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

This study has been completed.
Sponsor:
Collaborator:
Bristol-Myers Squibb
Information provided by:
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT00000988
First received: November 2, 1999
Last updated: August 25, 2008
Last verified: December 1994
  Purpose

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.


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 and Pharmacokinetics Study of BMY-27857 (2',3'-Didehydro-3'-Deoxythymidine) Administered Twice Daily to 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: 40
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.

  Eligibility

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

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.

  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: NCT00000988

Locations
United States, New York
Cornell Univ Med Ctr
New York, New York, United States, 10021
Mount Sinai Med Ctr
New York, New York, United States, 10029
Sponsors and Collaborators
Bristol-Myers Squibb
Investigators
Study Chair: HS Sacks
  More Information

Additional Information:
Publications:
ClinicalTrials.gov Identifier: NCT00000988     History of Changes
Other Study ID Numbers: ACTG 089, AI455-002, 070V3
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):
Injections, Intravenous
Drug Evaluation
Administration, Oral
Acquired Immunodeficiency Syndrome
AIDS-Related Complex
Antiviral Agents

Additional relevant MeSH terms:
Acquired Immunodeficiency Syndrome
AIDS-Related Complex
HIV Infections
Immune System Diseases
Immunologic Deficiency Syndromes
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Sexually Transmitted Diseases
Sexually Transmitted Diseases, Viral
Slow Virus Diseases
Virus Diseases
Stavudine
Anti-HIV Agents
Anti-Infective Agents
Anti-Retroviral Agents
Antimetabolites
Antiviral Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Nucleic Acid Synthesis Inhibitors
Pharmacologic Actions
Reverse Transcriptase Inhibitors
Therapeutic Uses

ClinicalTrials.gov processed this record on October 29, 2014