SBIR-STTR Award

The objective of this program is to further the development of a novel, stable, non-aqueous glucagon formulation - CSI (continuous subcutaneous infused) Glucagon(tm) in combination with a Insulet OmniPod(r) infusion pump for prevention of hypoglycemia in patients with congenital hyperinsulinism (HI). The addition of glucagon will meet a significant unmet need in the management of severe, persistent hypoglycemia and will allow greater control of blood glucose in this fragile pediatric patient population. This program intends to demonstrate the safety of the novel glucagon in a 3-month preclinical study and thereafter, establish safety and efficacy in pediatric patients with HI. The major clinical metric for this study will be the ability of CSI Glucagon(tm) to maintain normoglycemia, delivered as a basal subcutaneous infusion. The initial effort of this project will manufacture clinical supplies and put material on an ICH stability testing program. Thereafter, we will assess of the safety of CSI Glucagon(tm) in a 3-month animal study. Then, we will file an Investigational New Drug (IND) application with the FDA. Finally, the safety and efficacy of our soluble glucagon will be assessed in a Phase 2 clinical trial in pediatric patients with HI. The tral will entail a 3-6 day study in patients once they are stabilized with glucose and thereafter an outpatient phase, wherein patients will continue therapy with CSI Glucagon(tm) for a period of up to six months with monthly examinations. If after six months it is determined that blood glucose is being successfully managed i.e., they remain in a normal glycemic range on a daily basis, the parents will have the option to have their child continue treatment with CSI Glucagon(tm) until such time that the child metabolically "grows into" their insulin production. At this point, they ae typically consuming sufficient complex carbohydrates such that they can eventually discontinue treatment. This can be as short as 1 year, but can extend up to 5 years of age or longer.

Public Health Relevance Statement:


Public Health Relevance:
The objective of this program is to further the development of a novel, stable, non-aqueous glucagon formulation as continuous subcutaneous infusion - CSI Glucagon(tm) delivered by an Insulet OmniPod(r) patch pump for prevention of severe, persistent hypoglycemia in pediatric patients with congenital hyperinsulinism (HI). The addition of CSI Glucagon(tm) delivered as a basal infusion with a compatible and caregiver-friendly OmniPod(r) infusion pump will provide a valuable and needed tool for medical management of blood glucose in HI patients. CSI Glucagon(tm) delivered in this manner will lower the risk of severe, repeated hypoglycemic events and the attendant brain damage in a very fragile patient population in both an inpatient setting and particularly in the outpatient setting for parents and in-home nurses.

Project Terms:
5 year old; Adolescence; Adolescent; Adverse effects; Animals; base; Blood Glucose; Brain Injuries; Carbohydrates; Caregivers; Caring; Child; Chronic; Clinical; Clinical Trials; Complex; Conduct Clinical Trials; Continuous Infusion; Cyclic GMP; design; Development; Diet; Diffuse; Disease; drug clearance; Drug Formulations; Drug Interactions; Event; exposed human population; Fasting; Feeds; Glucagon; Glucose; Goals; Home environment; Hyperinsulinism; Hypoglycemia; Infant; Infusion procedures; Infusion Pumps; Inpatients; Insulin; Investigational Drugs; Investigational New Drug Application; Life; Medical; meetings; Neonatal; novel; Nurses; Outpatients; Pancreatectomy; Parents; patient population; Patients; Persistent Hyperinsulinemia Hypoglycemia of Infancy; Pharmaceutical Preparations; Phase; Phase II Clinical Trials; pre-clinical; preclinical study; prevent; Prevention; Production; programs; public health relevance; Pump; Rattus; response; Risk; Rodent; Safety; Somatostatin; stability testing; subcutaneous; Subcutaneous Injections; Syringes; System; Temperature; Time; tool; Toxicology; Vial device; Writing

The objective of this program is to further the development of a novel, stable, non-aqueous glucagon formulation - CSI (continuous subcutaneous infused) Glucagon(tm) in combination with a Insulet OmniPod(r) infusion pump for prevention of hypoglycemia in patients with congenital hyperinsulinism (HI). The addition of glucagon will meet a significant unmet need in the management of severe, persistent hypoglycemia and will allow greater control of blood glucose in this fragile pediatric patient population. This program intends to demonstrate the safety of the novel glucagon in a 3-month preclinical study and thereafter, establish safety and efficacy in pediatric patients with HI. The major clinical metric for this study will be the ability of CSI Glucagon(tm) to maintain normoglycemia, delivered as a basal subcutaneous infusion. The initial effort of this project will manufacture clinical supplies and put material on an ICH stability testing program. Thereafter, we will assess of the safety of CSI Glucagon(tm) in a 3-month animal study. Then, we will file an Investigational New Drug (IND) application with the FDA. Finally, the safety and efficacy of our soluble glucagon will be assessed in a Phase 2 clinical trial in pediatric patients with HI. The tral will entail a 3-6 day study in patients once they are stabilized with glucose and thereafter an outpatient phase, wherein patients will continue therapy with CSI Glucagon(tm) for a period of up to six months with monthly examinations. If after six months it is determined that blood glucose is being successfully managed i.e., they remain in a normal glycemic range on a daily basis, the parents will have the option to have their child continue treatment with CSI Glucagon(tm) until such time that the child metabolically "grows into" their insulin production. At this point, they ae typically consuming sufficient complex carbohydrates such that they can eventually discontinue treatment. This can be as short as 1 year, but can extend up to 5 years of age or longer.

Public Health Relevance Statement:


Public Health Relevance:
The objective of this program is to further the development of a novel, stable, non-aqueous glucagon formulation as continuous subcutaneous infusion - CSI Glucagon(tm) delivered by an Insulet OmniPod(r) patch pump for prevention of severe, persistent hypoglycemia in pediatric patients with congenital hyperinsulinism (HI). The addition of CSI Glucagon(tm) delivered as a basal infusion with a compatible and caregiver-friendly OmniPod(r) infusion pump will provide a valuable and needed tool for medical management of blood glucose in HI patients. CSI Glucagon(tm) delivered in this manner will lower the risk of severe, repeated hypoglycemic events and the attendant brain damage in a very fragile patient population in both an inpatient setting and particularly in the outpatient setting for parents and in-home nurses.

NIH Spending Category:
Clinical Research; Clinical Trials and Supportive Activities; Diabetes; Pediatric

Project Terms:
5 year old; Adolescence; Adolescent; Adverse effects; Animals; base; Blood Glucose; Brain Injuries; Carbohydrates; Caregivers; Caring; Child; Chronic; Clinical; Clinical Trials; Complex; Conduct Clinical Trials; Continuous Infusion; Cyclic GMP; design; Development; Diet; Diffuse; Disease; drug clearance; Drug Interactions; Event; exposed human population; Fasting; Feeds; Formulation; Glucagon; Glucose; Goals; Health; Home environment; Hyperinsulinism; Hypoglycemia; Infant; Infusion procedures; Infusion Pumps; Inpatients; Insulin; Investigational Drugs; Investigational New Drug Application; Life; Medical; meetings; Neonatal; novel; Nurses; Outpatients; Pancreatectomy; Parents; patient population; Patients; pediatric patients; Persistent Hyperinsulinemia Hypoglycemia of Infancy; Pharmaceutical Preparations; Phase; Phase II Clinical Trials; pre-clinical; preclinical study; prevent; Prevention; Production; programs; Pump; Rattus; response; Risk; Rodent; Safety; Somatostatin; stability testing; subcutaneous; Subcutaneous Injections; Syringes; System; Temperature; Time; tool; Toxicology; Vial device; Writing