Efficacy and Safety of Sotagliflozin Versus Placebo in Participants With Type 2 Diabetes Mellitus on Background of Sulfonylurea Alone or With Metformin

Study Overview
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Brief Summary
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Primary Objective: To demonstrate the superiority of Sotagliflozin 400 milligrams (mg) versus placebo on Hemoglobin A1c (HbA1c) reduction at Week 26 in participant with type 2 diabetes (T2D) who have inadequate glycemic control with a Sulfonylurea alone or in combination with Metformin. Secondary Objectives: To compare Sotagliflozin 400 mg versus placebo based on: Change from baseline in fasting plasma glucose (FPG). Change from baseline in systolic blood pressure (SBP) for participants with baseline SBP ≥130 millimeter of mercury (mm Hg). Change from baseline in SBP for all participants. Change from baseline in body weight. Percentage of participants with HbA1c <6.5% and <7.0%. To evaluate the safety of Sotagliflozin 400 mg versus placebo throughout the 79-week trial.

Detailed Description
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The duration per participants is up to 85 weeks, including a Screening Period consisting of a Screening phase of up to 2 weeks and a 2-week single-blind Run-in phase, a 26-week double blind Core Treatment Period, a 53 week double blind Extension, and a 2-week post treatment Follow-up period to collect safety information.

Official Title
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A Randomized, Double-blind, Placebo-controlled, Parallel-group, Multicenter Study to Evaluate the Efficacy and Safety of Sotagliflozin Added to a Sulfonylurea Alone or in Combination With Metformin in Patients With Type 2 Diabetes Who Have Inadequate Glycemic Control on a Sulfonylurea Alone or With Metformin

Conditions
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Type 2 Diabetes Mellitus

Intervention / Treatment
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* Drug: Sotagliflozin (SAR439954)
* Drug: Placebo
* Drug: Metformin
* Drug: Sulfonylurea


Participation Criteria
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Eligibility Criteria
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Inclusion criteria : Participants with T2D treated with a Sulfonylurea (≥half the maximum recommended dose as per local label or maximum tolerated dose [documented]) as monotherapy or in combination with Metformin (≥1500 mg per day or maximum tolerated dose [documented]) each at a stable dose for at least 12 weeks without a dose adjustment before screening. Signed written informed consent. Exclusion criteria: At the time of screening, age <18 years or < legal age of majority, whichever is greater. Body Mass Index (BMI) ≤20 or >45 kilograms per meter square (kg/m^2) at Screening. Hemoglobin A1c (HbA1c) <7% or HbA1c >10% via central lab test at screening. Fasting plasma glucose (FPG) >15 mmol/L (270 mg/dL) measured by the central laboratory at screening (Visit 1), and confirmed (>15 mmol/L [270 mg/dL]) by a repeat test before randomization. Women of childbearing potential with no effective contraceptive method. Treated with an antidiabetic pharmacological regimen other than a Sulfonylurea at a stable dose with or without Metformin within 12 weeks preceding the screening visit. Previous insulin use >1 month (at any time, aside from treatment of gestational diabetes). History of prior gastric surgical procedure including gastric banding or inflammatory bowel disease within 3 years before the Screening Visit. History of diabetic ketoacidosis or nonketotic hyperosmolar coma within 12 weeks prior to the Screening Visit. History of severe hypoglycemia within 6 months prior to the Screening visit. Systolic blood pressure (SBP) >180 millimeter per mercury (mmHg) or diastolic blood pressure (DBP) >100 mmHg or history of hypertensive emergency. Aspartate aminotransferase and/or alanine aminotransferase: >3 times the upper limit of the normal laboratory range (ULN). Total bilirubin: >1.5 times ULN (except in case of Gilbert's syndrome). Use of systemic glucocorticoids (excluding topical or ophthalmic, application or inhaled forms) for more than 10 consecutive days within 90 days prior to the Screening Visit. Pregnancy, breastfeeding. Participants is unwilling to perform self-monitoring of blood glucose (SMBG), and complete the participant's diary as required per protocol. The above information is not intended to contain all considerations relevant to a participant'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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Sotagliflozin 400 mg<br>Following a 2-week run-in phase, participants received two Sotagliflozin tablets of 200 mg, orally once daily, before the first meal of the day plus Metformin and Sulfonylurea as prescribed for up to 26 weeks in the Core Treatment Period. Participants were eligible to continue treatment in the Extension Period. The total treatment duration was planned for up to 79 weeks. | Drug: Sotagliflozin (SAR439954)<br>* Pharmaceutical form: tablet Route of administration: oral<br>|
| Placebo Comparator: Placebo<br>Following a 2-week run-in period, participants were randomized to matching placebo administered as 2 tablets, once daily, before the first meal of the day plus Metformin and Sulfonylurea as prescribed for up to 26 weeks in the Core Treatment Period. Participants were eligible to continue treatment in the Extension Period. The total treatment duration was planned for up to 79 weeks. | Drug: Placebo<br>* Pharmaceutical form: tablet Route of administration: oral<br>Drug: Metformin<br>* Pharmaceutical form: tablet Route of administration: oral<br>Drug: Sulfonylurea<br>* Pharmaceutical form: tablet Route of administration: oral<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Hemoglobin A1c (HbA1c) at Week 26 | Missing data are imputed using the retrieved dropouts imputation method. An analysis of covariance (ANCOVA) model was used for the analysis. | Baseline to Week 26 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Fasting Plasma Glucose (FPG) at Week 26 | Missing data are imputed using the retrieved dropouts imputation method. An ANCOVA model was used for the analysis. | Baseline to Week 26 | 
| Change From Baseline in Systolic Blood Pressure (SBP) for Participants With Baseline SBP ≥130 mmHg | Missing data are imputed using the washout imputation method under the missing, not at random framework. An ANCOVA model was used for the analysis. | Baseline to Week 12 | 
| Change From Baseline in SBP at Week 12 for All Participants | Missing data are imputed using washout imputation method under the missing not at random framework. An ANCOVA model was used for the analysis. | Baseline to Week 12 | 
| Change From Baseline in Body Weight at Week 26 | Missing data are imputed using the retrieved dropouts imputation method. An ANCOVA model was used for the analysis. | Baseline to Week 26 | 
| Percentage of Participants With HbA1c <6.5% at Week 26 |  | Week 26 | 
| Percentage of Participants With HbA1c <7.0% at Week 26 |  | Week 26 |