A Phase I/II Study of the Safety and Antiretroviral Activity of Nine Hydroxyurea Regimens in Combination With ddI and d4T in Subjects With HIV Infection

Safety and Effectiveness of Combining Hydroxyurea (HU) With Didanosine (ddI) and Stavudine (d4T) for Treatment of HIV-Infected Adults

Sponsors

Lead sponsor: Research Institute for Genetic and Human Therapy

Source NIH AIDS Clinical Trials Information Service
Brief Summary

The purpose of this study is to compare the safety and effectiveness of 9 doses of HU in order to find the best dose of HU to use with ddI and d4T in fighting HIV infection.

HU plus ddI plus d4T appears to be a suitable anti-HIV drug combination for long-term control of HIV. This combination can sharply decrease viral load (level of HIV in the body) with few side effects, making it easy to take.

Detailed Description

The combination of HU plus ddI plus d4T appears to be suitable for long-term control of HIV in that it: (1) has a novel resistance/rebound profile demonstrating virus suppression even in the presence of ddI-resistant mutants; (2) can produce a pronounced fall in viral load; and (3) is well tolerated (over 200 patients have been treated for up to 3 years with minimal side effects).

Patients are stratified by antiretroviral experience: naive (no more than 2 weeks of therapy) versus experienced (more than 2 weeks). Patients must discontinue all antiretroviral therapy for at least 28 days prior to randomization to 1 of 9 HU treatment arms. Treatment arms are divided into 3 HU dose categories: very low, low, and medium. Within each category HU is administered daily on 3 different dosing schedules. Depending on viral load, patients on the very low and low dose arms may have the opportunity to intensify their HU dose at any time beyond Week 12, provided no Grade 3 or 4 HU-related toxicity is present (these patients are monitored for an additional 8 weeks following intensification). All patients receive ddI and d4T at the same doses every day. When 50% of patients have completed 24 weeks of treatment, an analysis is made to determine whether or not to continue the 52-week study without modifications. Patients are monitored periodically for changes in plasma HIV RNA, CD4 cell counts, weight, and symptoms.

Overall Status Completed
Start Date May 1999
Phase Phase 1
Study Type Interventional
Enrollment 225
Condition
Intervention

Intervention type: Drug

Intervention name: Hydroxyurea

Intervention type: Drug

Intervention name: Stavudine

Intervention type: Drug

Intervention name: Didanosine

Eligibility

Criteria:

Inclusion Criteria

Patients may be eligible for this study if they:

- Are HIV-positive.

- Have a viral load of 5,000 to 100,000 copies/ml.

- Are willing to stop all anti-HIV medications for at least 28 days before receiving study drugs.

- Are at least 18 years old.

Exclusion Criteria

Patients will not be eligible for this study if they:

- Have a history of opportunistic (AIDS-related) infection.

- Have a history of pancreatitis or other serious condition.

- Have any cancer that will require chemotherapy within the next 24 weeks.

- Are allergic to ddI or d4T.

- Have received an HIV vaccine within 28 days of study entry.

- Have received a red blood cell transfusion within the past 60 days, or have had repeated transfusions at any time in the past.

- Abuse alcohol or drugs.

- Have received certain medications.

Gender: All

Minimum age: 18 Years

Maximum age: N/A

Healthy volunteers: No

Overall Official
Location
facility
AIDS Healthcare Foundation | Los Angeles, California, 90027, United States
San Francisco VA Med Ctr | San Francisco, California, 94121, United States
Gary Blick MD | Stamford, Connecticut, 06901, United States
Dr Bruce Rashbaum | Washington, District of Columbia, 20037, United States
IDC Research Initiative | Altamonte Springs, Florida, 32701, United States
Boulevard Comprehensive Care Ctr | Jacksonville, Florida, 32209, United States
Center for Quality Care | Tampa, Florida, 33609, United States
AIDS Research Consortium of Atlanta Inc | Atlanta, Georgia, 30308, United States
New England Med Ctr | Boston, Massachusetts, 02111, United States
Albany Med College | Albany, New York, 122083479, United States
Mt Vernon Hosp | Mt. Vernon, New York, 10550, United States
Univ of Pennsylvania Med Ctr | Philadelphia, Pennsylvania, 19104, United States
Thomas Jefferson Univ | Philadelphia, Pennsylvania, 19107, United States
Coastal Carolina Research Ctr | Mount Pleasant, South Carolina, 29464, United States
Univ of Texas Southwestern Med Ctr of Dallas | Dallas, Texas, 75235, United States
Univ of Texas Med Branch | Galveston, Texas, 775550835, United States
Montrose Clinic | Houston, Texas, 77006, United States
Swedish Med Ctr | Seattle, Washington, 98122, United States
Location Countries

United States

Verification Date

August 2000

Keywords
Has Expanded Access No
Condition Browse
Study Design Info

Intervention model: Factorial Assignment

Primary purpose: Treatment

Source: ClinicalTrials.gov