ACTG A5211 HIV-1 ENTRY INHIBITOR, SCH 417690, TO TREAT HIV INFECTED SUBJECTS

ACTG A5211 HIV-1 进入抑制剂，SCH 417690，用于治疗 HIV 感染者

• 批准号: 7604836
• 负责人: JEFFERY L MEIER
• 金额: $ 0.12万
• 依托单位: UNIVERSITY OF IOWA
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-03-01 至 2007-09-16
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7604836
• 关键词: AIDS clinical trial group; Anti-Retroviral Agents; CCR5 gene; Computer Retrieval of Information on Scientific Projects Database; Data; Development; Dose; Drug Kinetics; Funding; Grant; HIV; HIV Entry Inhibitors; HIV-1; Infection; Institution; Patients; Pharmaceutical Preparations; Phase; Phase I Clinical Trials; Phase II Clinical Trials; Protease Inhibitor; RNA; RNA-Directed DNA Polymerase; Range; Research; Research Personnel; Resistance; Resources; Ritonavir; Safety; Source; Testing; Treatment Protocols; United States National Institutes of Health; base; day; experience; inhibitor/antagonist

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. The development of new treatment options is critical for heavily treatment-experienced, HIV-infected patients. Drugs with new mechanisms of action, such as the HIV entry inhibitors, demonstrate activity even in patients with resistance to currently available reverse transcriptase and protease inhibitors. SCH 417690 (formerly known as Schering D) is an inhibitor of HIV-1 infection that acts by specifically blocking the CCR5 coreceptor. Data from phase I studies in HIV-infected treatment-naive subjects demonstrate that SCH 417690 given as monotherapy is safe and generally well-tolerated at doses of 10, 25, and 50 mg BID and demonstrates antiretroviral activity. At these doses, a nadir in HIV-1 RNA was observed after 10-14 days of dosing. SCH 417690 will be coadministered with a ritonavir-boosted protease inhibitor-based ART regimen in A5211. The proposed doses ranging from 5 to 15 mg QD were chosen based partly on the increases in Cmax and AUC of SCH 417690 observed in pharmacokinetic studies when SCH 417690 10 mg BID was administered with ritonavir (100 mg QD, 100 mg BID, 200 mg BID, or 400 mg BID), and on extrapolation from these data to predict the anticipated Cmax and AUC for the QD doses. Ritonavir has a similar effect at the doses tested and was shown to increase SCH 417690 Cmax approximately 2-3 fold and AUC approximately 4-6 fold. The current phase II study will validate the phase I findings and demonstrate longer-term safety and efficacy data for SCH 417690 with ritonavir pharmacokinetic enhancement in treatment-experienced subjects.

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 开发新的治疗方案对有大量治疗经验的艾滋病毒感染患者至关重要。具有新作用机制的药物，如艾滋病毒进入抑制剂，即使在对目前可用的逆转录酶和蛋白酶抑制剂具有耐药性的患者中也显示出活性。SCH 417690(以前称为先灵D)是一种艾滋病毒-1感染的抑制剂，通过特异性阻断CCR5辅助受体发挥作用。 来自艾滋病毒感染治疗初学者的I期研究的数据表明，作为单一疗法给予SCH 417690是安全的，通常耐受性良好，剂量分别为10、25和50毫克，并显示出抗逆转录病毒活性。在这些剂量下，在10-14天后观察到HIV-1RNA的最低点。SCH 417690将在A5211中与利托那韦增强的基于蛋白酶抑制剂的ART方案共同管理。建议的剂量范围为5到15毫克，每日一次，部分是根据药代动力学研究中观察到的SCH 417690与利托那韦(100毫克每日一次、两次100毫克、200毫克两次或400毫克两次)合用时SCH 417690的Cmax和AUC的增加，并根据这些数据外推以预测Qd剂量的预期Cmax和AUC。利托那韦在试验剂量下有类似的作用，其SCH 417690 Cmax增加约2-3倍，AUC增加约4-6倍。目前的第二阶段研究将验证第一阶段的发现，并证明在有治疗经验的受试者中使用利托那韦增强SCH 417690的长期安全性和有效性数据。