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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.
Sponsors and Collaborators: National Institute of Allergy and Infectious Diseases (NIAID)
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

MedlinePlus related topics: AIDS
Drug Information available for: Zidovudine Glycovir
U.S. FDA Resources
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

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

  Show 42 Study Locations
Sponsors and Collaborators
G D Searle
Glaxo Wellcome
Investigators
Study Chair: Fischl MA
Study Chair: Saag M
  More Information

Click here for more information about Zidovudine  This link exits the ClinicalTrials.gov site

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  
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

Study placed in the following topic categories:
Virus Diseases
Sexually Transmitted Diseases, Viral
HIV Infections
Sexually Transmitted Diseases
Acquired Immunodeficiency Syndrome
Zidovudine
AIDS-Related Complex
Retroviridae Infections
Immunologic Deficiency Syndromes

Additional relevant MeSH terms:
Antimetabolites
Anti-Infective Agents
RNA Virus Infections
Anti-HIV Agents
Slow Virus Diseases
Immune System Diseases
Molecular Mechanisms of Pharmacological Action
Enzyme Inhibitors
Infection
Antiviral Agents
Pharmacologic Actions
Reverse Transcriptase Inhibitors
Anti-Retroviral Agents
Therapeutic Uses
Lentivirus Infections
Nucleic Acid Synthesis Inhibitors

ClinicalTrials.gov processed this record on January 15, 2009