Evaluation of biosimilarity of RinGlar® (GEROPHARM LLC, Russia) and Lantus® (Sanofi-Aventis Deutschland GmbH, Germany) using the euglycemic hyperinsulinemic clamp technique in patients with type 1 diabetes: double-blind randomized clinical trial

Background: Prevention of the development of micro-and macrovascular complications in patients with diabetes melli-tus (DM) encouraged the search for insulin analogues that allow imitating, as close as possible, a normal physiological insulin secretion in healthy people. Biosimilars (bioanalogues of reference products) play an important role in the full provision with high-quality insulin medications throughout patients. The program of clinical trials of insulin bioanalogues includes pharmacology studies: pharmacokinetics (PK), pharmacodynamics (PD) and clinical safety research.Aims: To test whether RinGlar® (GEROPHARM LLC, Russia) and Lantus® (Sanofi-Aventis Deutschland GmbH, Germany) have similar PK and PD profiles in a hyperinsulinemic euglycaemic clamp (HEC) setting in patients with type 1 diabetes mellitus. Permission of the Ministry of Health of the Russian Federation No. 150 of 03/03/2016.Materials and methods: The study was conducted in 42 patients with type 1 diabetes aged 18 to 65 years. A doubleblind, randomized, crossover study of comparative PK and PD of drugs was chosen as a study design. The investigational products were injected after achieving a state of euglycemia before the HEC in a single dose of 0.6 U/kg subcutaneously into the subcutaneous fat of the anterior abdominal wall. During the study, regular blood sampling was performed, the amount of insulin glargine in the samples was determined by ELISA. The results are used to calculate the PK parameters and generate the concentration-time curves. The glucose infusion rate was corrected based on the measurement of glycemia. These data are used to calculate the PD parameters.Results: RinGlar® and Lantus® interventions have comparable PK and PD profiles in HEC setting in patients with type 1 diabetes. This is confirmed by the similarity of the main PK/PD parameters, PK/PD curves, and comparable safety. The confidence intervals of the geometric mean ratio were 81.02% - 120.62% for the PK parameter AUCins0-T, and 85.43% - 115.64% for the PD-parameter AUCGIR0_T, which fall within the specified limits of 80% - 125% to establish comparability between drugs.Conclusions: Results of the clinical trial demonstrate the biosimilarity of the products RinGlar® and Lantus®.

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Randomized, double‐blind clinical trial comparing basal insulin peglispro and insulin glargine, in combination with prandial insulin lispro, in patients with type 1 diabetes: IMAGINE 3

Diabetes Obesity and Metabolism ◽

10.1111/dom.12698 ◽

2016 ◽

Vol 18 (11) ◽

pp. 1081-1088 ◽

Cited By ~ 29

Author(s):

R. M. Bergenstal ◽

H. Lunt ◽

E. Franek ◽

F. Travert ◽

J. Mou ◽

...

Keyword(s):

Clinical Trial ◽

Type 1 Diabetes ◽

Insulin Glargine ◽

Insulin Lispro ◽

Basal Insulin ◽

Double Blind ◽

Prandial Insulin ◽

Double Blind Clinical Trial

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Efficacy and safety of Subetta add-on therapy in type 1 diabetes mellitus: The results of a multicenter, double-blind, placebo-controlled, randomized clinical trial

Diabetes Research and Clinical Practice ◽

10.1016/j.diabres.2018.04.044 ◽

2018 ◽

Vol 142 ◽

pp. 1-9 ◽

Cited By ~ 3

Author(s):

Ashot Mkrtumyan ◽

Tatyana Romantsova ◽

Sergei Vorobiev ◽

Anna Volkova ◽

Natalia Vorokhobina ◽

...

Keyword(s):

Diabetes Mellitus ◽

Clinical Trial ◽

Type 1 Diabetes ◽

Type 1 Diabetes Mellitus ◽

Randomized Clinical Trial ◽

Efficacy And Safety ◽

Double Blind ◽

Double Blind Placebo

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Results of the Estimation of Biosimilarity of RinLiz® (LLC «GEROPHARM», Russia) and Humalog® (Lilly France, France) Using the Method of the Hyperinsulinemic Eulygemic Clamp on Healthy Voluntary

Drug development & registration ◽

10.33380/2305-2066-2020-9-2-124-131 ◽

2020 ◽

Vol 9 (2) ◽

pp. 124-131

Author(s):

A. Yu. Mayorov ◽

I. A. Fedotov ◽

R. V. Drai ◽

O. I. Avdeeva ◽

I. E. Makarenko

Keyword(s):

Insulin Lispro ◽

Geometric Mean ◽

Subcutaneous Fat ◽

Subcutaneous Administration ◽

Recombinant Human Insulin ◽

Double Blind ◽

Clinical Safety ◽

Software Packages ◽

Blood Glucose Profile ◽

High Degree

Introduction. Insulin is the most effective hypoglycemic agent currently used in the clinical practice. Compared with recombinant human insulin, insulin lispro have a blood glucose profile that is much closer to physiological. The clinical trials program of insulin bioassays includes pharmacology studies: pharmacokinetics (PK), pharmacodynamics (PD), and a clinical safety study.Aim. To compare PK and PD of RinLiz® U100, solution for intravenous and subcutaneous administration (LLC «GEROFARM», Russia) and Humalog® U100, solution for intravenous and subcutaneous administration (Lilly France, France) in hyperinsulinemic euglycemic clamp.Materials and methods. This was randomized double-blind, two-arm crossover study in 28 healthy volunteers (NCT03604575). The studied preparations were injected before the clamp with a dose of 0.3 U/kg once subcutaneously in the area of subcutaneous fat in the anterior abdominal wall. During the study, regular blood sampling was performed; the amount of insulin lispro was determined by ELISA in the samples. The results of the determination were used to calculate the PK parameters and construct the curves «concentration – time». Based on the measurement of glycemia, the glucose infusion rate was adjusted. These data were used to calculate the PD parameters. The comparability of the studied drugs was considered proven if 90 % confidence intervals (CI) for the ratio of geometric mean PK parameters Cins. max and AUCins. 0-8 and 95 % CI for the ratio of geometric mean PD parameters GIRmax and AUCGIR0-8,5 were in the range of 80–125 %. Statistical data processing and presentation of the results was carried out using software packages R 3.4.2.Results and discussion. In the course of CI comparative PK and PD of RinLiz® and Humalog®, it was revealed that they have comparable PK and PD profiles. The CI for the logarithmically converted ratios of the values of the PK parameters was Cins. max 85.99–96.85 % and AUCins. 0-8 90.58–97.28 %, the PD of the parameters were 95.64–118.94 for GIRmax and 96.5–121.36 for AUCGIR0-8.5, all the CIs correspond to the set the boundaries of 80–125 % to establish comparability between RinLiz® and the original drug.Conclusion. The results demonstrated the high degree of similarity of RinLiz® U100 and Humalog® U100 in terms of PK, PD profiles and safety.

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