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

• Published in: Diabetes, obesity & metabolism Vol. 19; no. 5; pp. 622 - 627
• Main Authors: Kapitza, Christoph, Nowotny, Irene, Lehmann, Anne, Bergmann, Karin, Rotthaeuser, Baerbel, Nosek, Leszek, Becker, Reinhard H. A.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01-05-2017; Wiley Subscription Services, Inc
• Subjects: Adult; Biosimilar Pharmaceuticals - adverse effects; Biosimilar Pharmaceuticals - blood; Biosimilar Pharmaceuticals - pharmacokinetics; Biosimilar Pharmaceuticals - therapeutic use; Cross-Over Studies; Diabetes; Diabetes mellitus (insulin dependent); Diabetes Mellitus, Type 1 - blood; Diabetes Mellitus, Type 1 - drug therapy; Double-Blind Method; Drug Approval; EKG; European Union; Germany - epidemiology; Glucose Clamp Technique; Humans; Hyperglycemia - prevention & control; Hypoglycemia - chemically induced; Hypoglycemia - epidemiology; Hypoglycemia - prevention & control; Hypoglycemic Agents - adverse effects; Hypoglycemic Agents - blood; Hypoglycemic Agents - pharmacokinetics; Hypoglycemic Agents - therapeutic use; Incidence; Insulin; Insulin Lispro - adverse effects; Insulin Lispro - blood; Insulin Lispro - pharmacokinetics; Insulin Lispro - therapeutic use; insulin therapy; Male; Middle Aged; Pharmacodynamics; Pharmacokinetics; phase I‐II study; Recombinant Proteins - adverse effects; Recombinant Proteins - blood; Recombinant Proteins - pharmacokinetics; Recombinant Proteins - therapeutic use; type 1 diabetes; United States; Young Adult; United States > US; pharmacokinetics; type 1 diabetes; phase I-II study; insulin therapy; pharmacodynamics
• ISSN: 1462-8902; 1463-1326
• DOI: 10.1111/dom.12856

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.