Objective: The International Society for Pediatric and Adolescent Diabetes recommends age-specific dosing of glucagon for the rescue of severe hypoglycemia. A novel ready-to-use stable liquid glucagon auto-injector (GAI; Xeris Pharmaceuticals) was evaluated for the treatment of hypoglycemia in pediatric subjects with two age-specific doses.
Research Design and Methods: A sequential efficacy and safety study was conducted involving 31 children with T1D (ages 2-17 years) to evaluate two subcutaneous doses of GAI (0.5 mg or 1 mg) for treatment of hypoglycemia (PG < 80 mg/dL), induced via IV insulin or insulin pump. The primary efficacy endpoint was increase in mean plasma glucose from baseline at 30 minutes following administration of an age-appropriate glucagon dose. As secondary endpoints, subjects were assessed for time from dosing to achieve a 25 mg/dl increase in plasma glucose and other PD and PK parameters.
Results: Statistically significant increases in mean plasma glucose from baseline to 30 minutes post administration of glucagon were observed across the 3 pediatric age groups (81.4±18.3 mg/dL, 84.2±25.3 mg/dL, and 54.0±27.3 mg/dL in the 2 to < 6 years [n=7, 0.5 mg dose], 6 to < 12 years [n=13, 0.5 mg dose], and 12 to < 18 years [n=11, 1 mg dose] age groups, respectively). All evaluable subjects achieved the target glucose elevation of ≥25 mg/dL from baseline. Across age groups there were no notable differences with regards to mean glucose AUC0-90m, Cmax, and Tmax or median time to achieve a 25 mg/dl glucose increase. Plasma glucagon AUC0-240m, Cmax, and Tmax were similar across the age groups. Nausea (36.4%) and vomiting (18.2%) were the most commonly reported AEs.
Conclusions: To prevent medical complications and their sequalae, prompt management of severe hypoglycemia emergencies is critically important. These results demonstrate that age-appropriate doses of GAI were effective in treating hypoglycemia, safe, and well tolerated in pediatric subjects ages 2 through 17 years old.
B. Buckingham: Advisory Panel; Self; Novo Nordisk Inc., ConvaTec Inc.. Research Support; Self; Medtronic, Insulet Corporation, Dexcom, Inc., Tandem Diabetes Care, Inc.. Consultant; Self; Tandem Diabetes Care, Inc., Becton, Dickinson and Company. M.J. Cummins: Employee; Self; Xeris Pharmaceuticals, Inc. S.J. Prestrelski: Employee; Self; Xeris Pharmaceuticals, Inc. P. Strange: Other Relationship; Self; AstraZeneca. Consultant; Self; Valeritas, Inc.. Stock/Shareholder; Self; Valeritas, Inc..