Development of a first-in-class therapeutic for producing 'on-demand' voiding

PROJECT SUMMARYABSTRACTAging and diabetesas well as many neurological conditionssuch as multiple sclerosisParkinsonandapos s diseasespina bifidastrokeand spinal cord injurySCIcan result in loss of voluntary voiding of urine and require intermittent bladder catheterization for voidingCatheter use is associated with increased incidence of health problemspredominately repeated urinary tract infectionssepsisurethral trauma and hospitalizationA short actingeffectiveand safe product that induceson demandvoiding would provide a paradigm shift in the management of neurogenic bladder and could reduce or eliminate the need for intermittent catheterizationDignify Therapeutics is developing a novel drug treatmentDTIto provide anon demandrapid onsetshort durationdrug inducedvoiding therapyfor those who cannot void voluntarilyWhen administered intravenouslyIVor subcutaneouslySCto ratsdogsand minipigsDTIrapidly induces bladder voidingHowever IV and SC routes of administration may be impractical for the multiple daily dosing that will be required by individuals with neurogenic bladderThereforeintranasalINand orally disintegrating tabletODTformulations of DTIare being developedPreliminary studies have shown that efficacious plasma concentrations and dose dependent bladder contractions can be achieved using both ODT and IN formulationsPhaseof this fast track SBIR proposal will use repeated dosing and measurements of voiding efficiency in conscious minipigsa species with subcutaneousnasaland oral tissues similar to humansto identify the preferred formulation and route of administrationIN or ODTfor use in future clinical studiesIn Phasethis formulation will be optimized and manufactured according to FDA regulatory guidelinesThe optimized final formulation will then be used for preclinical in vivo testing in minipigs and rats to characterize the pharmacological mechanism of actionas well as for mandatory general toxicity studies required for submission of an investigational new drugINDapplication and the initiation of studies in humansWith proper supportour product could be available as a therapeutic agent with the next five to seven years PROJECT NARRATIVE The ultimate aim of this project is to provideto individuals with neurological conditionsa novel pharmaceutical alternative to multiple daily catheterizations of their bladder to void urineCatheter use can be embarrassing and uncomfortableand it is associated with urinary tract infections and various other complicationsThis grant will enable the development of a convenient intranasal or sublingual dosage formulation for a novel drug to provide on demand voidingSuccess of our project will restore individual dignityimprove daily quality of life and healthand reduce associated health care costs for individuals with neurogenic voiding dysfunction