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Assessment of chronic toxicity to support the use of topical pirenzepine for treating diabetic neuropathy

慢性毒性评估以支持使用局部哌仑西平治疗糖尿病神经病变

基本信息

批准号：
9345736
负责人：
Angela Hansen
金额：
$ 97.02万
依托单位：
WINSANTOR, INC.
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-09-30 至 2018-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9345736
关键词：
Address American Award Chronic Clinical Clinical Pathology Clinical Trials Country Data Dermal Detection Development Diabetes Mellitus Diabetic Neuropathies Diabetic mouse Diagnosis Disease Disease model Dose Drug Kinetics Evaluation FDA approved Fiber Formulation Funding Generations Goals Grant High Prevalence Histopathology Human Injectable Insulin-Dependent Diabetes Mellitus Investigation Methodology Methods Miniature Swine Modeling Motor Nerve Nerve Degeneration Nerve Fibers Nerve Regeneration Neural Conduction Neuropathy No-Observed-Adverse-Effect Level Non-Insulin-Dependent Diabetes Mellitus Oral Pain Pain management Participant Peripheral Nervous System Diseases Permeability Pharmaceutical Preparations Phase Phase II Clinical Trials Pirenzepine Plant Roots Plasma Population Protocols documentation Rattus Readiness Risk Rodent Model Safety Small Business Innovation Research Grant Streptozocin Testing Therapeutic Topical application Toxic effect Toxicology United States National Institutes of Health Validation analytical method base commercialization dermal exposure diabetic patient drug development effective therapy experience improved in vivo mortality mouse model novel novel therapeutics pre-clinical preclinical development prevent programs screening success

项目摘要

PROJECT SUMMARY The objective of this SBIR Commercialization Readiness Program (CRP) project is to evaluate chronic toxicity of a new therapeutic for diabetic neuropathy in support of an IND submission. Of the 25 million Americans who suffer from diabetes, approximately 50% will be diagnosed with neuropathy, which is characterized by nerve degeneration. Despite the high prevalence of the disease, there is currently no FDA-approved treatment to either prevent diabetes-induced nerve degeneration or promote nerve regeneration. Thus, there is a substantial unmet need to develop more effective treatments for diabetic neuropathy. The founders of WinSanTor have identified a promising candidate which both prevents and reverses neuropathy in rodent models of the disease. The candidate molecule, pirenzepine, was identified using a novel screening methodology developed in the labs of the company’s founders. Pirenzepine has subsequently been evaluated in over a dozen in vivo tests, and has demonstrated the unique ability to ameliorate both epidermal fiber loss and thermal hypoalgesia. Pirenzepine is an approved drug for other indications in non-US countries, and so it is substantially de-risked as a drug development candidate. In a SBIR Fast-track program, WinSanTor successfully executed an expedited pre-clinical program that included: 1) development and validation of bioanalytical methods; 2) pharmacokinetic analyses; 3) optimization of formulation to enhance delivery; 4) generation of a safety profile; and 5) GMP manufacturing of pirenzepine. These efforts fully support the continued execution of the pre-clinical program through the evaluation of chronic toxicity assessments. The focus of this CRP program will be to evaluate the toxicity of pirenzepine when applied topically for 9 months. A 9-month study was chosen to fulfill the 9-month chronic toxicity study requirement for an NDA submission and to support the duration of the anticipated Phase 2 clinical trial protocol that will involve administration for at least 5 months. This study will be executed in mini-pigs and will use a number of toxicity end points, such as mortality observations, clinical observations, Draize scoring, clinical pathology, and histopathology, to fully define a toxicological profile of pirenzepine. The metric of success for this Aim is to achieve to achieve a NOAEL at an exposure level such that there is up to a 10x safety margin for human studies. The completion of this study is critical to an IND submission to the FDA to support subsequent clinical trials.

项目总结