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的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 开发新的治疗方案对于接受过大量治疗的艾滋病毒感染患者至关重要。 具有新作用机制的药物，如HIV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耐药的患者中也显示出活性。 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CCR 5辅助受体发挥作用。 在HIV感染的初治受试者中开展的I期研究的数据表明，SCH 417690单药治疗安全，10、25和50 mg BID剂量的SCH 417690通常耐受良好，并显示出抗逆转录病毒活性。 在这些剂量下，在给药10-14天后观察到HIV-1 RNA的最低点。 在A5211中，SCH 417690将与利托那韦加强的基于蛋白酶通道的ART方案联合给药。 拟定剂量范围为5 - 15 mg QD，部分是基于药代动力学研究中观察到的SCH 417690 10 mg BID与利托那韦联合给药时SCH 417690的Cmax和AUC增加（100 mg QD、100 mg BID、200 mg BID或400 mg BID），并从这些数据外推，以预测QD剂量的预期Cmax和AUC。 利托那韦在试验剂量下具有相似的作用，显示可使SCH 417690 Cmax增加约2-3倍，AUC增加约4-6倍。 当前的II期研究将验证I期研究结果，并证明SCH 417690联合利托那韦药代动力学增强在经治疗受试者中的长期安全性和疗效数据。