Pharmacokinetic and pharmacodynamic bioequivalence between regular human insulin (rDNA origin) in 0.9% sodium chloride ready-to-use infusion 1 U/mL and 100 U/mL concentrate diluted to 1 U/mL in healthy males

Diabetes Obes Metab. 2021 Aug 10. doi: 10.1111/dom.14520. Online ahead of print.

Abstract

Aim: To show pharmacokinetic (PK) and pharmacodynamic (PD) bioequivalence between Myxredlin, a novel, ready-to-use regular human insulin 1 U/mL formulation (BAX-HI), and Novolin R 100 U/mL concentrate diluted to 1 U/mL (NOVO-HI).

Materials and methods: This phase 1, double-blind, randomized, two-way crossover study compared the PK and PD properties of BAX-HI and NOVO-HI. A total of 58 healthy males received 0.36 U/kg of each study drug, administered intravenously over a 6-hour period, concurrent with an 8-hour euglycaemic clamp at two treatment periods separated by a washout period of 7-10 days. The primary PK endpoint was the area under the insulin concentration-time curve at steady state (SS) measured from 300 to 360 minutes (AUCINS-SS 300-360 min ). The primary PD endpoint was the area under the glucose infusion rate-time curve at SS measured from 300 to 360 minutes (AUCGIR-SS 300-360 min ).

Results: All subjects completed the first treatment period and 54 subjects completed both treatment periods. Bioequivalence between BAX-HI and NOVO-HI was shown for the primary endpoints as the 90% confidence interval (CI) of the geometric least-squares (LS) mean ratio for AUCINS-SS 300-360 min , and the 90% CI and 95% CI of the geometric LS mean ratio for AUCGIR-SS 300-360 min were entirely contained within the prespecified limits of 80%-125%. Safety profiles were comparable for both study drugs and there were no serious adverse events.

Conclusions: The study showed bioequivalence between BAX-HI and NOVO-HI in terms of PK and PD characteristics in healthy males.

Keywords: biosimilar insulin; insulin therapy; pharmacodynamics; pharmacokinetics; phase I-II study.