A single‐dose euglycaemic clamp study in two cohorts to compare the exposure of SAR341402 (insulin aspart) Mix 70/30 with US‐ and European‐approved versions of insulin aspart Mix 70/30 and SAR341402 rapid‐acting solution in subjects with type 1 diabetes

AIM: To compare the pharmacokinetic exposure of SAR341402 Mix 70/30 (SAR(Asp)‐Mix) with US‐ and European (EU)‐approved versions of insulin aspart Mix 70/30 (NovoLog Mix 70/30 [NN‐Mix‐US]/NovoMix 30 [NN‐Mix‐EU]) and SAR341402 insulin aspart solution (SAR‐Asp) in subjects with type 1 diabetes. MATERIALS AND METHODS: This was a randomized, double‐blind, crossover trial in two cohorts. Fifty‐two subjects received a single subcutaneous 0.3 U/kg dose of each treatment and underwent a euglycaemic clamp procedure lasting for a maximum of 24 hours after dosing. In cohort 1, subjects (N = 36) were exposed once each to SAR(Asp)‐Mix, NN‐Mix‐US and NN‐Mix‐EU. In cohort 2, subjects (N = 16) were exposed once each to SAR(Asp)‐Mix and SAR‐Asp. RESULTS: Of the 52 subjects randomized, 48 completed all treatment periods. In cohort 1, the extent of exposure (total and maximum concentration) was similar among the three treatments, with the 90% confidence intervals for pairwise treatment ratios meeting the predefined acceptance range (0.80 to 1.25). In cohort 2, statistically significant differences (P < .001) in early (0‐4 hours) and intermediate (4‐12 hours) exposure to SAR(Asp)‐Mix compared with SAR‐Asp were observed, all exceeding a 20% difference. Pharmacodynamic results were in support of the pharmacokinetic findings for both cohorts. All treatments were well tolerated and there were no relevant differences in safety variables among treatments. CONCLUSIONS: SAR(Asp)‐Mix showed similar pharmacokinetic exposure to commercially available insulin aspart Mix 70/30 formulations, and a distinct exposure profile compared with SAR‐Asp.