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A Phase II Double-Blind Study of Two Doses of SC-49483 in Combination With Zidovudine (ZDV) Versus ZDV
This study has been completed.
First Received: November 2, 1999   Last Updated: August 25, 2008   History of Changes
Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Collaborators: G D Searle
Glaxo Wellcome
Information provided by: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT00000791
  Purpose

To determine the safety and anti-HIV activity of two doses of SC-49483 in combination with zidovudine (AZT) versus AZT alone. To determine the influences of viral phenotype on the anti-HIV activity of these treatment regimens.

SC-49483 has no inherent activity against HIV-1 but is converted in the intestinal wall to SC-48334, which has demonstrated anti-HIV activity. Since SC-49483 causes significantly less gastrointestinal toxicity than SC-48334, the combination of SC-49483 with AZT may improve the benefits of both drugs in patients with HIV infection.


Condition Intervention Phase
HIV Infections
Drug: Glycovir
Drug: Zidovudine
Phase II

Study Type: Interventional
Study Design: Treatment, Double-Blind, Safety Study
Official Title: A Phase II Double-Blind Study of Two Doses of SC-49483 in Combination With Zidovudine (ZDV) Versus ZDV

Resource links provided by NLM:


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

Estimated Enrollment: 210
Detailed Description:

SC-49483 has no inherent activity against HIV-1 but is converted in the intestinal wall to SC-48334, which has demonstrated anti-HIV activity. Since SC-49483 causes significantly less gastrointestinal toxicity than SC-48334, the combination of SC-49483 with AZT may improve the benefits of both drugs in patients with HIV infection.

Patients are randomized to receive AZT alone or in combination with one of two doses of SC-49483, administered three times daily. Treatment continues for 16 to 24 weeks. Per 07/19/94 amendment: At the end of 24 weeks, blinded treatment continues for an additional 4 weeks, at which time patients may receive open-label drug on an optional basis for 90 days.

  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 (trimethoprim/sulfamethoxazole, dapsone, or aerosolized pentamidine) in patients with CD4 count <= 200 cells/mm3.

Allowed:

  • Topical antifungal agents, ketoconazole, fluconazole, and itraconazole for candidiasis or disseminated fungal infections, as medically indicated.
  • Maintenance therapy for Mycobacteria disease with isoniazid, ethambutol, rifampin, pyrazinamide, clofazimine, ciprofloxacin, clarithromycin, or rifabutin.
  • Maintenance therapy for toxoplasmosis with pyrimethamine, sulfadiazine, or clindamycin.
  • Maintenance therapy for herpes simplex virus with acyclovir at <= 1000 mg/day.
  • Recombinant erythropoietin and G-CSF, if indicated.
  • Antibiotics for bacterial infections.
  • Symptomatic treatment such as antipyretics, analgesics, nonsteroidal anti-inflammatory agents, and antiemetics.

Concurrent Treatment:

Allowed:

  • Localized radiation therapy and limited intralesional therapy for cutaneous Kaposi's sarcoma.

Patients must have:

  • Documented HIV infection.
  • Per 07/19/94 amendment, one of the following:
  • CD4 count 150 - 350 cells/mm3 within 60 days prior to study entry AND prior AZT for no more than 12 months cumulative (given with or without ddI or ddC).
  • CD4 count 50 - 350 cells/mm3 within 60 days prior to study entry AND no prior antiretroviral therapy.
  • MT-2 cell assay within 60 days prior to study entry.

NOTE:

  • Minimal Kaposi's sarcoma is permitted.

Exclusion Criteria

Co-existing Condition:

Patients with the following condition are excluded:

  • Malignancy other than minimal Kaposi's sarcoma.

Concurrent Medication:

Excluded:

  • Antiretroviral therapies (other than study drug).
  • Biologic response modifiers.
  • Systemic corticosteroids for > 21 consecutive days.
  • Foscarnet.
  • Systemic cytotoxic chemotherapy for a malignancy.

Patients with the following prior conditions are excluded:

  • History of cataracts.
  • History of intolerance to AZT at <= 600 mg/day.
  • Unexplained temperature >= 38.5 degrees C that persists for any 7 days within the 30 days prior to study entry.
  • Chronic diarrhea (defined as >= 3 stools per day) that persists for any 15 days within the 30 days prior to study entry.

