Non-inferiority Study to Compare the Efficacy and Safety of Mylan's Insulin Glargine With Lantus® in Type 2 Diabetes Mellitus Patients (INSTRIDE 2)

Study Overview
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Brief Summary
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To test whether Mylan's insulin glargine once daily is non-inferior to Lantus® once daily (both administered in combination with other anti-diabetic drugs) based on the change in HbA1c from baseline to 24 weeks

Detailed Description
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This trial is a multi-center, open-label, randomized, parallel group trial in patients with T2DM comparing the efficacy and safety of Mylan's insulin glargine with that of Lantus®. Patients with an established diagnosis of T2DM per ADA 2014 criteria and who satisfy the selection criteria will be included in the trial. This will be followed by a 24-week randomized, comparative, parallel-assignment treatment period with Mylan's insulin glargine or Lantus® (in addition to other anti-diabetic drugs). After the treatment period, there will be a follow-up visit; 4 weeks after the patient has been put back on approved medications.

Official Title
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An Open-label, Randomized, Multi-center, Parallel Group Clinical Trial Comparing the Efficacy and Safety of Mylan's Insulin Glargine With Lantus® in Type 2 Diabetes Mellitus Patients

Conditions
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Type 2 Diabetes

Intervention / Treatment
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* Drug: Mylan's insulin glargine
* Drug: Lantus®


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with an established diagnosis of T2DM per ADA 2014 criteria who also fulfill the following: Diagnosis established 1 year prior to screening Insulin-naïve OR On Lantus® once daily at stable dose (±15% variation in dose) for at least 3 months prior to screening Body mass index (BMI) of 18.50 to 40.00 kg/m2 at screening (both values inclusive). Stable weight, with no more than 5 kg gain or loss, in the 3 months prior to screening; this information will be collected by patient interview during medical history. Hemoglobin ≥9.0 g/dL at screening Glycosylated hemoglobin (HbA1c) of <10.5% or between 7.5 to 10.5% for insulin naïve patients at screening. Exclusion Criteria: History of hypersensitivity to any of the active or inactive ingredients of the insulin/insulin analog preparations used in the trial, OR history of significant allergic drug reactions. History of use of animal insulin within the last 3 years, any insulin other than Lantus® within the last 3 months prior to screening, or use of biosimilar insulin glargine at any time prior to screening. Patients requiring basal-bolus insulin therapy or who in the opinion of the investigator require mealtime insulin in order to achieve glycemic control. Regular use of immune-modulator therapy in the 1 year prior to screening. History of ≥2 episodes of severe hypoglycemia within the 6 months before screening or history of hypoglycemia unawareness (a sample questionnaire is provided in Appendix I) as judged by the investigator. History of ≥1 episode of hyperglycemic hyperosmolar coma or emergency room visits for uncontrolled diabetes leading to hospitalization within the 6 months prior to screening. Serological evidence of human immunodeficiency virus (HIV), hepatitis B (HbSAg) or hepatitis C (HCVAb) antibodies at screening. History of drug or alcohol dependence or abuse during the 1 year prior to screening. Receipt of another investigational drug in the 3 months prior to screening (or as per local regulations), or if the screening visit is within 5 half-lives of another investigational drug (whichever is longer), or scheduled to receive another investigational drug during the current trial period.

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: Mylan's insulin Glargine<br>receive Mylan's insulin Glargine | Drug: Mylan's insulin glargine<br>* Patients who are randomized to receive Mylan's insulin glargine during the comparative phase will receive the same dose as the dose of Lantus® received during the screening period. The recommended starting dose of Mylan's insulin glargine or Lantus®, in patients with T2DM who are not currently treated with insulin is 10 units (or 0.2 Units/kg) once daily, which should subsequently be adjusted every week if essential.<br>|
| Active Comparator: Lantus®<br>receive Lantus® | Drug: Lantus®<br>* For patients who are randomized to receive Lantus® during the comparative phase the dose of Lantus® will be equal to the dose received during the screening period.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in HbA1c From Baseline to 24 Weeks |  | 24 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of Hypoglycemic Events Per 30 Days | The change from baseline at 12 and 24 weeks is reported | Baseline and up to 24 weeks | 
| Hypoglycemia Occurrence | Overall hypoglycemic incidence during treatment period | 24 weeks | 
| Change in Total Insulin Antibody Percent Binding for Mylan's Insulin Glargine Assay Over Time | Comparison of change from Baseline in Immunogenicity | Week 12 and week 24 | 
| Change in Total Insulin Antibody Percent Binding for Lantus Assay Over Time | Comparison of change from Baseline in Immunogenicity | week 12 and week 24 | 
| Change in Cross-Reactive Insulin Antibody Percent Binding for Mylan's Insulin Glargine Assay Over Time | Comparison of change from Baseline in Immunogenicity | week 12 and week 24 | 
| Change in Cross-Reactive Insulin Antibody Percent Binding for Lantus Assay Over Time | Comparison of change from Baseline in Immunogenicity | Week 12 and week 24 |