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

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 (AUC(INS‐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 (AUC(GIR‐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 AUC(INS‐SS 300‐360 min), and the 90% CI and 95% CI of the geometric LS mean ratio for AUC(GIR‐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.