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

项目总结（摘要）

PROJECT SUMMARY (ABSTRACT) Aging and diabetes, as well as many neurological conditions, such as multiple sclerosis, Parkinson's disease, spina bifida, 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. A short-acting, effective, and safe product that induces “on-demand” voiding would provide a paradigm shift in the management of neurogenic bladder and could reduce or eliminate the need for intermittent catheterization. Dignify Therapeutics is developing a novel drug treatment, DTI-100, to provide an “on-demand, rapid-onset, short-duration, drug-induced, voiding therapy” for those who cannot void voluntarily. When administered intravenously (IV) or subcutaneously (SC) to rats, dogs, and minipigs, DTI-100 rapidly induces bladder voiding. However IV and SC routes of administration may be impractical for the multiple daily dosing that will be required by individuals with neurogenic bladder. Therefore, intranasal (IN) and orally-disintegrating tablet (ODT) formulations of DTI-100 are being developed. Preliminary studies have shown that efficacious plasma concentrations and dose-dependent bladder contractions can be achieved using both ODT and IN formulations. Phase 1 of this fast-track SBIR proposal will use repeated dosing and measurements of voiding efficiency in conscious minipigs, a species with subcutaneous, nasal, and oral tissues similar to humans, to identify the preferred formulation and route of administration (IN or ODT) for use in future clinical studies. In Phase 2, this formulation will be optimized and manufactured according to FDA regulatory guidelines. The optimized final formulation will then be used for preclinical in vivo testing in minipigs and rats to characterize the pharmacological mechanism of action, as well as for mandatory general toxicity studies required for submission of an investigational new drug (IND) application and the initiation of studies in humans. With proper support, our product could be available as a therapeutic agent with the next five to seven years.