Efficacy and Safety of Sotagliflozin Versus Placebo in Patients With Type 2 Diabetes Mellitus Not Currently Treated With Antidiabetic Therapy

Study Overview
=================
Brief Summary
-----------------
Primary Objective: To demonstrate the superiority of Sotagliflozin 400 milligrams (mg) versus placebo on hemoglobin A1c (HbA1c) reduction in participants with type 2 diabetes (T2D) who have inadequate glycemic control on diet and exercise. Secondary Objectives: To compare Sotagliflozin 400 mg versus placebo based on: 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 per mercury (mmHg). Change from baseline in SBP for all participants. Change from baseline in body weight. Proportion of participants with HbA1c <6.5%, <7.0%. To compare Sotagliflozin 200 mg versus placebo based on: Change from baseline in HbA1c. Change from baseline in 2-hour postprandial glucose (PPG) following a mixed meal. Change from baseline in body weight. Change from baseline in SBP for all participants. To evaluate the safety of Sotagliflozin 400 and 200 mg versus placebo.

Detailed Description
-----------------
Up to 34 weeks, including a Screening Period consisting of a Screening Phase of up to 2 weeks and a 2-week single-blind placebo Run-in Phase, a 26-week double-blind Treatment Period, and a 4-week post-treatment Follow-up visit to collect safety information.

Official Title
-----------------
A Randomized, Double-blind, Placebo-controlled, Parallel-group, Multicenter Study to Evaluate the Efficacy and Safety of Sotagliflozin as Monotherapy in Patients With Type 2 Diabetes Mellitus Who Have Inadequate Glycemic Control

Conditions
-----------------
Type 2 Diabetes Mellitus

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


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion criteria : Participants (male and female) with T2D, who are treated with diet and exercise only during the 12 weeks prior to screening. 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 kilogram per meter square (kg/m^2) at Screening. Hemoglobin A1c (HbA1c) <7% or >10% via central laboratory test at Screening. Fasting plasma glucose (FPG) >15 millimole per liter (mmol/L) (270 milligram 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 contraceptive method(s) of birth control during the study treatment period and the follow up period or who are unwilling or unable to be tested for pregnancy during the study. Treated with an antidiabetic pharmacological agent within the 12 weeks prior to the Screening Visit. Previous use of any types of insulin for >1 month (at any time, except for treatment of gestational diabetes). History of 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 millimeter of mercury (mmHg) (systolic) or >100 mmHg (diastolic). History of hypertensive 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 that, according to the Investigator, will preclude their safe participation in this study, or will make 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. Current enrollment in any other clinical study involving an investigational study treatment or any other type of medical research. Pregnant (confirmed by serum pregnancy test at Screening) or breastfeeding women. Severe renal disease as defined by estimated glomerular filtration rate (eGFR) of <30 millimeter per minute (mL/min)/1.73 meter square (m^2)² at screening by the 4 variable Modification of Diet in Renal Disease (MDRD) equation. Participant 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. Lower extremity complications (such as skin ulcers, infection, osteomyelitis and gangrene) identified during the Screening period, and still requiring treatment at Randomization. The above information is not intended to contain all considerations relevant to a Participant potential participation in a clinical trial.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

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 period, participants were randomized to Sotagliflozin 400 milligrams (mg) administered as two 200 mg tablets, once daily (QD), before the first meal of the day in the double-blind treatment period for up to 26 weeks. | Drug: Sotagliflozin (SAR439954)<br>* Pharmaceutical form: tablet; Route of administration: oral<br>|
| Experimental: Sotagliflozin 200 mg<br>Following a 2-week run-in period, participants were randomized to Sotagliflozin 200 mg administered as 1 Sotagliflozin tablet and 1 matching placebo tablet, QD, before the first meal of the day in the double-blind treatment period for up to 26 weeks. | Drug: Sotagliflozin (SAR439954)<br>* Pharmaceutical form: tablet; Route of administration: oral<br>Drug: Placebo<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 to sotagliflozin administered as 2 tablets, QD, before the first meal of the day in the double-blind treatment period for up to 26 weeks. | Drug: Placebo<br>* Pharmaceutical form: tablet; Route of administration: oral<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Hemoglobin A1c (HbA1c) at Week 26 (Sotagliflozin 400 mg Versus Placebo) | 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 2-hour Postprandial Plasma Glucose (PPG) Following a Mixed Meal at Week 26 (Sotagliflozin 400 mg Versus Placebo) | An ANCOVA model was used for the analysis. | Baseline to Week 26 | 
| Change From Baseline in 2-hour Postprandial Plasma Glucose (PPG) Following a Mixed Meal at Week 26 (Sotagliflozin 200 mg Versus Placebo) | An ANCOVA model was used for the analysis. | Baseline to Week 26 | 
| Change From Baseline in Fasting Plasma Glucose (FPG) at Week 26 (Sotagliflozin 400 mg Versus Placebo) | An ANCOVA model was used for the analysis. | Baseline to Week 26 | 
| Change From Baseline in Systolic Blood Pressure (SBP) at Week 12 in Participants With Baseline SBP ≥130 Millimeter of Mercury (mmHg) (Sotagliflozin 400 mg Versus Placebo) | An ANCOVA model was used for the analysis. | Baseline to Week 12 | 
| Change From Baseline in SBP at Week 12 for All Participants (Sotagliflozin 400 mg Versus Placebo) | An ANCOVA model was used for the analysis. | Baseline to Week 12 | 
| Change From Baseline in SBP at Week 12 for All Participants (Sotagliflozin 200 mg Versus Placebo) | An ANCOVA model was used for the analysis. | Baseline to Week 12 | 
| Change From Baseline in Body Weight at Week 26 (Sotagliflozin 400 mg Versus Placebo) | An ANCOVA model was used for the analysis. | Baseline to Week 26 | 
| Change From Baseline in Body Weight at Week 26 (Sotagliflozin 200 mg Versus Placebo) | An ANCOVA model was used for the analysis. | Baseline to Week 26 | 
| Percentage of Participants With HbA1c <6.5% at Week 26 (Sotagliflozin 400 mg Versus Placebo) |  | Week 26 | 
| Percentage of Participants With HbA1c <7.0% at Week 26 (Sotagliflozin 400 mg Versus Placebo) |  | Week 26 | 
| Change From Baseline in HbA1c at Week 26 (Sotagliflozin 200 mg Versus Placebo) | An ANCOVA model was used for the analysis. | Baseline to Week 26 |