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

Abstract

<b><i>Background:</i></b> 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^®). <b><i>Materials and Methods:</i></b> 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_last), and extrapolated to infinity (INS-AUC_inf), maximum plasma insulin concentration (INS-C_max), and the area under the body weight-standardized glucose infusion rate (GIR)-time curve from 0 to 12 hours (GIR-AUC_0-12h) among the three treatments. GIR_max was the main secondary endpoint. <b><i>Results:</i></b> 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_max, INS-AUC_last, and INS-AUC_inf) and glucodynamic activity (GIR-AUC_0-12h, GIR_max) 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. <b><i>Conclusions:</i></b> 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.