Efficacy and Safety of Sotagliflozin Versus Placebo in Participants With Type 2 Diabetes Mellitus Who Have Inadequate Glycemic Control While Taking Insulin Alone or With Other Oral Antidiabetic Agents
Condition: Type 2 Diabetes Mellitus
MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 2
Intervention: Sotagliflozin; Insulin glargine (HOE901); Placebo; Oral Antidiabetes Drugs (OADs)
Intervention description: Pharmaceutical form: Tablet
Route of administration: Oral; Pharmaceutical form: Solution
Route of administration: Subcutaneous; Pharmaceutical form: Tablet
Route of administration: Oral; OADs (including metformin) as prescribed by the investigator as per local labeling.
Intervention MeSH terms: Insulin Glargine; (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: 571.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      Primary Objective:

      To demonstrate the superiority of sotagliflozin 400 milligrams (mg) versus placebo with
      respect to hemoglobin A1C (HbA1c) reduction in participants with type 2 diabetes mellitus
      (T2D) who have inadequate glycemic control on basal insulin alone or with oral antidiabetes
      drugs (OADs).

      Secondary Objectives:

        -  To assess the effects of sotagliflozin 400 mg versus placebo on fasting plasma glucose
           (FPG), body weight, systolic blood pressure (SBP), and HbA1c.

        -  To assess the effects of sotagliflozin 200 mg versus placebo on HbA1c, body weight, FPG,
           and SBP.

        -  To evaluate the safety of sotagliflozin 400 and 200 mg versus placebo.
    

Eligibility criteria:

        Inclusion criteria :

          -  Participants with Type 2 Diabetes Mellitus (T2DM) using any types of basal insulin
             alone or in combination with up to 2 OADs.

          -  Participants have given written informed consent to participate in the study in
             accordance with local regulations.

        Exclusion criteria:

          -  At the time of Screening age <18 years or <legal age of majority, whichever is
             greater.

          -  Type 1 diabetes mellitus.

          -  Oral antidiabetic drugs dose not stable for 8 weeks before Screening.

          -  Use of basal insulin therapy (e.g., insulin glargine, Neutral Protamine Hagedorn
             (NPH), detemir, or degludec) for less than 6 months before Screening.

          -  Dose of basal insulin (e.g., insulin glargine, NPH, detemir, or degludec) not stable
             for 8 weeks before Screening (i.e., total daily insulin dose increased or decreased by
             more than 20%).

          -  Known unstable proliferative diabetic retinopathy or any other rapidly progressive
             diabetic retinopathy or macular edema that is likely to require laser, surgical
             treatment during study period.

          -  Use of injectable diabetes drugs other than basal insulin (e.g., insulin glargine,
             NPH, detemir, or degludec), i.e., prandial or rapid-acting insulins, short-acting
             insulins, glucagon-like peptide 1 (GLP-1) receptor agonists, or inhaled prandial
             insulin (Afrezza) within 8 weeks of Screening.

          -  Use of a selective sodium-glucose cotransporter type 2 (SGLT2) inhibitor (e.g.,
             canagliflozin, dapagliflozin, or empagliflozin) within 3 months prior to the trial.

          -  Use of systemic glucocorticoids (excluding topical, intra articular, or ophthalmic
             application, nasal spray or inhaled forms) for more than 10 consecutive days within 90
             days prior to the Screening Visit.

          -  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 the Investigator, will preclude their safe participation in this study, or will
             make implementation of the protocol or interpretation of the study results difficult.

          -  Lower extremity complications (such as skin ulcers, infection, osteomyelitis and
             gangrene) identified during the Screening period, and still requiring treatment at
             Randomization.

          -  Known presence of factors that interfere with the Central Lab HbA1c measurement (e.g.,
             genetic hemoglobin (Hb) variants) compromising the reliability of HbA1c assessment or
             medical conditions that affect interpretation of HbA1c results (e.g., blood
             transfusion or severe blood loss in the last 3 months prior to randomization, any
             condition that shortens erythrocyte survival).

          -  Participants who has taken other investigational drugs or prohibited therapy for this
             study within 12 weeks or 5 half-lives from prior to Screening, whichever is longer.

          -  Participants unwilling to perform self-monitoring of blood glucose (SMBG), complete
             the patient diary, or comply with study visits and other study procedures as required
             per protocol.

          -  HbA1c <7.5% or HbA1c >10.5% measured by the central laboratory at Screening.

          -  HbA1c <7% measured by the central laboratory at Visit 5 (Week -1).

          -  History of diabetic ketoacidosis or nonketotic hyperosmolar coma within 12 weeks prior
             to the Screening Visit.

          -  Pregnant (confirmed by serum pregnancy test at Screening) or breastfeeding women.

          -  Women of childbearing potential 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 during the study.

          -  Mean of 3 separate blood pressure measurements >180 mmHg (systolic blood pressure
             [SBP]) or >100 mmHg (diastolic blood pressure [DBP]).

          -  History of gastric surgery including history of gastric banding or inflammatory bowel
             disease within 3 years prior to the Screening Visit.

          -  Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >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).

        The above information is not intended to contain all considerations relevant to a
        participant's potential participation in a clinical trial.