Dignify Therapeutics LLC — Department of Health and Human Services STTR Phase II: 106

Description

Abstract Neurological conditions such as multiple sclerosis Parkinson s disease dementia spina bifida diabetes stroke and spinal cord injury SCI can result in loss of voluntary voiding of urine and require intermittent bladder catheterization for voiding Catheter use is associated with increased incidence of health problems predominately repeated urinary tract infections sepsis urethral trauma and hospitalization Dignify Therapeutics is developing a novel drug treatment DTI to provide an on demand rapid onset short duration drug induced voiding therapy for those who cannot void voluntarily Results from our STTR Phase I grant award demonstrated that both intranasal IN solutions and sublingual orally disintegrating tablets ODTs that contain DTI exhibit pharmacokinetic PK and pharmacodynamic PD characteristics that support additional studies to select between these two formulations for subsequent clinical development Although both formulations induced voiding in rats ODT dosing was not as potent or effective as IN dosing presumably due to the highly keratinized oral mucosa of the rat compared to other species Because of this and because a non rodent species is required for use in safety studies prior to entering clinical trials this STTR Phase II application proposes to evaluate IN and sublingual ODT formulations in rabbits and dogs two species which are acceptable to the FDA for safety studies The ultimate goal of this application is to pick a final formulation for pharmaceutical development and select a suitable species for preclinical safety studies to enable our IND application to the FDA In Phase II DTI will be administered to rabbits and dogs using the most promising formulations from our Phase I rat studies to compare PK and PD responses across species Specific Aim SA will complete one year formulation stability tests that were initiated in Phase I Formulation optimization by modification of excipients is also performed in SA if results with Phase I formulations in rabbits and dogs are inferior to those from rats SA compares the IN and ODT formulations for PK profile and PD effects isovolumetric pressure recording and voiding cystometry in acute spinal and spinal intact anesthetized rabbits SA compares IN and ODT formulations for PK and PD effects in dogs Voiding parameters are measured in anesthetized isovolumetric pressure recording and voiding cystometry and conscious voiding onset and duration voided volume voiding efficiency dogs Based on their respective abilities to best meet the PK and PD of our ideal target product profile an IN or ODT formulation will be selected and used for subsequent IND enabling preclinical safety studies Narrative The ultimate aim of this project is to provide to individuals with neurological conditions a novel pharmaceutical alternative to multiple daily catheterization of their bladder to void urine Passage of a catheter into the urethra and bladder can be discomforting and is associated with urinary tract infections and various other complications This grant will enable the development of a convenient sublingual or intranasal dosage formulation for a novel drug to provide on demand voiding and hence an alternative to catheterization in individuals with neurogenic voiding dysfunction Success of our project will restore individual dignity improve daily quality of life and health and reduce associated health care costs for these individuals