A Multi-Center, Open-Label, Ascending, Multiple Oral Dose, Safety, Tolerance and Pharmacokinetic Study of 3'-Deoxy-3'-Fluorothymidine (FLT) in Patients With Acquired Immune Deficiency Syndrome (AIDS) or AIDS-Related Complex (ARC)

HIV Infections Clinical Trial

Official title:

A Multi-Center, Open-Label, Ascending, Multiple Oral Dose, Safety, Tolerance and Pharmacokinetic Study of 3'-Deoxy-3'-Fluorothymidine (FLT) in Patients With Acquired Immune Deficiency Syndrome (AIDS) or AIDS-Related Complex (ARC)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00002254
• Other study ID #: 054B
• Secondary ID: 81-2
• Status: Completed
• Phase: N/A
• First received: November 2, 1999
• Last updated: June 23, 2005

Study information

• Verified date: May 1991
• Source: NIH AIDS Clinical Trials Information Service
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

To assess the tolerance and toxicity profile of deoxy-3'-fluorothymidine (FLT) after multiple oral dosing for 16 weeks. To characterize the steady-state pharmacokinetics of FLT after multiple oral doses. To assess the effect of FLT on immunologic and virologic markers of HIV infection (CD4+ lymphocyte count, p24 antigen, viremia) in patients with AIDS or AIDS related complex (ARC) after multiple oral dosing for 16 weeks.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 0
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria

Concurrent Medication:

Allowed:

• Aerosolized pentamidine for Pneumocystis carinii pneumonia (PCP) prophylaxis.

• Up to 14 days of systemic therapy for minor opportunistic infections such as candidiasis, mucocutaneous Herpes simplex or cutaneous Herpes zoster infections.

Patients must have the following:

• AIDS or AIDS related complex (ARC) as defined by the CDC.

• Positive antibody to HIV as determined by a commercially licensed ELISA test kit, confirmed by Western blot analysis.

Exclusion Criteria

Co-existing Condition:

Patients with the following conditions or symptoms are excluded:

• Symptomatic visceral Kaposi's sarcoma or progression of Kaposi's sarcoma within the month prior to study entry (progression is defined as more than a 25 percent increase in the product of bidirectional measurement of indicator lesions and/or more than a 25 percent increase in the number of new lesions).

• Concurrent neoplasms other than Kaposi's sarcoma or basal cell carcinoma of the skin. Patients who have had a malignancy in the past that has been in complete remission for 1 year without therapy may be enrolled.

• Signs or symptoms of neuropathy and a Vibratron 2 score = or > 4 for either great toe.

Concurrent Medication:

Excluded:

• Acute therapy for AIDS-related infection.

• Systemic maintenance therapy for AIDS-defining opportunistic infection.

• Recombinant erythropoietin.

• Long term therapy with either aspirin or probenecid.

Concurrent Treatment:

Excluded:

• Blood transfusion more than once per month.

Patients with the following are excluded:

• Symptomatic visceral Kaposi's sarcoma or progression of Kaposi's sarcoma within the month prior to study entry.

• Unwilling to sign an informed consent or patients unwilling to be followed at the medical center where they were enrolled for the duration of the study and follow-up as required.

• History of intolerance to zidovudine (AZT) at any dose as demonstrated by an AZT related decrease in hemoglobin levels of at least 2 g/dl or AZT related depression of neutrophils of at least 200 cells/mm3 to < 750 cells/mm3 which required discontinuation of AZT therapy.

• Diseases or conditions listed in Exclusion Co-Existing Conditions.

Prior Medication:

Excluded:

• Antiretroviral agents within 14 days of study entry.

• Immunomodulating agents or corticosteroids within 30 days prior to study entry.

• Treatment for acute Pneumocystis carinii pneumonia within 2 weeks prior to study entry.

Prior Treatment:

Excluded:

• Blood transfusions within 7 days prior to study entry.

• Radiation therapy for Kaposi's sarcoma within 30 days prior to study entry.

Active substance abuse.

Study Design

Endpoint Classification: Pharmacokinetics Study, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Acquired Immunodeficiency Syndrome
• AIDS-Related Complex
• HIV Infections
• Immunologic Deficiency Syndromes

Intervention

Drug:
• Alovudine

Locations

Country	Name	City	State
United States	Johns Hopkins Hosp	Baltimore	Maryland
United States	Univ of North Carolina School of Medicine	Chapel Hill	North Carolina
United States	Mem Sloan - Kettering Cancer Ctr	New York	New York

Sponsors (1)

Lead Sponsor	Collaborator
Lederle Laboratories

Country where clinical trial is conducted

United States, 

References & Publications (1)

Barditch-Crovo PA, Kornhauser DM, Petty BG, Nerhood LJ, Lietman PS, Faulkner R, Ganes D, Kuye O, Flexner C. Phase I pharmacokinetic evaluation of 3'deoxy-3'-fluorothymidine (FLT), a new potent anti-HIV nucleoside. Int Conf AIDS. 1991 Jun 16-21;7(2):210 (abstract no WB2114)