1036-P: Bioequivalence of Ultra-Rapid Lispro (URLi) U100 and U200 Formulations in Healthy Subjects

URLi is a novel insulin lispro formulation developed to more closely match physiological insulin secretion. URLi U200 is a concentrated formulation. This randomized, double-blind, 4-period, replicated crossover, euglycemic clamp study (NCT03616977) assessed pharmacokinetics (PK) and glucodynamics (GD) after 15 U subcutaneous doses of U100 and U200 URLi in 68 healthy subjects (mean ± SD age 39.6 ± 9.6 y). Similar mean PK and GD profiles were observed after dosing U100 and U200 URLi. The formulations were bioequivalent (BE): the 90% CI of ratios of geometric least-square means for the maximum insulin concentration (Cmax) and total exposure (AUC0-∞) were within BE limits of 0.80-1.25. Additionally, the 90% CI for the ratios of geometric means for maximum (Gtot) and total glucose infused (Rmax) were within the BE limits. The time to early half Cmax (early 50% tmax) occurred at approximately the same time for both formulations. Additionally, insulin exposure within the first 15 and 30 minutes was similar for U100 and U200 URLi. The tolerability of the U200 and U100 URLi formulations were comparable. This study demonstrated that U100 and U200 URLi formulations were BE and the faster insulin absorption was maintained in the U200 formulation. The GD were similar and support the ability of patients to transfer from U100 to U200 URLi in a 1:1 unit conversion.