Glucose-Responsive Self-Regulated Insulin Delivery

描述(由申请人提供)： 具有里程碑意义的糖尿病控制和并发症试验(DCCT)和英国的前瞻性糖尿病 UKPDS的一项研究已经在临床上证明，以较低的糖化血红蛋白(HbAlc)水平衡量，更严格的血糖控制可显著降低糖尿病长期并发症的发生率。真正的血糖控制需要提供血糖调节的胰岛素替代治疗。SmartCells正在通过提供Smartlnsulin来满足这一需求，Smartlnsulin是唯一一种以临床相关方式检测和响应血糖水平变化的产品。 为了向FDA提交Smartlnsulin Ind并启动人体临床试验，第一年和第二年的安全性和有效性研究将解决以下关键问题，使用链脲佐菌素诱导的斯普拉格-道利(SD)糖尿病大鼠模型： -将Smartlnsulin从4L批次扩大到40L批次，同时保留体外葡萄糖设定点和体内葡萄糖耐量试验确定的性能 -工程师Smartlnsulin皮下注射配伍，并使用标准组织学评分验证是否存在纤维化和坏死组织以及巨噬细胞和淋巴细胞渗透 -Tailor Smartlnsulin用于快速吸收、作用和消除，通过关键的注射后药代动力学和药效学参数进行测量 -优化Smartlnsulin配方，使用单剂控制空腹和用餐时的血糖水平 -通过每天注射优化的Smartlnsulin降低60天的HbA1c水平

DESCRIPTION (provided by applicant): The landmark Diabetes Control and Complications Trial (DCCT) and the UK Prospective Diabetes Study (UKPDS), have clinically proven that tighter glycemic control, as measured by lower glycosylated hemoglobin A1c (HbAlc) levels, significantly reduces the incidence of long term diabetic complications. True glycemic control requires treatments that provide plasma glucose-regulated insulin replacement. SmartCells is addressing this need by offering Smartlnsulin, the only product to both sense and respond to altered serum glucose levels in a clinically relevant way. In order to file a Smartlnsulin IND with the FDA and initiate human clinical trials, safety and efficacy studies in Years 1 and 2 will address the following critical issues using streptozotocin-induced diabetic Sprague-Dawley (SD) rat models: - Scale-up Smartlnsulin from 4L to 40L batches while preserving performance as determined by in vitro glucose set point and in vivo glucose tolerance tests - Engineer Smartlnsulin subcutaneous injection compatibility and verify absence of fibrotic and necrotic tissue and macrophage and lymphocyte infiltration using standard histology scoring - Tailor Smartlnsulin for rapid absorption, action, and elimination as measured by key post-injection pharmacokinetic and pharmacodynamic parameters - Optimize Smartlnsulin formulation to control fasting and mealtime glucose levels using a single dose - Reduce 60-day HbA1c levels with daily injections of optimized Smartlnsulin