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

纳洛酮降落伞：新型可穿戴双传感器区域血氧计，用于检测阿片类药物引起的缺氧并实现紧急纳洛酮救援

• 批准号: 10612485
• 负责人: Desislava Zlatanova Hite
• 金额: $ 96.4万
• 依托单位: AYUDA MEDICAL
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-05-01 至 2025-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10612485
• 关键词: 911 call; Accidents; Acute; Adverse effects; Algorithms; Biosensor; Blood gas; Bluetooth; Body Weight; Breakthrough device; Cardiopulmonary Resuscitation; Certification; Charge; Chronic; Clinical; Clinical Research; Collaborations; Communication; Communities; Data; Data Analyses; Dedications; Development; Device Designs; Device Safety; Device or Instrument Development; Devices; Diagnostic Equipment; Distress; Drops; Early Diagnosis; Effectiveness; Emergency Situation; Engineering; Enrollment; Environment; Environmental Monitoring; Evaluation; Event; Exanthema; Fatality rate; Feasibility Studies; Formularies; Gases; Goals; Hearing; Home; Hour; Human; Hypoxia; Ingestion; Innovation Corps; Instruction; Intervention; Intravenous; Intuition; Label; Learning; Life; Light; Location; Logic; Longevity; Low Income Population; Marketing; Measures; Mediating; Medicaid; Medical; Medical emergency; Monitor; Motion; Naloxone; National Institute of Drug Abuse; Neighborhood Health Center; Opioid; Output; Parachuting; Patients; Performance; Persons; Phase; Physiologic Monitoring; Physiologic pulse; Physiological; Pilot Projects; Population; Populations at Risk; Probability; Protocols documentation; Recording of previous events; Reporting; Research Design; Research Personnel; Resolution; Respiration; Resuscitation; Risk; Safety; Signal Transduction; Sleep; Small Business Innovation Research Grant; Speed; Sunlight; System; Target Populations; Telephone; Testing; Time; Tourniquets; United States Food and Drug Administration; United States Substance Abuse and Mental Health Services Administration; Upper arm; Vision; Voice; arm; chronic pain; clinical diagnostics; cloud based; commercialization; communication device; data exchange; design; handheld mobile device; impression; improved; loved ones; mobile application; mobile medical application; novel; opioid overdose; opioid use; opioid use disorder; opioid user; patient safety; pressure; prevent; remifentanil; response; sensor; side effect; standard of care; stressor; success; transmission process; verbal; wearable device; wireless

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.

SBIR 第二阶段 - 摘要 Ayuda Medical 的愿景是没有人会死于可治疗的阿片类药物紧急情况。 药物过量 (OOD) 可以通过基本心肺复苏 (CPR) 来治疗，但他们声称超过 250 2020 年美国的日常生活。 OOD 风险最高的患者是接受阿片类药物使用治疗的患者 疾病 (OUD) 或高影响慢性疼痛 (HICP) 目前 OOD 的护理标准是旁观者。 反应（医疗或非医疗），但旁观者需要知道 OOD 正在发生。 可穿戴医疗诊断设备，用于检测 OOD 并弥补旁观者干预的差距。 我们的设备 Parachute ARMband 将持续佩戴，并监测生理参数 表明 OOD，然后将使用设备上逐渐升级的音调警报来召唤旁观者，以及 设备扬声器可口头识别寻求医疗帮助的紧急程度，无需无线连接。 这些功能还将向辅助移动医疗应用程序发送蓝牙警报。 (MMA) 在用户的手机上，可以联系设备用户之前选择的指定联系人。 功能需要移动设备连接，并且需要在医疗事件之前下载 MMA。 该公司已完成由国家药物滥用研究所 (NIDA) 赞助的第一阶段 SBIR， 表明上臂是可穿戴血氧计的可行位置，这是新型设备的主要部件。 第一阶段创新军团的加入使公司能够验证最小可行产品（MVP）的关键功能， 包括升级警报和无线警报。 (PI) 向 FDA 提交突破性器械认定 (BDD) 请求。 这项拟议的第二阶段应用将展示我们的新型设备组件检测气体的可行性 诱导血气，与动脉血气相比（目标 1）检测静脉注射瑞芬太尼的装置的灵敏度； “OOD”并开始报警算法（目标 2）以及设备通信发送实时无线信号的能力； 警报（目标 3）。这三个目标支持设备的安全性和有效性。 使用说明 (IFU) 在我们的目标人群、有 OUD 病史的人或 OOD 5 类似地在我们的目标人群中测试该设备，但还添加了我们的目标使用环境； 通过 48 小时和两到四周的家庭研究来测试设备的耐磨性。 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 提交进行 II 类营销，该设备适用于阿片类药物使用者 (PWUO) 包括 HICP 以及有 OUD 病史且有 OOD 风险的人群 迄今为止，FDA 尚未批准该药物。 我们提供连续监测仪，因为阿片类药物使用的压力源和触发因素可能会被消除。 出乎意料的是，De Novo 提交的文件将包括针对我们的目标临床场景设计的研究数据。 （急性阿片类药物摄入/给药）和目标使用环境（流动、在家）。 Ayuda Medical计划与美国食品和药物管理局进行多次讨论 (FDA)，整个设备开发和 BDD 已于 2021 年第三季度提交，公司计划 提交 Q-sub 澄清我们的里程碑，以便在 2021 年第四季度获得批准。我们计划使用早期气体缺氧研究 （目标1A）申请研究设备豁免（IDE），然后用阿片类药物进行临床研究- 具体方案（目标 2 和 3），其中包括可行性研究（2022 年第四季度）和关键研究（2023 年第四季度）。 由第二阶段赞助。与 FDA 的持续互动将使公司的里程碑与 FDA 的目标保持一致。 商业化战略包括在获得 FDA 批准的同时寻求联邦医疗补助覆盖， 作为双面板 (FDA-CMS) 上市前审查的一部分，公司计划直接销售 ARMband。 我们还与 OUD 市场中的战略合作伙伴共同营销该设备。 打算与 NIDA 和药物滥用和 精神健康服务管理局 (SAMHSA)，验证特定于 OUD/HICP 的设备系统 目标环境中的人群，并支持国家医疗补助计划的纳入。 覆盖范围确保了社区健康中心 (CHC) 能够负担得起并且可以使用该设备，这些中心治疗 大多数低收入人群患有慢性和急性疾病，包括 OUD 和 OOD。 通过州医疗补助和 CHC 建立可行的商业路径，然后扩展到 50 个州， 对于 OUD 市场的合作伙伴和潜在退出公司来说，这是一个有吸引力的建议。 第一阶段验证的设备需求和我们的开发方法的可行性将提供。 支持 De Novo 向 FDA 公司提交的适当临床和非临床测试已完全完成。 致力于Parachute ARMband OOD诊断设备的批准和商业化，并 向所有高危人群提供该服务，旨在扩大对意外阿片类药物过量的保护。