title: Similar pharmacokinetics and pharmacodynamics of rapid-acting insulin lispro products SAR342434 and US- and EU-approved Humalog in subjects with type 1 diabetes.
abstract: To compare the pharmacokinetics (PK) and pharmacodynamics (PD) of 3 rapid-acting insulin lispro products: SAR342434 solution, United States (US)-approved Humalog and European Union (EU)-approved Humalog.
  
  
  
  In a single-centre, randomized, double-blind, 3-treatment, 3-period, 6-sequence, crossover, euglycaemic clamp study (NCT02273258), adult male subjects with type 1 diabetes were randomized to receive 0.3 U/kg of SAR342434 solution, US-approved and EU-approved Humalog under fasted conditions. PK and PD (glucose infusion rate [GIR]) were assessed up to 12 hours.
  
  
  
  Of the 30 subjects randomized, 28 completed all 3 treatment periods. Mean concentration and GIR vs time profiles were similar for all 3 products. Exposure (INS-Cmax, INS-AUClastand INS-AUC) and activity (GIRmaxand GIR-AUC0-12h) of SAR342434, US-approved and EU-approved Humalog were similar in all comparisons (point estimates of treatment ratios, 0.95-1.03 for PK parameters and 1.00-1.07 for PD parameters), with 90% confidence intervals for the ratios of geometric least squares means within the pre-specified bioequivalence limit (0.80-1.25) and no significant differences in time-related parameters. Within-subject variability of exposure and activity was low across the 3 clamps, indicating high day-to-day reproducibility in clamp performance, irrespective of the individual product. Adverse events were similar for all 3 products. No safety concerns were noted in vital signs or in laboratory and electrocardiogram data.
  
  
  
  The results of this study demonstrate similarity in insulin lispro exposure profiles and PD activity of SAR342434 solution to both US- and EU-approved Humalog, and between both US- and EU-approved Humalog, supporting the use of SAR342434 solution for injection as a follow-on product.
authors.affiliation: Profil, Neuss, Germany.
authors.forename: Christoph
authors.identifier: 0000-0002-9700-2373
authors.initials: C
authors.lastname: Kapitza
authors.affiliation: Sanofi-Aventis Deutschland GmbH, Frankfurt Am Main, Germany.
authors.forename: Irene
authors.initials: I
authors.lastname: Nowotny
authors.affiliation: Sanofi-Aventis Deutschland GmbH, Frankfurt Am Main, Germany.
authors.forename: Anne
authors.initials: A
authors.lastname: Lehmann
authors.affiliation: Sanofi-Aventis Deutschland GmbH, Frankfurt Am Main, Germany.
authors.forename: Karin
authors.initials: K
authors.lastname: Bergmann
authors.affiliation: Sanofi-Aventis Deutschland GmbH, Frankfurt Am Main, Germany.
authors.forename: Baerbel
authors.initials: B
authors.lastname: Rotthaeuser
authors.affiliation: Profil, Neuss, Germany.
authors.forename: Leszek
authors.initials: L
authors.lastname: Nosek
authors.affiliation: Sanofi-Aventis Deutschland GmbH, Frankfurt Am Main, Germany.
authors.forename: Reinhard H A
authors.initials: RHA
authors.lastname: Becker
mesh_terms: D000328:Adult; D059451:Biosimilar Pharmaceuticals / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use*; D018592:Cross-Over Studies; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000188:drug therapy*; D004311:Double-Blind Method; D017277:Drug Approval; D005062:European Union; D005858:Germany / Q000453:epidemiology; D015309:Glucose Clamp Technique; D006801:Humans; D006943:Hyperglycemia / Q000517:prevention & control*; D007003:Hypoglycemia / Q000139:chemically induced / Q000453:epidemiology / Q000517:prevention & control*; D007004:Hypoglycemic Agents / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use*; D015994:Incidence; D061268:Insulin Lispro / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D011994:Recombinant Proteins / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use; D014481:United States; D055815:Young Adult
chemical_list: D059451:Biosimilar Pharmaceuticals; D007004:Hypoglycemic Agents; D061268:Insulin Lispro; D011994:Recombinant Proteins; C000623163:SAR342434
keywords: insulin therapy; pharmacodynamics; pharmacokinetics; phase I-II study; type 1 diabetes