Improved Hypoglycemia Rescue Device

描述(由申请人提供)：该项目的目标是证明即用的高血糖素救援笔的安全性、药代动力学和初步疗效，该笔将提供非常低的容量剂量的高血糖素，而不会在低血糖紧急情况下重建。为了实现这一目标，首先需要最终确定在第一阶段计划中开发的浓缩非水高血糖素溶液，然后为第一阶段-第二阶段试验生产胰高血糖素笔的cGMP临床用品。该计划的最后阶段将进行一项1-2阶段的临床试验，研究胰升糖素抢救笔的安全性、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、便携的胰高血糖素递送系统的安全性和初步有效性，以支持NDA使能阶段3(生物等效性)研究。这个拟议项目的第一个具体目标是优化非水高血糖素配方，并在预注满的自动注射笔中生产cGMP临床用品。第二个具体目标是提交IND文件，并获得FDA对1-2期临床计划的批准。第三个具体目标是用高血糖素抢救笔进行1-2期临床试验。成功的基准将包括：1)快速鉴定非水高血糖素配方；2)生产可进行长期加速稳定性测试并释放用于临床试验的自动注射器笔的GMP临床用品；3)全面纳入证明该产品安全性的1-2期临床研究；药代动力学特征(血浆高血糖素水平)和相当于水重组高血糖素的药效学特征(血糖水平)。达到这些标准将证明该产品进入NDA生物等效性研究是合理的。 与公共卫生相关：目前低血糖急症的护理标准是什么？血糖素急救试剂盒要求糖尿病患者的护理人员使用1毫升预装注射器重建小瓶中包含的多肽粉，并确保在注射前完全溶解。一款对患者友好的、随时可用的自动注射-葡萄糖笔将减少护理人员和患者的恐惧和风险，降低911电话和急诊室就诊的成本。

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. PUBLIC HEALTH RELEVANCE: The current standard of care for hypoglycemic emergencies?the Glucagon Emergency Kit requires a diabetic's caregiver to reconstitute the peptide powder contained in a vial using a 1 mL prefilled syringe and to assure complete solubilization prior to injection. A patient friendly, ready---to---use auto---injector Glucagon Pen will reduce caregiver and patient fear and risk, costs of 911 calls and emergency room visits.