IND-enabling development of a long-duration antagonist to treat opioid overdose

能够开发长效拮抗剂来治疗阿片类药物过量的 IND

基本信息

批准号：
10786015
负责人：
Lawrence J Zana
金额：
$ 133.08万
依托单位：
CONSEGNA PHARMA, INC.
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-09-15 至 2026-02-28
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10786015
关键词：
Acceleration Acute Address Advanced Development Agitation American Animals Antidotes Applications Grants Canis familiaris Cardiovascular system Caring Cessation of life Chemicals Clinical Clinical Research Complication Cyclic GMP Dangerousness Data Dehydration Delirium Development Documentation Dosage Forms Dose Drops Drug Delivery Systems Drug Kinetics Drug Packaging Electrolytes Emergency medical service Encapsulated Excretory function FDA approved Fentanyl Formulation Future Goals Half-Life Hospitals Hour Individual Intellectual Property Investigational Drugs Investigational New Drug Application Legal patent Life Medical Metabolism Monitor Naloxone Opiate Addiction Opioid Opioid Antagonist Outcome Overdose Overdose reduction Overdose reversal Patients Pharmaceutical Preparations Phase Poison Poisoning Procedures Process Production Public Health Pulmonary Edema Regulatory Pathway Research Design Residual state Risk Sales Secure Shapes Small Business Innovation Research Grant Symptoms Temperature Testing Therapeutic Toxicology United States National Institutes of Health Ventilatory Depression Vomiting Work Writing antagonist canine model commercialization design efficacy study first responder in vivo innovation manufacture manufacturing process manufacturing scale-up meetings mortality mu opioid receptors nalmefene novel opioid overdose opioid withdrawal particle pre-Investigational New Drug meeting prevent programs research and development rural area safety study synthetic opioid warfighter weapons

Acceleration Acute Address Advanced Development Agitation American Animals Antidotes Applications Grants Canis familiaris Cardiovascular system Caring Cessation of life Chemicals Clinical Clinical Research Complication Cyclic GMP Dangerousness Data Dehydration Delirium Development Documentation Dosage Forms Dose Drops Drug Delivery Systems Drug Kinetics Drug Packaging Electrolytes Emergency medical service Encapsulated Excretory function FDA approved Fentanyl Formulation Future Goals Half-Life Hospitals Hour Individual Intellectual Property Investigational Drugs Investigational New Drug Application Legal patent Life Medical Metabolism Monitor Naloxone Opiate Addiction Opioid Opioid Antagonist Outcome Overdose Overdose reduction Overdose reversal Patients Pharmaceutical Preparations Phase Poison Poisoning Procedures Process Production Public Health Pulmonary Edema Regulatory Pathway Research Design Residual state Risk Sales Secure Shapes Small Business Innovation Research Grant Symptoms Temperature Testing Therapeutic Toxicology United States National Institutes of Health Ventilatory Depression Vomiting Work Writing antagonist canine model commercialization design efficacy study first responder in vivo innovation manufacture manufacturing process manufacturing scale-up meetings mortality mu opioid receptors nalmefene novel opioid overdose opioid withdrawal particle pre-Investigational New Drug meeting prevent programs research and development rural area safety study synthetic opioid warfighter weapons

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项目摘要

PROJECT SUMMARY / ABSTRACT More than 80,000 Americans died in 2021 from fentanyl and other high-potency opioids. The emergence of illicit, highly potent synthetic opioids such as fentanyl is a key contributing factor to the recent spike in opioid- related mortality, increasing ten-fold since 2016. While the mu opioid receptor (MOR) antagonist naloxone has proven invaluable as an opioid overdose antidote, naloxone suffers from a very short duration of action (half- life ~1 hour) and is less effective against newer, longer-acting opioids, including fentanyl (half-life ~7-10 hours). This leads to a highly lethal and increasingly prevalent phenomenon known as “renarcotization,” whereby an overdose patient revived with naloxone re-enters an overdose state from residual fentanyl in the body. To counter renarcotization, naloxone must be given repeatedly and at significantly higher doses. While usually achievable in a hospital, renarcotization is often not recognized or monitored for outside of a medical setting and may lead to unexpected death. A critical, unmet need exists to develop a long-acting MOR antagonist formulation that prevents renarcotization by providing 12-24 hours of protection to allow opioid levels to drop below dangerous levels. The objective of this project is to advance development of CP216, a novel, long-acting naloxone formulation that utilizes an innovative design to address both primary and secondary overdose through a combination of free form naloxone for immediate effect and microencapsulated naloxone for sustained protection. This new formulation will be especially useful in rural areas, where access to emergency medical services is often delayed, or for Warfighters poisoned by weaponized opioids that need sustained protection while transported to definitive medical care. Other attempts to address renarcotization using high or frequent doses of naloxone or nalmefene have limited protection for high-potency opioids and can induce precipitated opioid withdrawal (POW) in those with opioid dependence. POW is a severe and potentially life-threatening condition and for this reason causes some overdose victims to refuse continued naloxone treatment after rescue. Still other efforts to chemically modify naloxone are subject to significant regulatory and technical risk. Consegna’s drug (CP216) is approvable through the accelerated 505(b)(2) regulatory pathway and is, according to recent studies, unlikely to induce POW and would therefore gain more acceptance among overdose patients. Consegna believes this project will have a positive impact on public health by leading to the first safe and effective product to completely address renarcotization.

项目摘要 /摘要 2021年，超过80,000名美国人因芬太尼和其他高产阿片类药物而丧生。出现非法，高潜在的合成阿片类药物（如芬太尼）是造成阿片类药物近期峰值的关键因素相关死亡率，自2016年以来增加了十倍。纳洛酮被证明是阿片类药物过量解毒剂的无价寿命〜1小时），并且对包括芬太尼在内的更新，更长时间的阿片类药物（半衰期约7-10小时）的有效性较低。这导致了一种高度致命的，日益普遍的现象，称为“肾脏化”，从而过量的患者通过纳洛酮重新进入体内残留的芬太尼过量状态。为了反肾脏化，必须反复给出纳洛酮，并以明显更高的剂量给出。通常在医院中可以实现的肾脏化，通常不会在医疗环境之外认识或监测并可能导致意外死亡。存在一个重要的，未满足的需求，以发展长效的MOR拮抗剂通过提供12-24小时的保护以允许阿片类药物水平下降来防止重骨化的形成低于危险水平。该项目的目的是推进CP216的开发，CP216是一种新型的长效纳洛酮公式，利用创新的设计通过免费的结合来解决初级和次级过量形成纳洛酮，以立即作用，并为持续保护的微封装纳洛酮。这个新公式将在艰难的地区特别有用，那里的紧急医疗服务通常会延迟，或者是被武器化阿片类药物中毒的战士，这些阿片类药物需要持续保护，同时运输到确定的医疗保健。使用高剂量或经常剂量的纳洛酮或纳米芬来解决肾脏化的其他尝试限制保护高功率阿片类药物，可以在阿片类药物中诱导反应的阿片类药物提取（POW）依赖。 POW是一种严重且潜在的威胁生命的状况，因此，某些原因导致某些情况过量服用令人惊讶的是拒绝营救后继续进行纳洛酮治疗。还有其他化学修改的努力纳洛酮受到严重的监管和技术风险。 Consegna的药物（CP216）通过加速的505（b）（2）监管途径，根据最近的研究，不太可能诱导POW和因此，过量患者将获得更多的接受。 Consegna认为，该项目将对公共卫生产生积极影响，从而导致第一个安全和有效的产品以完全解决肾脏化。