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

描述(由申请人提供)：该计划的目标是进一步开发一种新的、稳定的非水高血糖素配方，作为双激素(胰岛素-高血糖素)泵系统的组成部分，用于糖尿病患者的治疗。在目前以胰岛素为基础的系统中添加高血糖素将允许更好地控制血糖，同时降低发生低血糖的风险。当前提案的主要目标与NIDDK的研究重点直接相关，即为人工胰腺开发改进的输送系统。该计划旨在证明这种新的胰高血糖素制剂在动物和1型糖尿病患者中的安全性、药动学和药效学。这项研究的主要临床指标将是这种高血糖素制剂提高 即使在贴片泵室中短期老化后的血糖水平。该项目的初步工作将开发和优化用于双激素泵应用的非水、液体胰高血糖素配方，证明其安全性，并在临床前模型中表征其药理特性。第二项工作将把优化的配方纳入临床用品制造计划。该制造计划将在GMP设施中为临床试验生产用品，并包括保质期和在用稳定性测试。这项工作还包括在1型糖尿病患者的第一阶段临床试验中评估泵系统中非水高血糖素溶液的安全性、药代动力学和初步疗效(血糖动力学)。

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.