Efficacy and Safety of Sotagliflozin Versus Glimepiride and Placebo in Participants With Type 2 Diabetes Mellitus That Are Taking Metformin Monotherapy
Condition: Type 2 Diabetes Mellitus
MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 2
Intervention: Sotagliflozin (SAR439954); Glimepiride; Metformin; Placebo; Placebo
Intervention description: Pharmaceutical form: tablet
Route of administration: oral; Pharmaceutical form: capsule
Route of administration: oral; Pharmaceutical form: tablet
Route of administration: oral; Pharmaceutical form: tablet
Route of administration: oral; Pharmaceutical form: capsule
Route of administration: oral
Intervention MeSH terms: Metformin; Glimepiride; (2S,3R,4R,5S,6R)-2-(4-chloro-3-(4-ethoxybenzyl)phenyl)-6-(methylthio)tetrahydro-2H-pyran-3,4,5-triol
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 954.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      Primary Objective:

      To demonstrate the non-inferiority of Sotagliflozin 400 milligrams (mg) compared to
      Glimepiride on hemoglobin A1c (HbA1c) reduction at Week 52 in participants with Type 2
      Diabetes (T2D) who have inadequate glycemic control with metformin.

      Secondary Objectives:

      To demonstrate the superiority of Sotagliflozin 400 mg compared to Glimepiride on change in
      body weight, systolic blood pressure (SBP) in participants with baseline SBP ≥130 millimeter
      of mercury (mmHg), SBP in all participants, and proportion of participants with at least 1
      documented symptomatic hypoglycemic event (≤70 milligrams per deciliter [mg/dL]).

        -  To demonstrate the superiority of Sotagliflozin 400 mg compared to placebo on change in
           HbA1c, body weight, SBP in participants with baseline SBP ≥130 mmHg, SBP in all
           participants.

        -  To demonstrate the superiority of Sotagliflozin 200 mg compared to placebo on change in
           HbA1c.

        -  To demonstrate the non-inferiority of Sotagliflozin 400 mg compared to Glimepiride on
           change in HbA1c.

        -  To demonstrate the superiority of Sotagliflozin 400 mg compared to Glimepiride on change
           in HbA1c.

        -  To evaluate the safety and tolerability of Sotagliflozin compared to Glimepiride and
           placebo.
    

Eligibility criteria:

        Inclusion criteria :

          -  Participants with Type 2 Diabetes (T2D) treated with metformin at a stable dose ≥1500
             milligrams per day (mg/day) or maximum tolerated dose (documented) for at least 12
             weeks prior to Screening Visit; in case of documented lack of tolerance, metformin
             dose <1500 mg/day is acceptable, and the dose should be stable for at least 12 weeks
             prior to Screening Visit.

          -  Participants has given written informed consent to participate in the study in
             accordance with local regulations.

        Exclusion criteria:

          -  Age <18 years at the Screening Visit or <legal age of majority, whichever is greater.

          -  Type 1 diabetes mellitus.

          -  HbA1c, HbA1c <7.0% or HbA1c >10% at Screening.

          -  Fasting Plasma Glucose (FPG) >15 millimoles per liter (mmol/L) (>270 milligram per
             deciliter [mg/dL]) measured by the central laboratory at Screening (Visit 1) and
             confirmed by a repeat test (>15 mmol/L [>270 mg/dL]) before randomization.

          -  Body mass index ≤20 or >45 kilogram per meter square (kg/m^2) at Screening.

          -  Pregnant (confirmed by pregnancy test at the Screening) or breast-feeding women.

          -  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 (see Appendix A) during the study.

          -  Previous use of any antidiabetic drug other than Metformin within 12 weeks preceding
             the Screening Visit.

          -  Use of a selective Sodium-glucose co-transporter-2 (SGLT2) inhibitor (e.g.,
             Canagliflozin, Dapagliflozin, or Empagliflozin) within 3 months prior to the Screening
             visit.

          -  Use of systemic glucocorticoids (excluding topical, or ophthalmic application,
             intra-articular, nasal spray or inhaled forms) for more than 10 consecutive days
             within 90 days prior to the Screening Visit.

          -  Previous insulin use >1 month (at any time, except for treatment of gestational
             diabetes).

          -  History of prior gastric surgical procedure, including gastric banding, or
             inflammatory bowel disease within 3 years prior to the Screening Visit.

          -  Difficulty swallowing such that the participants cannot take the investigational
             medicinal product (IMP).

          -  History of diabetic ketoacidosis or nonketotic hyperosmolar coma within 12 weeks prior
             to the Screening Visit.

          -  Mean of 3 separate blood pressure measurements >180 millimeter of mercury (mmHg) (SBP)
             or >100 mmHg (DBP).

          -  History of hypertensive emergency within 12 weeks prior to Screening.

          -  Participants who have previously been randomized in any clinical trial of
             Sotagliflozin/LX4211.

          -  Participants with severe renal disease as defined by an estimated glomerular
             filtration rate (eGFR) of <30 milliliter per minute per meter square (mL/min/1.73 m^2)
             at Screening, based on the 4 variable Modification of Diet in Renal Disease (MDRD)
             equation (or according to the renal function restrictions of metformin use defined in
             the local approved label).

          -  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 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.

          -  Aspartate aminotransferase and/or alanine aminotransferase: >3 times the upper limit
             of the normal laboratory range (ULN).

          -  Total bilirubin: >1.5 times ULN (except in case of Gilbert's syndrome).

          -  Participants who have taken other investigational drugs within 12 weeks or 5
             half-lives from Screening whichever is longer.

          -  Participants unwilling or unable to perform self-monitoring blood glucose (SMBG),
             complete the participant diary, or comply with study visits and other study procedures
             as required per protocol.

          -  Participants with contraindication to glimepiride as per local labelling.

          -  Participants with contraindication to metformin as per local labelling.

        The above information is not intended to contain all considerations relevant to a
        Participants potential participation in a clinical trial.