Continuing Development of PPCM Vaginal Contraceptive Microbicide

PPCM阴道避孕杀菌剂的持续开发

• 批准号: 8709977
• 负责人: Betsy C. Herold
• 金额: $ 100万
• 依托单位: YASO THERAPEUTICS INC
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-01-15 至 2016-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8709977
• 关键词: Address; Adult; Agreement; Animals; Centers for Disease Control and Prevention (U.S.); Chemicals; Chemistry; Clinical; Clinical Research; Clinical Trials; Contraceptive Agents; Contraceptive methods; Contractor; Contracts; Cyclic GMP; Data; Development; Dosage Forms; Drug Formulations; Esthetics; Evaluation; Feedback; Film; Funding; GMP lots; Gel; Gelatin; Goals; Grant; HIV; Human; In Vitro; Industry; Investigational Drugs; Investigational New Drug Application; Laboratories; Liquid substance; Manufacturer Name; Marketing; Methods; Modeling; Monitor; Mus; National Institute of Child Health and Human Development; Oryctolagus cuniculus; Pharmaceutical Preparations; Pharmacology and Toxicology; Phase; Phase I Clinical Trials; Polymers; Preparation; Prevention; Price; Process; Production; Protocols documentation; Qualifying; Quality Control; Recipe; Research Design; Resources; Reverse Transcriptase Inhibitors; Safety; Sampling; Schedule; Sexually Transmitted Diseases; Simplexvirus; Small Business Innovation Research Grant; Teleconferences; Testing; Time; Toxicology; Unplanned pregnancy; Vagina; Water; Writing; analytical method; aqueous; capsule; clinical toxicology; compare effectiveness; contraceptive microbicide; cost; drug development; experience; genital herpes; in vitro Model; in vivo; irritation; meetings; microbicide; mouse model; non-drug; novel; polyanion; preclinical evaluation; preclinical study; product development; prototype; public health relevance; reproductive; research clinical testing; response; safety study; screening; sperm cell; statistics; vaginal microbicide

DESCRIPTION (provided by applicant): The goal of this project is to continue development of a novel, dual indication vaginal contraceptive anti-herpes microbicide product containing PPCM. We will conduct all tasks required to generate the Pharmacology/Toxicology and Chemistry Manufacturing and Controls (CMC) information required for IND submission, and outline the early clinical study designs with FDA. Development will be Go/No Go Decision and milestone driven to efficiently (resource, cost and time) evaluate the drug product in biologically relevant models for activity and safety, meet FDA and ICH requirements and manufacture drug and product suitable for early clinical trial material. We will address compliance issues experienced in recent HIV microbicide trials by developing three prototypes and evaluating their consumer acceptability, safety and efficacy; then selecting the superior product form for final preclinical studies. Within ten months of grant approval, prototype formulations of three different vaginal formulations (aqueous gel, ovule and thin film) will be quickly prepared using modified recipes from industry, analytically tested and evaluated in four non GLP models: 10-day Rabbit Vaginal Irritation (RVI), cutting edge in vitro models for safety, HSV-prevention in the mouse model and contraception in the rabbit (funded by NICHD) providing us with data to select one product form for further development. Utilizing the 1kg of PPCM manufactured by Regis Chemical in the Phase I SBIR, one dosage form will be selected, incorporating consumer feedback using vehicle control products, to be taken forward by a commercial contract manufacturer through thorough development of the product formula, process and package. The CMO will produce product for use in IND enabling GLP toxicology and product stability studies. Reasonably priced quotes were obtained from the most reputable CMOs in the field. From the initiation of Phase II SBIR grant approval, a pre-IND meeting briefing document will be compiled and issued. The document will be accompanied with IND development questions addressed to FDA for response. These will include questions to finalize the Pharmacology/Toxicology study protocols and Phase I-II clinical study designs. In parallel to that, preparations will be made for manufacturing and quality control testing of a 1kg GMP batch of drug substance (PPCM) for clinical use. The first item will be to implement the Quality Agreement (commitments by both parties to satisfy quality and regulatory requirements); manufacturing controls; and qualified/validated analytical test methods required to release and monitor the stability of the GMP lot of drug substance suitable for early clinical trials.

描述（由申请人提供）：该项目的目的是继续开发一种新型的双重指示，即含有PPCM的双重指示阴道避孕药抗赫性杀菌剂。我们将执行生成药理学/毒理学和化学制造和控制措施（CMC）信息所需的所有任务，并概述了使用FDA的早期临床研究设计。开发将是/没有去决定的，而里程碑则是有效地（资源，成本和时间）在生物学相关的活动和安全模型中评估药物，以满足FDA和ICH要求以及适合早期临床试验材料的药物和产品。我们将通过开发三种原型并评估其消费者的可接受性，安全性和有效性来解决最近HIV杀菌剂试验中遇到的合规性问题；然后选择最终临床前研究的优质产物形式。在批准批准后的十个月内，将快速使用三种不同的阴道配方（水性凝胶，胚珠和薄膜）的原型制剂，使用工业改进的食谱快速制备，在四种非GLP模型中进行了分析测试和评估：10天的兔子阴道刺激（RVI）（RVI），由较最先进的型号，用于使用HSV-PERCENT的较最先进的型号，用于HSV-PERCETID，NSV-PERCENT INDER，NSV-PERTAIND INDER INDER CORTAIND（在均采用了较小的型号）。选择一种产品形式以进行进一步开发。利用Regis Chemical在I期SBIR中生产的1公斤PPCM，将选择一种剂型，并通过彻底开发产品配方，流程和包装来将其纳入使用车辆控制产品的消费者反馈。 CMO将生产用于IND启用GLP毒理学和产品稳定性研究的产品。从该领域最有信誉的CMO获得了价格合理的报价。从启动II阶段SBIR赠款批准中，将汇编和发行一份预定的会议简报文件。该文件将伴随着有关FDA的IND开发问题以进行回应。这些将包括最终确定药理学/毒理学研究方案和I-II期临床研究设计的问题。与此并联，将进行1公斤GMP药物（PPCM）的制造和质量控制测试，以供临床使用。第一项将是执行质量协议（双方的承诺以满足质量和监管要求）；制造控件；以及释放和监测适用于早期临床试验的GMP药物的稳定性所需的合格/验证的分析测试方法。