Single-Dose Euglycemic Clamp Study Demonstrating Pharmacokinetic and Pharmacodynamic Similarity Between SAR341402 Insulin Aspart and US- and EU-Approved Versions of Insulin Aspart in Subjects with Type 1 Diabetes.

The objective of this study was to demonstrate the pharmacokinetic and pharmacodynamic similarity among SAR341402 insulin aspart biosimilar/follow-on product, United States-sourced insulin aspart (NovoLog), and European Union-sourced insulin aspart (NovoRapid). This was a single-center, randomized, double-blind, 3-treatment, 3-period, single-dose, crossover euglycemic study (NCT03202875) in 30 adult male subjects with type 1 diabetes (T1D). Subjects received 0.3 U/kg of each treatment under fasted conditions and underwent a 12-h euglycemic clamp technique to assess pharmacokinetic and pharmacodynamic activity for up to 12 h. Primary endpoints were area under the plasma insulin concentration-time curve from time zero to the last quantifiable concentration (INS-AUC), and extrapolated to infinity (INS-AUC), maximum plasma insulin concentration (INS-C), and the area under the body weight-standardized glucose infusion rate (GIR)-time curve from 0 to 12 hours (GIR-AUC) among the three treatments. GIR was the main secondary endpoint. Of the 30 subjects randomized, 29 completed all 3 treatment periods. Pharmacokinetic and pharmacodynamic profiles were similar in all groups. The extent of exposure (INS-C, INS-AUC, and INS-AUC) and glucodynamic activity (GIR-AUC, GIR) was similar among the three treatments. The corresponding 90% confidence intervals for pairwise treatment ratios were completely contained within the limits of 80%-125%. SAR341402 was well tolerated. The present study demonstrated similar pharmacokinetic exposure profiles and glucodynamic potency among SAR341402, NovoLog, and NovoRapid in subjects with T1D, supporting further clinical evaluation of SAR341402 as a biosimilar/follow-on product.