A Randomized Study of Activity, Safety, and Tolerance of Oral Ro 24-7429 (Tat Antagonist) in Patients With HIV Infection
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 96
- 试验地点
- 4
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 主要目的
- Treatment
入排标准
- 年龄范围
- 12 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Concurrent Medication:
- •Chemoprophylaxis for P. carinii pneumonia, TB, and mucocutaneous candidiasis.
- •Methadone maintenance.
- •Hormonal contraceptives.
- •Patients must have:
- •HIV-1 seropositivity.
- •CD4 count 50 - 500 cells/mm
- •Life expectancy of at least 24 weeks.
- •Stable weight (+/- 2 kg) by 28 days prior to study entry (by history).
- •At least 50 percent of patients must be p24 antigen positive (>= 50 pg/ml).
排除标准
- •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:
- •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:
- •Benzodiazepines within 14 days prior to study entry.
- •Active drug or alcohol abuse that would interfere with study compliance.