Study Comparing the Efficacy and Safety of Insulin Glargine (Basal Insulin)/Lixisenatide (GLP-1 Receptor Agonist) Combination (Soliqua™) in Patients With Type 2 Diabetes Mellitus (T2DM)

Study Overview
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Brief Summary
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Primary Objective: To demonstrate that the simple daily titration algorithm is non-inferior to the weekly titration algorithm according to Canadian labeling. Secondary Objective: To gain additional information on the efficacy and safety of using a simple patient-titration protocol for administration of insulin glargine/lixisenatide fixed-ratio combination (iGlarLixi).

Detailed Description
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The maximum duration of study per patient is approximately 29 weeks including a 2-week screening, a 26-week randomized active-controlled treatment period, and 3-day post-treatment safety follow-up period.

Official Title
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A Randomized, 26-week, Open-label, 2-treatment Arm, Parallel Group Multicenter Study Comparing the Efficacy and Safety of Insulin Glargine/Lixisenatide Fixed-ratio Combination (Soliqua™) Titrated Using a Simple Titration Algorithm (One Unit Daily Adjustment) Compared With Insulin Glargine/Lixisenatide Fixed-ratio Combination (Soliqua™) Titrated by Weekly Adjustment in Patients With Type 2 Diabetes Mellitus (T2DM)

Conditions
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Type 2 Diabetes Mellitus

Intervention / Treatment
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* Drug: INSULIN GLARGINE/LIXISENATIDE HOE901/AVE0010


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Adult subject ≥ 18 years Patients with type 2 diabetes mellitus (T2DM) based on Diabetes Canada 2018 Clinical Practice Guidelines criteria and diagnosed at least 6 months prior to the screening visit Uncontrolled glycemia with an A1c ≥7.5% and ≤10.5% Patients treated for at least 6 months on any basal insulin (including but not limited to insulin glargine, Toujeo®, Degludec®, etc.) ± oral anti-diabetic drug (OADs) The total basal insulin dose must be ≤ 40 units/day The OADs allowed at inclusion are metformin, insulin secretagogues, dipeptidyl-peptidase-4 inhibitors (DPP4) inhibitors and SGLT2 inhibitors; with no change in OAD dose for at least 2 months prior to randomization Body mass index (BMI) between 20 kg/m2 and 40 kg/m2 inclusively Exclusion criteria: History of severe hypoglycemia or hypoglycemia unawareness History of metabolic acidosis, including diabetic ketoacidosis within 1 year prior to screening visit Current or previous (known intolerance to GLP-1s) treatment with glucagon like peptide-1 (GLP-1) receptor agonist Current use of rapid-acting insulin or premix insulins or use of these insulins within 3 months prior to the screening visit Use of systemic glucocorticoids (excluding topical and inhaled forms) for a total duration of 1 week or more within 3 months prior to the screening visit Use of weight loss drugs within 3 months prior to the screening visit Patients with conditions/concomitant diseases that will affect safe participation in this study (e.g. active malignant tumor, major systemic diseases, presence of clinically significant diabetic retinopathy or presence of macular edema likely to require treatment within the study period, etc.) Women of childbearing potential (WOCBP) not protected by an effective contraceptive method of birth control and/or who are unwilling or unable to be tested for pregnancy Positive serum pregnancy test in WOCBP, pregnancy or lactation Clinically relevant history of gastrointestinal disease associated with prolonged nausea and vomiting, including (but not limited to): gastroparesis, unstable (i.e. worsening) or uncontrolled (i.e. prolonged nausea and vomiting) gastroesophageal reflux disease requiring medical treatment within 6 months prior to the time of screening visit History of pancreatitis (unless pancreatitis was related to gallstones and treated with cholecystectomy), pancreatitis during previous treatment with incretin therapies, chronic pancreatitis, pancreatectomy, or stomach/gastric surgery Personal or immediate family history of medullary thyroid cancer or genetic conditions that predispose the patient to medullary thyroid cancer (e.g. multiple endocrine neoplasia syndromes) 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

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: iGlarlixi DAILY<br>Titration Group 1: Addition of 1 unit per day until pre-stated fasting self-monitoring plasma glucose (SMBG) level is reached | Drug: INSULIN GLARGINE/LIXISENATIDE HOE901/AVE0010<br>* Pharmaceutical form: Solution for injection Route of administration: Subcutaneous<br>|
| Active Comparator: iGlarlixi WEEKLY<br>Titration Group 2: Algorithm of weekly adjustment until pre-stated fasting self-monitoring plasma glucose (SMBG) level is reached | Drug: INSULIN GLARGINE/LIXISENATIDE HOE901/AVE0010<br>* Pharmaceutical form: Solution for injection Route of administration: Subcutaneous<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in glycated hemoglobin (HbA1c)% | Absolute mean change in HbA1c from baseline to Week 26; HbA1c is expressed in % (unit) | Baseline to Week 26 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of patients achieving HbA1c ≤7% at Week 26 | Percentage of patients achieving A1c ≤7% | At Week 26 | 
| Change in fasting plasma glucose (FPG) from baseline to Week 12 | Change in FPG from baseline to Week 12 | Baseline to Week 12 | 
| Change in FPG from baseline to Week 26 | Change in FPG from baseline to Week 26 | Baseline to Week 26 | 
| Change in fasting self-monitoring plasma glucose (SMPG) from baseline to Week 12 | Change in fasting SMPG from baseline to Week 12 | Baseline to Week 12 | 
| Change in fasting SMPG from baseline to Week 26 | Change in fasting SMPG from baseline to Week 26 | Baseline to Week 26 | 
| Change in 7-point SMPG profile from baseline to Week 12 | Change in 7-point SMPG profile from baseline to Week 12 | Baseline to Week 12 | 
| Change in 7-point SMPG profile from baseline to Week 26 | Change in 7-point SMPG profile from baseline to Week 26 | Baseline to Week 26 | 
| Change in body weight from baseline to Week 26 | Change in body weight (kg) | Baseline to Week 26 | 
| Percentage of patients achieving A1c ≤7% with no body weight gain and/or hypoglycemia (severe or documented symptomatic (≤3.9 mmol/L) at Week 26 | Composite endpoint expressed as percentage of patients A1c ≤7% with no body weight gain and/or hypoglycemia (severe or documented symptomatic (≤3.9 mmol/L) | Baseline to Week 26 | 
| Insulin glargine dose | Insulin glargine dose (expressed in units) | At Week 26 | 
| Percentage of patients requiring rescue therapy | Percentage of patients requiring rescue therapy during the 26-week open-label treatment period | Baseline to Week 26 | 
| Percentage of patients experiencing at least 1 hypoglycemia episode (≤3.9 mmol/L) over 26 weeks | Percentage of patients experiencing at least 1 hypoglycemia episode defined as ≤3.9 mmol/L | Baseline to Week 26 | 
| Percentage of patients experiencing at least 1 hypoglycemia episode (<3.0 mmol/L) over 26 weeks | Percentage of patients experiencing at least 1 hypoglycemia episode defined as <3.0 mmol/L | Baseline to Week 26 | 
| Annualized rate of hypoglycemia (≤3.9 mmol/L) over 26 weeks | Mean number of hypoglycemia episodes (≤3.9 mmol/L) per patient year of exposure over 1 year | Baseline to Week 26 | 
| Annualized rate of hypoglycemia (<3.0 mmol/L) over 26 weeks | Mean number of hypoglycemia episodes (<3.0 mmol/L) per patient year of exposure over 1 year | Baseline to Week 26 |