DELAVIRDINE MESYLATE PLUS NELFINAVIR, DIDANOSINE, STAVUDINE FOR HIV 1

甲磺酸地拉韦啶加奈非那韦、地达诺辛、司他夫定治疗 HIV 1

• 批准号: 6265106
• 负责人: MITCHELL GOLDMAN
• 金额: $ 0.04万
• 依托单位: INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-12-01 至 1999-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6265106
• 关键词: 2'3' dideoxyinosine; AIDS therapy; HIV infections; antiAIDS agent; clinical research; clinical trial phase I; combination chemotherapy; delavirdine; drug screening /evaluation; human immunodeficiency virus 1; human subject; human therapy evaluation; pharmacokinetics; protease inhibitor; stavudine; virus load

This protocol features a multicenter, multiple-dose, randomized open-label design which will evaluate safety, tolerance, antiviral efficacy, and pharmacokinetics ( in a subset of patients). HIV-1 + males and females with a CD count of > or = 50 cells/mm and plasma HIV-1 RNA levels > or = 20,000 copies/mL will be treated with delavirdine (400 or 600 mg TID), didanosine (200 mg or 125 mg BID), nelfinavir (750 mg TID), and stavudine (30 mg or 40 mg BID). Patients must have no prior stavudine, protease inhibitor, (including nelfinavir), or NNRTI experience; didanosine experience must be less than six months. The study consists of four dosage regimens: DLV + NFV + d4T, DLV + NFV + ddI, NFV + d4T + ddI, DLV + NFV + d4T + ddI (40 patient per group) to be treated for 24 weeks with the option of continuing study participation for an additional 24 weeks at the discretion of the investigator. The first 20 patients receiving delavirdine and nelfinavir on the trial will be evaluated on weeks 1,2,3, and 4 for safety via chemistry and hematology panels and trough level evaluations for delavirdine and nelfinavir. On approximately week 4, the 20 patients will need to have one day for full pharmacokinetic evaluation. Based on the results from these patients, and additional 160 patients may receive an adjusted dose of study medication. For all patients, safety will be assessed at each patient visit. Viral burden will be measured by an FDA approved plasm aRNA JPCR real-time assay and results provided to investigators. Initially, patients will be stratified by HIV-1 RNA PCR levels (20,000 to 200,000 and > 200,000) and randomized into one of the four treatment groups.

该方案采用多中心、多剂量、随机开放标签设计，将(在部分患者中)评估安全性、耐受性、抗病毒疗效和药代动力学。CD计数为&gt；或=50 cell/mm，血浆HIV-1RNA水平为&gt；或=20,000拷贝/毫升的HIV-1阳性男性和女性将接受地拉韦丁(400或600毫克TID)、Ddanosine(200 mg或125 mg Bid)、奈非那韦(750 Mg TID)和司他夫定(30 mg或40 mg Bid)治疗。患者必须事先没有司他夫定、蛋白酶抑制剂(包括奈非那韦)或NNRTI的经验；Ddanosine的经验必须少于6个月。这项研究包括四种给药方案：DLV+NFV+d4T、DLV+NFV+DDI、NFV+D4T+DDI、DLV+NFV+D4T+DDI(每组40名患者)，治疗24周，研究人员可以选择继续参与研究24周。在试验中接受地拉韦丁和奈非那韦治疗的前20名患者将在第1、2、3和4周通过化学和血液学小组以及地拉韦丁和奈非那韦的低谷水平评估来评估安全性。大约在第4周，20名患者将需要有一天的时间进行全面的药代动力学评估。根据这些患者的结果，另外160名患者可能会接受调整剂量的研究药物。对于所有患者，将在每次就诊时对安全性进行评估。病毒载量将通过FDA批准的血浆Arna JPCR实时检测方法进行测量，并将结果提供给调查人员。最初，患者将根据HIV-1 RNA聚合酶链式反应水平(20,000至200,000和200,000)进行分层，并随机分为四个治疗组之一。