A Phase II Double-Blind Study of Two Doses of SC-49483 in Combination With Zidovudine (ZDV) Versus ZDV

This study has been completed.
Sponsor:
Collaborators:
G D Searle
Glaxo Wellcome
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT00000791
First received: November 2, 1999
Last updated: April 2, 2012
Last verified: April 2012
  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 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Masking: Double-Blind
Primary Purpose: Treatment
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
Study Completion Date: July 1995
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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00000791

Locations
United States, Alabama
Alabama Therapeutics CRS
Birmingham, Alabama, United States
United States, California
USC CRS
Los Angeles, California, United States, 90033
Stanford CRS
Palo Alto, California, United States
Ucsf Aids Crs
San Francisco, California, United States, 94110
United States, Colorado
University of Colorado Hospital CRS
Aurora, Colorado, United States
United States, Florida
Univ. of Miami AIDS CRS
Miami, Florida, United States
United States, Illinois
Cook County Hosp. CORE Ctr.
Chicago, Illinois, United States
Rush Univ. Med. Ctr. ACTG CRS
Chicago, Illinois, United States, 60612
Weiss Memorial Hosp.
Chicago, Illinois, United States, 60640
Northwestern University CRS
Chicago, Illinois, United States, 60611
United States, Indiana
Indiana Univ. School of Medicine, Infectious Disease Research Clinic
Indianapolis, Indiana, United States
Methodist Hosp. of Indiana
Indianapolis, Indiana, United States
United States, Missouri
St. Louis ConnectCare, Infectious Diseases Clinic
St. Louis, Missouri, United States, 63112
Washington U CRS
St. Louis, Missouri, United States
United States, New York
SUNY - Buffalo, Erie County Medical Ctr.
Buffalo, New York, United States, 14260
Beth Israel Med. Ctr. (Mt. Sinai)
New York, New York, United States
Univ. of Rochester ACTG CRS
Rochester, New York, United States
United States, North Carolina
Unc Aids Crs
Chapel Hill, North Carolina, United States, 27514
Wake County Health and Human Services CRS
Raleigh, North Carolina, United States
United States, Ohio
Univ. of Cincinnati CRS
Cincinnati, Ohio, United States
United States, Pennsylvania
Hosp. of the Univ. of Pennsylvania CRS
Philadelphia, Pennsylvania, United States
United States, Washington
University of Washington AIDS CRS
Seattle, Washington, United States, 98104
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)

Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT00000791     History of Changes
Other Study ID Numbers: ACTG 259, 11236
Study First Received: November 2, 1999
Last Updated: April 2, 2012
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:
HIV Infections
Acquired Immunodeficiency Syndrome
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Slow Virus Diseases
Zidovudine
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Anti-HIV Agents

ClinicalTrials.gov processed this record on September 16, 2014