GLP-1 Receptor Agonist Lixisenatide in Patients With Type 2 Diabetes for Glycemic Control and Safety Evaluation in Monotherapy (GETGOAL-MONO Japan LTS)
Condition: Diabetes Mellitus, Type 2
MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 2
Intervention: Lixisenatide (AVE0010); Pen auto-injector
Intervention description: 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: None (Open Label)
Enrollment: 69.0
Sex: All
Minimum age: 20 Years
Healthy volunteers: No
Keywords: hyperglycemia; GLP-1

Summary:

      The purpose of this study is to compare the benefits and risks of lixisenatide (AVE0010) used
      as 2-step initiation regimen and 1-step initiation regimen in Japan, over a period of 24
      weeks of treatment, followed by an extension up to Week 76.

      The primary objective of this study is to evaluate the safety of lixisenatide once daily
      treatment in monotherapy at Week 24 by a descriptive comparison of a 1-step initiation and a
      2-step initiation regimen in patients with type 2 diabetes in Japan.

      The secondary objectives are to assess the overall safety of lixisenatide once daily
      treatment in monotherapy at Week 52 and Week 76; to assess the effects of lixisenatide on
      glycosylated hemoglobin (HbA1c) reduction at Week 52 and Week 76, body weight, and fasting
      plasma glucose (FPG); to assess 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 screening
             visit, not treated by an antidiabetic agent in the 3 months before screening, except
             treatment with sulfonylureas or alpha-glucosidase inhibitors at a stable dose. In this
             case the oral antidiabetic treatment must be discontinued before starting single-blind
             run-in phase

        Exclusion Criteria:

          -  HbA1c less than (<) 7 percent (%) 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

          -  Type 2 diabetes treated by an antidiabetic pharmacological agent (except sulfonylurea
             or alpha-glucosidase inhibitors at a stable dose) within the 3 months preceding the
             screening. Insulin use is accepted if it is not within 3 months prior to screening
             visit and only for the following reasons: a) Prior insulin use for management of
             gestational diabetes; b) Short-term (less than or equal to [<=] 1 month) insulin use
             to maintain glycemic control for hospitalization, medical procedures, or intervention

          -  FPG at screening >250 milligram per deciliter (mg/dL) (>13.9 millimole per liter
             [mmol/L])

          -  Weight change of more than 5 kilogram (kg) during the 3 months preceding the screening
             visit

          -  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 supine systolic or diastolic blood pressure >180 millimeter of mercury (mmHg)
             or >95 mmHg, respectively

          -  Laboratory findings at the time of screening: aspartate aminotransferase (AST),
             alanine aminotransferase (ALT), or alkaline phosphatase (ALP): >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
             <100000/mm^3; positive test for Hepatitis B surface antigen (HBsAg) and/or Hepatitis C
             antibody (HCAb) and positive serum pregnancy test in females of childbearing potential

          -  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 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 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)

          -  Patient is an investigator or any sub-investigator, pharmacist, study coordinator,
             other study staff or relative thereof directly involved in the conduct of the protocol

          -  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 screening

          -  Participation in a previous study with lixisenatide

          -  End-stage renal disease as defined by a serum creatinine clearance of <15
             milliliter/minute (calculated by the Cockcroft and Gault formula) 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 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

          -  Additional exclusion criteria at the end of the run-in phase: informed consent
             withdrawal (patient not willing to continue or failed to return); lack of compliance
             during the single-blind placebo run-in phase (>2 injections missed); and patient with
             any adverse event which precludes the inclusion in the study, as assessed by the
             Investigator