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

ACCESS DATA

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

Similar Datasets

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.

Project description:Background: SAR341402 (SAR-Asp) is a biosimilar/follow-on of the originator insulin aspart-NovoLog®/NovoRapid® (NN-Asp). This study investigated whether the efficacy, safety, and immunogenicity findings for SAR-Asp versus NN-Asp, observed over 6 months in people with type 1 (n = 497) or type 2 diabetes (n = 100) treated with multiple daily injections in combination with insulin glargine (Lantus®), are maintained after 12 months. Materials and Methods: GEMELLI 1 was a multicenter, randomized, open-label, phase 3 study. Participants completing the initial 6-month treatment period continued on SAR-Asp or NN-Asp, as randomized, for a 6-month safety extension. Results: Of the 597 participants randomized, 264 out of 301 (87.7%) and 263 out of 296 (88.9%) assigned to SAR-Asp and NN-Asp, respectively, completed 12 months of treatment. Improved glycemic control was sustained at 12 months in both treatment groups, with similar least-squares mean reductions in glycated hemoglobin (HbA1c) from baseline (SAR-Asp: -0.25%; NN-Asp: -0.26%). Fasting plasma glucose and seven-point self-monitored plasma glucose profile changes, including postprandial glucose excursions, and changes in mealtime and basal insulin dosages were similar between groups. Safety and tolerability, including anti-insulin aspart antibodies (AIAs; incidence, prevalence, titers, cross-reactivity to human insulin), neutralizing antibodies (incidence, prevalence), hypoglycemia, and treatment-emergent adverse events (including hypersensitivity events and injection site reactions), were similar between groups. No relationship was observed between maximum individual AIA titers and change in HbA1c or insulin dose, hypoglycemia, or hypersensitivity reactions or between efficacy/safety measures and subgroups by presence or absence of treatment-emergent AIA. Conclusions: SAR-Asp and NN-Asp demonstrated similar efficacy and safety (including immunogenicity) in people with diabetes over 12 months of treatment.

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.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets