Status:

COMPLETED

24-week Treatment With Lixisenatide in Type 2 Diabetes Insufficiently Controlled With Metformin and Insulin Glargine

Lead Sponsor:

Sanofi

Conditions:

Type 2 Diabetes Mellitus

Eligibility:

All Genders

18+ years

Phase:

PHASE3

Brief Summary

The purpose of the study is to evaluate the benefits and risks of lixisenatide (AVE0010), in comparison to placebo, as an add-on treatment to insulin glargine and metformin with or without thiazolidin...

Detailed Description

The study comprises 3 periods: * An up to 14-week screening period, which includes an up to 2-week screening phase and a 12-week run-in phase with introduction and titration of insulin glargine on to...

Eligibility Criteria

Inclusion

  • Inclusion criteria:
  • \- Type 2 diabetes mellitus, diagnosed for at least 1 year before screening visit, insufficiently controlled with insulin glargine and metformin
  • Exclusion criteria:
  • HbA1c \<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
  • Metformin not at a stable dose of at least 1.5 gram per day for at least 3 months prior to the screening visit
  • Use of oral or injectable antidiabetic or hypoglycemic agents other than metformin, sulfonylurea (SU) and TZDs (for example, alpha glucosidase inhibitor, other glucagon like peptide-1 \[GLP-1\] receptor agonists, dipeptidyl peptidase-IV \[DPP-IV\] inhibitors, insulin etc.) within 3 months prior to the time of screening, use of weight loss drugs if not at a stable dose for at least 3 months prior to the screening visit
  • History of hypoglycemia unawareness
  • Body Mass Index (BMI) less than or equal to (\<=) 20 kilogram per square meter (kg/m\^2)
  • History of unexplained pancreatitis, chronic pancreatitis, pancreatectomy, stomach/gastric surgery, inflammatory bowel disease, personal or family history of medullary thyroid cancer (MTC) or genetic conditions that predispose to MTC (for example, multiple endocrine neoplasia syndromes)
  • History of metabolic acidosis, including diabetic ketoacidosis within 1 year prior to screening
  • Hemoglobinopathy or hemolytic anemia, blood or plasma products transfusion 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
  • 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 such as active malignant tumor or other major systemic diseases, presence of clinically significant diabetic retinopathy 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 or diastolic blood pressure \>180 millimeter of mercury (mmHg) or \>110 mmHg, respectively
  • Laboratory findings at the time of screening: amylase and/or lipase, alanine aminotransferase \>3 times upper limit of the normal (ULN) laboratory range; 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, positive serum pregnancy test in females of childbearing potential; and calcitonin \>=20 picogram per milliliter (pg/mL) (5.9 picomole per milliliter \[pmol/L\])
  • 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 being investigator or any sub investigator, pharmacist, study coordinator, other study staff or relative thereof directly involved in the conduct of the protocol etc.)
  • Use of systemic glucocorticoids (excluding topical application or inhaled forms) for one week or more within 3 months prior to the time of screening
  • Use of any investigational drug within 3 months prior to screening
  • Renal impairment defined with serum creatinine \> 1.4 mg/dL in women and \> 1.5 mg/dL in men
  • History of hypersensitivity to insulin glargine or to any of the excipients
  • Clinically relevant history of gastrointestinal disease associated with prolonged nausea and vomiting, including (but not limited to): gastroparesis, unstable (that is, worsening) and not controlled (that is, prolonged nausea and vomiting) gastroesophageal reflux disease requiring medical treatment, within 6 months prior to the time of screening
  • Any previous treatment with lixisenatide (for example, participation in a previous study with lixisenatide)
  • Allergic reaction to any GLP-1 receptor agonist in the past (for example, exenatide, liraglutide) or to metacresol
  • Additional exclusion criteria during or at the end of the run-in phase before randomization: informed consent withdrawal (patient who was not willing to continue or failed to return), mean fasting SMPG calculated from the self-measurements for the 7 days prior to Visit 12 (Week -1) was \>140 mg/dL (7.8 mmol/L) and HbA1c measured at Visit 12 (Week -1) is \<7% or \>9%, amylase and/or lipase \> 3 times the ULN at Visit 12 (Week -1), patients with fasting plasma glucose (FPG) above the threshold value described for rescue (that is, FPG \>240 mg/dL \[13.3 mmol/L\]), patients with any adverse event, which, by the judgment of the Investigator precludes the inclusion in the double-blind randomized treatment phase, and lack of compliance to protocol or to insulin glargine treatment during the run-in phase

Exclusion

    Key Trial Info

    Start Date :

    October 1 2009

    Trial Type :

    INTERVENTIONAL

    Allocation :

    ACTUAL

    End Date :

    August 1 2011

    Estimated Enrollment :

    446 Patients enrolled

    Trial Details

    Trial ID

    NCT00975286

    Start Date

    October 1 2009

    End Date

    August 1 2011

    Last Update

    October 11 2016

    Active Locations (140)

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    Page 1 of 35 (140 locations)

    1

    Sanofi-Aventis Investigational Site Number 840223

    Mesa, Arizona, United States, 85206

    2

    Sanofi-Aventis Investigational Site Number 840206

    Hot Springs, Arkansas, United States, 71913

    3

    Sanofi-Aventis Investigational Site Number 840201

    Little Rock, Arkansas, United States, 72205

    4

    Sanofi-Aventis Investigational Site Number 840212

    Mountain Home, Arkansas, United States, 72653