HIV Infections
Conditions
Keywords
Didanosine, Acquired Immunodeficiency Syndrome, AIDS-Related Complex, Antiviral Agents, Zidovudine, Gene Products, tat
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.
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.
Interventions
Sponsors
Hoffmann-La Roche
National Institute of Allergy and Infectious Diseases (NIAID)
Study design
Primary purpose
TREATMENT
Eligibility
Sex/Gender
ALL
Age
12 Years to No maximum
Healthy volunteers
No
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.
Countries
United States
Outcome results
None listed