Clinical Development of a Stable Glucagon Formulation for Bi-hormonal Pump

描述（由申请人提供）：该项目的目标是进一步开发一种新型、稳定、非水型胰高血糖素制剂，作为治疗糖尿病患者的双激素（胰岛素-胰高血糖素）泵系统的组成部分。将胰高血糖素添加到现有的以胰岛素为基础的系统中，可以更好地控制血糖，降低低血糖的风险。当前提案的主要目标与NIDDK的研究重点直接相关，即开发改进的人工胰腺输送系统。本项目旨在证明这种新型胰高血糖素配方在动物和1型糖尿病患者中的安全性、药代动力学和药效学。这项研究的主要临床指标将是胰高血糖素配方提高的能力

DESCRIPTION (provided by applicant): The objective of this program is to further the development of a novel, stable, non-aqueous glucagon formulation as an integral component of a bi-hormonal (insulin-glucagon) pump system for treatment of persons with diabetes. The addition of glucagon to the present insulin-based systems will allow greater control of blood glucose with a lower risk of hypoglycemia. The primary objective of the current proposal is directly relevant to an NIDDK research priority, the development of improved delivery systems for the artificial pancreas. This program intends to demonstrate the safety, pharmacokinetics and pharmacodynamics of this novel glucagon formulation in animals and in type 1 diabetics. The major clinical metric for this study will be the capacity of this glucagon formulation to raise glucose levels even after short-term aging in a patch pump chamber. The initial effort of this project will develop and optimize a non-aqueous, liquid glucagon formulation designed for the bi-hormonal pump application, demonstrate its safety, and characterize its pharmacology in preclinical models. The second effort will take the optimized formulation into a clinical supplies manufacturing program. The manufacturing program will produce supplies for the clinical trial in a GMP facility and include shelf-life and 'in-use' stability testing. This effort also includes assessment of the safety, pharmacokinetics and preliminary efficacy (glucodynamics) of the non-aqueous, glucagon solution in a pump system in a Phase 1 clinical trial in type 1 diabetics. PUBLIC HEALTH RELEVANCE: The objective of this program is to further the development of a novel, stable, non-aqueous glucagon formulation as an integral component of a bi-hormonal (insulin-glucagon) pump system for treatment of persons with diabetes. The addition of a glucagon component to the present insulin-based systems will allow greater control of blood glucose with a lower risk of hypoglycemia.