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Similar pharmacokinetics and pharmacodynamics of rapid‐acting insulin lispro products SAR342434 and US ‐ and EU ‐approved Humalog in subjects with type 1 diabetes
Author(s) -
Kapitza Christoph,
Nowotny Irene,
Lehmann Anne,
Bergmann Karin,
Rotthaeuser Baerbel,
Nosek Leszek,
Becker Reinhard H. A.
Publication year - 2017
Publication title -
diabetes, obesity and metabolism
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.445
H-Index - 128
eISSN - 1463-1326
pISSN - 1462-8902
DOI - 10.1111/dom.12856
Subject(s) - bioequivalence , medicine , insulin lispro , crossover study , pharmacodynamics , pharmacokinetics , confidence interval , european union , adverse effect , randomized controlled trial , type 2 diabetes , insulin glargine , pharmacology , diabetes mellitus , endocrinology , placebo , alternative medicine , pathology , business , economic policy
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 ‐C max , INS‐AUC last and INS‐AUC ) and activity ( GIR max and GIR‐AUC 0‐12h ) 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.