Development of a novel OTC naloxone product to be affordably priced and widely accessible

标题：开发一种负担得起的新型非处方纳洛酮产品以逆转阿片类药物过量 计划摘要(摘要) 每天有180名美国人死于阿片类药物过量。从滥用处方阿片类药物开始， 后来海洛因的使用增加了，现在随着合成和强大的阿片类药物的出现，如 芬太尼的过量死亡人数将继续居高不下。纳洛酮，首先由美国食品和药物管理局批准 FDA是近50年前用于治疗和逆转阿片类药物的安全有效的阿片类拮抗剂 吸毒过量。自动喷油器产品EVZIO于2014年获得批准(现已停产)定价为 一剂2,000美元零售价。鼻腔喷雾剂产品纳尔坎鼻喷剂于2015年获得批准 两剂的零售价为140美元。普通鼻腔喷雾剂目前被阻止进入 由于纳尔坎的所有者提起专利诉讼而导致的市场。此外，尽管许多州都这样做 不需要处方购买，这些产品继续被留在药房后面 柜台。除了代价，耻辱及其相关的尴尬和恐惧阻碍了与 药剂师购买纳洛酮产品。因此，FDA史无前例地呼吁 2019年1月推出的非处方药(OTC)纳洛酮产品，并测试并发布了一款消费者- 友好示范药品事实标签(DFL)，以支持此类产品的紧急开发。确实有 目前尚无FDA批准的非处方纳洛酮产品。为了解决这一未得到满足的需求，Pocket 纳洛酮公司(PNC)已经开发出一种新的纳洛酮鼻腔给药方法，该方法旨在 负担得起，在非处方药环境中使用(每剂10美元)。新的临床路径是有先例的 已获FDA批准的纳洛酮产品(尽管只有处方才能买到) 包括评价PNC鼻腔生物等效性的研究设计的适当方法 纳洛酮与参比产品的比较。一项首个人类先导性临床研究已经完成 完成，试点计划的第二部分将完善剂量和给药。这是 预计将于2021年下半年开始，随后进行最后一项关键的比较生物等效性研究。 这项U01拨款的具体目的是：(1)利用从第一个人类飞行员那里获得的数据 药代动力学研究和启动新的试点研究，以改进给药方法和目标剂量 并对纳洛酮鼻腔喷雾剂进行最终的关键生物等效性研究；(2)建立用户 目标公众(非专业人员)和消费性药物使用说明书--通过(A) FDA要求进行人为因素研究测试，以及(B)FDA建立标签理解研究；(3) 向FDA提交NDA，并申请OTC纳洛酮鼻拭子的优先审查状态。

Title: Development of an Affordable, Novel OTC Naloxone Product to Reverse Opioid Overdoses Program Summary (Abstract) Every day, 180 Americans die from opioid overdoses. Starting with the misuse of prescription opioids, then increased use of heroin, and now with the emergence of synthetic and powerful opioids such as fentanyl, the number of overdose deaths will continue to remain high. Naloxone, first approved by the FDA nearly 50 years ago, is a safe and effective opioid antagonist used to treat and reverse opioid overdoses. The auto-injector product EVZIO was approved in 2014 (now discontinued) was priced at $2,000 retail for one dose. The intranasal spray product, Narcan Nasal Spray was approved in 2015 and is priced at $140 retail for two doses. Generic intranasal sprays are currently blocked from entering the market due to patent litigation by the owners of Narcan. Additionally, even though many states do not require a prescription for purchase, these products continue to be kept behind-the-pharmacy counter. Apart from the price, stigma and its associated embarrassment and fear prevents speaking to a pharmacist to purchase a naloxone product. Therefore, the FDA has made an unprecedented call for an over-the-counter (OTC) naloxone products in January 2019 and tested and published a consumer- friendly model drug facts label (DFL) to support urgent development of such products. There are currently no OTC naloxone products approved by the FDA. To address this unmet need, Pocket Naloxone Corp. (PNC) has developed a novel intranasal delivery method for naloxone intended to be affordable and used in OTC settings ($10 per dose). There are precedent clinical pathways for new naloxone products that have been approved by the FDA (although only available with a prescription) including appropriate approaches on study designs to evaluate bioequivalence for PNC’s intranasal naloxone compared to reference naloxone product. A first-in-human pilot clinical study has been completed and the second part of the pilot program will refine dosing and administration. This is expected to begin in second half of 2021 followed by a final pivotal comparative bioequivalence study. The specific aims of this U01 grant are to: (1) Utilize data obtained from pilot first-in-human pharmacokinetic study and initiate new pilot studies to refine administration method and target doses and conduct final pivotal comparative bioequivalence study to naloxone nasal spray; (2) Establish user Instruction for Use for the target general public (lay persons) and consumer drug-fact label through (a) FDA required Human Factors study testing and (b) FDA established label comprehension study; (3) Submit an NDA to the FDA and apply for Priority Review status for the OTC naloxone nasal swab.