IND Enabling Critical Path Project

项目4摘要 电影抗逆转录病毒杀微生物剂评估（FAME）计划解决了开发高度 一种有效、安全、可接受的杀微生物阴道膜，具有延长的HIV防护窗口 感染，允许较低频率的产品给药。该计划建立在以前的数据显示阴道 膜是一种安全和可接受的剂型，用于将抗病毒药物递送到阴道。具体来说，一部电影 将开发整合酶抑制剂MK-2048的制剂，以达到可测量的药物水平 与单次应用后一周内宫颈和阴道组织中的HIV预防一致。 这样的产品可以每周持续使用以提供持续的保护，或者可以用于 为在感染风险增加期间计划保护的妇女提供更大的多样性。MK- 2048是一种有效的第二代整合酶抑制剂，大量的临床前数据，包括 安全性已经建立。项目4中开发的IND将交叉引用药物 MK-2048口服和阴道环产品先前批准的IND中包含的物质数据。 IND实现关键路径项目（项目4）的总体目标是确保GMP MK-2048 可用于计划内的研究。项目4将协调和监督制造 符合GMP的药品。项目1中开发的制剂将成为GMP的基础 制造。项目4还将管理临床前安全性研究，包括家兔阴道刺激和毒性研究 研究和兼容性研究。这些研究将与来自 既往IND提交资料、项目2的体外和离体安全性和疗效数据以及 核心B，用于生成支持在项目内进行计划的人体临床试验的安全性包 3.项目4将开发和整合用于提交IND申请的监管文件，以支持 美国首次人体研究性临床试验（FAME-101、FAME-102和FAME-103;项目3）。 最后，项目4还将生成所需的研究者手册。项目4的活动包括： 对于生成启动人类研究所需的数据和适当的监管文件至关重要 本研究设计的新型非性交依赖性（1周）薄膜剂型的临床试验 程序.

PROJECT 4 ABSTRACT The Film Antiretroviral Microbicide Evaluation (FAME) Program addresses the critical need to develop a highly effective, safe, and acceptable microbicide vaginal film with an extended window of protection from HIV infection that allows less frequent product dosing. The Program builds upon previous data showing vaginal films to be a safe and acceptable dosage form for delivery of antiviral drugs to the vagina. Specifically, a film formulation of the integrase inhibitor MK-2048 will be developed that achieves measurable drug levels consistent with HIV prevention in the cervical and vaginal tissues over one week following a single application. Such a product could be used consistently on a weekly basis to provide continuous protect or could be used to provide greater versatility for women planning for protection around a period of increased risk of infection. MK- 2048 is a potent 2nd generation integrase inhibitor for which an extensive amount of preclinical data including safety have already been established. The IND developed within Project 4 will cross reference drug substance data contained within previously approved INDs for the MK-2048 oral and intravaginal ring products. The overall goal of the IND Enabling Critical Path Project (Project 4) is to ensure that GMP MK-2048 is available for use in the planned studies within the program. Project 4 will coordinate and oversee manufacture of GMP compliant drug product. Formulations developed within Project 1 will be the basis for GMP manufacture. Project 4 will also manage preclinical safety studies including rabbit vaginal irritation and toxicity studies and lactobacillus compatiblity studies. These studies will be combined with existing data from previous IND submissions, in vitro and ex vivo safety and efficacy data from Project 2, and safety data from Core B to generate a safety package supportive of conducting the planned human clinical trials within Project 3. Project 4 will develop and integrate regulatory documents for submission of an IND application to support first-in-humans investigative clinical trials in the US (FAME-101, FAME-102, and FAME-103; Project 3). Finally, Project 4 will also generate the required Investigator Brochure. The activities within Project 4 are essential to generation of required data and appropriate regulatory documentation for initiation of human clinical trials of the novel non-coitally dependent (1 week) film dosage form that will be designed within this program.