Clinical Trial: A Study of BMY-27857 in Patients With AIDS or AIDS Related Complex

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: A Phase I Safety and Pharmacokinetics Study of BMY-27857 (2',3'-Didehydro-3'-Deoxythymidine) Administered Twice Daily to Patients With AIDS or AIDS Related Complex

Brief Summary:

To evaluate the safety, minimum effective dose (MED), pharmacokinetics and efficacy of orally administered 2',3'-dideoxy-2',3'-didehydrothymidine (d4T) in patients with AIDS or AIDS related complex (ARC). To establish an appropriate dosage regimen of d4T to be employed in Phase II and III trials. To evaluate the effects of de-escalating doses of d4T on markers associated with HIV infection.

Currently, the only FDA-approved therapy for patients with AIDS or ARC is zidovudine (AZT), a drug with significant value but limited use because of toxic effects on the bone marrow. d4T has not been tested in humans, but it has inhibited the reproduction of HIV (the virus that causes AIDS) in laboratory experiments. In some studies with laboratory animals, d4T was less toxic against blood cells than AZT.

Detailed Summary:

Currently, the only FDA-approved therapy for patients with AIDS or ARC is zidovudine (AZT), a drug with significant value but limited use because of toxic effects on the bone marrow. d4T has not been tested in humans, but it has inhibited the reproduction of HIV (the virus that causes AIDS) in laboratory experiments. In some studies with laboratory animals, d4T was less toxic against blood cells than AZT.

A maximum tolerated dose (MTD) has been found in Phase I trials to date. An MED will be determined. The daily dose of d4T is divided into 2 portions and administered approximately 12 hours apart for 10 weeks. 5 patients receive the initial dose level and successive groups of 5 patients enter the study at a lower dose level once 3 patients in the preceding group have successfully completed at least 3 weeks of dosing and shown a positive effect on CD4 cell count and p24 antigen levels. The initial group of patients continue dosing at their dose level for an additional 94 weeks as long as they are doing well as measured by p24 antigen levels and CD4 cell counts. The dose de-escalation scheme continues until a lack of efficacy is seen in 2 of 5 patients in any group. Patients are assigned to de-escalating dose level treatment groups in the order in which they are enrolled. Blood and urine samples are taken regularly to check for toxic effects and therapeutic effectiveness. In each dosing group, 3 of 5 patients will be p24 antigen positive greater than or equal to 70 pg/ml, and 2 of 5 patients will have CDC-defined AIDS.

Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)

Current Primary Outcome:

Original Primary Outcome:

Current Secondary Outcome:

Original Secondary Outcome:

Information By: National Institute of Allergy and Infectious Diseases (NIAID)

Dates:
Date Received: November 2, 1999
Date Started:
Date Completion:
Last Updated: August 25, 2008
Last Verified: December 1994