Bioequivalence and comparative pharmacodynamics of insulin lispro 200 U/mL relative to insulin lispro (Humalog®) 100 U/mL

Insulin lispro 200 U/mL (IL200) is a new strength formulation of insulin lispro (Humalog(R), IL100), developed as an option for diabetic patients on higher daily mealtime insulin doses. This phase 1, open-label, 2-sequence, 4-period crossover, randomized, 8-hour euglycemic clamp study aimed to demonstrate the bioequivalence of IL200 and IL100 after subcutaneous administration of 20 U (U) to healthy subjects (n = 38). Pharmacokinetic (PK) and pharmacodynamic (PD) responses were similar in both formulations. All 90% CIs for the ratios of area under the concentration-versus-time curve from time zero to the time of the last measurable concentration (AUC(0-tlast)) and maximum observed drug concentration (C-max), as well as the total glucose infused throughout the clamp (G(tot)) and the maximum glucose infusion rate (R-max), were contained within 0.80 and 1.25. Time of maximum observed drug concentration (t(max)) was similar between formulations, with a median difference of 15 minutes and a 95%CI of the difference that included zero. Inter- and intrasubject variability estimates were similar for both formulations. Both formulations were well tolerated. IL200 was bioequivalent to IL100 after subcutaneous administration of 20-U single doses, and PD responses were comparable between formulation strengths.