Effect of Insulin Glulisine Compared to Insulin Aspart and Insulin Lispro When Administered by Continuous Subcutaneous Insulin Infusion (CSII) on Specific Pump Parameters in Patient With Type 1 Diabetes Mellitus

Official Title: “Effect of Insulin Glulisine Compared to Insulin Aspart and Insulin Lispro When Administered by Continuous Subcutaneous Insulin Infusion (CSII) on Specific Pump Parameters in Patient With Type 1 Diabetes Mellitus”

Primary objective: To demonstrate the superiority of insulin glulisine over insulin aspart and insulin lispro administered by external pump in term of unexplained hyperglycemia and/or infusion set occlusion.

Main Secondary objectives:

To compare insulin glulisine, insulin aspart and insulin lispro on: - Unexplained hyperglycemia - Infusion set occlusion - Hypoglycemic episodes,7-point blood glucose profiles - Episodes of significant ketosis and/or risk level for impending diabetic ketoacidosis - Time to change the infusion set - HbA1c (Glycosylated hemoglobin) - Overall safety: incidence of adverse events

The maximal duration of the study participation for patients was 41 weeks and one day, split in: - a 2-week screening period, - a 39-week treatment period: 3 treatment periods of 13 weeks with a crossover alternative regimen, including a dose adjustment period of 1 week at the beginning of each period (sequence1: insulin glulisine, then insulin aspart, then insulin lispro; sequence2: insulin aspart, then insulin lispro, then insulin glulisine; sequence 3:

insulin lispro, then insulin glulisine, then insulin aspart) - and a follow-up period of 24 hours.

Intervention(s) in this Clinical Trial

• Drug: Insulin glulisine
  • 100 U/ml, administration by Continuous Subcutaneous Insulin Infusion with external pump
• Drug: Insulin lispro
  • 100 U/ml, administration by Continuous Subcutaneous Insulin Infusion with external pump
• Drug: Insulin aspart
  • 100 U/ml, administration by Continuous Subcutaneous Insulin Infusion with external pump

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: sequence 1
  • sequence 1: insulin glulisine / insulin aspart / insulin lispro.
• Experimental: Sequence 2
  • Sequence 2: insulin aspart / insulin lispro / insulin glulisine
• Experimental: Sequence 3
  • Sequence 3: insulin lispro / insulin glulisine / insulin aspart

Primary Measures

• Percentage of Patients With at Least One Unexplained Hyperglycemia and/ or Confirmed Infusion Set Occlusion
  • Time Frame: over 13 weeks of each treatment period
    Safety Issue?: No

Secondary Measures

• Monthly Rate of Unexplained Hyperglycemia and/ or Confirmed Infusion Set Occlusion
  • Time Frame: over 13 weeks of each treatment period
    Safety Issue?: No
• Percentage of Patients With at Least One Unexplained Hyperglycemia
  • Time Frame: over 13 weeks of each treatment period
    Safety Issue?: No
• Monthly Rate of Unexplained Hyperglycemia
  • Time Frame: over 13 weeks of each treatment period
    Safety Issue?: No
• Percentage of Patients With at Least One Confirmed Infusion Set Occlusion
  • Time Frame: over 13 weeks of each treatment period
    Safety Issue?: No
• Monthly Rate of Confirmed Infusion Set Occlusion
  • Time Frame: over 13 weeks of each treatment period
    Safety Issue?: No
• Percentage of Patients With at Least One Episode of Significant Ketosis and/ or Risk Level for Impending Diabetic Ketoacidosis
  • Time Frame: over 13 weeks of each treatment period
    Safety Issue?: No
• Monthly Rate of Episode of Significant Ketosis and/ or Risk Level for Impending Diabetic Ketoacidosis
  • Time Frame: over 13 weeks of each treatment period
    Safety Issue?: No
• Rate of Symptomatic Hypoglycemia With a Plasma Glucose (PG) ≤ 70 mg/dL Per Patient-year
  • Time Frame: over 13 weeks of each treatment period
    Safety Issue?: No
• Rate of Severe Symptomatic Hypoglycemia Per Patient-year
  • Time Frame: over 13 weeks of each treatment period
    Safety Issue?: No
• Rate of Nocturnal Symptomatic Hypoglycemia With a Plasma Glucose (PG) ≤70 mg/dL Per Patient-year
  • Time Frame: over 13 weeks of each treatment period
    Safety Issue?: No
• Patients With at Least One Site Infection, Site Inflammation/Erythema, Pruritus or Isolated Pain at Injection Site
  • Time Frame: over 13 weeks of each treatment period
    Safety Issue?: No
• Time Interval Between Infusion Set Changes: All Changes
  • Time Frame: over 13 weeks of each treatment period
    Safety Issue?: No
• Time Interval Between Infusion Set Changes in Routine
  • Time Frame: over 13 weeks of each treatment period
    Safety Issue?: No
• Glycosylated Hemoglobin: HbA1c
  • Time Frame: over 13 weeks of each treatment period
    Safety Issue?: No
• Total Daily Basal Insulin Infusion
  • Time Frame: over 13 weeks of each treatment period
    Safety Issue?: No
• Total Daily Bolus Insulin Dose
  • Time Frame: over 13 weeks of each treatment period
    Safety Issue?: No

