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迷你剂量笔的开发和商业化，以改变使用胰岛素的糖尿病患者治疗中度低血糖的范例。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。本项目的第一个目标是生产一批Xeris的非水型胰高血糖素抢救制剂，该制剂在预充式注射器中具有室温稳定性且不需要重构。这些临床用品将进行长期稳定性研究，为进行2a期临床试验做准备。该项目的第二个目标是在健康的1型糖尿病患者中进行2a期临床研究，允许患者友好地给药小剂量胰高血糖素。在此背景下，“健康”是指使用胰岛素控制良好/管理良好的T1D患者，没有慢性并发症的临床证据，如肾病、视网膜病变、神经病变等。临床试验将证明小剂量胰高血糖素在有效提高治疗患者血糖水平方面的剂量反应。圆满完成

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.