Glucagon Mini-Dosing Pen for Treatment of Hypoglycemia

用于治疗低血糖的胰高血糖素小剂量笔

• 批准号: 8521920
• 负责人: MOREY W HAYMOND
• 金额: $ 67.9万
• 依托单位: XERIS PHARMACEUTICALS, INC.
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-09-16 至 2014-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8521920
• 关键词: Adverse effects; Blood; Blood Glucose; Chronic; Clinical; Clinical Chemistry; Clinical Research; Clinical Trials; Coupled; Data; Development; Dose; Drug Formulations; Drug Kinetics; Dyes; Fasting; Glucagon; Glucose; Glucose Plasma Concentration; Grant; Hematology; Human; Hyperinsulinism; Hypoglycemia; Injection of therapeutic agent; Insulin; Insulin-Dependent Diabetes Mellitus; Kidney Diseases; Manufactured Supplies; Measurement; Modeling; National Institute of Diabetes and Digestive and Kidney Diseases; Neuropathy; Oryctolagus cuniculus; Patients; Pharmaceutical Preparations; Pharmacodynamics; Phase; Plasma; Preparation; Prevention; Research; Retinal Diseases; Safety; Site; Syringes; System; Temperature; Testing; Toxic effect; clinical material; commercialization; design; diabetic; innovative technologies; interest; irritation; meetings; pre-clinical; preclinical study; programs; public health relevance; reconstitution; response; subcutaneous; success; type I diabetic; Adverse effects; Blood; Blood Glucose; Chronic; Clinical; Clinical Chemistry; Clinical Research; Clinical Trials; Coupled; Data; Development; Dose; Drug Formulations; Drug Kinetics; Dyes; Fasting; Glucagon; Glucose; Glucose Plasma Concentration; Grant; Hematology; Human; Hyperinsulinism; Hypoglycemia; Injection of therapeutic agent; Insulin; Insulin-Dependent Diabetes Mellitus; Kidney Diseases; Manufactured Supplies; Measurement; Modeling; National Institute of Diabetes and Digestive and Kidney Diseases; Neuropathy; Oryctolagus cuniculus; Patients; Pharmaceutical Preparations; Pharmacodynamics; Phase; Plasma; Preparation; Prevention; Research; Retinal Diseases; Safety; Site; Syringes; System; Temperature; Testing; Toxic effect; clinical material; commercialization; design; diabetic; innovative technologies; interest; irritation; meetings; pre-clinical; preclinical study; programs; public health relevance; reconstitution; response; subcutaneous; success; type I diabetic

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.

描述（由申请人提供）：本申请中概述的程序旨在加速胰高血糖素剂量笔的开发和商业化，以改变胰岛素糖尿病患者中中度低血糖症的范式。这项研究与NIDDK直接相关，NIDDK明确对开发用于预防和治疗低血糖的创新技术感兴趣。该计划的第一个目的是制造一批Xeris在预填充的注射器中的非水胰高血糖素救援配方，该注射器是室温稳定的，不需要重建。这些临床供应将进行长期稳定研究，以准备进行2A期临床试验。 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在有效提高治疗患者血糖水平的能力方面，小剂量。成功完成 临床计划将证明胰高血糖量小剂量用于治疗中度低血糖的安全性，药代动力学和初始功效。第三个目标是生产一批GLP非水甘草，以在标准的3毫升药物墨盒格式中展示兼容性，旨在在多剂量笔中使用。实现这一特定目的将证明在室温下至少一年稳定的配方，可以作为多种小剂量进行交付，可以在临床前研究中使用，最终可以将其转向临床用品制造计划。该配方将进行测试以证明最初的稳定性，临床前研究将证明兔子的长期安全性 模型。这项工作中收集的数据将为长期2B人类临床研究提供包装，并提供商业产品。