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.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 新治疗选择的发展对于经验丰富的，受HIV感染的患者至关重要。 具有新作用机制的药物，例如HIV进入抑制剂，即使在对当前可用的逆转录酶和蛋白酶抑制剂耐药性的患者中也证明了活性。 SCH 417690（以前称为Schering D）是HIV-1感染的抑制剂，通过特异性阻断CCR5共肽来起作用。 I期研究中的I期研究的数据表明，作为单一疗法的SCH 417690是安全的，通常以10、25和50 mg竞标的剂量耐受耐受性良好，并且表现出抗逆转录病毒活性。 在这些剂量下，给药10-14天后，观察到HIV-1 RNA中的Nadir。 SCH 417690将与A5211中的利托纳维尔促进蛋白酶抑制剂基于蛋白酶抑制剂的ART方案共同占领。 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和QD剂量的AUC。 利托那韦在测试的剂量下具有相似的作用，并且被证明可以增加SCH 417690 CMAX约2-3倍，而AUC约为4-6倍。 当前的II期研究将验证I期发现，并证明SCH 417690的长期安全性和功效数据具有Ritonavir Pharmacokinetic在经验经验的受试者中的增强。