Development of Inhaled CPZEN-45 For Tuberculosis Therapy

开发用于结核病治疗的吸入式 CPZEN-45

基本信息

批准号：
10116257
负责人：
Anthony James Hickey
金额：
$ 148.36万
依托单位：
RESEARCH TRIANGLE INSTITUTE
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-03-01 至 2023-02-28
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10116257
关键词：
Aerosols Animal Model Animals Bioavailable Canis familiaris Cavia Cessation of life Chemistry Clinical Research Communicable Diseases Data Development Disease Dose Drug Kinetics Environment Extreme drug resistant tuberculosis HIV Incidence Inhalation International Investigational Drugs Investigational New Drug Application Lung Medical Methods Minimum Inhibitory Concentration measurement Multi-Drug Resistance Multidrug-Resistant Tuberculosis Mycobacterium tuberculosis NOEL Organism Patients Performance Pharmaceutical Preparations Phase Phase I Clinical Trials Population Preparation Product Approvals Rattus Research Activity Research Institute Route Safety Subcutaneous Injections Techniques Toxic effect Toxicology Tuberculosis United States Food and Drug Administration Validation analytical method co-infection data management drug development experimental study first-in-human good laboratory practice in vivo manufacturing facility meetings mouse model novel therapeutics patient population porcine model pre-clinical preclinical study protocol development respiratory scale up subcutaneous tuberculosis treatment vaccine development

项目摘要

PROJECT SUMMARY/ABSTRACT Tuberculosis (TB) is an insidious disease that kills between 1.5–2.0 million people annually. The increase in multiple and extensively drug-resistant TB globally presents an urgent unmet medical need that is underserved by the pace of new drug and vaccine development. Following a decade of research activity, CPZEN-45, a caprazamycin derivative, has been shown to be safe and efficacious when administered via both the subcutaneous and pulmonary routes in animals. The pulmonary route of administration is more desirable than subcutaneous delivery because it is non-invasive and more acceptable to the severely compromised target patient population. CPZEN-45 is poised for development in formal preclinical and initial clinical studies. It is proposed that in supporting scale up and technical transfer to a current Good Manufacturing Practice (cGMP) manufacturing facility, the performance of current Good Laboratory Practice (cGLP) preclinical toxicology studies and preparation of Investigational New Drug (IND) Application documents to support a Phase I single-dose escalating tolerability study would meet U.S. Food and Drug Administration (FDA) requirements for product approval. The experiments required to complete the IND materials are as follows: Specific Aim 1—Scale up and technical transfer of spray dried CPZEN-45 (scale up, technical transfer to a cGMP environment, development of validated analytical methods); Specific Aim 2— cGMP rat and dog 14-day toxicology studies (aerosol characterization, rat and dog studies, validated bioanalytical methods); Specific Aim 3—Document preparation and project management to support pre-IND meeting with the FDA (chemistry, manufacturing, and controls; data management; preclinical toxicology studies; data management, Phase I—Protocol development; single-dose escalation study of tolerability and pharmacokinetics).

项目摘要/摘要结核病（TB）是一种阴险的疾病，每年杀死1.5-20万人多种且可扩展的耐药性结核病在全球范围内提出了紧急的Unement医疗需求在研究活动十年之后，新药和疫苗的发展速度散布 CPZEN-45是一种二霉素衍生物，在通过动物的皮下和肺部途径。比皮下交付所期望的，因为它无创，更严重地接受妥协的目标人口。临床研究。制造实践（CGMP）制造设施，现任上帝实验室实践的表现（CGLP）临床前毒理学研究和研究新药的准备支持一日剂量日上升的耐受性研究的文件将满足美国食品和药品产品批准的管理要求（FDA）完成IND所需的实验材料如下：特定的目标1尺度和喷雾干燥CPZEN-45的技术转移（扩展，扩展，扩展，技术转移到CGMP环境，开发经过验证的分析方法）； CGMP大鼠和狗14天毒理学研究（气溶胶表征，大鼠和狗研究，已验证生物分析方法）；与FDA（化学，制造和控制；数据管理；研究; 药代动力学）。