Efficacy and Safety of Sotagliflozin Versus Placebo and Empagliflozin in Participants With Type 2 Diabetes Mellitus Who Have Inadequate Glycemic Control While Taking a DPP4 Inhibitor Alone or With Metformin
Condition: Type 2 Diabetes Mellitus
MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 2
Intervention: Sotagliflozin; Empagliflozin; Placebo; Placebo
Intervention description: Sotagliflozin 400 mg was administered as two tablets, once daily before the first meal of the day.; Empagliflozin 25 mg capsule was administered, once daily before the first meal of the day.; Placebo was administered as two tablets (identical to sotagliflozin in appearance), once daily before the first meal of the day.; Placebo was administered as one capsule (identical to the empagliflozin capsule in appearance), once daily before the first meal of the day.
Intervention MeSH terms: Empagliflozin; (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: 770.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      The purpose of the study is 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 on a DPP4(i) with or without metformin.
    

Eligibility criteria:

        Inclusion criteria :

          -  Participants with Type 2 Diabetes on Dipeptidyl peptidase-4 inhibitors(DPP4(i)) with
             or without metformin at a stable dose for at least 12 weeks prior to Screening Visit.
             Metformin dose will be ≥1500 mg per day (or maximum tolerated dose [documented]).
             DPP4(i) dose must be the appropriate dose as per local label.

          -  Signed written informed consent.

        Exclusion criteria:

          -  Body mass index (BMI) ≤20 kg/m^2 or >45 kg/m^2 at Screening.

          -  Use of any antidiabetic drug other than DPP4 inhibitors and metformin within 12 weeks
             preceding the Screening Visit.

          -  Participants who have previously participated in any clinical trial of
             sotagliflozin/LX4211.

          -  Use of a selective sodium-glucose co-transporter type 2 (SGLT2) inhibitor (e.g.,
             canagliflozin, dapagliflozin, or empagliflozin) within 3 months prior to the screening
             visit.

          -  Participants with severe anemia, severe cardiovascular disease (including congestive
             heart failure New York Heart Association IV), respiratory, hepatic, neurological,
             psychiatric, or active malignant tumor or other major systemic disease or participants
             with a short life expectancy that, according to Investigator, will preclude their safe
             participation in this study, or will make the implementation of the protocol or
             interpretation of the study results difficult.

          -  Current diagnosis of chronic hepatitis and/or other clinically active liver disease
             requiring treatment.

          -  Participants with contraindication to empagliflozin as per local labelling.

          -  Participants with contraindication to metformin as per local labelling.

          -  Hemoglobin A1c <7.0% or >11.0% at Screening (central laboratory).

          -  Fasting plasma glucose >270 mg/dL (>15.0 mmol/L) measured by the central laboratory at
             Screening (Visit 1), and confirmed by a repeat test (>270 mg/dL [>15.0 mmol/L]) before
             Randomization.

          -  Previous use of any type of insulin for >1 month (except for treatment of gestational
             diabetes).

          -  Pregnant (confirmed by serum pregnancy test at Screening) or breast-feeding women.

          -  Women of childbearing potential not willing to use highly effective method(s) of birth
             control during the study treatment period and follow-up period, or who are unwilling
             or unable to be tested for pregnancy during the study.

          -  Mean of 3 separate blood pressure (BP) measurements >180 mmHg (systolic blood pressure
             [SBP]) or >100 mmHg (diastolic blood pressure [DBP]).

          -  History of the hypertensive crisis resulting in emergency medical care within 12 weeks
             prior to Screening Visit.

          -  Lower extremity complications (such as skin ulcers, infection, osteomyelitis, and
             gangrene) identified during the Screening period, and still requiring treatment at
             Randomization.

          -  Laboratory findings with the central laboratory tests at Visit 1:

          -  Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >3 times the upper
             limit of the normal laboratory range (ULN);

          -  Total bilirubin >1.5 times the ULN (except in case of Gilbert's syndrome);

          -  Neutrophils <1 500/mm^3 (or according to ethnic group) and/or platelets <100 000/mm^3;

          -  Amylase and/or lipase >3 times the ULN;

          -  Participants with renal impairment as defined by the estimated glomerular filtration
             rate (eGFR) criterion that precludes initiation of empagliflozin as per the approved
             local label (eg, <45 mL/min/1.73 m^2 in US; <60 mL/min/1.73 m^2 in EU).

          -  Secondary hypertension of any etiology (eg, renovascular disease, pheochromocytoma,
             Cushing's syndrome).

          -  If the participant is on hypertensive medications, the antihypertensive has been
             changed in the 8 weeks prior to Screening (new drug or new dose).

        The above information is not intended to contain all considerations relevant to a
        participant's potential participation in a clinical trial.