Efficacy and safety of lixisenatide versus insulin glulisine on top of insulin glargine with or without metformin in type 2 diabetic patients

Conditions: Type 2 Diabetes mellitus
MedDRA version: 14.1Level: PTClassification code 10067585Term: Type 2 diabetes mellitusSystem Organ Class: 10027433 - Metabolism and nutrition disorders
Therapeutic area: Diseases [C] - Nutritional and Metabolic Diseases [C18]

Registration Number: EUCTR2012-004096-38-LT

Lead Sponsor: Sanofi-Aventis Recherche & Développement

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 855

Inclusion Criteria

• Patients with type 2 diabetes mellitus diagnosed at least 1 year before screening visit (V1) .
• Patients treated with basal insulin for at least 6 months.
• Patients treated for at least 3 months prior to visit 1 with a stable basal insulin regimen (ie 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.
• Patients treated with basal insulin alone or in combination with 1 to 3 oral anti-diabetic drugs (OADs) that can be: metformin (=1.5g/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.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 700
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 155

Exclusion Criteria

• At screening: age < legal age of majority
• At screening, HbA1c: < 7.5% and > 10.0% for patients treated with basal insulin alone or in combination with metformin only; < 7.0% and > 10.0% for patients treated with basal insulin and a combination of oral anti-diabetic drugs which includes a SU and/or a DPP4 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 GLP-1 receptor agonist due to safety/tolerability issue or lack of efficasy.
•At screening, Body Mass Index (BMI) =20 or >40 kg/m².
•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 predisposes to MTC (e.g. multiple endocrine neoplasia syndromes)
• Contraindication related to metformin (for patient receiving this treatment), insulin glargine, insulin glulisine or lixisenatide.
• Patients with severe renal impairment (creatinine clearance less than 30 ml/min) or end-stage renal disease, if no treatment with metformin
• At screening, amylase and/or lipase > 3 times the upper limit of the normal laboratory range (ULN)
• At screening ALT or AST>3ULN
• 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.

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To compare lixisenatide versus insulin glulisine in terms of HbA1c reduction and body weight change at week 26 in type 2 diabetic patients not adequately controlled on insulin glargine ± metformin.;Secondary Objective: To compare the treatments/regimens on:<br>• The percentage of patients reaching the target of HbA1c <7% or =6.5% <br>• Body weight;<br>• Self-Monitored Glucose profiles<br>• Fasting Plasma Glucose (FPG)<br>• Post-prandial plasma glucose /glucose excursions during a standardized<br> meal test (subset of patients)<br>• Daily doses of insulins<br>• Safety and tolerability<br>;Primary end point(s): - Change from baseline in HbA1c<br>- Change from baseline in body weight;Timepoint(s) of evaluation of this end point: week 26

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): - Percentage of patients reaching HbA1c <7% <br>- Percentage of patients reaching HbA1c =6.5%<br>- Change in body weight from baseline <br>- Percentage of patients with no weight gain.<br>- Change in 7-point SMPG profiles from baseline<br>- Change from baseline in FPG<br>- Change from baseline in post-prandial glucose /glucose excursions during a standardized meal test (subset of patients)<br>- Change from baseline in insulin glargine dose<br>- Daily dose of insulin glulisine<br>- Total daily dose of insulins<br>- Documented (PG <60 mg/dl) symptomatic hypoglycemia (percentage of subjects with at least one episode, number of events per patient-year)<br>- Severe hypoglycemia<br>;Timepoint(s) of evaluation of this end point: - week 26<br><br>- 26 weeks for:<br>Documented (PG <60 mg/dl) symptomatic hypoglycemia (percentage of subjects with at least one episode, number of events per patient-year)<br>and<br>Severe hypoglycemia<br>

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