Non-inferiority Study to Compare the Efficacy and Safety of Mylan's Insulin Glargine With Lantus® in Type 1 Diabetes Mellitus Patients (INSTRIDE 1)

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 (based on change in HbA1c from baseline to 24 weeks) when administered in combination with mealtime insulin lispro.

Detailed Description
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This trial is a multicenter, open-label, randomized, parallel-group trial in patients with Type 1 Diabetes Mellitus (T1DM) comparing the efficacy and safety of Mylan's insulin glargine with that of Lantus®.

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 1 Diabetes Mellitus Patients

Conditions
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Type 1 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 T1DM per ADA 2014 criteria Body mass index (BMI) of 18.5 to 35 kg/m2 at screening (both values inclusive). Glycosylated hemoglobin (HbA1c) ≤9.5% at screening. Hemoglobin ≥9.0 g/dL at screening. Exclusion Criteria: 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 use of animal insulin within the last 3 years or use of biosimilar insulin glargine at any time prior. History of use of a regular immunomodulator 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 episodes of diabetic ketoacidosis 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.

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 plus insulin lispro. | Drug: Mylan's insulin glargine<br>* All patients will be shifted from their current mealtime insulin to insulin lispro at the start of the run-in period, and will continue on this for the complete trial. During the 6 week run-in period the doses of Lantus® and insulin lispro will be titrated (if required) to ensure diabetes control. After the run-in period, patients will be randomized to receive either Mylan's insulin glargine (in place of Lantus®), or to continue on Lantus®. During the period from 12 to 24 weeks dose titration will be kept to a minimum.<br>|
| Active Comparator: Lantus®<br>Receive Lantus® plus insulin lispro | Drug: Lantus®<br>* All patients will be shifted from their current mealtime insulin to insulin lispro at the start of the run-in period; and will continue on this for the complete trial. During the 6week run-in period the doses of Lantus® and insulin lispro will be titrated (if required) to ensure diabetes control. After the run-in period, patients will be randomized to receive either Mylan's insulin glargine (in place of Lantus®), or to continue on Lantus®. During the period from 12 to 24 weeks dose titration will be kept to a minimum.<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 |
| --- | --- | --- |
| Summary of Actual and Change From Baseline in HbA1c |  | 24 and 52 weeks | 
| Change From Baseline in FPG Over Time |  | 24 and 52 weeks | 
| Change From Baseline in 8-point SMBG Profile Over Time |  | 24 and 52 weeks | 
| Change in Total Daily Insulin Dose Per Unit Body Weight From Baseline Over Time |  | 24 and 52 weeks | 
| Rate of Hypoglycemic Events Per 30 Days Over Time |  | 24 and 52 weeks | 
| Hypoglycemia Occurrence |  | 52 weeks | 
| Occurrence of Local and Systematic Reactions |  | 52 weeks | 
| Change in Total Insulin Antibody Percent Binding for Mylan's Insulin Glargine Assay Over Time |  | 24 and 52 weeks | 
| Change in Total Insulin Antibody Percent Binding for Lantus Assay Over Time |  | 24 and 52 weeks | 
| Change in Cross-reactive Insulin Antibody Percent Binding for Mylan's Insulin Glargine Assay Over Time |  | 24 and 52 weeks | 
| Change in Cross-reactive Insulin Antibody Percent Binding for Lantus Assay Over Time |  | 24 and 52 weeks | 
| Proportion of Patients With HbA1c < 7% |  | 24 and 52 weeks |