Pharmacodynamic and Pharmacokinetic Effects of Insulin Glulisine in Obese Subjects With Type 2 Diabetes After a Standard Meal in Comparison to Insulin Aspart

Study Overview
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Brief Summary
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Primary Objective: To assess the effect of insulin glulisine on the post-prandial plasma glucose excursion during the first hour after a standard meal in comparison to insulin aspart in obese subjects with type 2 diabetes. Secondary Objectives: Pharmacodynamic objectives: To assess the effect of insulin glulisine on the postprandial plasma glucose excursion during 6 hours after a standard meal in comparison to insulin aspart. Pharmacokinetic objective: To assess post-prandial plasma insulin excursion after a standard meal, in each treatment groups Safety objective: To assess the safety of insulin glulisine in comparison to insulin aspart

Detailed Description
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Duration of treatment: two study days separated by a 7-day wash-out period Duration of observation: screening period of 1-2 weeks, >2 study days (with a wash-out period of 7 days between the study days), Follow-up visit (within 2 weeks after the end of the study treatment period).

Official Title
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A Randomized, Double Blind Study to Assess the Pharmacodynamic and Pharmacokinetic Effects of Insulin Glulisine in Obese Subjects With Type 2 Diabetes After a Standard Meal in Comparison to Insulin Aspart

Conditions
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Type 2 Diabetes Mellitus

Intervention / Treatment
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* Drug: Insulin glulisine
* Drug: Insulin aspart


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: patients with type 2 diabetes for at least one year treated with oral antidiabetic agents (OADs) for at least 6 months Baseline C-peptide ≥0.1 nmol/L BMI (body mass index) between 30 and 40 kg/m2 HbA1c (glycosylated hemoglobin) < 8.5% signed informed consent Exclusion Criteria: type I diabetes mellitus current treatment with insulin pregnant and breast-feeding women any medication known to influence insulin sensitivity current treatment with systemic corticosteroids history of acute metabolic complications in the past 3 months recurrent severe hypoglycaemia or hypoglycaemic unawareness active proliferative diabetic retinopathy and known diabetic gastroparesis impaired hepatic function, as shown but not limited to ALT or AST above 2 times the upper limit of normal clinically relevant illness such as nephropathy and impaired renal function as shown by clearance < 30 ml/min any history or presence of clinically relevant abnormality, medical condition (cardiovascular, pulmonary, gastro-intestinal, hepatic, renal, metabolic, hematological, neurologic, psychiatric, systemic, ocular or infectious disease; any acute infectious disease or signs of acute illness making implementation of the protocol or interpretation of the results difficult hypersensitivity to insulins or insulin analogs The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: insulin glulisine + insulin aspart<br>insulin glulisine (1 day) + wash-out (7 days) + insulin aspart (1 day) | Drug: Insulin glulisine<br>* Insulin glulisine 100 U/ml, solution for injection in vial Dose: 0.2 U/Kg Administration: single subcutaneous injection with syringe in the periumbilical abdomen within 2 minutes before the standard meal<br>* Other names: Apidra;Drug: Insulin aspart<br>* Insulin aspart: 100 U/mL, solution for injection in vial Dose: 0.2 U/Kg Administration: single subcutaneous injection with syringe in the periumbilical abdomen within 2 minutes before the standard meal<br>* Other names: NovoRapid;|
| Experimental: insulin aspart + insulin glulisine<br>insulin glulisine (1 day) + wash-out (7 days) + insulin aspart (1 day) | Drug: Insulin glulisine<br>* Insulin glulisine 100 U/ml, solution for injection in vial Dose: 0.2 U/Kg Administration: single subcutaneous injection with syringe in the periumbilical abdomen within 2 minutes before the standard meal<br>* Other names: Apidra;Drug: Insulin aspart<br>* Insulin aspart: 100 U/mL, solution for injection in vial Dose: 0.2 U/Kg Administration: single subcutaneous injection with syringe in the periumbilical abdomen within 2 minutes before the standard meal<br>* Other names: NovoRapid;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area under the plasma glucose concentration curve (AUC) between 0 and 1 hour after insulin injection AUC(0-1h) |  | At day 1 of each treatment period | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area under the curve of plasma glucose concentration AUC(0-2h) |  | At day 1 of each treatment period | 
| Area under the curve of plasma glucose concentration AUC(0-4h) |  | At day 1 of each treatment period | 
| Area under the curve of plasma glucose concentration AUC(0-6h) |  | At day 1 of each treatment period | 
| Delta plasma glucose at 1h after standard meal |  | At day 1 of each treatment period | 
| Maximum glucose concentration (GLU max) |  | At day 1 of each treatment period | 
| Maximum glucose excursion (delta GLU max) |  | At day 1 of each treatment period | 
| Time to delta GLU max |  | At day 1 of each treatment period | 
| Time to fraction of total glucose AUC(10%, 20%) |  | At day 1 of each treatment period | 
| Area under the plasma insulin concentration curve AUC (0-1h) |  | At day 1 of each treatment period | 
| Area under the plasma insulin concentration curve AUC (0-2h) |  | At day 1 of each treatment period | 
| Area under the plasma insulin concentration curve AUC (0-4h) |  | At day 1 of each treatment period | 
| Area under the plasma insulin concentration curve AUC (0-6h) |  | At day 1 of each treatment period | 
| Maximum insulin concentration (Cmax) |  | At day 1 of each treatment period | 
| Time to fraction of total insulin AUC (10%, 20%) |  | At day 1 of each treatment period | 
| Time to Cmax |  | At day 1 of each treatment period | 
| Hypoglycaemia and adverse events |  | from randomization to the end of study |