Effect of Sotagliflozin on Cardiovascular and Renal Events in Participants With Type 2 Diabetes and Moderate Renal Impairment Who Are at Cardiovascular Risk

Study Overview
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Brief Summary
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The primary objective of the study was to compare the effect of sotagliflozin to placebo on total occurrences of cardiovascular (CV) death, hospitalization for heart failure [HHF], and urgent visit for heart failure [HF] in participants with type 2 diabetes, cardiovascular risk factors, and moderate to severely impaired renal function.

Official Title
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A Randomized, Double-blind, Placebo-controlled, Parallel-group, Multicenter Study to Demonstrate the Effects of Sotagliflozin on Cardiovascular and Renal Events in Patients With Type 2 Diabetes, Cardiovascular Risk Factors and Moderately Impaired Renal Function

Conditions
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Chronic Kidney Diseases, Heart Failure, 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 : Type 2 Diabetes Mellitus with glycosylated hemoglobin (HbA1c) ≥7%. Estimated glomerular filtration rate (eGFR) ≥25 and ≤60 milliliter/minute (mL/min)/1.73 square meter (m^2). Age 18 years or older with at least one major cardiovascular risk factor or age 55 years or older with at least two minor cardiovascular risk factors. Signed written informed consent. Exclusion criteria: Antihyperglycemic treatment has not been stable within 12 weeks prior to screening. Planned coronary procedure or surgery after randomization. Lower extremity complications (such as skin ulcer, infection, osteomyelitis, and gangrene) identified during screening and requiring treatment at randomization. Planning to start a sodium-glucose linked transporter-2 (SGLT2) inhibitor during the study. 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: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Sotagliflozin<br>Sotagliflozin 200 mg tablet once daily, with possible up-titration in the first 6 months to 400 mg, for up to 28.9 months. | Drug: Sotagliflozin<br>* Sotagliflozin was administered as a tablet(s), orally once daily.<br>* Other names: SAR439954;|
| Placebo Comparator: Placebo<br>Matching placebo to sotagliflozin 200 mg once daily, with possible up-titration in the first 6 months to matching placebo to sotagliflozin 400 mg, for up to 29.6 months. | Drug: Placebo<br>* Placebo was administered as a tablet(s) (identical to the sotagliflozin tablet in appearance), orally once daily.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Total Occurrences of Cardiovascular (CV) Death, Hospitalizations for Heart Failure (HHF) and Urgent Visits for Heart Failure (HF) | Combined endpoint of the total number of occurrences (first and potentially subsequent) of CV death, HHF, and urgent HF visits after randomization. Events that occurred during the study were calculated as the total number of events per 100 person-years of follow-up. | Up to 30 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Total Number of Occurrences of HHF and Urgent HF Visits | Combined endpoint of the total occurrences (first and potentially subsequent) of HHF and urgent HF visits after randomization. Events that occurred during the study were calculated as the total number of events per 100 person-years of follow-up. | Up to 30 months | 
| Number of Deaths From Cardiovascular Causes | Number of events that occurred during the study were calculated as the total number of events per 100 person-years of follow-up. | Up to 30 months | 
| Total Number of Occurrences of CV Death, HHF, Non-fatal Myocardial Infarction and Non-fatal Stroke | Combined endpoint of the total number of occurrences (first and potentially subsequent) of CV death, HHF, non-fatal stroke, and non-fatal myocardial infarction after randomization. Events that occurred during the study were calculated as the total number of events per 100 person-years of follow-up. | Up to 30 months | 
| Total Number of Occurrences of HHF, Urgent HF Visit, CV Death, and HF While Hospitalized | Combined endpoint of the total number of occurrences (first and potentially subsequent) after randomization of HHF, urgent HF visits, CV Death, and HF while hospitalized. Events that occurred during the study were calculated as the total number of events per 100 person-years of follow-up. | Up to 30 months | 
| Number of Occurrences After Randomization of the Composite of Sustained ≥50% Decrease in Estimated Glomerular Filtration Rate (eGFR) From Baseline (for ≥30 Days), Chronic Dialysis, Renal Transplant, or Sustained eGFR <15 mL/Min/1.73 m^2 (for ≥30 Days) | Events that occurred during the study were calculated as the total number of events per 100 person-years of follow-up. | Up to 30 months | 
| Number of Deaths From Any Cause | Number of events that occurred during the study were calculated as the total number of events per 100 person-years of follow-up. | Up to 30 months | 
| Total Number of Occurrences of CV Death, Non-fatal Myocardial Infarction and Non-fatal Stroke | Combined endpoint of the total number of occurrences (first and potentially subsequent) of CV death and urgent HF visits after randomization. Events that occurred during the study were calculated as the total number of events per 100 person-years of follow-up. | Up to 30 months |