Two-Way Crossover Phase 1 Bioequivalence and Safety Studies in Healthy Adults for a Ready-to-Use, Room-Temperature, Liquid-Stable Glucagon Administered by Autoinjector, Prefilled Syringe, or Vial and Syringe.

Abstract

To demonstrate bioequivalence and safety for a ready-to-use room-temperature liquid-stable glucagon administered subcutaneously (SC) through a glucagon autoinjector (GAI) or a glucagon vial and syringe kit (GVS), versus a glucagon prefilled syringe (G-PFS). Healthy adults (N = 32) were randomly assigned to receive 1-mg glucagon as GAI or G-PFS, and then as the alternative three to seven days later. Other healthy adults (N = 40) were randomly assigned to receive 1-mg glucagon as GVS or G-PFS, and then as the alternative two days later. Samples for plasma glucagon were obtained through 240 minutes after glucagon injection. Bioequivalence was declared when the geometric mean estimate ratio of the area under-the-concentration-versus-time curve from 0 to 240 minutes (AUC0-240) and maximum concentration (Cmax) for plasma glucagon between treatment groups was contained within the bounds of 80% and 125%. Adverse events (AEs) were recorded. The 90% confidence intervals (CIs) for AUC0-240 and Cmax geometric mean ratios for G-PFS to GAI and GVS to G-PFS were contained within the bounds 80% to 125% (G-PFS:GAI AUC0-240 95.05%, 119.67% and Cmax 88.01%, 120.24%; GVS:G-PFS AUC0-240 87.39%, 100.66% and Cmax 89.08%, 106.08%). At least one AE occurred in 15.6% (5/32) participants with GAI, 25% (18/72) with G-PFS, and 32.5% (13/40) with GVS. Sixty-nine of 73 (94.5%) AEs were mild, and none were serious. Nausea was the most common (33/73 [45%]). Bioequivalence and safety were established after 1 mg of this ready-to-use room-temperature liquid-stable glucagon, administered SC to healthy adults, by autoinjector, prefilled syringe, or vial and syringe kit.