Research Project
10339144
ABSTRACT The United States has lost 500,000 Americans to the Opioid Epidemic; over 125 people died each day in 2018 alone. Naloxone is the standard of care for first-responders to reverse opioid overdose (OD), and its use by bystanders is advocated by the US Surgeon General. However, many fatal OD occurs when subjects are alone. There is an urgent need for new opioid overdose detection and reversal methods that do not rely upon bystanders to intervene. The Naloxone Parachute is a combination drug-device product with two key components: a wearable biosensor (ERDx) to detect overdose and a wearable, device-activated, autoinjector to automatically deliver a rescue dose of naloxone HCl. This device can reduce the risk of fatal overdose and the public health impact of opioid use. The biosensor, the Emergency Respiratory Diagnostic (ERDx) device, contains multiple medical-grade oximeters to monitor vital signs and stand-alone cellular modem (no phone necessary) to contact help. This novel device is the first to use two PPG and a NIRS independent oximeters to detect apnea and hypoxia with clinical relevance, and utilize them in ?intelligent? device logic to determine if life-threatening overdose is suspected and intervention is required. Intervention includes calling designated help, audible alert, and eventually activating the device-mediated naloxone rescue. This Phase I study will evaluate the performance of the novel ERDx device as well as commercial regional oximeters in Human Subjects under conditions of gas induced hypoxia to 70%, and then opioid (remifentanil)-induced apnea with hypoxia to 80%. Sensor function and Naloxone PK/PD data will also be obtained following deltoid intramuscular (IM) naloxone recovery, in this study administered by clinical staff. This data will lay the groundwork for future studies when we test the ERDx integrated with a novel wearable connected IM autoinjector, which is being developed separately by Ayuda. Our objectives are to demonstrate that somatic (arm, leg, trunk) sensor oximetry correlates with finger pulse oximetry and arterial blood gas (ABG) controls during gas induced and opioid induced hypoxia. We intend to evaluate the accuracy of detection of two optical oximetry sensor types photoplethysmography (PPG) and near-infrared spectroscopy (NIRS) in a series of controlled plateaus under conditions of mild (85-89% SaO2), moderate (80-84% SaO2) and severe (<80% SaO2) hypoxia. Further objectives are to measure pharmacokinetics and pharmacodynamics (PK/PD) of remifentanil including the induction of apnea/hypoxia, and PK/PD of Naloxone 1-2mg IM and its ability to reverse symptoms. We also intend to request an Early Collaboration meeting with the FDA to discuss the regulatory path for the ERDx and Naloxone Parachute devices, and the use of the remifentanil-naloxone approach as an opioid overdose model in future studies.
