A Randomized Study of Activity, Safety, and Tolerance of Oral Ro 24-7429 (Tat Antagonist) in Patients With HIV Infection

NCT00000760 | Completed Phase 1

• 2 other identifiers: ACTG 213NV14224A
• Study Type: interventional
• Target: 96
• Locations: 1 country
• Sites: 4

Brief Summary

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.

Conditions

HIV Infections

Keywords

Didanosine; Acquired Immunodeficiency Syndrome; AIDS-Related Complex; Antiviral Agents; Zidovudine; Gene Products, tat

Interventions

Ro 24-7429 DRUG

Zidovudine DRUG

Didanosine DRUG

Eligibility Criteria

• Age: 12 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

• 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.

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead
• Hoffmann-La Roche: collaborator

Study Sites (4)

UCSD

San Diego, California, 92103, United States

Location

Johns Hopkins Hosp

Baltimore, Maryland, 21205, United States

Location

Harvard (Massachusetts Gen Hosp)

Boston, Massachusetts, 02114, United States

Location

Case Western Reserve Univ

Cleveland, Ohio, 44106, United States

Location

Related Publications (3)

• Haubrich RH, Flexner C, Lederman MM, Hirsch M, Pettinelli CP, Ginsberg R, Lietman P, Hamzeh FM, Spector SA, Richman DD. A randomized trial of the activity and safety of Ro 24-7429 (Tat antagonist) versus nucleoside for human immunodeficiency virus infection. The AIDS Clinical Trials Group 213 Team. J Infect Dis. 1995 Nov;172(5):1246-52. doi: 10.1093/infdis/172.5.1246.

  PMID: 7594660 BACKGROUND

• Haubrich RH. A randomized study of safety, tolerance, pharmacokinetics, and activity of oral Ro 24-7429 (TAT antagonist) in patients with HIV infection. The ACTG 213 Team. Int Conf AIDS. 1993 Jun 6-11;9(1):69 (abstract no WS-B26-5)

  BACKGROUND

• Lathey JL, Marschner IC, Kabat B, Spector SA. Deterioration of detectable human immunodeficiency virus serum p24 antigen in samples stored for batch testing. J Clin Microbiol. 1997 Mar;35(3):631-5. doi: 10.1128/jcm.35.3.631-635.1997.

  PMID: 9041402 BACKGROUND

MeSH Terms

Conditions

HIV Infections; Acquired Immunodeficiency Syndrome; AIDS-Related Complex

Interventions

Ro 24-7429; Zidovudine; Didanosine

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases; Slow Virus Diseases

Intervention Hierarchy (Ancestors)

Thymidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Dideoxynucleosides; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Inosine; Purine Nucleosides; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Ribonucleosides

Study Officials

• Richman DD

  STUDY CHAIR

• Haubrich R

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Purpose: TREATMENT
• Sponsor Type: NIH

Study Record Dates

• First Submitted: November 2, 1999
• First Posted: August 31, 2001
• Last Updated: August 4, 2008

Record last verified: 1998-11

Locations

US (4)