The Safety and Effectiveness of Hydroxyurea and ddI Used Individually or Together in HIV-Infected Patients

HIV Infections Clinical Trial

Official title: A Phase I/II Dosing Study of the Safety and Antiretroviral Activity of Hydroxyurea Alone and in Combination With ddI Compared With ddI Alone in Subjects With HIV Infection

Status Completed

Clinical Trial Summary

To determine the safety and tolerability of hydroxyurea at two doses alone and in combination with didanosine (ddI). To compare the short term antiviral effect of ddI monotherapy versus hydroxyurea plus ddI, as measured by plasma RNA levels at 8 weeks of therapy. [AS PER AMENDMENT 10/1/97: Accrual to arms involving hydroxyurea alone has been closed.] Current antiviral therapies for HIV-1 are limited by a few choices, and the lack of sustained clinical benefit from the drugs. The mechanisms that account for the lack of prolonged inhibition of viral replication by these agents are not fully understood. The activity of RT inhibitors might be potentiated by inhibiting host cellular enzymes essential for efficient HIV reverse transcription. Based on this information, comparisons of the antiviral effects of ddI monotherapy and hydroxyurea plus ddI, with the cellular enzyme ribonucleotide reductase as a potential target, should be done.

Clinical Trial Description

Current antiviral therapies for HIV-1 are limited by a few choices, and the lack of sustained clinical benefit from the drugs. The mechanisms that account for the lack of prolonged inhibition of viral replication by these agents are not fully understood. The activity of RT inhibitors might be potentiated by inhibiting host cellular enzymes essential for efficient HIV reverse transcription. Based on this information, comparisons of the antiviral effects of ddI monotherapy and hydroxyurea plus ddI, with the cellular enzyme ribonucleotide reductase as a potential target, should be done.

This is a 24-week study, with two 12-week treatment periods. Patients are randomized to one of five treatment arms based upon a patient's history of antiretroviral therapy (naive vs. experienced). The five treatment arms are:

1. ddI plus hydroxyurea placebo.

2. hydroxyurea (lower dose) plus ddI placebo for 4 weeks; then hydroxyurea (higher dose) plus ddI.

3. hydroxyurea (higher dose) plus ddI placebo for 4 weeks; then hydroxyurea (higher dose) plus ddI.

4. hydroxyurea (lower dose) plus ddI.

5. hydroxyurea (higher dose) plus ddI. After the completion of week 12, patients on combination therapy remain on their current therapy and patients on ddI plus placebo have hydroxyurea replace the placebo at 1 of 2 assigned doses (1:1 randomization). AS PER AMENDMENT 5/5/97: If after the 24-week treatment period, a patient has an RNA level less than or equal to 5,000 copies/ml or less than 20,000 copies/ml with a greater than 1 log10 decline from baseline, she has the option to continue therapy open-label ddI plus hydroxyurea for an additional 24 weeks.

AS PER AMENDMENT 10/1/97: Accrual to the arms involving hydroxyurea alone has been closed. Patients are randomized to one of the three treatment arms, as follows:

1. hydroxyurea placebo plus ddI.

2. hydroxyurea (lower dose) plus ddI.

3. hydroxyurea (higher dose) plus ddI. ;

Related Conditions & MeSH terms

• Acquired Immunodeficiency Syndrome
• HIV Infections
• Infections

• NCT number: NCT00001074
• Study type: Interventional
• Source: National Institute of Allergy and Infectious Diseases (NIAID)
• Status: Completed
• Phase: Phase 1
• Completion date: January 2000