Efficacy and Safety of Sotagliflozin Versus Placebo in Patients With Type 2 Diabetes Mellitus on Background of Metformin
Condition: Type 2 Diabetes Mellitus
MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 2
Intervention: Sotagliflozin (SAR439954); Placebo; Metformin
Intervention description: Pharmaceutical form: tablet. Route of administration: oral.; Pharmaceutical form: tablet. Route of administration: oral.; Pharmaceutical form: tablet. Route of administration: oral.
Intervention MeSH terms: Metformin; (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: Double (Participant, Investigator)
Enrollment: 518.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      Primary Objective:

      To demonstrate the superiority of Sotagliflozin versus placebo on hemoglobin A1c (HbA1c)
      reduction in participants with type 2 diabetes (T2D) who have inadequate glycemic control
      with metformin.

      Secondary Objectives:

        -  To compare Sotagliflozin versus placebo for.

        -  Change from baseline in 2-hour postprandial glucose (PPG) following a mixed meal.

        -  Change from baseline in fasting plasma glucose (FPG).

        -  Change from Baseline in systolic blood pressure (SBP) for participants with baseline SBP
           ≥130 millimeter of mercury (mmHg).

        -  Change from baseline in SBP for all participants.

        -  Change from baseline in body weight.

        -  Proportion of participants with HbA1c <6.5% and <7.0%.

        -  To evaluate the safety of Sotagliflozin versus placebo.
    

Eligibility criteria:

        Inclusion criteria :

          -  Participants with Type 2 Diabetes currently treated with diet and exercise and on
             metformin at a stable dose ≥1500 milligrams per day (mg/day) for at least 12 weeks.
             However, participants on metformin at a dose <1500 mg/day at the time of enrollment
             (stable dose for at least 12 weeks before enrollment) may be eligible for screening if
             documentation of lack of tolerance of a metformin dose ≥1500 mg/day can be provided.

          -  Signed written informed consent.

        Exclusion criteria:

          -  Age <18 years at Screening or < legal age of majority, whichever is greater.

          -  Type 1 diabetes mellitus.

          -  Body Mass Index (BMI) ≤20 or >45 kilograms per meter square (kg/m^2) at Screening

          -  Hemoglobin A1c <7% or >10% via central laboratory test at screening.

          -  Fasting plasma glucose (FPG) >15 millimole per liter (mmol/L) (270 milligrams 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.

          -  Women of childbearing potential not willing to use highly effective method(s) of birth
             control or who are unwilling or unable to be tested for pregnancy during the study.

          -  Treated with an antidiabetic pharmacological regimen other than metformin ≥1500 mg per
             day (or maximum tolerated dose) within the 12 weeks preceding the Screening Visit.

          -  Previous use of any types of insulin for >1 month (at any time, aside from pregnancy
             for treatment of gestational diabetes).

          -  History of prior gastric surgical procedure, including gastric banding, within 3 years
             before the Screening Visit.

          -  History of diabetic ketoacidosis or nonketotic hyperosmolar coma within 12 weeks prior
             to the Screening Visit.

          -  Mean of 3 separate blood pressure measurements >180 mmHg (SBP) or >100 mmHg (diastolic
             blood pressure [DBP]).

          -  History of hypertensive urgency or emergency within 12 weeks prior to Screening.

          -  Participants with severe anemia, severe cardiovascular (including congestive heart
             failure New York Heart Association [NYHA] IV), respiratory, hepatic, neurological,
             psychiatric, or active malignant tumor or other major systemic disease or participants
             with short life expectancy making 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.

          -  Total bilirubin: >1.5 times the upper limit of the normal laboratory range (except in
             case of Gilbert's syndrome).

          -  Use of systemic glucocorticoids (excluding topical or ophthalmic application or
             inhaled forms) for more than 10 consecutive days within 90 days prior to the Screening
             Visit.

          -  Participants who has taken other investigational drugs or prohibited therapy for this
             study within 12 weeks or 5 half-lives from screening or randomization, whichever is
             longer.

          -  Pregnant (confirmed by serum pregnancy test at Screening) or breastfeeding women.

          -  Participants is unwilling or unable to perform self-monitoring of blood glucose
             (SMBG), complete the participants diary, or comply with study visits and other study
             procedures as required per protocol.

          -  Contraindication to metformin as per local labelling.

        The above information is not intended to contain all considerations relevant to a
        participant's potential participation in a clinical trial.