Aerosolized Liposome-Encapsulated Fentanyl (AeroLEF™) via pulmonary administration allows patients with moderate to severe post-surgical acute pain to self-titrate to effective analgesia

Acute pain is characterized by rapid onset, unpredictable and variable intensity confounded by highly variable patient responses to analgesics. Consequently, a successful dose is difficult to predict and maintain. AeroLEF^TM, a proprietary combination of free and liposome-encapsulated fentanyl for inhalation provides micro-doses of fentanyl per breath designed to allow real-time patient-controlled dose selection. In this study, nineteen post-surgical patients with moderate to severe pain following ACL surgery, were instructed to self-administer AeroLEF^TM via breath actuated nebulizer until they had achieved analgesia, experienced dose-limiting side effects, or completed the maximum available dose (1000µg emitted per nebulizer, ≤2 nebulizers allowed). Eighteen (95%) of the patients achieved analgesia following self-administration of AeroLEF^TM. The median time to first perceptible analgesia was 2.7min. Mean plasma fentanyl concentration at first perceptible analgesia was 0.801ng.mL^-1. Median time to effective analgesia was 17min. At analgesia, the mean plasma fentanyl level was 1.30ng.mL^-1 but varied widely among patients, covering a 6.5-fold concentration range (0.39 to 2.5 ng.mL^-1) The mean duration of analgesia was 3.7h and the request for additional analgesics was associated with a decrease in mean plasma fentanyl levels to 0.887ng.mL^-1 (ranging from o.36ngmL^-1 to 1.584ngmL^-1), comparable to the concentrations at first perceptible analgesia and consistent with reported ranges for minimal effective plasma fentanyl in post-surgical patients (0.34 to 1.58ng.mL^-1). A 9-fold dosing range was selected by patients in order to obtain analgesia with AeroLEF^TM, emphasizing the inter-patient variability associated with opioid use. AeroLEF^TM, at doses sufficient to establish analgesia, was well tolerated with no serious adverse events were reported. Adverse events were generally mild and commonly associated with opioid use in the post-operative period. These data suggest that self-titration to analgesia with AeroLEF^TM offers a novel and effective approach to address the variability inherent in pain.

Industry support provided by YM BioSciences Inc.