Efficacy and Safety of GP40081 Сompared to NovoMix® 30 FlexPen® in Type 2 Diabetes Mellitus Patients

Study Overview
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Brief Summary
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This trial is a multi-center, open-label, randomized, parallel group trial in adult patients with T2DM comparing the efficacy and safety of GP40081 (insulin asapart mix 30, GEROPHARM) with that of NovoMix® 30 FlexPen®.

Official Title
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An Open-label, Randomized, Multi-center, Parallel-group Clinical Trial Comparing the Efficacy and Safety of GP40081 (OOO GEROPHARM, Russia) Compared to NovoMix® 30 FlexPen® (Novo Nordisk A/S, Denmark) in Type 2 Diabetes Mellitus Patients

Conditions
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Diabetes Mellitus, Type 2, Diabetes Mellitus

Intervention / Treatment
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* Drug: GP40081
* Drug: NovoMix 30


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed written consent Diabetes mellitus type 2 for at least 6 months before the screening (WHO criteria 1999-2013). Glycated haemoglobin (HbA1c) level of 7.6 to 12.0 % at screening (both values inclusive). Indications for exogenous insulin therapy. Body mass index (BMI) of 18.5 to 40 kg/m2 at screening (both values inclusive). Insulin-naive patients or prior insulin therapy at least 6 months before randomization. The subject is able and willing to comply with the requirements of the study protocol Exclusion Criteria: Contraindication to the use of insulin aspart 30 mix. History of hypersensitivity to any of the active or inactive ingredients of the insulin/insulin analogue preparations used in the trial, OR history of significant allergic drug reactions. History of severe hypoglycemia for 6 months before the screening. History of severe hyperglycemia for 6 months before the screening. Bariatric surgery for 12 months to screening. Glucagon-like peptide-1 (GLP-1)-based therapies for 8 weeks to screening. Insulin resistance over 1.5 U/kg insulin pro day. Change INN of insulin for 6 months before the randomisation. History of treatment any experimental drugs or medical devices for 3 months before the randomisation. Presence of severe diabetes complications. Night work. History of administration of glucocorticoids (14 days or more) for 1 year before the screening. Administration of any immunosuppressive drugs (Cyclosporinum, Methotrexate, Rituximab, etc.). History of vaccination for 6 months before the randomisation. History of autoimmune disease, except vitiligo and controlled autoimmune polyglandular syndrome (APS) types 1-3, except vetiligo and Hashimoto's thyroiditis. Pregnant and breast-feeding women. Deviation of the laboratory results conducted during the screening: Hemoglobin value < 9,0 g/dl; Hematocrit value < 30 %; ALT and AST value > 2 folds or ALT or AST value > 3 folds as high as maximal normal value; Serum bilirubin value > 2 folds as high as maximal normal value (except Gilbert's syndrome). History of haematological disorders that can affect the reliability of HbA1c estimation (haemoglobinopathies, hemolytic anaemia, etc.). Serological evidence of human immunodeficiency virus (HIV), hepatitis B (HbSAg), hepatitis C (HCVAb) or syphilis (Treponema pallidum) antibodies at the screening. Acute inflammation disease for 3 weeks before the screening. History of unstable angina, myocardial infarction, severe arrhythmia, heart failure III or IV NYHA for 1 year before the screening. History of stroke or TIA for 6 months before the screening. Serious blood loss for 3 months before the screening (blood donation, surgery procedure, etc.). The inability of the patient to assess their condition because of mental or physical disorders. History of drug, alcohol abuse for 3 years before the screening. History of oncology disorders for 5 years before the screening. History of transplantation, except 3 months after a corneal transplant. History or presence of a medical condition or disease that in the investigator's opinion would embarrass glycemic control and completion of the study

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: GP40081<br>Subcutaneous (SC), up to Week 26 | Drug: GP40081<br>* 1 ml of the GP40081 contains 100 units soluble insulin aspart/protamine-crystallised insulin aspart in the ratio 30/70. Insulin aspart 30 mix is self-administered drug by SC injection 1-3 times per day before meal intake.<br>* Other names: Insulin aspart 30 mix;|
| Active Comparator: NovoMix® 30 FlexPen®<br>Subcutaneous (SC), up to Week 26 | Drug: NovoMix 30<br>* 1 ml of the NovoMix 30 contains 100 units soluble insulin aspart/protamine-crystallised insulin aspart in the ratio 30/70. Insulin aspart 30 mix is self-administered drug by SC injection 1-3 times per day before meal intake.<br>* Other names: Insulin aspart 30 mix;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Immunogenicity | Change from baseline in titer of antibodies to human insulin | 26 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Glycated hemoglobin | Change in HbA1c from baseline | 26 weeks | 
| Adverse Events frequency and degree | Hypoglycemic episodes (glucose level < 3.9 mmol/l) frequency; Occurrence of local reactions at injection sites; Occurrence allergic reactions | 26 weeks | 
| Fasting Plasma Glucose Level | Change in fasting plasma glucose level from baseline | 26 weeks | 
| Seven-Point Glucose Testing | Change in seven-point glucose testing results from baseline | 22 weeks | 
| Total Insulin Dose | Change in total insulin dose per body weight (U/kg) from baseline | 22 weeks | 
| Body Mass Index | Change in BMI from baseline | 26 weeks | 
| Treatment Satisfaction: The Diabetes Treatment Satisfaction Questionnaire | Change in treatment satisfaction from baseline. Questions 1, 4, 5, 6, 7 and 8 assesses treatment satisfaction (summed these 6 questions). Questions 2 and 3 assess the burden from hyper- and hypoglycemia. DTSQ is The Diabetes Treatment Satisfaction Questionnaire, scored from 0-36 points with higher scores indicating better satisfaction. | 26 weeks | 
| Achievement of Glycated Hemoglobin Goals | The frequency of achievement glycated hemoglobin goals | 26 weeks | 
| Achievement of Glycated Hemoglobin < 7% | The frequency of achievement glycated hemoglobin < 7% ( 7% inclusive) | 26 weeks |