Efficacy and Safety of Lixisenatide Versus Insulin Glulisine on Top of Insulin Glargine With or Without Metformin in Type 2 Diabetic Patients
Condition: Type 2 Diabetes
MeSH terms: Diabetes Mellitus, Type 2
Intervention: Lixisenatide (AVE0010); Insulin glulisine QD; Insulin glulisine TID; Insulin Glargine (Mandatory background drug); Metformin (Background drug)
Intervention description: Pharmaceutical form: Solution for injection; Route of administration: Self-administered by subcutaneous injection 30 to 60 minutes before breakfast or dinner.; Pharmaceutical form: Solution for injection; Route of administration: Self-administered by subcutaneous injection within 15 minutes before breakfast or dinner. The initial dose was 3-5 units and then individually titrated to obtain the SMPG value >5.6 mmol/L (100 mg/dL) and ≤7.8 mmol/L (140 mg/dL) before lunch (if administered at breakfast) or at bedtime (if administered at dinner).; Pharmaceutical form: Solution for injection; Route of administration: Self-administered by subcutaneous injection within 15 minutes before each meal. The initial dose was 3-5 units for each meal and then individually titrated to obtain the SMPG value >5.6 mmol/L (100 mg/dL) and ≤7.8 mmol/L (140 mg/dL) before the next meal or at bedtime (for injection at dinner).; Pharmaceutical form: Solution for injection; Route of administration: Self-administered by subcutaneous injection at breakfast or dinner. Doses were adjusted to maintain a fasting self-monitored plasma glucose (SMPG) between 4.4 to 5.6 mmol/L (80 to 100 mg/dL).; Pharmaceutical form: Tablet; Route of administration: Oral administration. If previously taken, Metformin to be continued at stable dose (≥1.5 g/day) throughout the study.
Intervention MeSH terms: Insulin; Insulin, Globin Zinc; Metformin; Insulin Glargine; Insulin glulisine; Lixisenatide
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 894.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      Primary Objective:

      - To compare lixisenatide versus insulin glulisine in terms of glycosylated hemoglobin
      (HbA1c) reduction and body weight change at Week 26 in type 2 diabetic participants not
      adequately controlled on insulin glargine ± metformin.

      Secondary Objectives:

      - To compare the treatments/regimens on:

        -  The percentage of participants reaching the target of HbA1c <7% or ≤6.5%,

        -  Body weight,

        -  Self-Monitored Glucose profiles,

        -  Fasting Plasma Glucose (FPG),

        -  Post-prandial plasma glucose (PPG) /glucose excursions during a standardized meal test
           (subset of participants),

        -  Daily doses of insulins,

        -  Safety and tolerability.
    

Eligibility criteria:

        Inclusion criteria :

          -  Participants with type 2 diabetes mellitus diagnosed at least 1 year before screening
             visit (V1).

          -  Participants treated with basal insulin for at least 6 months.

          -  Participants treated for at least 3 months prior to visit 1 with a stable basal
             insulin regimen (i.e. type of insulin and time/frequency of the injection). The
             insulin dose should be stable (± 20%) and ≥20 U/day for at least 2 months prior to
             visit 1.

          -  Participants treated with basal insulin alone or in combination with 1 to 3 oral
             anti-diabetic drugs (OADs) that could be: metformin (≥1.5 g/day or maximal tolerated
             dose), a sulfonylurea (SU), a dipeptidyl-peptidase-4 (DPP-4) inhibitor, a glinide. The
             dose of OADs should be stable for at least 3 months prior to visit 1.

        Exclusion criteria:

          -  At screening: age < legal age of majority.

          -  At screening, HbA1c: <7.5% and >10.0% for participants treated with basal insulin
             alone or in combination with metformin only; < 7.0% and > 10.0% for participants
             treated with basal insulin and a combination of oral anti-diabetic drugs which
             included a SU and/or a DPP-4 inhibitor and/or a glinide.

          -  Women of childbearing potential with no effective contraceptive method, pregnancy or
             lactation.

          -  Type 1 diabetes mellitus.

          -  Treatment with glucose-lowering agent(s) other than stated in the inclusion criteria
             within 3 months prior to screening.

          -  Previous treatment with short or rapid acting insulin other than in relation to
             hospitalization or an acute illness.

          -  Any previous treatment with lixisenatide, or any discontinuation from another
             glucagon-like peptide 1 (GLP-1) receptor agonist due to safety/tolerability issue or
             lack of efficacy.

          -  At screening, Body Mass Index (BMI) ≤20 or >40 kg/m^2.

          -  Weight change of more than 5 kg during the 3 months prior to the screening visit; use
             of weight loss drugs within 3 months prior to screening.

          -  Within the last 6 months prior to screening: history of myocardial infarction, stroke,
             or heart failure requiring hospitalization. Planned coronary, carotid or peripheral
             artery revascularisation procedures.

          -  History of unexplained pancreatitis, chronic pancreatitis, pancreatectomy,
             stomach/gastric surgery.

          -  At screening resting systolic blood pressure >180 mmHg or diastolic blood pressure >95
             mmHg.

          -  Personal or immediate family history of medullary thyroid cancer (MTC) or genetic
             condition that predisposed to MTC (e.g. multiple endocrine neoplasia syndromes).

          -  Contraindication related to metformin (for participant receiving this treatment),
             insulin glargine, insulin glulisine or lixisenatide.

          -  Participants with severe renal impairment (creatinine clearance less than 30 ml/min)
             or end-stage renal disease.

          -  At screening, amylase and/or lipase >3 times the upper limit of the normal laboratory
             range (ULN).

          -  At screening alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >3
             ULN.

          -  At screening calcitonin ≥20 pg/ml (5.9 pmol/L).

        Exclusion Criteria for randomization at the end of the screening period before
        randomization:

          -  HbA1c <7.0% or >9.0%.

          -  7-day mean fasting SMPG >140 mg/dl (7.8 mmol/L).

          -  Amylase and/or lipase >3 times ULN.

        The above information is not intended to contain all considerations relevant to a
        participant's potential participation in a clinical trial.