Evaluation of pharmacokinetic and pharmacodynamic similarity of an IDegAsp biosimilar versus the originator in healthy Chinese volunteers.

Abstract

Objectives: 22011 is an insulin degludec/insulin aspart co-formulation (IDegAsp) that shares an identical amino acid sequence with Ryzodeg, the originator IDegAsp. This study aimed to compare the pharmacokinetics (PK), pharmacodynamics (PD), and safety of 22,011 with Ryzodeg.

Methods: In a single-center, randomized, open-label, two-treatment, two-period, two-sequence, crossover, euglycemic clamp study, healthy Chinese adults were randomized to receive 0.5 U/kg of 22,011 and Ryzodeg under fasting conditions. PK was evaluated for up to 120 hours and PD (represented by glucose infusion rate [GIR]) was assessed for up to 24 hours.

Results: Of 46 subjects randomized, all completed both treatment periods and were included in the PK/PD and safety analysis set. Insulin exposure (AUC_{IDeg, 0-24 h}, AUC_{IAsp, 0-12 h}, and C_{max, IAsp}) and activity (GIR_max and AUC_{GIR, 0-24 h}) were comparable (estimates of treatment ratios 0.916 ~ 1.076 for primary PK parameters and 0.946 ~ 1.037 for primary PD parameters), with 90% confidence intervals for the ratios of least square means falling within the range of 0.80 ~ 1.25. Adverse events were similar for both products and no significant safety concerns were noted in the laboratory results, vital signs, or electrocardiogram.

Conclusion: This study demonstrated the PK/PD similarity of 22,011 to Ryzodeg with a comparable safety profile.