Accelerated Development of Lofexidine for Neonatal Opioid Withdrawal Syndrome

洛非西定的加速开发用于治疗新生儿阿片类药物戒断综合征

• 批准号: 9788408
• 负责人: Kristen Leann Gullo
• 金额: $ 233万
• 依托单位: US WORLDMEDS, LLC
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-09-30 至 2021-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9788408
• 关键词: Adolescent; Adrenergic Agonists; Adrenergic Receptor; Adult; Animals; Benzodiazepines; Biological Availability; Birth; Blood; Brain; Caring; Childhood; Clinical Research; Clinical Trials; Clinical assessments; Collaborations; Cytoplasmic Granules; Data; Deglutition; Development; Distress; Dosage Forms; Dose; Drug Kinetics; Drug Prescriptions; Drug user; Effectiveness; Ensure; Epidemic; Exposure to; Fees; Female; Formulation; General Population; Goals; Government; Grant; Growth; Health Care Costs; Healthcare Systems; Human; Incidence; Infant; Intervention; Investigation; Label; Length of Stay; Literature; Manufactured Materials; Medical; Metabolism; National Institute of Drug Abuse; Neonatal; Neonatal Abstinence Syndrome; Neurologic; Opioid; Patients; Pharmaceutical Preparations; Pharmacology; Pharmacology Study; Phase III Clinical Trials; Production; Program Development; Rattus; Receptor Activation; Reporting; Reproductive system; Research; Rodent Model; Role; Safety; Symptoms; Systems Development; Tablets; Testing; Toxic effect; Toxicokinetics; Toxicology; United Kingdom; United States; United States Food and Drug Administration; Withdrawal; Work; care costs; comparative; cost; human subject; in utero; inpatient service; lofexidine; neonatal brain; neonatal patient; neonate; nervous system development; neurodevelopment; non-opioid analgesic; novel therapeutics; off-label use; opioid abuse; opioid epidemic; opioid use; opioid withdrawal; patient population; pregnant; programs; public health emergency; reconstitution; reproductive development; safety study; scale up; volunteer

PROJECT SUMMARY: Over the past decade, rates of opioid use among the general population has continued to rise in the United States. This astounding increase in opioid use has resulted in the government declaring a public health emergency in 2017. Compounding the problem, a concurrent rise in opioid use among pregnant females has resulted in a massive increase in infants born suffering from opioid withdrawal, termed Neonatal Opioid Withdrawal Syndrome (NOWS). The NOWS epidemic has led to significant increases in healthcare costs and burden on the healthcare system due to increased length of hospital stay and level of required care. A normal infant averages 2.1 days of hospital care post-birth costing $3,500, whereas an infant born with NOWS averages 16.9 days of inpatient care costing $66,700. Currently, there are no FDA-approved medications available for treatment of NOWS. US WorldMeds (USWM) has developed lofexidine in collaboration with NIDA for the treatment of opioid withdrawal in adults, and anticipates possible Food and Drug Administration (FDA) approval for this use in May 2018. USWM now proposes to extend this successful co-development program through investigation of the safety and efficacy of lofexidine in NOWS. This application proposes a strategic alliance between USWM and the National Institute on Drug Abuse (NIDA) to complete development and registration prerequisites prior to initiation of clinical assessment of lofexidine in the neonatal patient population. The FDA has requested that USWM develop and establish safety information on lofexidine for neonate patient use. Initial requirements for registration of lofexidine for pediatric use are clearly defined and agreed upon with the FDA and include a total of five nonclinical studies in animals, seven clinical studies, and commitment to developing a pediatric specific formulation. The overall goal of this project is to develop a strategic alliance with NIDA and leverage this partnership to accelerate the development of the pediatric lofexidine program, with specific emphasis on the activities relevant for NOWS development. The research strategy in this proposal specifically targets the FDA requested development of lofexidine for NOWS treatment and will be supported by: 1) the development, scale up, and clinical trial material production of a neonatal-appropriate lofexidine formulation (Specific Aims 1 and 5), 2) completion of pivotal nonclinical studies to establish safety margins in nonclinical juvenile rodent models considered appropriate to assess safety related to early brain development and general toxicity (Specific Aims 2, 3, and 4), and 3) completion of a comparative bioavailability study with adult and pediatric formulations in normal healthy adult volunteers (Specific Aim 6).

项目摘要： 在过去的十年中，曼联的普通民众使用率持续上升 国家。阿片类药物使用的惊人增加导致政府宣布公共卫生 2017年紧急情况。加剧了这个问题，怀孕女性的阿片类药物使用同时增加 导致阿片类药物戒断的婴儿大幅增加，称为新生儿阿片类药物 戒断综合征（现在）。现在的流行病已导致医疗成本显着上升和 由于住院时间增加和所需护理水平，医疗保健系统负担负担。正常 婴儿平均分别为2.1天的医院护理，出生后的住院费用为3500美元，而生于现有的婴儿 16.9天的住院护理费用为66,700美元。目前，没有FDA批准的药物可用于 现在的处理。美国WorldMeds（USWM）与NIDA合作开发了Lofexidine 在成人中治疗阿片类药物的戒断，并预计可能会批准食品和药物管理局（FDA） 对于2018年5月的使用。USWM现在建议通过 lofexidine在NOWS中的安全性和有效性调查。该申请提出了战略联盟 在USWM和美国国家药物滥用研究所（NIDA）之间完成开发和注册 在新生儿患者人群中对洛芬丁胺进行临床评估之前的先决条件。 FDA已要求USWM为Neonate患者开发并建立有关Lofexidine的安全信息 使用。明确定义并同意了对小儿使用的初始要求 FDA，包括动物中的五项非临床研究，七项临床研究以及对 开发小儿特异性配方。该项目的总体目标是与 NIDA并利用这种合作伙伴关系来加速儿科Lofexidine计划的发展 对与现在发展相关的活动的具体强调。该提案中的研究策略 特别针对FDA要求开发Lofexidine进行NOWS治疗，并将得到以下支持： 1）开发，扩展和临床试验材料生产新生儿 - 适合洛芬丁胺 配方（特定目的1和5），2）完成关键非临床研究以建立安全边缘 被认为适合评估与早期大脑发育相关的安全性的非临床青少年啮齿动物模型 以及一般毒性（特定目的2、3和4）和3）与比较生物利用度研究完成 正常健康的成人志愿者中的成人和小儿配方（特定目标6）。