Efficacy and Bone Safety of Sotagliflozin 400 and 200 mg Versus Placebo in Participants With Type 2 Diabetes Mellitus Who Have Inadequate Glycemic Control

Study Overview
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Brief Summary
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The primary objective is to demonstrate the superiority of Sotagliflozin 400 milligrams (mg) versus placebo with respect to hemoglobin A1c (Hb1Ac) reduction in participants with type 2 diabetes (T2D) who have inadequate glycemic control on diet and exercise only or with a stable antidiabetes regimen.

Detailed Description
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Study duration per participant is approximately 110 weeks (Screening period of up to 2 weeks, 2 week single-blind run-in period), a 26-week double-blind core treatment period, a 78-week double-blind extension period, and a 2- week post treatment follow up period. Dual-energy X-ray absorptiometry (DXA) scans will be performed to assess Bone Mineral Density and Fat vs. Lean body mass at baseline and Weeks 26, 52, and 104.

Official Title
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A 26-week Randomized, Double-blind, Placebo-controlled, Parallel-group, Multicenter, Phase 3 Study With a 78-week Extension Period to Evaluate the Efficacy and Bone Safety of Sotagliflozin in Patients 55 Years or Older With Type 2 Diabetes Mellitus and Inadequate Glycemic Control

Conditions
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Type 2 Diabetes Mellitus

Intervention / Treatment
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* Drug: Sotagliflozin
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion criteria : Participants with T2D managed with diet and exercise only or with a stable antidiabetes regimen (in monotherapy or combination therapy that can include oral antidiabetes medications, insulin, or glucagon-like peptide-1 agonists) for more than 12 weeks. Participants has given written informed consent to participate in the study in accordance with local regulations. Exclusion criteria: Age <55 years. Women who have been postmenopausal (or undergone bilateral oophorectomy) for less than 5 years. Type 1 diabetes mellitus. Body mass index (BMI) ≤20 or >45 kilogram per meter square kg/m^2 or bodyweight that exceeds the weight limits of the DXA scanner. Hemoglobin A1C (HbA1c) <7.0% or HbA1c >11.0%. Use of a selective sodium-glucose cotransporter type 2 (SGLT2) inhibitor or thiazolidinedione within 24 months. Bone mineral density (BMD) T- score <-2.0 at any site (ie, lumbar spine, total hip, or femoral neck). History of fracture within 12 months (except for fractures of the hand/fingers, foot/toes, facial bones, and skull). Treatment with medications known to affect bone mass or modify the risk of fractures within 36 months (eg, bisphosphonates, selective estrogen receptor modulators, calcitonin, teriparatide, denosumab, strontium ranelate, growth hormone, aromatase inhibitors, androgen deprivation therapy, carbamazepine, phenytoin, and phenobarbital). Use of hormonal replacement that includes systemic or transdermal estrogen or testosterone is excluded unless is stable for at least 24 months prior to Screening. Lower extremity complications (such as skin ulcers, infection, osteomyelitis and gangrene) identified during the Screening period, and still requiring treatment at randomization. Uncontrolled high blood pressure, severe anemia, severe cardiovascular problems, such as heart failure, active cancer, or other conditions that the Investigator believes with result in a short life expectancy. Renal disease as defined by an estimated glomerular filtration rate (eGFR) <30 milliliter per minute (mL/min)/1.73 meter square (m^2) at the Screening Visit by the 4 variable Modification of Diet in Renal Disease equation. 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: 55 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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Following a 2 week run-in period, participants were randomized to matching placebo to sotagliflozin administered as 2 tablets, once daily, before the first meal of the day, 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 106 weeks. | Drug: Placebo<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, once daily, before the first meal of the day, 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 104 weeks. | Drug: Sotagliflozin<br>* Pharmaceutical form: Tablet; Route of administration: Oral<br>* Other names: SAR439954;Drug: Placebo<br>* Pharmaceutical form: Tablet; Route of administration: Oral<br>|
| Experimental: Sotagliflozin 400 mg<br>Following a 2 week run-in period, participants were randomized to Sotagliflozin 400 mg administered as two 200 mg sotagliflozin tablets, once daily, before the first meal of the day, 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 104 weeks. | Drug: Sotagliflozin<br>* Pharmaceutical form: Tablet; Route of administration: Oral<br>* Other names: SAR439954;|

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 is used for analysis. | Baseline to Week 26 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent Change From Baseline in Bone Mineral Density (BMD) of Lumbar Spine at Week 26 | An ANCOVA model is used for analysis. | Baseline to Week 26 | 
| Percent Change From Baseline in Bone Mineral Density (BMD) of Total Hip at Week 26 | An ANCOVA model is used for analysis. | Baseline to Week 26 | 
| Percent Change From Baseline in Bone Mineral Density (BMD) of Femoral Neck at Week 26 | An ANCOVA model is used for analysis. | Baseline to Week 26 | 
| Change From Baseline in Body Weight at Week 26 | An ANCOVA model is used for analysis. | Baseline to Week 26 | 
| Change From Baseline in Fasting Plasma Glucose (FPG) at Week 26 | An ANCOVA model is used for analysis. | Baseline to Week 26 | 
| Change From Baseline in Systolic Blood Pressure (SBP) at Week 12 | An ANCOVA model is used for analysis. | Baseline to Week 12 | 
| Percentage of Participants With Hemoglobin A1c (HbA1c) <7.0% at Week 26 |  | Week 26 | 
| Percentage of Participants With Adverse Events (AEs) | An AE is any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. | up to 106 weeks |