GLP-1 Receptor Agonist Lixisenatide in Patients With Type 2 Diabetes for Glycemic Control and Safety Evaluation in Monotherapy
Condition: Diabetes Mellitus, Type 2
MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 2
Intervention: Lixisenatide (AVE0010); Placebo; Pen auto-injector
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.
Intervention MeSH terms: Lixisenatide
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 361.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: hyperglycemia, GLP-1

Summary:

      The purpose of this study is to evaluate the benefits and risks of lixisenatide (AVE0010), in
      comparison to placebo, used in a 2-step dose titration regimen in monotherapy, over a period
      of 12 weeks of treatment.

      The primary objective is to assess the effects of lixisenatide, in comparison to placebo, on
      glycemic control using a 2-step dose titration regimen in terms of glycosylated hemoglobin
      (HbA1c) reduction (absolute change) at Week 12.

      Secondary objectives are to assess the effects of lixisenatide, in comparison to placebo, on
      glycemic control in terms of HbA1c reduction when it is used in a one-step dose titration
      regimen over a period of 12 weeks, body weight, fasting plasma glucose (FPG), 2-hour
      postprandial plasma glucose (PPG) after a standardized meal, to assess the safety and
      tolerability, pharmacokinetics (PK) and anti-lixisenatide antibody development.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Type 2 diabetes mellitus, diagnosed for at least 2 months at the time of the screening
             visit, not treated with any antidiabetic agent

        Exclusion Criteria:

          -  HbA1c less than (<) 7 percent (%) or greater than (>) 10%

          -  At the time of screening age < legal age of majority

          -  Pregnant or breastfeeding women and women of childbearing potential without effective
             contraceptive method of birth control

          -  Type 1 diabetes mellitus

          -  Type 2 diabetes treated by an antidiabetic agent within the 3 months preceding the
             study

          -  Fasting plasma glucose at screening >250 milligram per deciliter (mg/dL) (>13.9
             millimole per liter [mmol/L])

          -  Body mass index less than or equal to (<=) 20 kilogram per square meter (kg/m^2)

          -  Weight change of more than 5 kg during the previous 3 months

          -  History of unexplained pancreatitis, chronic pancreatitis, pancreatectomy,
             stomach/gastric surgery, inflammatory bowel disease

          -  History of metabolic acidosis, including diabetic ketoacidosis within the previous
             year

          -  Hemoglobinopathy or hemolytic anemia, receipt of blood or plasma products within the
             previous 3 months

          -  History of myocardial infarction, stroke, or heart failure requiring hospitalization
             within the previous 6 months

          -  Known history of drug or alcohol abuse within the previous 6 months

          -  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 with a resting supine systolic 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 the upper limit of the normal (ULN)
             laboratory range; amylase and/or lipase: >3 ULN; total bilirubin: >1.5 ULN (except in
             case of Gilbert's syndrome); hemoglobin <11 gram/deciliter (g/dL) and/or neutrophils
             <1,500 per cubic mm (mm^3) and/or platelets <100,000/mm^3; positive test for Hepatitis
             B surface antigen and/or hepatitis C antibody

          -  Any clinically significant abnormality identified by physical examination, laboratory
             tests, electrocardiogram or vital sign at the time of screening that in the judgment
             of the investigator or any sub investigator precludes safe completion of the study or
             hinders the efficacy assessment

          -  Patients who are considered by the investigator or any sub-investigator as
             inappropriate for this study for any reason

          -  Use of systemic glucocorticoids (excluding topical application or inhaled forms)
             within the previous 3 months

          -  Participation in any previous study with lixisenatide

          -  Use of any investigational drug within 3 months prior to study

          -  End-stage renal disease as defined by a calculated serum creatinine clearance of <15
             milliliter/minute and/or patients on dialysis

          -  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 the previous 6 months

          -  History of allergic reaction to any glucagon like peptide-1 (GLP-1) agonist in the
             past or to metacresol

          -  Additional exclusion criteria at the end of the run-in phase: informed consent
             withdrawal; lack of compliance during the single-blind placebo run-in phase: more than
             2 injections missed; and patient with any adverse event which precludes the inclusion
             in the study, as assessed by the investigator