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

NCT ID: NCT00000791

Last Updated: 2021-10-28

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

210 participants

Study Classification

INTERVENTIONAL

Study Completion Date

1995-07-31

Brief Summary

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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.

Detailed Description

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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.

Conditions

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HIV Infections

Keywords

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Drug Therapy, Combination Acquired Immunodeficiency Syndrome AIDS-Related Complex Antiviral Agents Zidovudine

Study Design

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Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Interventions

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Glycovir

Intervention Type DRUG

Zidovudine

Intervention Type DRUG

Eligibility Criteria

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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.
Minimum Eligible Age

13 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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G D Searle

INDUSTRY

Sponsor Role collaborator

Glaxo Wellcome

INDUSTRY

Sponsor Role collaborator

National Institute of Allergy and Infectious Diseases (NIAID)

NIH

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Fischl MA

Role: STUDY_CHAIR

Saag M

Role: STUDY_CHAIR

Locations

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Alabama Therapeutics CRS

Birmingham, Alabama, United States

Site Status

USC CRS

Los Angeles, California, United States

Site Status

Stanford CRS

Palo Alto, California, United States

Site Status

Ucsf Aids Crs

San Francisco, California, United States

Site Status

University of Colorado Hospital CRS

Aurora, Colorado, United States

Site Status

Univ. of Miami AIDS CRS

Miami, Florida, United States

Site Status

Northwestern University CRS

Chicago, Illinois, United States

Site Status

Rush Univ. Med. Ctr. ACTG CRS

Chicago, Illinois, United States

Site Status

Weiss Memorial Hosp.

Chicago, Illinois, United States

Site Status

Cook County Hosp. CORE Ctr.

Chicago, Illinois, United States

Site Status

Indiana Univ. School of Medicine, Infectious Disease Research Clinic

Indianapolis, Indiana, United States

Site Status

Methodist Hosp. of Indiana

Indianapolis, Indiana, United States

Site Status

St. Louis ConnectCare, Infectious Diseases Clinic

St Louis, Missouri, United States

Site Status

Washington U CRS

St Louis, Missouri, United States

Site Status

SUNY - Buffalo, Erie County Medical Ctr.

Buffalo, New York, United States

Site Status

Beth Israel Med. Ctr. (Mt. Sinai)

New York, New York, United States

Site Status

Univ. of Rochester ACTG CRS

Rochester, New York, United States

Site Status

Unc Aids Crs

Chapel Hill, North Carolina, United States

Site Status

Wake County Health and Human Services CRS

Raleigh, North Carolina, United States

Site Status

Univ. of Cincinnati CRS

Cincinnati, Ohio, United States

Site Status

Hosp. of the Univ. of Pennsylvania CRS

Philadelphia, Pennsylvania, United States

Site Status

University of Washington AIDS CRS

Seattle, Washington, United States

Site Status

Countries

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United States

References

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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)

Reference Type BACKGROUND

Other Identifiers

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11236

Identifier Type: REGISTRY

Identifier Source: secondary_id

ACTG 259

Identifier Type: -

Identifier Source: org_study_id