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

Diabetes Technol Ther. 2020 Apr;22(4):278-284. doi: 10.1089/dia.2019.0351. Epub 2019 Dec 30.


Background: 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®). Materials and Methods: 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-AUClast), and extrapolated to infinity (INS-AUCinf), maximum plasma insulin concentration (INS-Cmax), and the area under the body weight-standardized glucose infusion rate (GIR)-time curve from 0 to 12 hours (GIR-AUC0-12h) among the three treatments. GIRmax was the main secondary endpoint. Results: 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-Cmax, INS-AUClast, and INS-AUCinf) and glucodynamic activity (GIR-AUC0-12h, GIRmax) 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. Conclusions: 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.

Keywords: Biosimilar; Insulin aspart; Pharmacodynamics; Pharmacokinetics; Phase I study; Type 1 diabetes.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Biosimilar Pharmaceuticals / pharmacokinetics*
  • Blood Glucose / drug effects
  • Cross-Over Studies
  • Diabetes Mellitus, Type 1 / blood
  • Diabetes Mellitus, Type 1 / drug therapy*
  • Double-Blind Method
  • European Union
  • Glucose Clamp Technique*
  • Humans
  • Hypoglycemic Agents / pharmacokinetics*
  • Insulin Aspart / pharmacokinetics*
  • Male
  • Middle Aged
  • Treatment Outcome
  • United States
  • Young Adult


  • Biosimilar Pharmaceuticals
  • Blood Glucose
  • Hypoglycemic Agents
  • Insulin Aspart

Associated data