Pharmacodynamics, pharmacokinetics, safety, and tolerability of a ready-to-use, room temperature, liquid stable glucagon administered via an autoinjector pen to youth with type 1 diabetes.

Abstract

Prompt and reliable management of hypoglycemia in youth with diabetes is important to prevent serious medical complications. To determine efficacy, pharmacodynamics (PD), pharmacokinetics (PK), safety, and tolerability of a ready-to-use, liquid stable glucagon formulation administered subcutaneously via an autoinjector pen to youth with type 1 diabetes (T1D). After plasma glucose concentration was < 80 mg/dL (< 4.4 mmol/L) after insulin, participants aged 2 to < 12 years with T1D were administered 0.5mg of glucagon; participants aged 12 to < 18 years instead received 1mg of glucagon. Then, adolescents were challenged with 0.5mg after a 7- to 28-day washout period. Primary endpoint was mean plasma glucose concentration at 30min after glucagon. Plasma glucose concentrations significantly (p< 0.001) increased from baseline to 30min after glucagon, with mean change in plasma glucose concentration between baseline and 30min for each age cohort as follows: 2 to < 6 years (n= 7; 81.4mg/dL [4.5 mmol/L]); 6 to < 12 years (13; 84.2mg/dL [4.7 mmol/L]); 12 to < 18 years (11; dose, 1mg; 54.0mg/dL [3.0 mmol/L]); and 12 to < 18 years (11; 0.5mg; 52.4mg/dL [2.9 mmol/L]). Among age cohorts, no clinically relevant differences were observed for PD and PK parameters. Common adverse events were nausea, vomiting, and hypoglycemia. Age-appropriate dosing of this glucagon formulation was effective at 30min in reversing plasma glucose concentrations from < 80 mg/dL in youth with T1D.