Pharmacokinetic and Pharmacodynamic Equivalence of Biosimilar and Reference Ultra-Rapid Lispro: A Comparative Clamp Study in Healthy Volunteers.

Abstract

Ultra-rapid insulin lispro is an innovative insulin analogue designed to achieve rapid onset and short duration of action, aimed at optimizing glycemic control in patients with diabetes. This was a double-blind, randomized, 2-period, crossover clamp study to evaluate the pharmacokinetics (PK) and pharmacodynamics (PD), along with safety profiles, of a potential biosimilar ultra-rapid insulin lispro compared to the reference product in healthy White men. A total of 35 healthy volunteers completed hyperinsulinemic euglycemic clamp procedures across both study periods. Blood samples were collected at predefined intervals up to 8 hours to assess PK parameters. Plasma glucose levels were monitored every 5 minutes during the 8-hour clamps, with adjustments to the glucose infusion rate to maintain the target range. Insulin quantification in plasma was conducted using a validated enzyme-linked immunosorbent assay method. PD assessment was based on glucose infusion rate profiles during both clamps. Geometric mean ratios for maximum plasma concentration and area under the concentration-time curve from insulin administration to the last measurable concentration for the test and reference drugs fell within the bioequivalence range of 80%-125%. Furthermore, the investigational drugs demonstrated comparable PK/PD profiles of insulin lispro. Both formulations exhibited similar safety profiles primarily characterized by mild injection site reactions.