Safety and Efficacy Study of Sotagliflozin on Glucose Control in Participants With Type 2 Diabetes, Moderate Impairment of Kidney Function, and Inadequate Blood Sugar Control

Study Overview
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Brief Summary
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Primary Objective: To demonstrate the superiority of Sotagliflozin 200 milligrams (mg) and Sotagliflozin 400 mg versus placebo on HbA1c reduction at 26 Weeks in participants with Type 2 diabetes who have inadequate glycemic control and moderate renal impairment. Secondary Objectives: To assess the effects of Sotagliflozin 200 mg and 400 mg versus placebo with respect to additional measures of glycemic control, blood pressure, and body weight. To evaluate the safety of Sotagliflozin 200 mg and 400 mg versus placebo.

Detailed Description
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The study duration is up to 60 weeks including 4 weeks prior to randomization, 52 weeks of randomized treatment, and a visit 4 weeks after completion of the randomized treatment period.

Official Title
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A Randomized, Double-blind, Placebo-controlled, 3-arm, Parallel-group 52-week Multicenter Study to Evaluate the Efficacy and Safety of Sotagliflozin in Patients With Type 2 Diabetes Mellitus and Moderate Renal Impairment Who Have Inadequate Glycemic Control

Conditions
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Type 2 Diabetes Mellitus, Chronic Kidney Disease Stage 3

Intervention / Treatment
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* Drug: Placebo
* Drug: Sotagliflozin


Participation Criteria
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Eligibility Criteria
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Inclusion criteria : Participants with Type 2 Diabetes (drug-naïve or on antidiabetic therapy) and documented moderate renal insufficiency defined by an estimated glomerular filtration rate (eGFR) (based on the 4 variable Modification of Diet in Renal Disease (MDRD) equation) of ≥30 and <60 milliliter per minute (mL/min)/1.73 meter square (m^2) (chronic kidney disease [CKD] 3A, 3B). Participants has given written informed consent to participate in the study in accordance with local regulations. Exclusion criteria: Hemoglobin A1c (HbA1c) of <7.0% or >11.0%. Type 1 diabetes. Women of childbearing potential (WOCBP) 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. Treatment with a sodium-glucose cotransporter type 2 (SGLT2) inhibitor (Canagliflozin, Dapagliflozin, Empagliflozin) during the last 12 months. Uncontrolled high blood pressure. Participants with severe anemia, severe cardiovascular (including congestive heart failure New York Heart Association IV), respiratory, hepatic, neurological, psychiatric, or active malignant tumor or other major systemic disease or patients 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. 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'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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Following a 2-week run-in period, participants received two placebo tablets (identical to sotagliflozin 200 mg in appearance), orally once daily, before the first meal of the day for up to 54 weeks. | Drug: Placebo<br>* Placebo tablet (identical to sotagliflozin 200 mg in appearance), orally once daily. Route of administration: Oral<br>|
| Experimental: Sotagliflozin 200 mg<br>Following a 2-week run-in period, participants received two tablets, 1 sotagliflozin 200 mg tablet and 1 placebo tablet (identical to sotagliflozin 200 mg in appearance), orally once daily, before the first meal of the day for up to 58 weeks. | Drug: Placebo<br>* Placebo tablet (identical to sotagliflozin 200 mg in appearance), orally once daily. Route of administration: Oral<br>Drug: Sotagliflozin<br>* Sotagliflozin 200 mg, tablet, orally once daily. Route of administration: Oral<br>* Other names: SAR439954;|
| Experimental: Sotagliflozin 400 mg<br>Following a 2-week run-in period, participants received sotagliflozin 400 mg, administered as two 200 mg sotagliflozin tablets, orally once daily, before the first meal of the day for up to 60 weeks. | Drug: Sotagliflozin<br>* Sotagliflozin 200 mg, tablet, orally once daily. 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 HbA1c at Week 26 | An Analysis of covariance (ANCOVA) model was used for 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 | An ANCOVA model was used for analysis. | Baseline to Week 26 | 
| Change From Baseline in SBP for Participants With Baseline SBP ≥130 mmHg at Week 12 | An ANCOVA model was used for analysis. | Baseline to Week 12 | 
| Change From Baseline in SBP at Week 12 for All Participants | An ANCOVA model was used for analysis. | Baseline to Week 12 | 
| Change From Baseline in Body Weight at Week 26 | An ANCOVA model was used for analysis. | Baseline to Week 26 | 
| Percentage Change From Baseline in the Urine Albumin: Creatinine Ratio (UACR) at Week 26 in Participants With Baseline UACR >30 Milligrams Per Gram (mg/g) | An ANCOVA model was used for analysis. No Measure of Dispersion was pre-specified to be calculated. | 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 | 
| Percentage of Participants With Treatment-emergent Adverse Events (TEAEs) |  | Up to 60 weeks |