Clinical trial NCT00000704: A Multicenter Dose Ranging Clinical Trial of 2',3'-Dideoxycytidine in the Treatment of Patients With AIDS and Advanced ARC.
Official title: A Multicenter Dose Ranging Clinical Trial of 2',3'-Dideoxycytidine in the Treatment of Patients With AIDS and Advanced ARC.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: HIV Infections
Keywords: HIV Antigens
Immunologic Surveillance
Zalcitabine
Dose-Response Relationship, Drug
Acquired Immunodeficiency Syndrome
AIDS-Related Complex
CD4-Positive T-Lymphocytes
Lead sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Sponsor class: NIH
First posted: 2001-08-31
Enrollment: 64
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Primary purpose: TREATMENT

Brief summary: To evaluate the long-term safety and effectiveness of the drug 2',3'-dideoxycytidine ( zalcitabine; ddC ) in treating patients with AIDS or advanced AIDS related complex ( ARC ).

Recent studies show that a certain group of drugs (dideoxynucleosides) are effective in treating patients with HIV infection. ddC is a dideoxynucleoside and test tube studies show that it may be valuable in treating AIDS patients. ddC has been shown to be well tolerated in certain patients with AIDS.

Detailed description: Recent studies show that a certain group of drugs (dideoxynucleosides) are effective in treating patients with HIV infection. ddC is a dideoxynucleoside and test tube studies show that it may be valuable in treating AIDS patients. ddC has been shown to be well tolerated in certain patients with AIDS.

A range of doses of ddC is given to patients with AIDS and ARC. Eight patients with AIDS and eight patients with ARC are given ddC at the lowest level for 12 weeks. Patients who respond with a rise in their number of T4 cells or with a fall in HIV antigen in their serum (the fluid portion of the blood) are continued at that dose for an additional 12 weeks. Patients who do not respond at a given dose level (no rise in T4 or fall in serum HIV antigen) stop treatment at 12 weeks. All patients are followed off therapy for 4 weeks. As each dose level is found to be well tolerated for 10 weeks in five of the eight patients in each group, additional patients will be entered at higher dose levels until eight AIDS and eight ARC patients are receiving the drug at a given level.

Eligibility criteria: Inclusion Criteria

Concurrent Medication:

Allowed:

* Aspirin, acetaminophen, and nonsteroidal anti-inflammatory agents.
* Acute therapy (7 days) with oral acyclovir.
* Acute therapy with ketoconazole.

Exclusion Criteria

Co-existing Condition:

Patients with the following are excluded:

* Negative antigen test within 2 weeks of starting therapy.
* Significant malabsorption (\> 10 percent weight loss within past 3 months with serum carotene \< 75 IU/ml or vitamin A \< 75 IU/ml).
* Significant cardiac, liver, or neurologic disease.
* For group A:
* Opportunistic infection or malignancy fulfilling definition of AIDS, or with concurrent neoplasm other than basal cell carcinoma of the skin or in situ carcinoma of the cervix.
* For group B:
* Active opportunistic infection, symptomatic visceral Kaposi's sarcoma (KS), progression of KS within the month prior to study entry, or with concurrent neoplasms other than KS, basal cell carcinoma of the skin, or in situ carcinoma of the cervix.

Concurrent Medication:

Excluded:

* Acyclovir therapy.
* Chemoprophylaxis for Pneumocystis carinii pneumonia.
* Other antiretroviral agents, biologic modifiers, or systemic corticosteroids.
* Other experimental medications, sedatives, and barbiturates.
* Group B:
* Therapy and/or prophylaxis for AIDS-defining opportunistic infection, antineoplastic therapy.

Concurrent Treatment:

Excluded:

- Transfusion dependency (requiring 2 units of blood more than once per month). Patients with history of idiopathic thrombocytopenia purpura are excluded.

Prior Medication:

Excluded within 30 days of study entry:

* Biologic modifiers or corticosteroids.
* Excluded within 90 days of study entry:
* Antiretroviral agents.

Prior Treatment:

Excluded within 2 weeks of study entry:

* Transfusion.

Inclusion criteria are:

* Consistently positive HIV antigen as defined by Abbott HIV antigen test. This demonstration will be seen on two occasions, each separated by at least 72 hours, the last of which must be within 2 weeks of starting therapy.
* HIV antigen titer must be = or \> 100 pg.
* Positive antibody to HIV confirmed by any federally licensed enzyme-linked immunosorbent assay (ELISA) test kit.

The following conditions are allowed:

- Basal cell carcinoma of the skin or in situ carcinoma of the cervix. Active substance abuse.

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Miami
country: United States
facility: Univ. of Miami AIDS CRS
state: Florida
Study officials:
name: Merigan TC
role: STUDY_CHAIR
References:
citation: Merigan TC, Skowron G, Bozzette SA, Richman D, Uttamchandani R, Fischl M, Schooley R, Hirsch M, Soo W, Pettinelli C, et al. Circulating p24 antigen levels and responses to dideoxycytidine in human immunodeficiency virus (HIV) infections. A phase I and II study. Ann Intern Med. 1989 Feb 1;110(3):189-94. doi: 10.7326/0003-4819-110-3-189.
citation: Merigan TC, Skowron G. Safety and tolerance of dideoxycytidine as a single agent. Results of early-phase studies in patients with acquired immunodeficiency syndrome (AIDS) or advanced AIDS-related complex. Study Group of the AIDS Clinical Trials Group of the National Institute of Allergy and Infectious Diseases. Am J Med. 1990 May 21;88(5B):11S-15S. doi: 10.1016/0002-9343(90)90415-a.