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

开发用于产生“按需”排尿的一流疗法

基本信息

批准号：
9344769
负责人：
KARL B THOR
金额：
$ 30万
依托单位：
DIGNIFY THERAPEUTICS, LLC
依托单位国家：
美国
项目类别：
财政年份：
2017
资助国家：
美国
起止时间：
2017-08-07 至 2018-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9344769
关键词：
Adverse effects Adverse event Aging Agonist Bladder Canis familiaris Catheterization Catheters Clinical Clinical Research Clinical Trials Conscious Contracts Data Development Diabetes Mellitus Dose Drug Delivery Systems Drug Formulations Feces Formulation Functional disorder Future Goals Grant Guidelines Health Health Care Costs Hospitalization Human Hypotension In Vitro Incidence Incontinence Individual Intestines Intravenous Investigational Drugs Investigational New Drug Application Measurement Mediating Miniature Swine Multiple Sclerosis Muscle Cramp Neurogenic Bladder Neurologic Nose Oral Parkinson Disease Pathway interactions Patients Pharmaceutical Preparations Pharmacodynamics Pharmacologic Substance Pharmacology Phase Plasma Quality of life Rattus Route Sepsis Site Small Business Innovation Research Grant Smooth Muscle Spinal Dysraphism Spinal cord injury Stroke Substance K Receptor TAC1 gene TACR1 gene Tablets Technology Testing Therapeutic Therapeutic Agents Tissues Toxic effect Toxicity Tests Toxicology Trauma Urethra Urinary tract infection Urination Urine Vomiting awake base cell motility dosage good laboratory practice human tissue improved in vivo loss of function novel novel therapeutics oral tissue pharmacokinetic characteristic pre-clinical preclinical development preclinical study prototype receptor safety study subcutaneous success tablet formulation

项目摘要

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.

项目总结（摘要）