Efficacy and Safety of Insulin Lispro Biphasic 25 Compared to Humalog® Mix 25 in Type 2 Diabetes Mellitus Patients

Study Overview
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Brief Summary
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The study is designed to approve non-inferior efficacy and safety of Insulin Lispro Biphasic 25 (Geropharm) compared to Humalog® Mix 25 in Type 2 Diabetes Mellitus Patients.

Official Title
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An Open-label, Randomized, Multi-center, Parallel-group Clinical Trial Comparing the Efficacy and Safety of Insulin Lispro Biphasic 25 (Geropharm, Russia) Humalog® Mix 25 (Lilly France, France) in Type 2 Diabetes Mellitus Patients

Conditions
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Diabetes Mellitus, Type 2, Diabetes Mellitus

Intervention / Treatment
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* Drug: Humalog Mix25
* Drug: Insulin Lispro Biphasic 25


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed written consent Clinical diagnosis of type 2 diabetes mellitus for at least 6 months prior to screening Glycosylated hemoglobin (HbA1c) level of 7.6 to 12.0 % at screening (both values inclusive) Body mass index (BMI) of 18.0 to 35 kg/m2 at screening (both values inclusive) Stable doses OADs for at least 3 months prior to treatment of experimental drug Female patients of childbearing potential who are willing to use two acceptable methods of contraception, (e.g., intra-uterine device plus condom, spermicidal gel plus condom, diaphragm plus condom, etc.), from the time of screening and for the duration of the trial, through trial completion Exclusion Criteria: Acute inflammation disease for 3 weeks prior to screening Deviation of the laboratory results conducted during the screening: Hemoglobin value < 9,0 g/dl; Hematocrit value < 30 %; ALT and AST value > 2 folds as high as maximal normal value; Serum bilirubin value > 1.5 folds as high as maximal normal value History of hematological disorders that can affect the reliability of HbA1c estimation (hemoglobinopathies, hemolytic anemia, etc.) Serious blood loss for 3 months prior to screening (blood donation, surgery procedure, etc.) Contraindication to the use of insulin Lispro Biphasic 25 Insulin resistance over 1.5 U/kg insulin pro day Presence of insulin antibodies in the blood at the screening ˃10 U/ml Use of 3 or more oral antidiabetic drugs (OAD) Presence of severe diabetes complications History or presence of uncontrolled diabetes mellitus for 6 months prior to screening Deviation of vital signs, which can influence to results History of administration of glucocorticoids for 1 year prior to screening History of autoimmune disease, except controlled autoimmune thyroid disease Pregnant and breast-feeding women 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 Administration of any immunosuppressive drugs (Cyclosporinum, Methotrexatum) Incomplete recovery after surgery procedure

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 |
| --- | --- |
| Active Comparator: Humalog® Mix 25<br>Insulin Humalog® Mix 25 twice daily, individually glucose-level based administered doses +/- 1 or 2 OADs in stable doses, started before enrollement | Drug: Humalog Mix25<br>* Subcutaneus injections Humalog® Mix 25 twice daily during 4 weeks of glucose-level based dose titration, 24 weeks of treatment with stable doses<br>|
| Experimental: Insulin Lispro Biphasic 25<br>Insulin Lispro Biphasic 25 twice daily, individually glucose-level based administered doses +/- 1 or 2 OADs in stable doses, started before enrollement | Drug: Insulin Lispro Biphasic 25<br>* Subcutaneus injections Insulin Lispro Biphasic 25 (Geropharm) twice daily during 4 weeks of glucose-level based dose titration, 24 weeks of treatment with stable doses<br>|

What is the study measuring?
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Primary Outcome Measures

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

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 (4+22 weeks) | 
| HbA1c | Change in HbA1c from baseline | 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 | 26 weeks | 
| Insulin Dose | Change in total insulin dose per body weight (U/kg) from baseline | 26 weeks | 
| Body Mass Index | Change in BMI from baseline | 26 weeks | 
| Treatment Satisfaction | Change in overall treatment satisfaction (DTSQ score) from baseline | 26 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Diabetes Mellitus, Type 2, Lispro Biphasic, Insulin