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

描述（由申请方提供）：本项目的目的是进一步开发一种新型、稳定的非水性胰高血糖素制剂，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目前的基于胰岛素的系统中将允许更好地控制血糖，同时降低低血糖症的风险。当前提案的主要目标与NIDDK的研究优先事项直接相关，即开发改进的人工胰腺输送系统。该项目旨在证明这种新型胰高血糖素制剂在动物和1型糖尿病患者中的安全性、药代动力学和药效学。本研究的主要临床指标将是这种胰高血糖素制剂提高胰岛素抵抗的能力。 即使在贴片泵室中短期老化后，也能保持血糖水平。该项目的初步工作将开发和优化一种非水性液体胰高血糖素制剂，用于双激素泵应用，证明其安全性，并在临床前模型中表征其药理学。第二项工作将把优化的配方纳入临床用品生产计划。生产计划将在GMP设施中生产用于临床试验的供应品，并包括有效期和“使用中”稳定性试验。这项工作还包括在1型糖尿病患者的1期临床试验中评估泵系统中非水性胰高血糖素溶液的安全性、药代动力学和初步疗效（葡萄糖动力学）。 公共卫生相关性：该项目的目的是进一步开发一种新型、稳定的非水性胰高血糖素制剂，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。将胰高血糖素组分添加到目前的基于胰岛素的系统中将允许更好地控制血糖，同时低血糖症的风险更低。

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.