Clinical trial NCT00000791: A Phase II Double-Blind Study of Two Doses of SC-49483 in Combination With Zidovudine (ZDV) Versus ZDV
Official title: A Phase II Double-Blind Study of Two Doses of SC-49483 in Combination With Zidovudine (ZDV) Versus ZDV
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: HIV Infections
Keywords: Drug Therapy, Combination
Acquired Immunodeficiency Syndrome
AIDS-Related Complex
Antiviral Agents
Zidovudine
Lead sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Sponsor class: NIH
Collaborators: name: G D Searle
name: Glaxo Wellcome
First posted: 2001-08-31
Enrollment: 210
Sex: ALL
Minimum age (years): 13
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Primary purpose: TREATMENT

Brief summary: 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: 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 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.

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Alabama Therapeutics CRS
state: Alabama
city: Los Angeles
country: United States
facility: USC CRS
state: California
city: Palo Alto
country: United States
facility: Stanford CRS
state: California
city: San Francisco
country: United States
facility: Ucsf Aids Crs
state: California
city: Aurora
country: United States
facility: University of Colorado Hospital CRS
state: Colorado
city: Miami
country: United States
facility: Univ. of Miami AIDS CRS
state: Florida
city: Chicago
country: United States
facility: Northwestern University CRS
state: Illinois
city: Chicago
country: United States
facility: Rush Univ. Med. Ctr. ACTG CRS
state: Illinois
city: Chicago
country: United States
facility: Weiss Memorial Hosp.
state: Illinois
city: Chicago
country: United States
facility: Cook County Hosp. CORE Ctr.
state: Illinois
city: Indianapolis
country: United States
facility: Indiana Univ. School of Medicine, Infectious Disease Research Clinic
state: Indiana
city: Indianapolis
country: United States
facility: Methodist Hosp. of Indiana
state: Indiana
city: Saint Louis
country: United States
facility: St. Louis ConnectCare, Infectious Diseases Clinic
state: Missouri
city: Saint Louis
country: United States
facility: Washington U CRS
state: Missouri
city: Buffalo
country: United States
facility: SUNY - Buffalo, Erie County Medical Ctr.
state: New York
city: New York
country: United States
facility: Beth Israel Med. Ctr. (Mt. Sinai)
state: New York
city: Rochester
country: United States
facility: Univ. of Rochester ACTG CRS
state: New York
city: Chapel Hill
country: United States
facility: Unc Aids Crs
state: North Carolina
city: Raleigh
country: United States
facility: Wake County Health and Human Services CRS
state: North Carolina
city: Cincinnati
country: United States
facility: Univ. of Cincinnati CRS
state: Ohio
city: Philadelphia
country: United States
facility: Hosp. of the Univ. of Pennsylvania CRS
state: Pennsylvania
city: Seattle
country: United States
facility: University of Washington AIDS CRS
state: Washington
Study officials:
name: Fischl MA
role: STUDY_CHAIR
name: Saag M
role: STUDY_CHAIR
References:
citation: 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)