Pharmacokinetic and pharmacodynamic similarity between SAR341402 insulin aspart and Japan-approved NovoRapid in healthy Japanese subjects

Masanari Shiramoto,Hiroki Takagi,Hideya Muto,Wolfgang Schmider,Irene Nowotny,Tatsuya Yoshihara,Miyuki Kajiwara

doi:10.1038/s41598-021-02410-z

Abstract

This study compared the pharmacokinetic and glucodynamic profiles of biosimilar SAR341402 insulin aspart to Japan-approved insulin aspart (NovoRapid) in healthy Japanese males. In this single-center, randomized, double-blind, single-dose, two-period, crossover study, subjects received 0.3 U/kg of SAR341402 or NovoRapid before undergoing a 10 h euglycemic clamp procedure. Plasma insulin aspart concentrations and blood glucose levels were measured, and glucose infusion rates (GIRs) were assessed. Primary endpoints were maximum plasma insulin aspart concentration (INS-Cmax), area under the plasma insulin concentration–time curve to the last quantifiable concentration (INS-AUClast), area under the GIR–time curve during the clamp (GIR-AUC0–10 h), and maximum GIR (GIRmax). Forty subjects were randomized with 39 completing both treatment periods. Pharmacokinetic exposure showed a mean ratio between products of 1.00 (90% confidence interval [CI] 0.94–1.05) for INS-Cmax and 1.02 (90% CI 1.00–1.04) for INS-AUClast. Glucodynamic activity showed a mean ratio between products of 1.00 (95% CI 0.93–1.06) for GIR-AUC0–10 h and 1.01 (95% CI 0.95–1.08) for GIRmax. The 90% CIs for pairwise treatment ratios were within the predefined equivalence range of 0.80–1.25. Both treatments were well tolerated. We concluded that similar pharmacokinetic exposure and glucodynamic potency were shown for SAR341402 and NovoRapid in healthy Japanese males.

Highlights

This study compared the pharmacokinetic and glucodynamic profiles of biosimilar SAR341402 insulin aspart to Japan-approved insulin aspart (NovoRapid) in healthy Japanese males
Similar pharmacokinetic exposure and pharmacodynamic activity were shown for SAR-Asp versus both United States (US)-reference and EU-reference NN-Asp in a euglycemic clamp study in subjects with type 1 diabetes (T1D)[9]
Similar efficacy, safety and immunogenicity of SAR-Asp and NN-Asp were reported in a multinational, randomized phase 3 study among patients with T1D and type 2 diabetes (T2D) using insulin glargine 100 U/mL (Lantus) as the basal insulin[10,11]

Summary

Introduction

This study compared the pharmacokinetic and glucodynamic profiles of biosimilar SAR341402 insulin aspart to Japan-approved insulin aspart (NovoRapid) in healthy Japanese males. In this single-center, randomized, double-blind, single-dose, two-period, crossover study, subjects received 0.3 U/kg of SAR341402 or NovoRapid before undergoing a 10 h euglycemic clamp procedure. Similar pharmacokinetic exposure and pharmacodynamic activity were shown for SAR-Asp versus both US-reference and EU-reference NN-Asp in a euglycemic clamp study in subjects with type 1 diabetes (T1D)[9]. The present study was designed to show similar pharmacokinetic and glucodynamic profiles for SAR-Asp versus Japan-reference NovoRapid (hereafter called NN-Asp-Jp) in healthy Japanese subjects. Subjects were enrolled at Hakata Clinic and included Japanese males aged 20–55 years (both inclusive) with a body mass index of 18.0–28.0 kg/m2, certified as healthy by a comprehensive clinical assessment that included his past medical history, normal vital signs, normal 12-lead electrocardiogram (ECG) parameters and laboratory parameters within the normal ranges

Methods

Results

Conclusion