Dataset Information

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.

SUBMITTER: Hovelmann U

PROVIDER: S-EPMC9292719 | biostudies-literature |

REPOSITORIES: biostudies-literature

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