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A Randomized Study of Activity, Safety, and Tolerance of Oral Ro 24-7429 (Tat Antagonist) in Patients With HIV Infection
This study has been completed.
Sponsors and Collaborators: National Institute of Allergy and Infectious Diseases (NIAID)
Hoffmann-La Roche
Information provided by: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT00000760
  Purpose

To study the anti-HIV activity of the various doses of Ro 24-7429 monotherapy based on virologic and immunologic endpoints. To study the safety and tolerance of Ro 24-7429. To explore relationships between exposure to Ro 24-7429 and its metabolites and antiviral activity and drug toxicity. To determine a safe, tolerable, and active dose regimen of Ro 24-7429, and to make preliminary observations of Ro 24-7429 in combination with another antiretroviral nucleoside.

The HIV genome contains a number of genes that regulate viral replication. Control of the activity of these genes and their encoded proteins represents a potential target for development of new antiretroviral drugs. The tat (transactivator of transcription of HIV) antagonist Ro 24-7429 is the first compound for clinical testing that utilizes this approach for therapy of HIV infection.


Condition Intervention Phase
HIV Infections
Drug: Ro 24-7429
Drug: Zidovudine
Drug: Didanosine
Phase I

MedlinePlus related topics: AIDS
Drug Information available for: Zidovudine Didanosine Ro 24-7429
U.S. FDA Resources
Study Type: Interventional
Study Design: Treatment, Safety Study
Official Title: A Randomized Study of Activity, Safety, and Tolerance of Oral Ro 24-7429 (Tat Antagonist) in Patients With HIV Infection

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

Estimated Enrollment: 96
Detailed Description:

The HIV genome contains a number of genes that regulate viral replication. Control of the activity of these genes and their encoded proteins represents a potential target for development of new antiretroviral drugs. The tat (transactivator of transcription of HIV) antagonist Ro 24-7429 is the first compound for clinical testing that utilizes this approach for therapy of HIV infection.

Ninety-six patients (four treatment arms of 24 patients each) are randomized to receive oral Ro 24-7429 at 1 of 3 doses or nucleoside control (either zidovudine or didanosine). The study will be blinded only for the arms receiving Ro 24-7429. Treatment continues for 12 weeks. After 12 weeks, patients on the nucleoside control arm receive the highest tolerated dose of Ro 24-7429 in addition to their nucleoside.

  Eligibility

Ages Eligible for Study:   12 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria

Concurrent Medication:

Allowed:

  • Chemoprophylaxis for P. carinii pneumonia, TB, and mucocutaneous candidiasis.
  • Methadone maintenance.
  • Hormonal contraceptives.

Patients must have:

  • HIV-1 seropositivity.
  • CD4 count 50 - 500 cells/mm3.
  • Life expectancy of at least 24 weeks.
  • Stable weight (+/- 2 kg) by 28 days prior to study entry (by history).

NOTE:

  • At least 50 percent of patients must be p24 antigen positive (>= 50 pg/ml).

Exclusion Criteria

Co-existing Condition:

Patients with the following symptoms and conditions are excluded:

  • Known or suspected hypersensitivity to benzodiazepines.
  • Presence of any malignancy other than basal cell carcinoma or limited cutaneous Kaposi's sarcoma (defined as no more than five lesions with no mucosal involvement).
  • Ongoing diarrhea, defined as more than 2 liquid stools per day.
  • History, physical exam, or laboratory results consistent with a subclinical AIDS-defining opportunistic infection.
  • Grade 2 or greater signs and symptoms of AIDS Dementia Complex.
  • Evidence of clinically significant cardiac, respiratory, hepatic, gastrointestinal, endocrine, hematologic, psychiatric, neurologic, dermatologic, or allergic disease.

Concurrent Medication:

Excluded:

  • Chronic suppressive therapy for CMV, MAI, toxoplasmosis, cryptococcosis, cryptosporidiosis, coccidioidomycosis, and histoplasmosis.
  • ddC, ddI, AZT (except for control groups) or other experimental antiretrovirals or immunomodulating agents.
  • Other medications excluded from the study.

Patients with the following prior conditions are excluded:

  • History of serious adverse reactions to benzodiazepines.
  • History of intolerance to AZT at 600 mg/day or less or ddI at 400 mg/day or less.
  • History of unexplained fever, defined as a temperature of 38.5 deg C or greater with or without night sweats for more than 7 of the past 28 days.

Prior Medication:

Excluded:

  • Benzodiazepines within 14 days prior to study entry.

Active drug or alcohol abuse that would interfere with study compliance.

  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00000760

Locations
United States, California
UCSD
San Diego, California, United States, 92103
United States, Maryland
Johns Hopkins Hosp
Baltimore, Maryland, United States, 21205
United States, Massachusetts
Harvard (Massachusetts Gen Hosp)
Boston, Massachusetts, United States, 02114
United States, Ohio
Case Western Reserve Univ
Cleveland, Ohio, United States, 44106
Sponsors and Collaborators
Hoffmann-La Roche
Investigators
Study Chair: Richman DD
Study Chair: Haubrich R
  More Information

Click here for more information about Zidovudine  This link exits the ClinicalTrials.gov site
Click here for more information about Didanosine  This link exits the ClinicalTrials.gov site

Publications:
Study ID Numbers: ACTG 213, NV14224A
Study First Received: November 2, 1999
Last Updated: July 31, 2008
ClinicalTrials.gov Identifier: NCT00000760  
Health Authority: United States: Federal Government

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
Didanosine
Acquired Immunodeficiency Syndrome
AIDS-Related Complex
Antiviral Agents
Zidovudine
Gene Products, tat

Study placed in the following topic categories:
Virus Diseases
Sexually Transmitted Diseases, Viral
Didanosine
HIV Infections
Sexually Transmitted Diseases
Acquired Immunodeficiency Syndrome
Zidovudine
AIDS-Related Complex
Retroviridae Infections
Immunologic Deficiency Syndromes

Additional relevant MeSH terms:
Antimetabolites
Anti-Infective Agents
Communicable Diseases
RNA Virus Infections
Anti-HIV Agents
Slow Virus Diseases
Immune System Diseases
Molecular Mechanisms of Pharmacological Action
Enzyme Inhibitors
Infection
Antiviral Agents
Pharmacologic Actions
Reverse Transcriptase Inhibitors
Anti-Retroviral Agents
Therapeutic Uses
Lentivirus Infections
Nucleic Acid Synthesis Inhibitors

ClinicalTrials.gov processed this record on January 15, 2009