Glucagon Mini-Dosing Pen for Treatment of Hypoglycemia

描述（由申请人提供）：本申请中概述的项目旨在加速胰高血糖素微剂量笔的开发和商业化，以改变使用胰岛素的糖尿病患者中度低血糖的治疗模式。这项研究与NIDDK直接相关，NIDDK明确对开发预防和治疗低血糖的创新技术感兴趣。该计划的第一个目标是生产一批预充式注射器中的Xeris非水胰高血糖素救援制剂，该制剂在室温下稳定，不需要复溶。这些临床供应品将进行长期稳定性研究，为开展2a期临床试验做准备。该计划的第二个目的是在健康的1型糖尿病患者中进行2a期临床研究，其允许患者友好地施用小剂量胰高血糖素。在这种情况下，“健康”是指良好控制/管理的使用胰岛素的T1 D患者，没有慢性并发症如肾病、视网膜病、神经病变、临床试验将证明胰高血糖素小剂量在有效提高治疗患者血糖水平的能力方面的剂量反应。成功完成 临床计划将证明用于治疗中度低血糖症的胰高血糖素小剂量的安全性、药代动力学和初始功效。第三个目标是生产非水性胰高血糖素的GLP批次，以证明在设计用于多剂量笔的标准3 mL笔芯规格中的相容性。这一特定目标的实现将证明制剂在室温下稳定至少一年，可作为多个小剂量递送，可用于临床前研究，并最终可用于临床供应品生产计划。将对该制剂进行检测，以证明其初始稳定性，临床前研究将证明其在家兔中的长期安全性 模型在这项工作中收集的数据将为商业产品的长期2b期人体临床研究提供一个包。

DESCRIPTION (provided by applicant): The program outlined in this application has been designed to accelerate the development and commercialization of a Glucagon Mini-Dose Pen to change the paradigm for treatment of moderate hypoglycemia in insulin-using diabetics. This research is directly relevant to the NIDDK which is explicitly interested in the development of innovative technologies for the prevention and treatment of hypoglycemia. The first objective of this program is to manufacture a batch of Xeris' non-aqueous glucagon rescue formulation in pre-filled syringes, which is room-temperature stable and does not require reconstitution. These clinical supplies will be put on a long-term stability study in preparation for conducting a Phase 2a clinical trial. The second objective of this program is to conduct a Phase 2a clinical study in healthy, type 1 diabetics that allows for patient-friendly administration of mini-doses of glucagon In this context, "healthy" refers to well controlled/managed insulin-using T1D patients without clinical evidence of chronic complications such as nephropathy, retinopathy, neuropathy, etc. The clinical trial will demonstrate the dose-response of glucagon mini-doses in terms of the ability to effectively raise blood glucose levels of treated patients. Successful completion of the clinical program will demonstrate the safety, pharmacokinetics and initial efficacy of glucagon mini-doses for use in treatment of moderate hypoglycemia. The third objective is to manufacture a GLP batch of non-aqueous glucagon to demonstrate compatibility in a standard 3 mL drug cartridge format designed for use in a multi-dose pen. Accomplishment of this specific aim will demonstrate a formulation that is stable for at least one year at room temperature, can be delivered as multiple mini-doses, can be used in a preclinical study, and can ultimately be carried forward into a clinical supplies manufacturing program. The formulation will be tested to demonstrate initial stability and a preclinical study will demonstrate long-term safety in a rabbit model. The data collected in this effort will provide a package for a longer-term Phase 2b human clinical study with a commercial product.