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

August 25, 2008 updated by: National Institute of Allergy and Infectious Diseases (NIAID)

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

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.

Study Type

Interventional

Enrollment

40

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • New York
      • New York, New York, United States, 10021
        • Cornell Univ Med Ctr
      • New York, New York, United States, 10029
        • Mount Sinai Med Ctr

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria

Concurrent Medication:

Allowed:

  • Aerosolized pentamidine for Pneumocystis carinii pneumonia prophylaxis.
  • TMP/SMX as an alternative prophylactic agent, 1 DS tablet orally per day.
  • Acute therapy with oral acyclovir for herpes simplex infections for no more than 7 days, providing d4t is suspended Symptomatic therapy such as analgesics, antihistamines, antiemetics, antidiarrheal agents, or other supportive therapy may be administered for toxicities as deemed necessary by the principal investigator. For therapy of fever, aspirin rather than acetaminophen should be used.

Concurrent Treatment:

Allowed:

  • Transfusion of up to 2 units of packed red blood cells every 3 weeks for grade 3 or grade 4 anemia (see Recommendations for Grading of Acute and Subacute Toxic Effects (Adults)) until patient returns to baseline from grade 3 or to baseline or grade 1 from grade 4.

Patient must have:

  • AIDS or AIDS related complex (CDC Group IVA or CDC Group IVC-2 with thrush or oral leukoplakia).
  • Ability to provide informed consent.
  • Availability to follow-up for at least 6 months.
  • Absence of active, AIDS-defining opportunistic infection on study entry.

Exclusion Criteria

Co-existing Condition:

Patients with the following are excluded:

  • Active, AIDS-defining opportunistic infection.
  • Intractable diarrhea.
  • History or propensity for seizure disorders requiring anticonvulsants for control.
  • Any other clinical condition which in the opinion of the investigator would make the patient unsuitable or unable to comply with the dosing requirements.

Concurrent Medication:

Excluded:

  • Systemic therapy with this or any other antiretroviral drug (including AL-721, ddI, ddC, interferon, immunomodulating drugs) or investigational drug.
  • Ribavirin.
  • Cytotoxic anticancer therapy.
  • Therapy with any agent known as a potent inducer or inhibitor of drug-metabolizing enzymes, such as rifampin or barbiturates.
  • Systemic maintenance or chemoprophylaxis for opportunistic infections.
  • Trimethoprim / sulfamethoxazole for Pneumocystis carinii infections.
  • Acute therapy with ketoconazole for thrush.
  • Neurotoxic agents listed in the protocol.

Patients with the following are excluded:

  • Previous intolerance to zidovudine (AZT) as demonstrated by transfusion dependent anemia (transfusion required every 3 weeks or less and AZT-related depression of neutrophils to < 500 cells/mm3).
  • Life expectancy < 6 months.

Prior Medication:

Excluded:

  • Any other prior therapy which in the opinion of the investigator would make the patient unsuitable or unable to comply with the dosing requirements.

Excluded within 2 weeks of study entry:

  • Therapy with any agent known as a potent inducer or inhibitor of drug-metabolizing enzymes, such as rifampin or barbiturates.

Excluded within 1 month of study entry:

  • Systemic therapy with this or any other antiretroviral drug (including AL-721, interferon, immunomodulating drugs, ddI, ddC) or any investigational drug.

Excluded within 3 months of study entry:

  • Ribavirin.
  • Cytotoxic anticancer therapy.

Prior Treatment:

Excluded:

  • Any prior therapy which in the opinion of the investigator would make the patient unsuitable or unable to comply with the dosing requirements.

Preference:

  • Tolerating zidovudine (AZT) at time of study entry.

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Masking: None (Open Label)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

National Institute of Allergy and Infectious Diseases (NIAID)

Collaborators

Bristol-Myers Squibb

Investigators

  • Study Chair: HS Sacks

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

First Submitted

November 2, 1999

First Submitted That Met QC Criteria

August 30, 2001

First Posted (Estimate)

August 31, 2001

Study Record Updates

Last Update Posted (Estimate)

August 26, 2008

Last Update Submitted That Met QC Criteria

August 25, 2008

Last Verified

December 1, 1994

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ACTG 089
  • AI455-002
  • 070V3

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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