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-CZ

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 efficacy.
•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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