The objective of this program is to further the development of a novel, stable, non-aqueous glucagon formulation as an integral component of a bi-hormonal (insulin-glucagon) pump system for treatment of persons with diabetes. The addition of glucagon to the present insulin-based systems will allow greater control of blood glucose with a lower risk of hypoglycemia. The primary objective of the current proposal is directly relevant to an NIDDK research priority, the development of improved delivery systems for the artificial pancreas. This program intends to demonstrate the safety, pharmacokinetics and pharmacodynamics of this novel glucagon formulation in animals and in type 1 diabetics. The major clinical metric for this study will be the capacity of this glucagon formulation to raise glucose levels even after short-term aging in a patch pump chamber. The initial effort of this project will develop and optimize a non-aqueous, liquid glucagon formulation designed for the bi-hormonal pump application, demonstrate its safety, and characterize its pharmacology in preclinical models. The second effort will take the optimized formulation into a clinical supplies manufacturing program. The manufacturing program will produce supplies for the clinical trial in a GMP facility and include shelf-life and 'in-use' stability testing. This effort also includes assessment of the safety, pharmacokinetics and preliminary efficacy (glucodynamics) of the non-aqueous, glucagon solution in a pump system in a Phase 1 clinical trial in type 1 diabetics.
Public Health Relevance: The objective of this program is to further the development of a novel, stable, non-aqueous glucagon formulation as an integral component of a bi-hormonal (insulin-glucagon) pump system for treatment of persons with diabetes. The addition of a glucagon component to the present insulin-based systems will allow greater control of blood glucose with a lower risk of hypoglycemia.
Public Health Relevance Statement: The objective of this program is to further the development of a novel, stable, non-aqueous glucagon formulation as an integral component of a bi-hormonal (insulin-glucagon) pump system for treatment of persons with diabetes. The addition of a glucagon component to the present insulin-based systems will allow greater control of blood glucose with a lower risk of hypoglycemia.
Project Terms: aged; Aging; Animals; aqueous; Artificial Pancreas; base; Blood Glucose; blood glucose regulation; Blood Tests; Body Temperature; Cells; Clinical; Clinical Chemistry; Clinical Trials; Conduct Clinical Trials; Cyclic AMP-Dependent Protein Kinases; design; Development; Diabetes Mellitus; Dose; Drug Formulations; Drug Kinetics; Family suidae; Glucagon; Glucose; Glycogen; High Pressure Liquid Chromatography; Hormonal; Human; Hyperglycemia; Hypoglycemia; improved; Insulin; Insulin Infusion Systems; Insulin-Dependent Diabetes Mellitus; Life; Liquid substance; Manufactured Supplies; Measures; Metric; Modeling; National Institute of Diabetes and Digestive and Kidney Diseases; novel; Octreotide; Oryctolagus cuniculus; Persons; Pharmaceutical Preparations; Pharmacodynamics; Pharmacology; Phase; Phase I Clinical Trials; Plasma; Pre-Clinical Model; preclinical study; Preparation; programs; Pump; Rattus; Research Priority; research study; response; Risk; Safety; skin irritation; Solutions; stability testing; subcutaneous; Syringes; System; Temperature; type I diabetic
