Clinical Trial: 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.

Sponsored by: National Institute of Allergy and Infectious Diseases (NIAID)
Information provided by: National Institute of Allergy and Infectious Diseases (NIAID)

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 Treatment or Intervention Phase
HIV Infections
 Drug: Delavirdine mesylate
 Drug: Zidovudine
 Drug: Didanosine
Phase II

MedlinePlus related topics:  AIDS

Study Type: Interventional
Study Design: Treatment, Double-Blind, Safety Study

Further Study Details: 

Expected Total Enrollment:  471

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 above,  Genders Eligible for Study:  Both

Criteria

Inclusion Criteria

Concurrent Medication: Required:

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

Allowed:

Concurrent Treatment: Allowed for cutaneous Kaposi's sarcoma:

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:

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.


Location Information


Alabama
      Univ of Alabama at Birmingham, Birmingham,  Alabama,  35294,  United States

California
      Univ of California / San Diego Treatment Ctr, San Diego,  California,  921036325,  United States

      VA Hosp at San Diego / Pediatrics, San Diego,  California,  92161,  United States

      Stanford at Kaiser / Kaiser Permanente Med Ctr, San Francisco,  California,  94115,  United States

      San Francisco Gen Hosp, San Francisco,  California,  941102859,  United States

      Stanford Univ Med Ctr, Stanford,  California,  943055107,  United States

      Summitt Med Ctr / San Francisco Gen Hosp, Oakland,  California,  94609,  United States

      Univ of Southern California / LA County USC Med Ctr, Los Angeles,  California,  900331079,  United States

      Olive View Med Ctr, Sylmar,  California,  91342,  United States

      USC Univ Hosp & Ambulatory Hlth Care Ctr / USC Med Ctr, Los Angeles,  California,  900334508,  United States

Colorado
      Denver Dept of Health and Hosps, Denver,  Colorado,  80262,  United States

      Kaiser Permanente Franklin Med Ctr, Denver,  Colorado,  80262,  United States

      Rose Med Ctr, Denver,  Colorado,  80262,  United States

Connecticut
      Yale Univ / New Haven, New Haven,  Connecticut,  065102483,  United States

District of Columbia
      Howard Univ, Washington,  District of Columbia,  20059,  United States

      George Washington Univ / Hershey Med Ctr, Washington,  District of Columbia,  20037,  United States

Florida
      Univ of Miami School of Medicine, Miami,  Florida,  331361013,  United States

Hawaii
      Queens Med Ctr, Honolulu,  Hawaii,  96816,  United States

      Univ of Hawaii, Honolulu,  Hawaii,  96816,  United States

Indiana
      Indiana Univ Hosp, Indianapolis,  Indiana,  462025250,  United States

      Methodist Hosp of Indiana / Life Care Clinic, Indianapolis,  Indiana,  46202,  United States

Louisiana
      Tulane Univ / Charity Hosp of New Orleans, New Orleans,  Louisiana,  701122699,  United States

Maryland
      Johns Hopkins Hosp, Baltimore,  Maryland,  21287,  United States

      State of MD Div of Corrections / Johns Hopkins Univ Hosp, Baltimore,  Maryland,  212052196,  United States

Massachusetts
      Harvard (Massachusetts Gen Hosp), Boston,  Massachusetts,  02114,  United States

      Beth Israel Deaconess Med Ctr, Boston,  Massachusetts,  02215,  United States

      Beth Israel Deaconess - West Campus, Boston,  Massachusetts,  02215,  United States

      Boston Med Ctr, Boston,  Massachusetts,  02118,  United States

      Worcester Memorial Hosp / Med Ctr of Cntrl MA-Memorial, Worcester,  Massachusetts,  01605,  United States

Minnesota
      Univ of Minnesota, Minneapolis,  Minnesota,  55455,  United States

Missouri
      St Louis Regional Hosp / St Louis Regional Med Ctr, St. Louis,  Missouri,  63112,  United States

New York
      Montefiore Family Health Ctr / Bronx Municipal Hosp, Bronx,  New York,  10461,  United States

      SUNY / State Univ of New York, Syracuse,  New York,  13210,  United States

      Univ of Rochester Medical Center, Rochester,  New York,  14642,  United States

      Mem Sloan - Kettering Cancer Ctr, New York,  New York,  10021,  United States

      Bellevue Hosp / New York Univ Med Ctr, New York,  New York,  10016,  United States

      Mount Sinai Med Ctr, New York,  New York,  10029,  United States

      Jack Weiler Hosp / Bronx Municipal Hosp, Bronx,  New York,  10465,  United States

      Cornell Univ Med Ctr, New York,  New York,  10021,  United States

      Bronx Municipal Hosp Ctr/Jacobi Med Ctr, Bronx,  New York,  10461,  United States

      Montefiore Med Ctr / Bronx Municipal Hosp, Bronx,  New York,  10467,  United States

      Bronx Veterans Administration / Mount Sinai Hosp, Bronx,  New York,  10468,  United States

      SUNY / Erie County Med Ctr at Buffalo, Buffalo,  New York,  14215,  United States

      Beth Israel Med Ctr, New York,  New York,  10003,  United States

      City Hosp Ctr at Elmhurst / Mount Sinai Hosp, Elmhurst,  New York,  11373,  United States

      SUNY / Health Sciences Ctr at Brooklyn, Brooklyn,  New York,  112032098,  United States

      North Shore Univ Hosp, Manhasset,  New York,  11030,  United States

      North Central Bronx Hosp / Bronx Municipal Hosp, Bronx,  New York,  10467,  United States

      Comprehensive Health Care Ctr / Bronx Municipal Hosp, Bronx,  New York,  10461,  United States

      Columbia Presbyterian Med Ctr, New York,  New York,  100323784,  United States

      Adirondack Med Ctr at Saranac Lake, Albany,  New York,  122083479,  United States

      Mid - Hudson Care Ctr, Albany,  New York,  122083479,  United States

      Albany Med College / Division of HIV Medicine A158, Albany,  New York,  122083479,  United States

      Harlem Hosp Ctr, New York,  New York,  10037,  United States

      Montefiore Adolescent AIDS Prog / Bronx Municipal Hosp, Bronx,  New York,  10461,  United States

Ohio
      Case Western Reserve Univ, Cleveland,  Ohio,  44106,  United States

      Univ of Cincinnati, Cincinnati,  Ohio,  452670405,  United States

      Ohio State Univ Hosp Clinic, Columbus,  Ohio,  432101228,  United States

Pennsylvania
      Thomas Jefferson Univ Hosp, Philadelphia,  Pennsylvania,  191075098,  United States

South Carolina
      Julio Arroyo, West Columbia,  South Carolina,  29169,  United States

Texas
      Univ of Texas Galveston, Galveston,  Texas,  775550435,  United States

Washington
      Univ of Washington, Seattle,  Washington,  981224304,  United States

Wisconsin
      Youngstown Hemophilia Ctr / Great Lakes Hemophilia Fdn, Wauwatosa,  Wisconsin,  53213,  United States

Puerto Rico
      Univ of Puerto Rico, San Juan,  009365067,  Puerto Rico

Study chairs or principal investigators

Friedland G,  Study Chair
Fischl MA,  Study Chair
Pollard R,  Study Chair

More Information

Click here for more information about Zidovudine

Click here for more information about Didanosine

Click here for more information about Delavirdine mesylate

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
Record last reviewed:  September 1995
Last Updated:  April 7, 2005
Record first received:  November 2, 1999
ClinicalTrials.gov Identifier:  NCT00000803
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08


Source: ClinicalTrials.gov
Cache Date: April 9, 2005

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