Efficacy and Safety of Lixisenatide Versus Placebo on Top of Basal Insulin and/or Oral Antidiabetic Treatment in Older Type 2 Diabetic Patients

A Randomized, Double-blind, Placebo-controlled, 2-arm Parallel-group, Multicenter, 24 Week Study Assessing the Safety and Efficacy of Lixisenatide in Older Patients With Type 2 Diabetes Inadequately Controlled on Their Current Diabetes Treatment Regimen

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.

Approximately 31 weeks including 24 week treatment period.

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.