Evaluation of the Safety and Tolerability of ENA-001 in Addressing Pharmacologically-induced Respiratory Depression

Depression of the respiratory drive (respiratory depression; RD) is a potential contributor to the long-term complications following anesthesia, a substantial risk to the use of medications for pain management and leading cause of death amongst drug abusers.  ENA-001 is being developed as a short-duration intravenous agent acting through inhibition of BK(Ca2+) (Maxi K channels) in the carotid body to stimulate respiration and increase minute ventilation by primarily increasing tidal volume and secondarily through minor increases to respiratory rate. As the mechanism is independent of opioid and other agents used for pain and anesthesia, ENA-001 should provide reversal of respiratory depressant effects of these compounds without interfering with their primary pharmacology.  In this study, the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics of ENA-001 administered through continuous intravenous (IV) infusion were assessed in healthy adults, covering a higher dosage range than previously evaluated.