Efficacy and Safety of Sotagliflozin Versus Placebo in Chinese Patients With Type 2 Diabetes Mellitus Not Adequately Controlled by Metformin With or Without Sulfonylurea

Study Overview
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Brief Summary
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Primary Objective: To demonstrate the superiority of sotagliflozin dose 1 versus placebo on hemoglobin A1c (HbA1c) reduction in Chinese patients with type 2 diabetes (T2D) who have inadequate glycemic control on metformin alone or metformin in combination with sulfonylurea. Secondary Objectives: To compare sotagliflozin dose 1 versus placebo for change in 2-hour postprandial glucose (PPG) following a mixed meal tolerance test (MMTT), change in fasting plasma glucose (FPG), and change in body weight. To compare sotagliflozin dose 2 versus placebo for change in HbA1c, change in 2-hour PPG following a MMTT, change in FPG, and change in body weight. To compare sotagliflozin dose 2 and sotagliflozin dose 1 versus placebo for change in systolic blood pressure (SBP) for all patients, and change in SBP for patients with baseline SBP ≥130 mmHg. To evaluate the safety of sotagliflozin dose 2 and sotagliflozin dose 1 versus placebo.

Detailed Description
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Total study duration is up to 30 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 24-week double-blind treatment period, and a 2-week post-treatment follow-up visit 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 in Chinese Patients With Type 2 Diabetes Who Have Inadequate Glycemic Control on Metformin Alone or Metformin in Combination With Sulfonylurea

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 : Chinese patients with T2D diagnosed for at least 1 year, who are treated with diet/exercise and: Metformin alone at a stable dose ( ≥1500 mg/day or maximum tolerated dose [documented]) for at least 8 weeks before the screening visit OR Metformin in combination with sulfonylurea (≥ half maximum-labelled dose or maximum tolerated dose [documented]) each at a stable dose for at least 8 weeks before the screening visit. Signed written informed consent. Exclusion criteria: Age <18 years at the screening visit. Type 1 diabetes. Hemoglobin A1c <7% or >10.5% measured by the central laboratory at the screening visit. Fasting plasma glucose >15 mmol/L (>270 mg/dL) measured by the central laboratory at the screening visit and confirmed by a repeat test (>15 mmol/L [>270 mg/dL]) before randomization. Body mass index (BMI) ≤20 or >45 kg/m2 at the screening visit. Women of childbearing potential not willing to use highly effective 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. Previous use of any antidiabetic drug other than metformin and sulphonylurea within the 12 weeks prior to the screening visit. Previous use of any types of insulin for >1 month within 12 months before screening. History of gastric surgery including history of gastric banding or inflammatory bowel disease within 3 years prior to the screening visit. History of diabetic ketoacidosis (DKA) or non-ketotic hyperosmolar coma within 12 weeks prior to the screening visit. History of serious hypoglycemia resulting in unconsciousness, seizure or hospitalization within 6 months prior to the screening visit. Mean of 3 separate blood pressure measurements >180 mmHg (SBP) or >100 mmHg (diastolic blood pressure DBP (DBP)). History of hypertensive emergency within 12 weeks prior to the screening visit. Patients with severe anemia, severe cardiovascular (CV) (including congestive heart failure New York Heart Association (NYHA) IV), respiratory, hepatic, neurological, psychiatric, or active malignant tumor or other major systemic disease or patients with short life expectancy that, according to Investigator, will preclude their safe participation in this study, or will make implementation of the protocol or interpretation of the study results difficult. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >3 times the upper limit of the normal (ULN) laboratory range. Total bilirubin >1.5 times the ULN (except in case of Gilbert's syndrome). Use of systemic glucocorticoids (excluding topical or ophthalmic application, nasal spray, or inhaled forms) for more than 10 consecutive days within 90 days prior to the screening visit. Patient who has taken other investigational drugs or prohibited therapy for this study within 12 weeks or 5 half-lives prior to the screening visit, whichever is longer. Use of a selective SGLT2 inhibitor (eg, canagliflozin, dapagliflozin, or empagliflozin) within 3 months prior to the screening visit. Pregnant (confirmed by serum pregnancy test at the screening visit) or breastfeeding women. Patients with severe renal disease as defined by an eGFR of <30 mL/min/1.73m² at the screening visit, based on the 4 variable Modification of Diet in Renal Disease (MDRD) equation. Patients with contraindication to metformin as per local labelling. Patients with contraindication to sulfonylurea as per local labelling if the patient is taking metformin with sulfonylurea. Patient unwilling or unable to perform self-monitoring of blood glucose (SMBG), complete the patient diary, or comply with study visits and other study procedures as required per protocol. Patients unable to consume at least 50% of the standard meal during the MMTT at baseline (Day 1, Visit 3) before randomization. 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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Sotagliflozin dose 1<br>Sotagliflozin dose 1, given as two (2) dose 2 tablets, once daily, before the first meal of the day | Drug: sotagliflozin (SAR439954)<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>|
| Experimental: Sotagliflozin dose 2<br>Sotagliflozin dose 2, given as 1 sotagliflozin dose 2 tablet and 1 sotagliflozin-matching placebo tablet (identical to sotagliflozin dose 2 in appearance), once daily, before the first meal of the day | Drug: sotagliflozin (SAR439954)<br>* Pharmaceutical form: tablet Route of administration: oral<br>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>|
| Placebo Comparator: Placebo<br>Two sotagliflozin-matching placebo tablets (identical to sotagliflozin dose 2 in appearance), once daily, before the first meal of the day | 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 in hemoglobin A1c (HbA1c) | Absolute change from baseline to week 24 in HbA1c (for sotagliflozin dose 1) | Baseline to Week 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in 2-hour postprandial glucose (PPG) following a mixed meal tolerance test (MMTT) | Absolute change from baseline to week 24 in 2-hour PPG following a MMTT (for sotagliflozin dose1 and 2) | Baseline to Week 24 | 
| Change in fasting plasma glucose (FPG) | Absolute change from baseline to week 24 in FPG (for sotagliflozin dose 1 and 2) | Baseline to Week 24 | 
| Change in body weight | Absolute change from baseline to week 24 in body weight (for sotagliflozin dose1 and 2) | Baseline to Week 24 | 
| Change in HbA1c | Absolute change from baseline to week 24 in HbA1c (for sotagliflozin dose 2) | Baseline to Week 24 | 
| Change in systolic blood pressure (SBP) for all patients | Absolute change from baseline to week 12 in SBP for all patients (for sotagliflozin dose 1 and 2) | Baseline to Week 12 | 
| Change in SBP for patients with baseline SBP ≥130 mmHg | Absolute change from baseline to week 12 in SBP for patients with baseline SBP ≥130 mmHg (for sotagliflozin dose 1 and 2) | Baseline to Week 12 | 
| Adverse events | Number of patients with adverse events | Up to Week 24 |