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

Phase 1

Completed

• Conditions: Type 2 Diabetes Mellitus
• Interventions: Drug: Insulin glulisine; Drug: Insulin aspart

• Registration Number: NCT01159353
• Lead Sponsor: Sanofi

Brief Summary

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

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).

Study Timeline

• Study Start: 2007-09
• Primary Completion: 2008-04
• Study Completion: 2008-04
• Status Verified: 2010-07
• Study First Submitted: 2010-07-08
• Study First Submitted QC: 2010-07-08
• Study First Posted: 2010-07-09
• Last Update Submitted: 2010-07-15
• Last Update Posted: 2010-07-16

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 37

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
insulin glulisine + insulin aspart	Insulin aspart	insulin glulisine (1 day) + wash-out (7 days) + insulin aspart (1 day)
insulin glulisine + insulin aspart	Insulin glulisine	insulin glulisine (1 day) + wash-out (7 days) + insulin aspart (1 day)
insulin aspart + insulin glulisine	Insulin aspart	insulin glulisine (1 day) + wash-out (7 days) + insulin aspart (1 day)
insulin aspart + insulin glulisine	Insulin glulisine	insulin glulisine (1 day) + wash-out (7 days) + insulin aspart (1 day)

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
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 (0-2h)	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 (0-1h)	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

Trial Locations

Locations (1)

Sanofi-Aventis Administrative Office; 🇫🇷 Paris, France