Efficacy and Safety of Sotagliflozin Versus Placebo in Patients With Type 2 Diabetes Mellitus on Background of Metformin

Study Overview
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Brief Summary
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Primary Objective: To demonstrate the superiority of Sotagliflozin versus placebo on hemoglobin A1c (HbA1c) reduction in participants with type 2 diabetes (T2D) who have inadequate glycemic control with metformin. Secondary Objectives: To compare Sotagliflozin versus placebo for. Change from baseline in 2-hour postprandial glucose (PPG) following a mixed meal. 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 (mmHg). Change from baseline in SBP for all participants. Change from baseline in body weight. Proportion of participants with HbA1c <6.5% and <7.0%. To evaluate the safety of Sotagliflozin versus placebo.

Detailed Description
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The duration of the study period is up to 87 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 Period, a 4 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 Metformin in Patients With Type 2 Diabetes Mellitus Who Have Inadequate Glycemic Control on Metformin

Conditions
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Type 2 Diabetes Mellitus

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


Participation Criteria
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Eligibility Criteria
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Inclusion criteria : Participants with Type 2 Diabetes currently treated with diet and exercise and on metformin at a stable dose ≥1500 milligrams per day (mg/day) for at least 12 weeks. However, participants on metformin at a dose <1500 mg/day at the time of enrollment (stable dose for at least 12 weeks before enrollment) may be eligible for screening if documentation of lack of tolerance of a metformin dose ≥1500 mg/day can be provided. Signed written informed consent. Exclusion criteria: Age <18 years at Screening or < legal age of majority, whichever is greater. Type 1 diabetes mellitus. Body Mass Index (BMI) ≤20 or >45 kilograms per meter square (kg/m^2) at Screening Hemoglobin A1c <7% or >10% via central laboratory test at screening. Fasting plasma glucose (FPG) >15 millimole per liter (mmol/L) (270 milligrams per deciliter [mg/dL]) measured by the central laboratory at screening (Visit 1) and confirmed by a repeat test (>15 mmol/L [270 mg/dL]) before randomization. Women of childbearing potential not willing to use highly effective method(s) of birth control or who are unwilling or unable to be tested for pregnancy during the study. Treated with an antidiabetic pharmacological regimen other than metformin ≥1500 mg per day (or maximum tolerated dose) within the 12 weeks preceding the Screening Visit. Previous use of any types of insulin for >1 month (at any time, aside from pregnancy for treatment of gestational diabetes). History of prior gastric surgical procedure, including gastric banding, within 3 years before the Screening Visit. History of diabetic ketoacidosis or nonketotic hyperosmolar coma within 12 weeks prior to the Screening Visit. Mean of 3 separate blood pressure measurements >180 mmHg (SBP) or >100 mmHg (diastolic blood pressure [DBP]). History of hypertensive urgency or emergency within 12 weeks prior to Screening. Participants with severe anemia, severe cardiovascular (including congestive heart failure New York Heart Association [NYHA] IV), respiratory, hepatic, neurological, psychiatric, or active malignant tumor or other major systemic disease or participants with short life expectancy making implementation of the protocol or interpretation of the study results difficult. Aspartate aminotransferase and/or alanine aminotransferase: >3 times the upper limit of the normal laboratory range. Total bilirubin: >1.5 times the upper limit of the normal laboratory range (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. Participants who has taken other investigational drugs or prohibited therapy for this study within 12 weeks or 5 half-lives from screening or randomization, whichever is longer. Pregnant (confirmed by serum pregnancy test at Screening) or breastfeeding women. Participants is unwilling or unable to perform self-monitoring of blood glucose (SMBG), complete the participants diary, or comply with study visits and other study procedures as required per protocol. Contraindication to metformin as per local labelling. 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 + Metformin<br>Following a 2-week run-in period, sotagliflozin 400 mg was administered as 2 tablets, once daily, before the first meal of the day plus metformin as prescribed by the Principal Investigator for up to 26 weeks in the double-blind Core Treatment Period, and participants continued the same treatment in the double-blind Extension Period for up to 53 weeks. | Drug: Sotagliflozin (SAR439954)<br>* Pharmaceutical form: tablet. Route of administration: oral.<br>Drug: Metformin<br>* Pharmaceutical form: tablet. Route of administration: oral.<br>|
| Placebo Comparator: Placebo + Metformin<br>Following a 2-week run-in period, matching placebo was administered as 2 tablets, once daily, before the first meal of the day plus metformin as prescribed by the Principal Investigator for up to 26 weeks in the double-blind Core Treatment Period, and participants continued the same treatment in the double-blind Extension Period for up to 53 weeks. | Drug: Placebo<br>* Pharmaceutical form: tablet. Route of administration: oral.<br>Drug: Metformin<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 | An analysis of covariance (ANCOVA) model was used for the analysis. | Baseline and Week 26 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in 2-hour Postprandial Glucose (PPG) Following a Mixed Meal at Week 26 | An ANCOVA model was used for the analysis. | Baseline and Week 26 | 
| Change From Baseline in Fasting Plasma Glucose (FPG) at Week 26 | An ANCOVA model was used for the analysis. | Baseline and Week 26 | 
| Change From Baseline in Body Weight at Week 26 | An ANCOVA model was used for the analysis. | Baseline and Week 26 | 
| Change From Baseline in Systolic Blood Pressure (SBP) at Week 12 in Participants With Baseline SBP ≥130 mmHg | An ANCOVA model was used for the analysis. | Baseline and Week 12 | 
| Change From Baseline in SBP at Week 12 for All Participants | An ANCOVA model was used for the analysis. | Baseline and Week 12 | 
| Percentage of Participants With HbA1c <6.5% at Week 26 |  | Week 26 | 
| Percentage of Participants With HbA1c <7.0% at Week 26 |  | Week 26 |