Acquir Immune Defic Syndr. 1999 Aug 1;21(4):281-92.
Demeter LM, Meehan PM, Morse G, Gerondelis P, Dexter A, Berrios L, Cox S, Freimuth W, Reichman RC. HIV-1 drug susceptibilities and reverse transcriptase mutations in patients receiving combination therapy with didanosine and delavirdine. J Acquir Immune Defic Syndr Hum Retrovirol. 1997 Feb 1;14(2):136-44.

Study ID Numbers: ACTG 261
Study First Received: November 2, 1999
Last Updated: July 11, 2008
ClinicalTrials.gov Identifier: NCT00000803     History of Changes
Health Authority: United States: Federal Government

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
Didanosine
Drug Therapy, Combination
Acquired Immunodeficiency Syndrome
AIDS-Related Complex
Antiviral Agents
Zidovudine

Additional relevant MeSH terms:
Antimetabolites
Anti-Infective Agents
Sexually Transmitted Diseases, Viral
Slow Virus Diseases
Molecular Mechanisms of Pharmacological Action
Zidovudine
Delavirdine
Infection
Reverse Transcriptase Inhibitors
Anti-Retroviral Agents
Therapeutic Uses
Retroviridae Infections
Nucleic Acid Synthesis Inhibitors
RNA Virus Infections
Anti-HIV Agents
Immune System Diseases
Acquired Immunodeficiency Syndrome
Enzyme Inhibitors
Antiviral Agents
Immunologic Deficiency Syndromes
Pharmacologic Actions
Virus Diseases
Didanosine
HIV Infections
Sexually Transmitted Diseases
Lentivirus Infections

ClinicalTrials.gov processed this record on November 27, 2009