Efficacy and Safety of the Insulin Glargine/Lixisenatide Fixed Ratio Combination Versus Insulin Glargine in Patients With Type 2 Diabetes (LixiLan-India)

Study Overview
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Brief Summary
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Primary Objective: To demonstrate the superiority of the insulin glargine/lixisenatide fixed ratio combination (FRC) to insulin glargine by demonstrating change in glycosylated hemoglobin (HbA1c). Secondary Objectives: To assess the effects of the FRC in comparison with insulin glargine on: Percentage of patients reaching HbA1c targets (<7% ); Glycemic control in relation to a meal as evaluated by 2-hour Post-prandial Plasma Glucose; (PPG); Body weight Fasting Plasma Glucose (FPG); Percentage of patients reaching HbA1c targets of <7% with no body weight gain and no hypoglycemia (as defined in the evaluation criteria); 7-point Self-Monitoring Plasma Glucose (SMPG) profile; Insulin glargine dose. To assess the safety and tolerability in each treatment group.

Detailed Description
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The maximum study duration per patient is 33 weeks.

Official Title
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A Randomized, 24-week, Controlled, Open Label, Parallel Arm, Multicenter Study Comparing the Efficacy and Safety of the Insulin Glargine/Lixisenatide Fixed Ratio Combination to Insulin Glargine in Type 2 Diabetes Patients, Inadequately Controlled on Basal Insulin With or Without Metformin

Conditions
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Type 2 Diabetes Mellitus

Intervention / Treatment
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* Drug: INSULIN GLARGINE/LIXISENATIDE (HOE901/AVE0010)
* Drug: INSULIN GLARGINE (HOE901)
* Drug: Metformin
* Drug: Insulin Glulisine (HMR1964)


Participation Criteria
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Eligibility Criteria
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Inclusion criteria : Patients with type 2 diabetes mellitus (T2DM) diagnosed for at least 1 year before the screening visit, At screening: Age should be ≥ 18 years of age to < 65 years; Glycosylated hemoglobin (HbA1c) at screening visit ≥ 7.5% or ≤ 10%; Body mass index (BMI) ≥ 19 kg/m2 and ≤ 40 kg/m2. Patients who have been treated with a basal insulin for at least 6 months before the screening visit, and who have been on a stable basal insulin regimen (ie, type of insulin and time/frequency of the injection), for at least 3 months before the screening visit. The stable total daily dose should be within the range of 15-40 U, both inclusive, on the day of screening, but individual fluctuations of ± 20% within 2 months prior to screening are acceptable. Exclusion criteria: Use of oral or injectable glucose-lowering agents other than those stated in the inclusion criteria in the 3 months before screening. Previous use of insulin regimen other than basal insulin eg, prandial or pre-mixed insulin (Note: Short term treatment due to intercurrent illness including gestational diabetes is allowed at the discretion of the investigator). For patients taking metformin, any contraindication to metformin use, according to local labeling. For patient not treated with metformin at screening: severe renal function impairment with an estimated glomerular filtration rate (eGFR) <30 mL/min/1.73m2 or end-stage renal disease. Personal or immediate family history of medullary thyroid cancer (MTC) or genetic condition that predisposes to MTC (eg, multiple endocrine neoplasia syndromes). Clinically relevant history of gastrointestinal disease associated with prolonged nausea and vomiting, including (but not limited to): gastroparesis, unstable (ie, worsening) or not controlled (ie, prolonged nausea and vomiting) gastroesophageal reflux disease requiring medical treatment, within 6 months prior to the time of screening visit; or history of surgery affecting gastric emptying. History of pancreatitis (unless pancreatitis was related to gallstones and cholecystectomy has been performed), pancreatitis during previous treatment with incretin therapies, chronic pancreatitis, pancreatectomy. Average insulin glargine daily dose <20 U or >50 U calculated for the last 3 days before Visit 6. Amylase and/or lipase >3 upper limit normal (ULN) at Visit 5 (Week -1). The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 64 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: Tested Drug<br>Insulin glargine/lixisenatide fixed ratio combination (FRC) | Drug: INSULIN GLARGINE/LIXISENATIDE (HOE901/AVE0010)<br>* Pharmaceutical form: Injection Route of administration: Subcutaneous<br>* Other names: Soliqua, Insulin Glargine/Lixisenatide Fixed Ratio Combination;Drug: Metformin<br>* Pharmaceutical form: Tablet Route of administration: Oral<br>Drug: Insulin Glulisine (HMR1964)<br>* Pharmaceutical form: Injection Route of administration: Subcutaneous<br>* Other names: Apidra;|
| Active Comparator: Control Drug<br>Insulin glargine (Lantus®) | Drug: INSULIN GLARGINE (HOE901)<br>* Pharmaceutical form: Injection Route of administration: Subcutaneous<br>* Other names: Lantus®;Drug: Metformin<br>* Pharmaceutical form: Tablet Route of administration: Oral<br>Drug: Insulin Glulisine (HMR1964)<br>* Pharmaceutical form: Injection Route of administration: Subcutaneous<br>* Other names: Apidra;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in HbA1c | Mean change in glycosylated hemoglobin (HbA1c) from baseline to Week 24 | From baseline to Week 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Patients with HbA1c <7% | Number of patients reaching HbA1c <7 % at the end of Week 24 | At Week 24 | 
| Change in 2-hour Post prandial glucose (PPG) | Change in 2-hour PPG from baseline to Week 24 | From baseline to Week 24 | 
| Change in body weight | Change in body weight from baseline to Week 24 | From baseline to Week 24 | 
| Patients with HbA1c <7% with no body weight gain and no hypoglycemia | Number of patients reaching HbA1c <7% with no body weight gain and no hypoglycemia at the end of Week 24 | At Week 24 | 
| Change in Fasting Plasma Glucose | Mean change in FPG from baseline to Week 24 | From baseline to Week 24 | 
| Adverse events (AE) | Number of AEs | Up to 33 weeks | 
| Patients with HbA1c <7% with no body weight gain | Number of patients reaching HbA1c <7% with no body weight gain at the end of Week 24 | At Week 24 | 
| Change in SMPG profiles | Change in 7-point self-monitoring plasma glucose (SMPG) profiles from baseline to Week 24 | From baseline to Week 24 |