A Novel Fast Acting Nalmefene Formulation for the Prevention and Treatment of Opioid Overdose

Principal InvestigatorVasishtNiraj ABSTRACTThe opioid epidemic is ravaging the United Statesas drug overdose deaths reported have risen almost fourfold fromtoInoverdeaths from opioid overdose occurred in the USwhich predominantly occur due to respiratory depression as a result of agonism of theopioid receptorMORRescue of victims of opioid overdose is accomplished by treatment with antagonist drugs that can reverse the respiratory depressionThe currently used rescue medication is naloxone that is available in generic injectionNarcanintranasalIN Narcanand an auto injectorEvzioformsHowevernaloxone has serious liver toxicitya short half lifeand its complete antagonism results in emesis due to a withdrawal effectNalmefene is a FDA approved opioid derivative that is an antagonist of the MOR and a weak agonist of the k opioid receptorsKORAn immediate release intravenous injectable formulation was approved by the US FDA infor opioid overdosehoweverthe requirement for intravenous administration has limited its clinical useSince nalmefene has a longer elimination half life than naloxonethe need for repeat dosing in the case of accidental overdose of long acting opioids is decreasedFurthermorenalmefene has significantly less hepatotoxicity than compared to naloxonethus providing a safer option for opioid users that have hepatic impairmentAvior aims to develop a fast onsetrapidly dissolvingmucoadhesive thin film formulation that carries a uniformly distributed nalmefene nanoparticles on the surface of the filmThis filmproduced using Avior s proprietary Speedittransmucosal drug delivery technologyrapidly delivers nalmefene when the film is placed in contact with the lower lining of the inner lipThis innovative product is designed for simplicity for non medical personnel to administer in case of emergencythus offering an alternative option for the first responder in the treatment of accidental opioid overdoseDuring this Phase I SBIRAvior will prepare nalmefene nanoparticlebasedmucoadhesivetransmucosal films and evaluate the pharmacokinetic profile of nalmefene formulations to determine the suitability for overdose rescue and or use as prophylaxis by first responders and emergency care personnel because of its safer drug profile as compared to NaloxoneThrough this Phase I projectwe will generate non clinical data to support critical human clinical trials to determine if a transmucosal film can be developed with a rapid onset of action that is required for rescue of opioid overdose patients or taken prophylactically to prevent respiratory depressionOur goal is to assess the effective speed of deliveryIf successful in demonstrating that a plasma concentrationCpequal tong mLthe mean dose achieved by IV nalmefene that is effective in overdose reversalis achieved byminuteswe will move forward to conduct a human clinical trial using Phase II grant fundsPrincipal InvestigatorVasishtNiraj NARRATIVEAmongdrug overdose deaths that occurred inin the United Statesinvolved an opioidThis problem is accelerating with overdeaths from opioid overdose inThe majority of deaths is a result of respiratory depression caused by agonist binding to theopioid receptorMORThusrapid delivery of antagonists of the MOR provide the ability to rescue the overdosed patientsAvior aims to develop a fast onsetrapidly dissolvingmucoadhesive transmucosal thin film that carries a uniformly distributed nalmefene nanoparticlesThis filmproduced using Avior s proprietary Speedittransmucosal drug delivery technologyrapidly delivers nalmefene when the film is placed in contact with the lower lining of the inner lipImportantlythe product is simple so that non medical personnel can administer the rescue medication in case of overdoseDuring this Phase I SBIRAvior will evaluate the suitability of the nalmefene formulations to provide this lifesaving medication in a rapid manner that is required for overdose rescueThrough this Phase I projectwe will generate non clinical data to support critical human clinical trials to determine if a transmucosal film can be developed with a rapid onset of action that is required for rescue of opioid overdose patients or taken prophylactically to prevent respiratory depressionOur goal is to assess the effective speed of onsetIf successful in demonstrating equal to or superior absorption as compared to naloxoneour goal is to conduct a human clinical trial using Phase II grant funds