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: 7377046
• 负责人: JEFFERY L MEIER
• 金额: $ 2.42万
• 依托单位: UNIVERSITY OF IOWA
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-03-01 至 2007-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7377046
• 关键词: ACTG; A5211; HIV; ENTRY; INHIBITOR

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.

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。开发新的治疗方案对有大量治疗经验的艾滋病毒感染者至关重要。具有新的作用机制的药物，如HIV进入抑制剂，即使对目前可用的逆转录酶和蛋白酶抑制剂有耐药性的患者也显示出活性。SCH 417690（以前称为Schering D）是一种HIV-1感染抑制剂，通过特异性阻断CCR5辅助受体起作用。来自hiv感染治疗初期受试者的I期研究数据表明，SCH 417690作为单药治疗在10、25和50 mg BID剂量下是安全的，通常耐受性良好，并显示出抗逆转录病毒活性。在这些剂量下，10-14天后观察到HIV-1 RNA的最低点。在A5211中，SCH 417690将与利托那韦增强的基于蛋白酶抑制剂的ART方案共同给药。建议的剂量范围为5 - 15mg QD，其选择部分基于在利托那韦（100mg QD, 100mg BID， 200mg BID或400mg BID）给药时，在药代动力学研究中观察到的sch417690的Cmax和AUC的增加，以及根据这些数据推断QD剂量的预期Cmax和AUC。利托那韦在测试剂量下也有类似的效果，并显示可使SCH 417690 Cmax增加约2-3倍，AUC增加约4-6倍。目前的II期研究将验证I期研究结果，并证明SCH 417690在治疗经验丰富的受试者中具有利托那韦药代动力学增强的长期安全性和有效性数据。