A Naloxone Parachute: Novel Wearable Dual-Sensor Regional Oximeter to Detect Opioid-Induced Hypoxia and Enable Emergent Naloxone Rescue

SBIR第二阶段-摘要 Ayuda Medical的愿景是，没有人应该死于可治疗的医疗紧急情况。阿片类药物 过量(Oods)可以用基本的心肺复苏(CPR)治疗，但他们声称有超过250人 2020年，她每天都生活在美国。OOD风险最大的患者是正在接受阿片类药物治疗的人 精神障碍(OUD)或高冲击性慢性疼痛(HICP)。目前对OOD的照顾标准是旁观者 响应(医疗或非医疗)，但旁观者需要知道正在发生OOD。我们向您介绍一种 可穿戴的医疗诊断设备，用于检测OOD并弥合与旁观者干预的差距。 我们的设备，降落伞臂章，将连续佩戴，并将监测生理参数 然后，将使用设备上升级的音调警报来召唤旁观者，以及- 设备扬声器，以口头方式确定寻求医疗帮助的紧迫性。无需无线连接即可实现 这些功能。臂章还将向附属的移动医疗应用程序发送蓝牙警报 (MMA)在用户的电话上，可以访问设备用户先前选择的指定联系人。这 功能需要移动设备连接，并且在医疗事件之前下载MMA。 该公司已经完成了由国家药物滥用研究所(NIDA)赞助的第一阶段SBIR， 表明上臂是可穿戴式血氧计的可行位置，可穿戴式血氧计是新型设备的主要组件。这个 添加第一阶段创新团队使公司能够验证最低可行产品(MVP)关键功能， 包括升级警报和无线警报。我们的第一阶段学习允许首席调查员一起 (PI)向FDA提交突破设备指定(BDD)请求。 这一拟议的第二阶段应用将显示我们的新设备组件用于检测气体- 诱导低氧，与动脉血气比较(目标1)；检测静脉注射瑞芬太尼装置的灵敏度 “OOD”和Begin Alarm算法(目标2)；以及设备通信发送实时无线 警报(目标3)。这三个目标支持设备的安全性和有效性。在目标4中，人为因素和 使用说明(IFU)在我们的目标人群、有OUD或OUD病史的人中进行了专门测试 太棒了。Aim 5同样在我们的目标人群中测试该设备，但也增加了我们的目标使用环境；它将 测试设备的佩戴性需要48小时和两到四周的时间带回家进行研究。 所有五个目标，连同设备设计和警报的非临床测试，将支持寻求 通过De Novo提交的II类营销，该设备指示为使用阿片类药物的人(PWUO) 包括HICP，以及有OOD病史的人。到目前为止还没有FDA批准的 要监控OOD的设备。我们提供持续监测，因为阿片类药物使用的应激源和诱因可能是 出乎意料。De Novo提交的报告将包括针对我们的目标临床场景设计的研究数据 (急性阿片类药物摄取/给药)和目标使用环境(门诊、在家)。 Ayuda Medical计划与美国食品和药物管理局进行几次讨论 (FDA)，在整个设备开发和第二阶段。BDD于2021年第三季度提交，公司计划 在2021年第四季度提交一份Q-Sub，澄清我们的里程碑以供批准。我们计划利用早期的气体缺氧研究 (目标1A)申请研究设备豁免，然后用阿片类药物进行临床研究- 具体议定书(目标2和3)。这包括可行性(2022年第4季度)和关键研究(2023年第4季度) 与FDA的持续互动将使公司的里程碑与FDA的目标保持一致。 商业化战略包括在FDA批准的同时寻求联邦医疗补助覆盖范围， 作为双小组(FDA-CMS)上市前审查的一部分。该公司计划直接销售这种臂章 在OUD市场内，并与HICP市场内的战略合作伙伴共同营销该设备。我们也 打算与NIDA和药物滥用协会合作开展以社区为基础的试点研究，并 精神卫生服务管理局(SAMHSA)，以验证特定于OUD/HICP的设备系统 目标环境中的人口，并通过国家医疗补助支持处方纳入。州医疗补助计划 覆盖范围确保该设备是负担得起的，并可由社区卫生中心(CHC)访问，这些中心治疗 大多数低收入人口患有慢性病和急性病，包括OUD和OOD。 通过州医疗补助和CHC建立一条可行的商业道路，然后可以扩展到50个州， 对于OUD市场上的合作伙伴和潜在的退出公司来说，是一个有吸引力的提议。 第一阶段验证了我们开发方法的设备需求和可行性。第二阶段将提供 适当的临床和非临床测试，以支持向FDA提交的De Novo。公司完全是 致力于批准和商业化降落伞臂带OOD诊断设备，并 将其提供给所有高危人群，旨在扩大对意外阿片类药物过量的保护。

SBIR PHASE II - ABSTRACT Ayuda Medical has the vision that no-one should die from a treatable medical emergency. Opioid overdoses (OODs) are treatable with basic CardioPulmonary Resuscitation (CPR), but they claimed over 250 lives each day in the US in 2020. Patients most at risk for OOD are people in treatment for Opioid Use Disorder (OUD) or High Impact Chronic Pain (HICP). The current standard of care to OOD is bystander response (medical or nonmedical), but the bystander needs to know that an OOD is occurring. We present a wearable medical diagnostic device to detect OOD and bridge the gap to bystander intervention. Our device, Parachute ARMband, will be worn continuously, and will monitor physiologic parameters that indicate OOD, then will use an on-device escalating tonal alarm to summon bystanders, as well as on- device speaker to verbally identify the urgency to get medical help. No wireless connectivity is required for these functions. The ARMband will also send a Bluetooth alert to an adjunct Mobile Medical Application (MMA) on the User’s phone, that can reach designated contacts, previously chosen by the device user. This function requires mobile device connectivity, and that the MMA be downloaded prior to the medical event. Company has completed a Phase I SBIR, sponsored by National Institute of Drug Abuse (NIDA), that showed the upper arm is a viable location for wearable oximeters, main components of novel device. The addition of Phase I Innovation Corps enabled company to validate Minimal Viable Product (MVP) key features, including escalating alarm and wireless alert. Together our Phase I learnings