Pharmacokinetic and pharmacodynamic bioequivalence of biosimilar MYL‐1601D with US and European insulin aspart in healthy volunteers: A randomized, double‐blind, crossover, euglycaemic glucose clamp study

Abstract Aim To evaluate the pharmacokinetic (PK) and pharmacodynamic (PD) bioequivalence (BE) of MYL‐1601D biosimilar with originator, NovoLog (Ref‐InsAsp‐US), and NovoRapid (Ref‐InsAsp‐EU). Materials and Methods This was a double‐blind, randomized, crossover study that enrolled 71 healthy subjects to receive a single subcutaneous dose (0.2 U/kg) of each formulation under automated euglycaemic clamp conditions (ClampArt, level 81 mg/dL, duration 12 hours postdose). Primary PK endpoints were area under the plasma insulin aspart concentration‐time curve from 0 to 12 hours (AUC 0‐12h ) and maximum plasma insulin aspart concentration (C max ). Primary PD endpoints were area under the glucose infusion rate (GIR) time curve from 0 to 12 hours (AUC GIR0‐12h ) and maximum GIR (GIR max ). Insulin aspart in plasma was quantified using immunoaffinity purification followed by ultraperformance liquid chromatography and tandem mass spectrometric detection. The pairwise comparisons of geometric least square mean (LS‐mean) ratio for a 90% confidence interval (CI) of primary PK, and 90% CIs (MYL‐1601D vs. Ref‐InsAsp‐US) and 95% CIs (MYL‐1601D vs. Ref‐InsAsp‐EU) of primary PD variables, were to be within 80% to 125% to show BE. Results MYL‐1601D showed PK BE to both Ref‐InsAsp‐US (AUC 0‐12h geometric LS‐mean ratio 102.17, 90% CI [100.26; 104.11]; C max 106.13 [100.71; 111.85]) and Ref‐InsAsp‐EU (AUC 0‐12h 101.84 [100.04; 103.67]; C max 105.74 [101.09; 110.60]). Likewise, MYL‐1601D showed PD BE to Ref‐InsAsp‐US (AUC GIR_0‐last 99.93; 90% CI [95.74; 104.30]; GIR _max 100.12 [94.46; 106.12]) and Ref‐InsAsp‐EU (AUC GIR_0‐last 96.42; 95% CI [91.17; 101.98]; GIR _max 95.10 [89.37; 101.19]). All three insulin aspart products were well tolerated. Conclusion MYL‐1601D showed BE to Ref‐InsAsp‐US and Ref‐InsAsp‐EU with a comparable safety profile.