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Phase I Rising Dose Tolerability Study of SC-48334 in Patients With Acquired Immunodeficiency Syndrome (AIDS) and Advanced AIDS Related Complex
This study has been completed.
First Received: November 2, 1999   Last Updated: June 23, 2005   History of Changes
Sponsor: G D Searle
Collaborator: National Institute of Allergy and Infectious Diseases (NIAID)
Information provided by: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT00000692
  Purpose

To determine the following about the use of SC-48334 in patients with AIDS and advanced AIDS related complex (ARC):

1. The largest maximum tolerated dose (MTD); 2. Effectiveness against HIV; 3. Pharmacokinetics - how fast SC-48334 reaches the bloodstream, what concentration is reached, and how long it remains in the patient's blood.

SC-48334 is a chemical that prevents the biochemical actions of certain enzymes in the body, and recent studies have shown that it may also prevent the activity of HIV. The study will attempt to show whether SC-48334 can safely and effectively break the cycle of HIV infection in AIDS and advanced ARC by progressively eliminating HIV.


Condition Intervention Phase
HIV Infections
Drug: Butyldeoxynojirimycin
Phase I

Study Type: Interventional
Study Design: Treatment, Open Label, Pharmacokinetics Study
Official Title: Phase I Rising Dose Tolerability Study of SC-48334 in Patients With Acquired Immunodeficiency Syndrome (AIDS) and Advanced AIDS Related Complex

Resource links provided by NLM:


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

Estimated Enrollment: 48
Detailed Description:

SC-48334 is a chemical that prevents the biochemical actions of certain enzymes in the body, and recent studies have shown that it may also prevent the activity of HIV. The study will attempt to show whether SC-48334 can safely and effectively break the cycle of HIV infection in AIDS and advanced ARC by progressively eliminating HIV.

Six patients are enrolled sequentially into each of eight different dose levels and the drug is administered by mouth at least 60 minutes before meals according to the following schedule: Day 1: One-quarter of total assigned daily dose. Patients receive the dosage in the hospital as either an inpatient or outpatient and are observed for 12 hours, during which time they are evaluated and blood is drawn for pharmacokinetic studies. Patients return at 24 and 48 hours for a limited physical examination and additional pharmacokinetic studies. Days 4 - 31: Total assigned daily dose, one-quarter 4 times a day. Patients are observed for at least 5 days in the hospital following the start of this part of the program, during which time clinical, laboratory, and pharmacokinetic information is obtained in order to establish baseline values. After the 6th day, patients are evaluated with a complete physical exam, urinalysis, and laboratory studies once a week and a limited physical exam and brief laboratory studies 3 times a week. At each of the eight dose levels, the second and third patients receive their first dose only after the first patient has been followed for 72 hours after receiving the first dose. Patients 4, 5, and 6 begin treatment only after patients 2 and 3 have completed 14 days of the four-part total dose. Patients are treated on an outpatient basis, with 5 to 6 days spent in the hospital for evaluation.

  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.
  • Nystatin.
  • Clotrimazole.
  • Topical acyclovir.

Concurrent Treatment:

Allowed:

  • Blood transfusions for = or > grade 3 hemoglobin toxicity.

Exclusion Criteria

Co-existing Condition:

Patients with the following conditions will be excluded:

  • Clinical significant diarrhea (> 3 stools per day for > 7 days without definable cause).
  • Active opportunistic infection, requiring ongoing therapy, at time of enrollment.
  • Any malignancy besides Kaposi's sarcoma, basal cell carcinoma, or squamous cell carcinoma unless the squamous cell carcinoma requires ongoing therapy.
  • Neurologic disease including dementia, peripheral neuropathy, myelopathy (CDC category IVb).

Concurrent Medication:

Excluded:

  • Antimetabolites.
  • Alkylating agents.
  • Drugs with known hepatic or bone marrow toxicity.

Patients with significant organ dysfunction will be excluded.

Prior Medication:

Excluded:

  • Antimetabolites.
  • Alkylating agents.
  • Excluded within 30 days of study entry:
  • Any investigational medication.
  • Drugs with anti-HIV activity.
  • Excluded within 90 days of study entry:
  • Ribavirin treatment.
  • Excluded within 6 months of study entry:
  • Cancer chemotherapy.

Prior Treatment:

Excluded within 6 months of study entry:

  • Radiation therapy.

Patients must demonstrate the following clinical and laboratory findings:

  • AIDS or advanced AIDS related complex (ARC), according to Centers for Disease Control (CDC) category IV, excluding neurologic disease in IVb.
  • Ability to understand the terms of study participation.

Current use of illicit drugs or abuse of alcohol.

  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00000692

Locations
United States, California
Univ of California / San Diego Treatment Ctr
San Diego, California, United States, 921036325
Stanford Univ School of Medicine
Stanford, California, United States, 94305
United States, Florida
Univ of Miami School of Medicine
Miami, Florida, United States, 331361013
United States, Illinois
Rush Presbyterian - Saint Luke's Med Ctr
Chicago, Illinois, United States, 60612
United States, Massachusetts
Harvard (Massachusetts Gen Hosp)
Boston, Massachusetts, United States, 02114
United States, South Carolina
Julio Arroyo
West Columbia, South Carolina, United States, 29169
Sponsors and Collaborators
G D Searle
Investigators
Study Chair: MS Hirsch
  More Information

Publications:
Study ID Numbers: ACTG 100
Study First Received: November 2, 1999
Last Updated: June 23, 2005
ClinicalTrials.gov Identifier: NCT00000692     History of Changes
Health Authority: Unspecified

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
Acquired Immunodeficiency Syndrome
AIDS-Related Complex
Antiviral Agents
Biological Availability
1-Deoxynojirimycin

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

ClinicalTrials.gov processed this record on November 25, 2009