allowed Principle Investigator (PI) to submit a Breakthrough Device Designation (BDD) request to the FDA. This proposed Phase II application will show feasibility of our novel device components to detect gas- induced hypoxia, compared to arterial blood gas (Aim 1); sensitivity of device to detect intravenous remifentanil “OOD” and begin alarm algorithm (Aim 2); and ability of device communications to send a real-time wireless alert (Aim 3). These three aims support device safety and effectiveness. In Aim 4, Human Factors and Instructions for Use (IFU) are specifically tested in our target population, persons with a history of OUD or OOD. Aim 5 likewise tests the device in our target population, but also adds our target use environment; it will test device’s wearability via 48hr and and two-to-four week take home studies. Together all five Aims, along with non-clinical testing of device design and alarms, will support seeking Class II marketing via a De Novo submission, with the device indicated for People Who Use Opioids (PWUOs) including HICP, and people with a history of OUD that are at risk for OOD. To date there is no FDA approved device to monitor for OOD. We offer a continuous monitor because stressors and triggers to opioid use can be unexpected. The De Novo submission will include data from studies designed for our target clinical scenario (acute opioid ingestion/ administration), and target use environment (ambulatory, at-home). Ayuda Medical plans to have several discussions with the United States Food and Drug Administration (FDA), throughout device development and Phase II. BDD was submitted in Q3, 2021, and company plans to submit a Q-sub clarifying our milestones to approval in Q4, 2021. We plan to use early gas hypoxia studies (Aim 1A) to apply for Investigational Device Exemption (IDE), and then perform clinical studies with opioid- specific protocols (Aims 2 and 3). This includes feasibility (Q4, 2022) and pivotal (Q4, 2023) studies sponsored by Phase II. Continuous interactions with FDA will align company milestones with FDA objectives. Commercialization strategy includes seeking federal Medicaid coverage in tandem with FDA approval, as part of a dual-panel (FDA-CMS) pre-marketing review. Company plans to market the ARMband directly within the OUD market, and co-market the device with a strategic partner within the HICP market. We also intend to conduct community-based pilot studies in collaboration with NIDA and the Substance Abuse and Mental Health Services Administration (SAMHSA), to validate device system in specific to the OUD/HICP populations in target environment, and to support formulary inclusion by State Medicaid. State Medicaid coverage assures that the device is affordable and accessible by Community Health Centers (CHCs), that treat the majority of the low-income populations for both chronic and acute illnesses, including OUD and OOD. Establishing a viable commercial path via state Medicaid and CHCs, that can then be expanded into 50 states, is an attractive proposal to partnerships and potential exit companies in the OUD market. Phase I validated device need and feasibility of our development approach. Phase II will provide the appropriate clinical and non-clinical testing to support a De Novo submission to the FDA. Company is fully dedicated to the approval and commercialization of the Parachute ARMband OOD diagnostic device, and to making it available to all at-risk groups, aiming to expand the protection against accidental opioid overdose.