Effects of Lixisenatide Compared to Liraglutide on the Postprandial Plasma Glucose in Patients With Type 2 Diabetes
Condition: Type 2 Diabetes Mellitus
MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 2
Intervention: Lixisenatide (AVE0010); Pen auto-injector; Liraglutide; Pre-filled pen injector; Metformin
Intervention description: Self administered by subcutaneous injections once daily 30 minutes before breakfast.; Self administered by subcutaneous injections once daily 30 minutes before breakfast.; Metformin to be continued at stable dose (1.5 gram per day) up to Week 4.
Intervention MeSH terms: Metformin; Liraglutide; Lixisenatide
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 148.0
Sex: All
Minimum age: 18 Years
Maximum age: 74 Years
Healthy volunteers: No

Summary:

      The purpose of the study is to compare the pharmacodynamic effects of lixisenatide (AVE0010),
      in comparison to liraglutide, as an add-on treatment to metformin, over a period of 4 weeks
      of treatment.

      The primary objective is to assess the effects of lixisenatide, in comparison to liraglutide,
      in reducing postprandial plasma glucose (PPG) assessed as area under the plasma glucose
      concentration curve (AUC) after a standardized breakfast at Week 4.

      The secondary objectives are to assess the effects of lixisenatide on the maximum PPG
      excursion, and on the changes in insulin, pro-insulin, C-peptide and glucagon plasma
      concentrations following a standardized breakfast, 24-hour profile of plasma glucose,
      glycosylated hemoglobin (HbA1c), satiety markers (obestatin, peptide YY [PYY3-36] and
      oxyntomodulin); and to assess the clinical and laboratory safety profile.
    

Eligibility criteria:

        Inclusion criteria:

          -  Type 2 diabetes mellitus diagnosed for at least 1 year at the time of screening visit,
             not adequately controlled by metformin at a dose of at least 1.5 gram per day for at
             least 3 months prior to screening

          -  HbA1c greater than or equal to (>=) 6.5% (as recommended by the American Diabetes
             Association) and HbA1c less than or equal to (<=) 9% at screening

          -  Covered by Health Insurance System where applicable and/or in compliance with the
             recommendations of the National (German) Law in force relating to biomedical research

          -  Not under any administrative or legal supervision

        Exclusion criteria:

          -  At the time of screening age <18 years or >=75 years

          -  Body Mass Index (BMI): <=20 kilogram per square meter (kg/m^2) or >=37 kg/m^2

          -  History of metabolic acidosis, including diabetic ketoacidosis within 1 year prior to
             screening

          -  Hemoglobinopathy or hemolytic anemia

          -  History of myocardial infarction, stroke, or heart failure requiring hospitalization
             within 6 months prior to the time of screening, history or presence of clinically
             significant diabetic retinopathy, history or presence of macular edema likely to
             require laser treatment within the study period

          -  Cardiovascular, hepatic, neurological, or 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
             (euthyroid patients on replacement therapy are to be included if the dosage of
             thyroxin is stable for at least 3 months prior to the screening visit)

          -  Uncontrolled or inadequately controlled hypertension at the time of screening with a
             resting systolic or diastolic blood pressure >160 millimeter of mercury (mmHg) or >95
             mmHg, respectively

          -  Any clinically significant abnormality identified on physical examination, laboratory
             tests, 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

          -  Receipt of blood or plasma products within 3 months prior to the time of screening

          -  Investigator or any sub-investigator, pharmacist, study coordinator, or their study
             staff or relative thereof directly involved in the conduct of the protocol

          -  Patients who are considered by the investigator or any sub-investigator as
             inappropriate for this study for any reason (for example, impossibility of meeting
             specific protocol requirements such as scheduled visits, being unable to do
             self-injections, etc.)

          -  Use of other oral or injectable antidiabetic or hypoglycemic agents other than
             metformin (for example, alpha glucosidase inhibitor, exenatide, dipeptidyl peptidase
             IV [DPP-IV] inhibitors, insulin, thiazolidinedione, sulfonylurea, etc.) 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

          -  Likelihood of requiring treatment during the screening phase and treatment phase with
             drugs not permitted by the clinical study protocol

          -  Use of any investigational drug within 3 months prior to screening

          -  Pregnant or breastfeeding women or women of childbearing potential with no effective
             contraceptive method

          -  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

          -  Any previous treatment with lixisenatide or liraglutide

          -  Allergic reaction to any glucagon like peptide - 1 (GLP-1) agonist in the past (for
             example, exenatide) or to metacresol

          -  History of unexplained pancreatitis, chronic pancreatitis, pancreatectomy,
             stomach/gastric surgery, inflammatory bowel disease

          -  Personal or family history of medullary thyroid cancer (MTC) or a genetic condition
             that predisposes to MTC

          -  Known history of drug or alcohol abuse within 6 months prior to the time of screening

          -  Laboratory findings at the time of screening: alanine aminotransferase: >3 times the
             upper limit of the normal (ULN) laboratory range; calcitonin >=20 picogram per
             milliliter (pg/mL); amylase and 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 reaction
             to tests for anti-human immunodeficiency virus (HIV) type 1 (HIV1) and anti-HIV2
             antibodies

          -  Renal impairment defined by creatinine clearance <60 milliliter per minute (mL/min)
             using the Cockcroft-Gault formula