A Study to Evaluate Safety and Effects of Sotagliflozin 400 and 200 mg on Glucose Control in Participants With Type 2 Diabetes, Severe 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 400 milligrams (mg) versus placebo with respect to hemoglobin A1c (HbA1c) reduction at Week 26 in participants with Type 2 diabetes who have inadequate glycemic control and severe renal impairment Secondary Objectives: To assess the effects of sotagliflozin 200 mg versus placebo based on change from baseline in HbA1c To assess the effects of sotagloflozin 400 mg and 200 mg versus placebo To evaluate the safety of sotagliflozin 400 mg and 200 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 Severe Renal Impairment Who Have Inadequate Glycemic Control

Conditions
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Type 2 Diabetes Mellitus, Chronic Kidney Disease Stage 4

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 severe renal insufficiency - CKD4 - defined by an estimated glomerular filtration rate (eGFR) equation (based on the 4 variable modification of diet in renal disease (MDRD) equation) of ≥15 and <30 milliliter per minute (mL/min)/1.73 per meter square (m^2). Signed written informed consent to participate in the study in accordance with local regulations. Exclusion criteria: At the time of screening, age <18 years. Hemoglobin A1c (HbA1c) <7% or >11%. 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 an sodium-glucose cotransporter type 2 (SGLT2) inhibitor (canagliflozin, dapagliflozin, empagliflozin) during the last 12 months. 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, 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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Following a 2-week run-in phase, participants received two placebo tablets (identical to sotagliflozin 200 milligrams [mg] in appearance) orally once daily for up to 56 weeks. | Drug: Placebo<br>* Placebo tablet (identical to sotagliflozin 200 mg in appearance) orally, once daily.<br>|
| Experimental: Sotagliflozin 200 mg<br>Following a 2-week run-in phase, participants received two tablets, one sotagliflozin 200 mg tablet and one placebo tablet (identical to sotagliflozin 200 mg in appearance), orally once daily for up to 56 weeks. | Drug: Placebo<br>* Placebo tablet (identical to sotagliflozin 200 mg in appearance) orally, once daily.<br>Drug: Sotagliflozin<br>* Sotagliflozin 200 mg, tablet, orally, once daily.<br>* Other names: SAR439954;|
| Experimental: Sotagliflozin 400 mg<br>Following a 2-week run-in phase, participants received sotagliflozin 400 mg, administered as 2 sotagliflozin 200 mg tablets, orally once daily for up to 56 weeks. | Drug: Sotagliflozin<br>* Sotagliflozin 200 mg, tablet, orally, once daily.<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 Comparing 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 HbA1c at Week 26 Comparing 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 | An ANCOVA model was used for the analysis. | Baseline to Week 26 | 
| Change From Baseline in Body Weight at Week 26 | An ANCOVA model was used for the analysis. | Baseline to Week 26 | 
| Change From Baseline in SBP at Week 12 in Participants With Baseline SBP ≥130 mmHg | An ANCOVA model was used for the analysis. | Baseline to Week 12 | 
| Change From Baseline in SBP at Week 12 for All Participants | An ANCOVA model was used for the analysis. | Baseline to Week 12 | 
| 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) | An adverse event (AE) is any untoward medical occurrence in a participants or clinical investigation participants administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the investigational medicinal product (IMP). | First dose of study drug to last dose of study drug (up to 56.3 weeks) + 4 weeks |