Similar pharmacokinetics and pharmacodynamics of rapid-acting insulin lispro products SAR342434 and US- and EU-approved Humalog in subjects with type 1 diabetes.

Abstract

AIM:

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.

METHODS:

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.

RESULTS:

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-AUClast and INS-AUC) and activity (GIRmax and 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.

CONCLUSIONS:

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: Christoph Kapitza, Irene Nowotny, Anne Lehmann, Karin Bergmann, Baerbel Rotthaeuser, Leszek Nosek, Reinhard H A Becker
• Journal: Diabetes, obesity & metabolism (Diabetes Obes Metab) Vol. 19 Issue 5 Pg. 622-627 (05 2017) ISSN: 1463-1326 [Electronic] England
• PMID: 27987252 (Publication Type: Clinical Trial, Comparative Study, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: © 2016 John Wiley & Sons Ltd.

Chemical References

• Biosimilar Pharmaceuticals
• Hypoglycemic Agents
• Insulin Lispro
• Recombinant Proteins
• SAR342434

Topics

• Adult
• Biosimilar Pharmaceuticals (adverse effects, blood, pharmacokinetics, therapeutic use)
• Cross-Over Studies
• Diabetes Mellitus, Type 1 (blood, drug therapy)
• Double-Blind Method
• Drug Approval
• European Union
• Germany (epidemiology)
• Glucose Clamp Technique
• Humans
• Hyperglycemia (prevention & control)
• Hypoglycemia (chemically induced, epidemiology, prevention & control)
• Hypoglycemic Agents (adverse effects, blood, pharmacokinetics, therapeutic use)
• Incidence
• Insulin Lispro (adverse effects, blood, pharmacokinetics, therapeutic use)
• Male
• Middle Aged
• Recombinant Proteins (adverse effects, blood, pharmacokinetics, therapeutic use)
• United States
• Young Adult