GLP-1 Receptor Agonist Lixisenatide Versus Exenatide in Patients With Type 2 Diabetes for Glycemic Control and Safety Evaluation, on Top of Metformin
Condition: Diabetes Mellitus, Type 2
MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 2
Intervention: Lixisenatide (AVE0010); Pen auto-injector; Exenatide; Prefilled pen injector; Metformin
Intervention description: Self administered by subcutaneous injections once daily within the hour preceding breakfast.; Self administered by subcutaneous injections twice daily within the hour preceding breakfast and within the hour preceding dinner.; Metformin to be continued at stable dose (at least 1.5 gram per day) up to the end of treatment.
Intervention MeSH terms: Metformin; Exenatide; Lixisenatide
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 639.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: hyperglycemia, GLP-1, metformin

Summary:

      The purpose of this study is to compare the benefits and risks of lixisenatide (AVE0010) in
      comparison to exenatide (Byetta®), as an add-on treatment to metformin, over a period of 24
      weeks of treatment, followed by an extension.

      The primary objective is to assess the effects of lixisenatide in comparison to exenatide
      (Byetta®), as an add-on treatment to metformin, on glycemic control in terms of glycosylated
      hemoglobin (HbA1c) reduction (absolute change) at Week 24.

      The secondary objectives are to assess the effects of lixisenatide on percentage of patients
      reaching HbA1c less than 7 percent (%) or HbA1c less than or equal to (<=) 6.5%, fasting
      plasma glucose (FPG), body weight; to evaluate safety, tolerability and to assess the impact
      of gastrointestinal tolerance on quality of life (QoL) (patient assessment of upper
      gastrointestinal disorders - quality of life [PAGI-QOL]).
    

Eligibility criteria:

        Inclusion Criteria:

          -  Type 2 diabetes mellitus, diagnosed for at least 1 year before screening visit,
             insufficiently controlled with metformin at a stable dose of at least 1.5 gram per day
             for at least 3 months prior to screening visit

        Exclusion Criteria:

          -  HbA1c less than (<) 7% or greater than (>) 10% at screening

          -  At the time of screening age < legal age of majority

          -  Pregnant or breastfeeding women or women of childbearing potential with no effective
             contraceptive method

          -  Type 1 diabetes mellitus

          -  Treatment with another antidiabetic pharmacological agent than metformin within the 3
             months preceding the screening

          -  FPG at screening >250 milligram per deciliter (mg/dL) (13.9 millimole per liter
             [mmol/L])

          -  Body mass index (BMI) less than or equal to (<=) 20 kilogram per square meter (kg/m^2)

          -  Weight change of >5 kg during the 3 months preceding the study

          -  History of unexplained pancreatitis, chronic pancreatitis, pancreatectomy,
             stomach/gastric surgery, inflammatory bowel disease

          -  History of metabolic acidosis, including diabetic ketoacidosis, within 1 year prior to
             screening

          -  Hemoglobinopathy or hemolytic anemia, 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

          -  Cardiovascular, hepatic, neurological, endocrine disease, active malignant tumor or
             other major systemic disease or patients with short life expectancy making
             implementation of the protocol or interpretation of the study results difficult,
             history or presence of clinically significant diabetic retinopathy, history 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 blood pressure or diastolic blood pressure >180 millimeter of mercury
             (mmHg) or >95 mmHg, respectively

          -  Laboratory findings at the time of screening: aspartate aminotransferase, alanine
             aminotransferase, or alkaline phosphatase: >2 times upper limit of the normal (ULN)
             laboratory range; amylase and/or lipase: >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 and/or Hepatitis C antibody; and
             positive serum pregnancy test in females of childbearing potential

          -  Any clinically significant abnormality identified on physical examination, laboratory
             tests, electrocardiogram or vital signs at the time of screening that, in the judgment
             of the investigator or any sub-investigator, precludes safe completion of the study or
             constrains efficacy assessment

          -  Patients who are considered by the investigator or any sub-investigator as
             inappropriate for this study for any reason (for example, impossibility to meet
             specific protocol requirements, such as attending 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,
             rimonabant, exenatide, dipeptidyl-peptidase-4 inhibitors, insulin) within 3 months
             prior to the time of screening

          -  Use of systemic glucocorticoids (excluding topical application or inhaled forms) for 1
             week or more within 3 months prior to the time of screening

          -  Use of any investigational drug within 3 months prior to study

          -  Participation in any previous study with lixisenatide

          -  Renal impairment defined with serum creatinine >1.4 mg/dL in women and serum
             creatinine >1.5 mg/dL in men

          -  Clinically relevant history of gastrointestinal disease associated with prolonged
             nausea and vomiting, including, but not limited to, gastroparesis and gastroesophageal
             reflux disease requiring medical treatment, within 6 months prior to the time of
             screening

          -  Allergic reaction to any glucagon like peptide-1 (GLP-1) agonist in the past (for
             example, exenatide, liraglutide) or to metacresol