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

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

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

Study Overview

• Status: Completed
• Conditions: Type 2 Diabetes Mellitus
• Intervention / Treatment: Drug: Insulin glulisine; Drug: 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 Type: Interventional
• Enrollment (Actual): 37
• Phase: Phase 1

Contacts and Locations

Study Locations

• France
  • Paris, France
    • Sanofi-Aventis Administrative Office

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: insulin glulisine + insulin aspart; insulin glulisine (1 day) + wash-out (7 days) + insulin aspart (1 day)	Drug: Insulin glulisine; 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; Other Names: Apidra; Drug: Insulin aspart; 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; Other Names: NovoRapid
Experimental: insulin aspart + insulin glulisine; insulin glulisine (1 day) + wash-out (7 days) + insulin aspart (1 day)	Drug: Insulin glulisine; 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; Other Names: Apidra; Drug: Insulin aspart; 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; Other Names: NovoRapid

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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

Collaborators and Investigators

• Sponsor: Sanofi

Study record dates

Study Major Dates

• Study Start: September 1, 2007
• Primary Completion (Actual): April 1, 2008
• Study Completion (Actual): April 1, 2008

Study Registration Dates

• First Submitted: July 8, 2010
• First Submitted That Met QC Criteria: July 8, 2010
• First Posted (Estimate): July 9, 2010

Study Record Updates

• Last Update Posted (Estimate): July 16, 2010
• Last Update Submitted That Met QC Criteria: July 15, 2010
• Last Verified: July 1, 2010

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2; Hypoglycemic Agents; Physiological Effects of Drugs; Insulin; Insulin, Globin Zinc; Insulin Aspart; Insulin glulisine
• Other Study ID Numbers: APIDR_C_01160; 2006-005536-24 (EudraCT Number)