GLP-1 Receptor Agonist Lixisenatide in Patients With Type 2 Diabetes for Glycemic Control and Safety Evaluation, on Top of Basal Insulin +/- Sulfonylurea (GETGOAL-L-ASIA)
Condition: Diabetes Mellitus, Type 2
MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 2
Intervention: Lixisenatide (AVE0010); Placebo; Pen auto-injector; Sulfonylurea; Basal Insulin
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.; Sulfonylurea if given, to be continued at a stable dose.; To be continued at a stable dose.
Intervention MeSH terms: Lixisenatide
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 311.0
Sex: All
Minimum age: 19 Years
Healthy volunteers: No
Keywords: hyperglycemia; GLP-1; sulfonylurea; insulin

Summary:

      The purpose of this study is to evaluate the benefits and risks of lixisenatide (AVE0010), in
      comparison to placebo, as an add-on treatment to basal insulin with or without sulfonylurea,
      over a period of 24 weeks of treatment.

      The primary objective is to assess the effects of lixisenatide, when added to basal insulin,
      on glycemic control in terms of glycosylated hemoglobin (HbA1c) reduction at Week 24.

      The secondary objectives are to assess the effects of lixisenatide on body weight, 2-hour
      postprandial plasma glucose (PPG) after standardized meal challenge test, percentage of
      patients reaching HbA1c less than 7 percent (%), percentage of patients reaching HbA1c less
      than or equal to 6.5%, fasting plasma glucose (FPG), change in 7-point self-monitored plasma
      glucose (SMPG) profiles, change in daily basal insulin and total insulin doses; to evaluate
      safety, tolerability, pharmacokinetics (PK), and anti-lixisenatide antibody development.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Type 2 diabetes mellitus, diagnosed for at least 1 year at the time of the screening
             visit, insufficiently controlled with basal insulin with or without sulfonylurea

        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

          -  Treatment with basal insulin for less than 3 months prior to screening or insulin
             regimen changed during the last 3 months prior to screening

          -  Basal insulin dose at screening <10 units/day and/or during the last 2 months dose not
             stable (+/- 20%)

          -  Sulfonylurea not at a stable (unchanged) dose for at least 3 months prior to screening

          -  FPG at screening >250 milligram/deciliter (mg/dL) (>13.9 millimole/liter [mmol/L])

          -  History of hypoglycemia unawareness

          -  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 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 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 was 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 other oral or injectable antidiabetic or hypoglycemic agents other than
             sulfonylurea or basal insulin (for example, metformin, alpha glucosidase inhibitor,
             thiazolidinedione, rimonabant, exenatide, dipeptidyl peptidase 4 inhibitors, fast
             acting insulin for 1 week or more 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

          -  Use of any investigational drug within 3 months prior to screening

          -  Participation in any previous study with lixisenatide

          -  End-stage renal disease defined by a serum creatinine clearance of <15
             milliliter/minute (mL/min) (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; lack of compliance during the single-blind placebo run-in phase (>2
             injections missed); and patient with any adverse event which could have precludes the
             inclusion in the study, as assessed by the investigator