Improved Hypoglycemia Rescue Device

描述（由申请方提供）：本项目的目的是证明即用型胰高血糖素急救笔的安全性、药代动力学和初步疗效，该笔将在不复溶的情况下输送极低体积剂量的胰高血糖素，用于低血糖紧急情况。为了实现这一目标，有必要首先完成1期项目中开发的胰高血糖素浓缩非水溶液，然后生产1-2期试验胰高血糖素注射笔的cGMP临床供应品。本项目的最后阶段将进行1-2期临床试验，研究胰高血糖素急救笔的安全性、药代动力学和初步疗效。如果成功，这些实验将证明一种简单、便携的胰高血糖素给药系统的安全性和初始有效性，以支持NDA启动的3期（生物等效性）研究。该拟定项目的第一个具体目标是优化非水性胰高血糖素制剂，并在预充式自动注射笔中生产cGMP临床供应品。第二个具体目标是提交IND文件，并获得FDA批准的1-2期临床计划。第三个具体目标是对胰高血糖素急救笔进行1-2期临床试验。成功基准将包括：1）快速鉴定非水性胰高血糖素制剂; 2）生产自动注射笔的GMP临床供应品，其可以进行长期和加速稳定性测试并放行用于临床试验; 3）证明产品安全性的1-2期临床研究的全部入组;在一些实施方案中，本发明提供了与水性重构胰高血糖素相当的药代动力学特征（血浆胰高血糖素水平）和药效学特征（血糖水平）。满足这些基准将证明将产品推进到NDA使能生物等效性研究。

DESCRIPTION (provided by applicant): The objective of this project is to demonstrate the safety, pharmacokinetics and initial efficacy of a ready-to-use Glucagon Rescue Pen that will deliver a very low volume dose of a glucagon without reconstitution for hypoglycemic emergencies. To execute on this objective, it is necessary to first finalize the concentrated non-aqueous glucagon solution developed in the Phase 1 program and thereafter, manufacture cGMP clinical supplies of the glucagon pen for the Phase 1-2 trial. The final phase in this program will be to conduct a Phase 1-2 clinical trial that will study the safety, pharmacokinetics and preliminary efficacy of the Glucagon Rescue Pen. If successful, these experiments will demonstrate the safety and initial effectiveness of a simple, portable, glucagon delivery system to support an NDA-enabling Phase 3 (bioequivalency) study. The first Specific Aim of this proposed project is to optimize the non-aqueous glucagon formulation and produce cGMP clinical supplies in a pre-filled auto-injection pen. The second Specific Aim is to file IND documentation and get FDA approval for a Phase 1-2 clinical plan. The Third Specific Aim will be to conduct a Phase 1-2 clinical trial with the Glucagon Rescue Pen. Success Benchmarks will include: 1) rapid identification of non-aqueous glucagon formulation; 2) manufacture of GMP clinical supplies of the autoinjector pen that can proceed into long and accelerated stability testing and release for use in the clinical trial; 3) Full enrollment of the Phase 1-2 clinical study that demonstrates the product's safety; pharmacokinetic profile (plasma glucagon levels) and a pharmacodynamic profile (blood glucose levels) that are equivalent to an aqueous-reconstituted glucagon. Meeting these benchmarks will justify advancing the product into an NDA-enabling bioequivalency study.