Inclusion Criteria:

• Type 1 diabetic subjects
• Treated with insulin for at least 2 years and by CSII for at least 6 months
• Using the same insulin (insulin glulisine, insulin aspart or insulin lispro) in CSII for at least 3 months with the same external pump compatible with the 3 short acting insulin analogues used in the study
• Using the same type of infusion set (catheter and cannula) for at least 3 months
• Performing at least 3 blood glucose controls per day
• HbA1c < 8.5%
• Body mass index (BMI) < 35 kg/m²
• Ability and willingness to perform blood glucose and ketone monitoring using the Sponsor-provided combined glucose and ketone meter and patient diary at home

Exclusion Criteria:

• Diabetes other than Type 1
• Total daily dose of insulin greater than 90 U/day
• Using an insulin pump requiring pre-filled cartridges
• History of infection at infusion site requiring a drainage in the last 3 months
• History of severe episodes of ketosis requiring hospitalization in the last 6 months
• Active proliferative retinopathy, as defined by a photocoagulation or vitrectomy occurrence in the 6 months prior to visit 1, or any other unstable (rapidly progressing) retinopathy that may require photocoagulation or surgical treatment during the study. An ophthalmoscopic examination should have been performed in the 2 years prior to study entry
• Pregnancy (women of childbearing potential must have a negative pregnancy test at study entry and a medically approved contraception method) or breastfeeding
• Treatment with systemic corticosteroids or medication known to influence insulin sensitivity in the 3 months prior to visit 1
• Treatment with antidiabetic drug other than insulin in the 3 months prior to visit 1
• Likelihood of requiring treatments during the study which are not permitted
• Treatment with an investigational product in the 30 days prior to visit 1
• History of sensitivity to the study drugs or to drugs with a similar chemical structure
• Presence of any condition (medical, including clinically significant abnormal laboratory test, psychological, social or geographical) actual or anticipated that the Investigator feels would compromise the patient safety or limit his/her successful participation in the study
• Night shift workers
• Impaired renal function as shown by serum creatinine ≥1.5 mg/dL (133 μmol/L) or ≥1.4 mg/dL (124 μmol/L) in men and women, respectively
• Impaired hepatic function as shown by Alanine aminotransferase (ALT) and/or Aspart aminotransferase (AST) greater than three times the upper limit of normal range)
• Alcohol or drug abuse in the last year
• Mental condition rendering the patient unable to understand the nature, scope and possible consequences of the study
• The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: 75 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Investigator: Sanofi-Aventis Industry

Overall Clinical Trial Officials and Contacts

Medical Affairs Study Director Sanofi-Aventis  

Information obtained from ClinicalTrials.gov on February 12, 2012

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00607087

Study ID Number: APIDR_C_02083

ClinicalTrials.gov Identifier: NCT00607087

Health Authority: Sweden: Regional Ethical Review Board