ACTG 382: ANTIVIRAL ACTIVITY OF DMP 266 WITH NELFINAVIR IN CHILDREN (HIV)

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。这是一项为期48周的开放标签、AUC控制的多中心研究。将有60名儿童入学。所有受试者将接受DMP 266和奈非那韦。同时使用核苷逆转录酶抑制剂(NRTI)将被允许，但它们不会通过该方案提供。DMP 266的初始目标AUC将在190至380之间。儿童的初始剂量将是600毫克，根据身体大小进行调整。受试者的起始剂量将根据耐受性和前六名受试者在两周内接受该剂量的DMP 266血浆浓度进行调整。如果剂量是耐受的，并且6名受试者中至少有4名达到了目标AUC，则认为已经达到了目标AUC。受试者的登记将在进行中，开始于给定起始剂量的受试者将继续使用该剂量，直到需要根据他们的个人药代动力学评估调整个体受试者剂量。基线和研究疗效评估将包括血浆HIV RNA水平、CD4计数以及病毒基因型和表型耐药性分析。基线和研究安全性评估将包括监测不良经历、临床实验室测试、体检和生命体征。在48周结束时，受试者将被允许选择通过杜邦-默克方案继续DMP 266课外研究。截止注册，新版本的方案将随访时间延长了52周。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. This is a 48-week, open-label, AUC-controlled, multicenter study. Sixty children will be enrolled. All subjects will receive DMP 266 and nelfinavir. Concomitant use of nucleoside reverse transcriptase inhibitors (NRTI) will be permitted, but they will not be supplied through this protocol. The initial target AUC for DMP 266 will be between 190 and 380. The initial starting dose for children will be 600 mg adjusted for body size. The starting dose for subjects will be adjusted on the basis of the tolerability and DMP 266 plasma concentrations of the first six subjects receiving that dose for two weeks. The target AUC is considered to have been achieved if the dose was tolerated and at least 4 of 6 subjects reached the target AUC. Enrollment of subjects will be ongoing and those begun on a given starting dose will continue on that dose until individual subject dose adjustments are needed according to their individual pharmacokinetics evaluations. Baseline and study efficacy evaluations will include plasma HIV RNA levels, CD4 counts, and viral genotypic and phenotypic resistance analyses. Baseline and study safety evaluations will include the monitoring of adverse experiences, clinical laboratory tests, physical examinations and vital signs. At the end of 48 weeks, subjects will be given the option to continue DMP 266 off-study through a DuPont Merck protocol. Closed to enrollment, new version of protocol extends follow up an additional 52 weeks.