Microbicide intravaginal ring IND enabling studies

杀菌剂阴道环 IND 启用研究

• 批准号: 8467256
• 负责人: Amanda Malone
• 金额: $ 33.9万
• 依托单位: AURITEC PHARMACEUTICALS, INC.
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-02-01 至 2015-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8467256
• 关键词: Agreement; Animal Model; Animals; Anti-Retroviral Agents; Antiviral Agents; Cessation of life; Chemistry; Clinical; Clinical Research; Clinical Trials; Collaborations; Communities; Consensus; Development; Devices; Drug Combinations; Drug Delivery Systems; Drug Formulations; Drug Kinetics; Engineering; Environment; FDA approved; Funding; Ganciclovir; Goals; Grant; HIV; HIV therapy; Highly Active Antiretroviral Therapy; Human; Implant; In Vitro; Investigational Drugs; Lead; Licensing; Macaca; Malaria; Manufacturer Name; Marketing; Minor; National Institute of Allergy and Infectious Disease; Oryctolagus cuniculus; Pharmaceutical Preparations; Pharmacologic Substance; Phase; Phase III Clinical Trials; Prevention; Process; Qualifying; Research Personnel; Resistance; Resolution; Safety; Sheep; Small Business Innovation Research Grant; Solubility; Tenofovir; Tenofovir disoproxil fumarate; Testing; Toxicity Tests; Tuberculosis; Vaginal Ring; Work; World Health; aqueous; base; controlled release; drinking water; drug development; emtricitabine; experience; improved; in vitro testing; in vivo; inhibitor/antagonist; innovation; material transfer agreement; microbicide; prevent; programs; public health relevance; research clinical testing; safety testing; simian human immunodeficiency virus; transmission process

DESCRIPTION (provided by applicant): The long term goal of this project is to prevent HIV transmission. Using the drug delivery platform we developed for the ganciclovir intraocular implant, Vitrasert(R), we propose to develop an intravaginal ring microbicide formulation releasing the antiretroviral agents tenofovir DF, emtricitabine and maraviroc. This drug combination has been chosen for potency, synergistic action, and the prevention of resistance. The rationale for the choice of tenofovir DF and emtricitabine is very strong as these are currently the only drugs to have demonstrated efficacy in clinical studies of HIV transmission. Maraviroc the only other antiretroviral to show protection against SHIV transmission in macaques. Funded in part by R21, R33, and SBIR grants from the NIAID, we have successfully adapted the Vitrasert(R) platform and safely delivered multiple antiretrovirals in multiple animal models. An Investigational New Drug Exemption from the FDA, no 114173 has been allowed pending the resolution of two clinical hold items comprising manufacturing specifications and animal toxicity testing. The specific aims of the Phase 1 portion of this proposal are to resolve these hold issues. The development of an effective microbicide IVR could save millions of lives per year and is therefore highly significant. As the developers of the only FDA approved antiviral delivery device we believe we are uniquely qualified to develop such a product. We believe our IVRs demonstrate dramatic improvement over the current state of the art. We can deliver drugs of high and low aqueous solubility simultaneously, with control of release rate over a wide range. The team of investigators is expert in chemistry, pharmacokinetics, engineering, gynecological clinical trials and drug development, and we have experience in all aspects of the drug development process, from concept to approval and marketing. The milestone defining successful completion of this work will be the granting of IND No 114173 to enable Phase I clinical studies.

描述（由申请人提供）：该项目的长期目标是防止HIV传播。使用我们为眼部内植入物（R）开发的药物输送平台，我们建议开发出腔内杀菌物菌培制剂，释放抗逆转录病毒药物Tenofovir DF，Emtricyabine和Maraviroc。已选择该药物组合以进行效力，协同作用和预防抗性。选择Tenofovir DF和Emtricerabine的基本原理非常强大，因为这些目前是唯一在HIV传播临床研究中证明有效性的药物。马拉维罗克（Maraviroc）是唯一显示猕猴中SHIV传播的唯一其他抗逆转录病毒。由NIAID的R21，R33和SBIR赠款部分资助，我们成功地改编了Vitrasert（R）平台，并在多个动物模型中安全地提供了多个抗逆转录病毒。从FDA进行了调查新药物的豁免，在解决包括制造规格和动物毒性测试的两个临床持有项目之前，已允许No 114173。本提案的第一阶段部分的具体目的是解决这些持有问题。有效的菌心IVR的发展可以挽救每年数百万的生命，因此非常重要。作为FDA唯一批准的抗病毒装置的开发商，我们认为我们具有开发这种产品的独特资格。我们认为，我们的IVR对目前的艺术状态表现出巨大的改进。我们可以同时输送高水性溶解度的药物，并控制释放速率在较大范围内。研究人员团队是化学，药代动力学，工程，妇科临床试验和药物开发方面的专家，我们在药物开发过程的各个方面都有从概念到批准和营销的各个方面的经验。 定义这项工作成功完成的里程碑将是授予IND No 114173以实现I期临床研究。