Efficacy and Safety of Lixisenatide Versus Placebo on Top of Basal Insulin and/or Oral Antidiabetic Treatment in Older Type 2 Diabetic Patients
Condition: Type 2 Diabetes
MeSH terms: Diabetes Mellitus, Type 2
Intervention: Lixisenatide (AVE0010); Placebo; Antidiabetic background therapy
Intervention description: Pharmaceutical form: Solution for injection in pre-filled pen administered 30 to 60 minutes before breakfast in the morning
Route of administration: Subcutaneous injection; Pharmaceutical form: Solution for injection in pre-filled pen administered 30 to 60 minutes before breakfast in the morning
Route of administration: Subcutaneous injection; Participants received a stable regimen of anti-diabetic background therapy for at least 3 months prior to screening, during the placebo run-in period and the 24 week treatment period. Allowed background antidiabetic therapy included metformin, sulfonylurea (except glibenclamide >10 mg, gliclazide >160 mg), meglitinides (except repaglinide >6 mg), pioglitazone and basal insulin. Insulin glargine, neutral protamine hagedorn (NPH) insulin, detemir, lente and ultralente were considered as basal insulin.
Intervention MeSH terms: Lixisenatide; Hypoglycemic Agents
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 350.0
Sex: All
Minimum age: 70 Years
Healthy volunteers: No

Summary:

      Primary objective:

      - To evaluate the effect of lixisenatide versus placebo over a period of 24 weeks on glycemic
      control, as evaluated by glycosylated hemoglobin (HbA1c) reduction, in older type 2 diabetes
      participants (T2DM) who are inadequately controlled with their current anti-diabetic
      treatment regimen.

      Main secondary objective:

      - To assess the safety and tolerability of lixisenatide compared to placebo in older T2DM
      participants (including occurrence of documented (Plasma Glucose PG < 60 mg/dL) symptomatic
      hypoglycemia and gastrointestinal side effects).

      Other secondary objectives:

        -  To assess the effect of lixisenatide compared to placebo after 24-week treatment on:

             -  Fasting plasma glucose (FPG);

             -  During liquid standardized breakfast meal challenge test : 2 hour- Postprandial
                Plasma Glucose (PPG) and Plasma Glucose Excursion;

             -  7-point Self-monitored plasma glucose (SMPG) profile;

             -  Body weight;

             -  Change in total daily dose of basal insulin (if taken);

             -  Percentage of participants requiring rescue therapy

             -  Safety and tolerability;

        -  To assess lixisenatide pharmacokinetic profile;

        -  To assess anti-lixisenatide antibody development.
    

Eligibility criteria:

        Inclusion criteria :

          -  Older participants, aged 70 years and above, with T2DM inadequately controlled on
             their current anti-diabetic pharmaceutical treatment regimen.

          -  Signed written informed consent.

        Exclusion criteria:

          -  At screening HbA1c ≤7.0% or >10% (Acknowledging that the threshold of 7% may not be
             appropriate for all older participants and that this was the responsibility of the
             investigator to include the participant based on an individual evaluation of the
             expected benefits of better glycemic control versus risk of hypoglycemia).

          -  At screening participants on both basal insulin and sulfonylurea or basal insulin and
             meglitinides.

          -  At screening FPG >250 mg/dL (>13.9 mmol/L).

          -  Type 1 diabetes mellitus or history of ketoacidosis within one year prior to the
             screening visit.

          -  Type 2 diabetes mellitus diagnosed less than 1 year prior to screening.

          -  Anti-diabetic treatment not at a stable regimen or initiated within the last 3 months
             prior to screening.

          -  Treatment within the 3 months preceding the screening with other anti-diabetic agent
             than allowed background therapy. Allowed therapy includes metformin, sulfonylurea
             (except glibenclamide >10mg, gliclazide >160mg), meglitinides (except repaglinide
             >6mg), pioglitazone and basal insulin and should follow local product circulars and
             labeling restrictions for the study population.

          -  Participants who had been on an approved or an investigational Glucagon-like peptide 1
             (GLP-1) medication (exenatide, liraglutide, lixisenatide or others).

          -  History of severe hypoglycemia associated with symptoms unawareness or results in
             unconsciousness/coma/seizure in the 6 months prior to screening.

          -  BMI <22 or >40 kg/m^2.

          -  Malnutrition assessed clinically by the investigator or any sub-investigator and by
             Mini-Nutritional Assessment-Short Form (MNA-SF) score <12 in countries (the judgment
             of the investigator prevails on questionnaires scores).

          -  Cognitive disorder and dementia assessed clinically by the investigator or any sub
             investigator and by Mini Mental State Examination (MMSE) score <24 (the judgment of
             the investigator prevails on questionnaires scores), or any neurologic disorder that
             affected the participant's ability to participate in the study.

          -  Participant who had a glomerular filtration rate (eGFR) (using the Modification of
             Diet in Renal Disease (MDRD) formula <30ml/min/1.73m^2).

          -  Participant with severe or uncontrolled disease, or any clinically significant
             abnormality identified on physical examination or investigational clinical procedure
             that, in the judgment of the investigator or any sub-investigator, would preclude safe
             completion of the study or constrains efficacy assessment.

          -  Laboratory findings at the time of screening:

               -  Amylase and/or lipase: >3 times the upper limit of the normal (ULN) laboratory
                  range

               -  Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >3 times ULN

               -  Calcitonin >20 pg/mL (5.9 pmol/L).

          -  Clinically relevant history of gastrointestinal disease associated with prolonged
             nausea and vomiting, including (but not limited to): gastroparesis, unstable (i.e.
             worsening) and not controlled (i.e. prolonged nausea and vomiting) gastroesophageal
             reflux disease within 6 months prior to screening.

          -  History of unexplained pancreatitis, chronic pancreatitis, pancreatectomy,
             stomach/gastric surgery, inflammatory bowel disease.

          -  Personal or immediate family history of medullary thyroid cancer or genetic conditions
             that predisposed to medullary thyroid cancer (e.g., multiple endocrine neoplasia
             syndromes).

        The above information is not intended to contain all considerations relevant to a
        participant's potential participation in a clinical trial.