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

Sci Rep. 2021 Nov 25;11(1):22931. 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.

Publication types

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

MeSH terms

  • Adult
  • Biomarkers / blood
  • Biosimilar Pharmaceuticals / administration & dosage
  • Biosimilar Pharmaceuticals / adverse effects
  • Biosimilar Pharmaceuticals / pharmacokinetics*
  • Blood Glucose / drug effects*
  • Blood Glucose / metabolism
  • Cross-Over Studies
  • Double-Blind Method
  • Healthy Volunteers
  • Humans
  • Hypoglycemic Agents / administration & dosage
  • Hypoglycemic Agents / adverse effects
  • Hypoglycemic Agents / pharmacokinetics*
  • Insulin Aspart / administration & dosage
  • Insulin Aspart / adverse effects
  • Insulin Aspart / pharmacokinetics*
  • Japan
  • Male
  • Middle Aged
  • Therapeutic Equivalency
  • Young Adult

Substances

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