Prior Medication:

Excluded:

  • More than 6 months (more than 12 months per 07/19/94 amendment) cumulative prior therapy with AZT.
  • Prior induction or maintenance therapy with foscarnet.
  • Any investigational drug within 30 days prior to study entry.
  • Prior SC-49483 or SC-48334.
  • Prior ddC, ddI, or stavudine (d4T) as monotherapy.
  • Interferon or interleukin within 30 days prior to study entry.
  • Prior non-nucleoside reverse transcriptase inhibitors (e.g., NVP, ATV).
  • Systemic corticosteroids for > 21 consecutive days.
  • Acute treatment for a serious infection or any opportunistic infection within 14 days prior to study entry.
  • Prior combination therapy with AZT, ddI, and/or ddC within 30 days prior to study entry.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00000791

  Hide Study Locations
Locations
United States, Alabama
Univ of Alabama at Birmingham
Birmingham, Alabama, United States, 352942041
United States, California
San Francisco Gen Hosp
San Francisco, California, United States, 941102859
San Francisco AIDS Clinic / San Francisco Gen Hosp
San Francisco, California, United States, 941102859
Stanford Univ Med Ctr
Stanford, California, United States, 943055107
Summitt Med Ctr / San Francisco Gen Hosp
Oakland, California, United States, 94609
Univ of Southern California / LA County USC Med Ctr
Los Angeles, California, United States, 900331079
Highland Gen Hosp / San Francisco Gen Hosp
Oakland, California, United States, 946021018
United States, Colorado
Univ of Colorado Health Sciences 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
Georgetown Univ Med Ctr
Washington, District of Columbia, United States, 20007
United States, Florida
Univ of Miami School of Medicine
Miami, Florida, United States, 331361013
United States, Illinois
Northwestern Univ Med School
Chicago, Illinois, United States, 60611
Rush Presbyterian - Saint Luke's Med Ctr
Chicago, Illinois, United States, 60612
Cook County Hosp
Chicago, Illinois, United States, 60612
Illinois Masonic Med Ctr
Chicago, Illinois, United States, 606575147
Louis A Weiss Memorial Hosp
Chicago, Illinois, United States, 60640
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, New York
Montefiore Drug Treatment Ctr / Bronx Municipal Hosp
Bronx, New York, United States, 10461
Montefiore Family Health Ctr / Bronx Municipal Hosp
Bronx, New York, United States, 10461
Samaritan Village Inc / 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
Mount Sinai Med Ctr
New York, New York, United States, 10029
Jack Weiler Hosp / Bronx Municipal Hosp
Bronx, New York, United States, 10465
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
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
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
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, North Carolina
Univ of North Carolina
Chapel Hill, North Carolina, United States, 275997215
Wake County Dept of Health
Raleigh, North Carolina, United States, 27610
United States, Ohio
Univ of Cincinnati
Cincinnati, Ohio, United States, 452670405
United States, Pennsylvania
Univ of Pennsylvania at Philadelphia
Philadelphia, Pennsylvania, United States, 19104
United States, South Carolina
Julio Arroyo
West Columbia, South Carolina, United States, 29169
United States, Washington
Univ of Washington
Seattle, Washington, United States, 981224304
Sponsors and Collaborators
G D Searle
Glaxo Wellcome
Investigators
Study Chair: Fischl MA
Study Chair: Saag M
  More Information

Additional Information:
Publications:
Johnson VA, Bassett RL, Stanley KE, Saag MS, Fischl MA. Predictors of syncytium-inducing viral phenotype in a phase II double-blind trial of SC-49483 plus ZDV vs. ZDV. Conf Retroviruses Opportunistic Infect. 1997 Jan 22-26;4th:102 (abstract no 205)

Study ID Numbers: ACTG 259
Study First Received: November 2, 1999
Last Updated: August 25, 2008
ClinicalTrials.gov Identifier: NCT00000791     History of Changes
Health Authority: United States: Federal Government

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

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

ClinicalTrials.gov processed this record on November 27, 2009