Efficacy and Safety of Sotagliflozin Versus Placebo in Patients With Type 2 Diabetes Mellitus Not Currently Treated With Antidiabetic Therapy
Condition: Type 2 Diabetes Mellitus
MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 2
Intervention: Sotagliflozin (SAR439954); Placebo
Intervention description: Pharmaceutical form: tablet;
Route of administration: oral; Pharmaceutical form: tablet;
Route of administration: oral
Intervention MeSH terms: (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: 399.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      Primary Objective:

      To demonstrate the superiority of Sotagliflozin 400 milligrams (mg) versus placebo on
      hemoglobin A1c (HbA1c) reduction in participants with type 2 diabetes (T2D) who have
      inadequate glycemic control on diet and exercise.

      Secondary Objectives:

        -  To compare Sotagliflozin 400 mg versus placebo based on:

        -  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 per mercury (mmHg).

        -  Change from baseline in SBP for all participants.

        -  Change from baseline in body weight.

        -  Proportion of participants with HbA1c <6.5%, <7.0%.

        -  To compare Sotagliflozin 200 mg versus placebo based on:

        -  Change from baseline in HbA1c.

        -  Change from baseline in 2-hour postprandial glucose (PPG) following a mixed meal.

        -  Change from baseline in body weight.

        -  Change from baseline in SBP for all participants.

        -  To evaluate the safety of Sotagliflozin 400 and 200 mg versus placebo.
    

Eligibility criteria:

        Inclusion criteria :

          -  Participants (male and female) with T2D, who are treated with diet and exercise only
             during the 12 weeks prior to screening.

          -  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 kilogram per meter square (kg/m^2) at Screening.

          -  Hemoglobin A1c (HbA1c) <7% or >10% via central laboratory test at Screening.

          -  Fasting plasma glucose (FPG) >15 millimole 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.

          -  Women of childbearing potential not willing to use highly effective contraceptive
             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.

          -  Treated with an antidiabetic pharmacological agent within the 12 weeks prior to the
             Screening Visit.

          -  Previous use of any types of insulin for >1 month (at any time, except for treatment
             of gestational diabetes).

          -  History of 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 millimeter of mercury (mmHg)
             (systolic) or >100 mmHg (diastolic).

          -  History of hypertensive 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 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.

          -  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. Current enrollment in any other clinical study involving an investigational
             study treatment or any other type of medical research.

          -  Pregnant (confirmed by serum pregnancy test at Screening) or breastfeeding women.

          -  Severe renal disease as defined by estimated glomerular filtration rate (eGFR) of <30
             millimeter per minute (mL/min)/1.73 meter square (m^2)² at screening by the 4 variable
             Modification of Diet in Renal Disease (MDRD) equation.

          -  Participant 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.

          -  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 potential participation in a clinical trial.