A Study to Assess the Safety and Efficacy of SAR425899 in Patients With Type 2 Diabetes Mellitus
Condition: Type 2 Diabetes Mellitus
MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 2
Intervention: SAR425899; Placebo; Liraglutide; Metformin
Intervention description: Self-administered by SC injection using a solution for injection in cartridge.; Self-administered by SC injection using a solution for injection in cartridge.; Self-administered by SC injection using a pre-filled pen.; Orally administered at a stable dose , >=1500 mg daily stable dose or maximal tolerated dose.
Intervention MeSH terms: Metformin; Liraglutide
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 296.0
Sex: All
Minimum age: 18 Years
Maximum age: 80 Years
Healthy volunteers: No

Summary:

      Primary Objective:

      The primary objective of this study was to assess the dose-response relationship of SAR425899
      versus placebo in terms of glycemic control as measured by the change in glycosylated
      hemoglobin (HbA1c).

      Secondary Objectives:

        -  To assess the effect of SAR425899 on body weight.

        -  To assess the safety and immunogenicity profile of SAR425899, including assessment of
           the heart rate (HR) change by electrocardiogram (ECG) and Holter monitor.

        -  To assess the proportion of participants achieving predefined HbA1c targets of <7% and
           <6.5% as well as the proportion of participants achieving >=5% and >=10% body weight
           loss.

        -  To assess the effect of once daily dosing of SAR425899 on additional parameters of
           glycemic control and lipid metabolism.

        -  To assess the effect of once daily dosing of SAR425899 on additional pharmacodynamic
           (PD) biomarkers.

        -  To assess the pharmacokinetic (PK) profile and parameters of SAR425899, inter-individual
           and inter-occasion variability in PK parameters using a population PK approach.
    

Eligibility criteria:

        Inclusion criteria :

          -  Participants with type-2 diabetes mellitus (T2DM) for at least 3 months before the
             screening visit.

          -  On diet/exercise and/or treatment with metformin (stable dose of ≥1500 mg/day or
             maximal tolerated dose) for at least 3 months prior to screening.

          -  Signed informed consent.

        Exclusion criteria:

          -  At screening, participant's age < legal age of adulthood and >80 years.

          -  Glycated hemoglobin at screening visit <7.0% or >10.0%.

          -  Body mass index (BMI) <25 kg/m^2 or >45.0 kg/m^2.

          -  Pregnant or lactating women.

          -  Women of childbearing potential (WOCBP) not protected by highly-effective method(s) of
             birth control and/or who are unwilling or unable to be tested for pregnancy.

          -  Diagnosis of type 1 diabetes mellitus.

          -  Fasting plasma glucose of >15 mmol/L (270 mg/dL) measured by the central laboratory at
             screening (Visit 1), and confirmed (>15 mmol/L [270 mg/dL]) by a repeat test before
             randomization.

          -  Treatment with glucose-lowering agents(s) other than metformin, currently or within
             the 3 months prior to screening.

          -  Previous insulin use, except for episode(s) of short-term treatment (≤15 consecutive
             days) for intercurrent illness or pregnancy, or use of insulin within the last 6
             months.

          -  Contraindication(s) to metformin use.

          -  Contraindication(s) to liraglutide use.

          -  Significant change in body weight in the 3 months before screening.

          -  Poorly controlled hypertension (a resting systolic blood pressure (SBP) >160 mm Hg
             and/or diastolic blood pressure (DBP) >95 mm Hg at screening).

          -  History of long QT syndrome and/or QTc more than 450 ms at screening visit.

          -  History of pancreatitis or pancreatectomy.

          -  History of weight loss surgery.

          -  Personal or immediate family history of medullary thyroid cancer (MTC) or genetic
             conditions that predispose to MTC.

          -  Any prior exposure to drugs belonging to the class of glucagon-like peptide-1 (GLP-1)
             receptor agonists/GLP-1 analogs.

          -  Contraindications or known hypersensitivity reaction to glucagon.

        The above information is not intended to contain all considerations relevant to a
        participant's potential participation in a clinical trial.