24-week Study Comparing Lixisenatide to Sitagliptin as add-on to Metformin in Obese Type 2 Diabetic Patients Younger Than 50 Years
Condition: Type 2 Diabetes Mellitus
MeSH terms: Diabetes Mellitus, Type 2
Intervention: Lixisenatide (AVE0010); Lixisenatide Placebo; Pen auto-injector; Sitagliptin; Sitagliptin Placebo; Metformin
Intervention description: Self-administered by subcutaneous injections once daily within the hour preceding breakfast.; Self-administered by subcutaneous injections once daily within the hour preceding breakfast.; Administered orally once a day in the morning with or without food at approximately the same time each day.; Administered orally once a day in the morning with or without food at approximately the same time each day.; Metformin to be continued at stable dose (at least 1.5 gram per day) up to Week 24.
Intervention MeSH terms: Metformin; Sitagliptin Phosphate; Lixisenatide
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 319.0
Sex: All
Minimum age: 18 Years
Maximum age: 49 Years
Healthy volunteers: No

Summary:

      The purpose of this study is to evaluate benefits and risks of lixisenatide (AVE0010), in
      comparison to sitagliptin, as an add-on treatment to metformin, in obese (body mass index
      [BMI] greater than or equal to 30 kilogram per square meter [kg/m^2]) type 2 diabetic
      patients less than 50 years of age, over a period of 24 weeks of treatment.

      The primary objective of this study is to assess the efficacy of lixisenatide, in comparison
      to sitagliptin, as an add-on treatment to metformin on a composite endpoint of glycemic
      control in terms of glycosylated hemoglobin (HbA1c) and body weight, at Week 24.

      Secondary objectives are to assess the effects of lixisenatide, in comparison to sitagliptin,
      as an add-on treatment to metformin on absolute changes in HbA1c values and body weight;
      fasting plasma glucose (FPG); plasma glucose, insulin, C-peptide, glucagon, and proinsulin
      during a 2-hour standardized meal test; insulin resistance assessed by homeostatic model
      assessment of insulin resistance (HOMA-IR); beta cell function assessed by homeostatic model
      assessment of beta-cell function (HOMA-beta); to evaluate safety, tolerability, and
      anti-lixisenatide antibody development.
    

Eligibility criteria:

        Inclusion criteria

          -  Type 2 diabetes mellitus, diagnosed for at least 1 year at the time of screening
             visit, insufficiently controlled with metformin at a stable dose of at least 1.5
             gram/day (g/day) for at least 3 months prior to the screening visit

          -  Patients with obesity (BMI greater than equal to [>=] 30 kg/m^2) and aged from 18
             years to less than 50 years

        Exclusion criteria

          -  HbA1c less than (<) 7.0 percent (%) or HbA1c greater than (>) 10% at screening

          -  Type 1 diabetes mellitus

          -  Pregnant or breastfeeding women or women of childbearing potential with no effective
             contraceptive method

          -  FPG at screening >250 milligram/deciliter (mg/dL) (>13.9 millimole/ liter [mmol/L])

          -  Weight change of more than 5 kg during the 3 months preceding the screening visit

          -  History of unexplained pancreatitis, chronic pancreatitis, pancreatectomy,
             stomach/gastric surgery, inflammatory bowel disease, personal or family history of
             medullary thyroid cancer (MTC) or genetic conditions that predispose to MTC (for
             example, multiple endocrine neoplasia syndromes)

          -  History of metabolic acidosis, including diabetic ketoacidosis within 1 year prior to
             screening

          -  Hemoglobinopathy or hemolytic anemia or receipt of blood or plasma products within 3
             months prior to the time of screening

          -  Within the last 6 months prior to screening: history of myocardial infarction, stroke,
             or heart failure requiring hospitalization

          -  Known history of drug or alcohol abuse within 6 months prior to the time of screening

          -  Any clinically significant abnormality identified on physical examination, laboratory
             tests, electrocardiogram (ECG) or vital signs at the time of screening that in the
             judgment of the investigator or any sub-investigator could have precludes safe
             completion of the study or constrains efficacy assessment such as major systemic
             diseases, presence of clinically significant diabetic retinopathy or presence of
             macular edema likely to require laser treatment within the study period

          -  Uncontrolled or inadequately controlled hypertension at the time of screening with a
             resting systolic or diastolic blood pressure >180 millimeter of mercury (mmHg) or >110
             mmHg, respectively

          -  Laboratory findings at the time of screening : Amylase and/or lipase >3 times the
             upper limit of normal (ULN) laboratory range; alanine aminotransferase (ALT): >3 times
             ULN; total bilirubin: >1.5 times ULN (except in case of Gilbert's syndrome);
             hemoglobin <11 gram/deciliter and/or neutrophils <1500 per cubic millimeter (mm^3)
             and/or platelets <100 000/mm^3; positive test for Hepatitis B surface antigen (HBsAg)
             and/or Hepatitis C antibody (HCAb), positive serum pregnancy test in females of
             childbearing potential, and calcitonin >=20 picogram per milliliter (pg/mL) (5.9
             picomole per liter)

          -  Patients who are considered by the investigator or any sub-investigator as
             inappropriate for the study for any reason (for example, impossibility to meet
             specific protocol requirements [such as scheduled visits, being able to do
             self-injections], likelihood of requiring treatment during the screening phase and
             treatment phase with drugs not permitted by the clinical study protocol, investigator
             or any sub-investigator, pharmacist, study coordinator, other study staff or relative
             thereof directly involved in the conduct of the protocol)

          -  Use of other oral or injectable antidiabetic or hypoglycemic agents than metformin
             (for example, sulfonylurea, alpha glucosidase inhibitor, thiazolidinedione, exenatide,
             dipeptidyl peptidase IV (DPP-IV) inhibitors, insulin) within 3 months prior to the
             time of screening

          -  History of bariatric surgery, anti-obesity treatment, or unstable diet within 3 months
             prior to the time of screening

          -  Use of systemic glucocorticoids (excluding topical application or inhaled forms) for
             one week or more within 3 months prior to the time of screening

          -  Use of any investigational drug within 3 months prior to screening

          -  Clinically relevant history of gastrointestinal disease associated with prolonged
             nausea and vomiting, including (but not limited to): gastroparesis, unstable (that is,
             worsening) and not controlled (that is, prolonged nausea and vomiting)
             gastroesophageal reflux disease requiring medical treatment, within 6 months prior to
             the time of screening

          -  Any previous treatment with lixisenatide (for example, participation in a previous
             study with lixisenatide)

          -  Allergic reaction to any glucagon like peptide-1 (GLP 1) agonist in the past (for
             example, exenatide, liraglutide) or to metacresol

          -  History of a serious hypersensitivity reaction to sitagliptin

          -  Moderate or severe renal impairment (creatinine clearance inferior to 50
             milliliter/minute [mL/min])

          -  Additional exclusion criteria at the end of the run-in phase: informed consent
             withdrawal; lack of compliance during the single-blind placebo run-in period (>2
             injections missed or >2 capsules missed); and patient with any adverse event which
             could have precludes the inclusion in the study, as assessed by the investigator