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.