A Study of d4T in Patients With AIDS or AIDS-Related Complex Who Cannot Take AZT

This study has been terminated.
Sponsor:
Collaborator:
Bristol-Myers Squibb
Information provided by:
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT00000686
First received: November 2, 1999
Last updated: August 25, 2008
Last verified: May 1999
  Purpose

To determine the safety and maximum tolerated dose (MTD) of 2',3'-dideoxy-2',3'-didehydrothymidine (d4T) administered to patients with AIDS or AIDS related complex (ARC) who are intolerant of zidovudine (AZT). The study also begins an assessment of the effectiveness of d4T therapy on HIV replication, on plasma levels of p24 antigen, and clinical or immunologic parameters associated with AIDS.

Of the methods that are being evaluated to treat HIV-infected individuals, AZT has produced the best results to date. Toxic effects in approximately 50 percent of patients receiving AZT may limit its usefulness for prolonged treatment. Long-term treatment may be necessary to prevent progression of early stage HIV infection to AIDS and to prevent secondary transmission. Other drugs that may be equally or more effective than AZT and useful in the long- term treatment of HIV infection must be developed and evaluated. Test-tube and animal studies of d4T show that the drug can inhibit replication (reproduction) of HIV at concentrations similar to concentrations of AZT that have anti-HIV activity. These studies also indicate that the drug may stay in the bloodstream longer than AZT. Thus, it may be possible for the drug to be as effective as AZT when taken less frequently than AZT. It also may have a less disturbing effect on other body functions (such as thymidine metabolism).


Condition Intervention Phase
HIV Infections
Drug: Stavudine
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Pharmacokinetics Study
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I Safety Study of BMY-27857 (2',3'-Dideoxy-2',3'-Didehydrothymidine [d4T]) Administered Four Times Daily to AZT-Intolerant Patients With AIDS or AIDS-Related Complex

Resource links provided by NLM:


Further study details as provided by National Institute of Allergy and Infectious Diseases (NIAID):

Estimated Enrollment: 35
Detailed Description:

Of the methods that are being evaluated to treat HIV-infected individuals, AZT has produced the best results to date. Toxic effects in approximately 50 percent of patients receiving AZT may limit its usefulness for prolonged treatment. Long-term treatment may be necessary to prevent progression of early stage HIV infection to AIDS and to prevent secondary transmission. Other drugs that may be equally or more effective than AZT and useful in the long- term treatment of HIV infection must be developed and evaluated. Test-tube and animal studies of d4T show that the drug can inhibit replication (reproduction) of HIV at concentrations similar to concentrations of AZT that have anti-HIV activity. These studies also indicate that the drug may stay in the bloodstream longer than AZT. Thus, it may be possible for the drug to be as effective as AZT when taken less frequently than AZT. It also may have a less disturbing effect on other body functions (such as thymidine metabolism).

Five patients are enrolled at each dose level and receive d4T for 10 weeks at their initial dose level. Escalation to the next higher dose level, using a different group of five patients, occurs after three patients in the preceding group have successfully completed at least 3 weeks of oral dosing.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria

Patients must have:

  • Diagnosis of AIDS or AIDS related complex (ARC).
  • Previous intolerance to daily doses of up to 1200 mg of zidovudine (AZT) demonstrated by a decrease in hemoglobin levels of 2 - 8.5 g/dl or AZT-related depression of neutrophils of 200 - 750 cells/mm3.
  • Ability to provide informed consent.

Prior Medication:

Allowed:

  • Zidovudine (AZT).

Exclusion Criteria

Co-existing Condition:

Patients with the following are excluded:

  • AIDS-defining opportunistic infection on enrollment.
  • Intractable diarrhea.
  • History of seizures within past 2 years or currently requiring anticonvulsants for control.
  • Any other clinical conditions or prior therapy which in the opinion of the investigator would make the patient unsuitable for study or unable to comply with the dosing requirements.

Concurrent Medication:

Excluded:

  • Systemic maintenance or chemoprophylaxis for opportunistic infection (includes dapsone, acyclovir).
  • Systemic therapy with this or any other antiretroviral drug (except zidovudine (AZT)) or investigational drug.
  • Ribavirin.
  • Cytotoxic anticancer therapy.
  • Any agent known as a potent inducer or inhibitor of drug-metabolizing enzymes (includes rifampin and barbiturates).
  • Trimethoprim / sulfamethoxazole (TMP / SMX).

Patients with the following are excluded:

  • AIDS-defining opportunistic infection on enrollment.
  • Intractable diarrhea.
  • History of seizures within past 2 years or currently requiring anticonvulsants for control.
  • Any other clinical conditions or prior therapy which in the opinion of the investigator would make the patient unsuitable for study or unable to comply with the dosing requirements.

Prior Medication:

Excluded within 2 weeks of study entry:

  • Any agent known as a potent inducer or inhibitor of drug-metabolizing enzymes (includes rifampin and barbiturates).

Excluded within 1 month of study entry:

  • Systemic therapy with this or any other antiretroviral drug (except zidovudine (AZT)) or investigational drug.

Excluded within 3 months of study entry:

  • Ribavirin.
  • Cytotoxic anticancer therapy.

Active alcohol or drug abuse sufficient in investigator's opinion to prevent adequate compliance with study therapy.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00000686

Locations
United States, New York
Cornell Univ Med Ctr
New York, New York, United States, 10021
Sponsors and Collaborators
Bristol-Myers Squibb
  More Information

Additional Information:
Publications:
ClinicalTrials.gov Identifier: NCT00000686     History of Changes
Other Study ID Numbers: ACTG 111, AI455-004
Study First Received: November 2, 1999
Last Updated: August 25, 2008
Health Authority: United States: Federal Government

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
Drug Evaluation
Acquired Immunodeficiency Syndrome
AIDS-Related Complex
Antiviral Agents
Zidovudine

Additional relevant MeSH terms:
HIV Infections
Acquired Immunodeficiency Syndrome
AIDS-Related Complex
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Slow Virus Diseases

ClinicalTrials.gov processed this record on September 30, 2014