Dataset Information

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.

ABSTRACT:

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 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.

SUBMITTER: Kapitza C

PROVIDER: S-EPMC7898688 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature

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Publications

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.

Kapitza Christoph C Nosek Leszek L Schmider Wolfgang W Teichert Lenore L Mukherjee Bhaswati B Nowotny Irene I

Diabetes, obesity & metabolism 20201210 3

<h4>Aim</h4>To compare the pharmacokinetic exposure of SAR341402 Mix 70/30 (SAR<sub>Asp</sub> -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.<h4>Materials and methods</h4>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 underw ...[more]

PMID: 33236518

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Project description:IntroductionThe biosimilar SAR341402 insulin aspart (SAR-Asp) was compared to its originator NovoLog®/NovoRapid® insulin aspart (NN-Asp) in terms of efficacy, safety, and immunogenicity, in adults with type 1 or type 2 diabetes switching from different rapid-acting insulin analogs.MethodsThis phase 3, randomized, open-label, multinational, 52-week study (GEMELLI 1) enrolled participants with type 1 or type 2 diabetes (n?=?597). At randomization, participants transitioned from NovoLog/NovoRapid (n?=?380) or Humalog®/Liprolog® (n?=?217) to equivalent (1:1) doses (or a dose at the discretion of the investigator) of either SAR-Asp or NN-Asp (1:1 randomization). Participants were treated with multiple daily injections in combination with insulin glargine 100 U/mL (Lantus®). In this subgroup analysis, efficacy measures (change in hemoglobin A1c [HbA1c], insulin dose [total, basal and mealtime]), and safety outcomes (hypoglycemia incidence, adverse events, anti-insulin aspart antibodies) of SAR-Asp were compared with those of NN-Asp separately according to the participants' prestudy mealtime insulin.ResultsAt week 26 (primary efficacy endpoint), change in HbA1c was similar between SAR-Asp and NN-Asp in those participants pre-treated with NovoLog/NovoRapid (least squares [LS] mean difference?-?0.04%, 95% confidence interval [CI]?-?0.182 to 0.106%) or Humalog/Liprolog (LS mean difference -?0.15%, 95% CI?-?0.336 to 0.043%) (P value for treatment by subgroup interaction?=?0.36). This HbA1c response persisted over the 52 weeks of the study similarly for both treatments within each subgroup. In both subgroups, changes in insulin doses were similar between treatments over 26 weeks and 52 weeks, as were the incidences of severe or any hypoglycemia, adverse events (including hypersensitivity and injection site reactions), and anti-insulin aspart antibodies.ConclusionsEfficacy and safety (including immunogenicity) profiles of SAR-Asp are similar to those of NN-Asp over 52 weeks in adults with diabetes irrespective of prior type of mealtime insulin.Trial registrationClinicalTrials.gov identifier: NCT03211858.

Dataset Information

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

Materials and methods

Results

Conclusions

Publications

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.

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