Clinical trial NCT00607087: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Diabetes Mellitus, Type 1
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
First posted: 2008-02-05
Enrollment: 289
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: 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

Detailed description: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Percentage of Patients With at Least One Unexplained Hyperglycemia and/ or Confirmed Infusion Set Occlusion
timeFrame: over 13 weeks of each treatment period
Secondary outcomes:
measure: Monthly Rate of Unexplained Hyperglycemia and/ or Confirmed Infusion Set Occlusion
timeFrame: over 13 weeks of each treatment period
measure: Percentage of Patients With at Least One Unexplained Hyperglycemia
timeFrame: over 13 weeks of each treatment period
measure: Monthly Rate of Unexplained Hyperglycemia
timeFrame: over 13 weeks of each treatment period
measure: Percentage of Patients With at Least One Confirmed Infusion Set Occlusion
timeFrame: over 13 weeks of each treatment period
measure: Monthly Rate of Confirmed Infusion Set Occlusion
timeFrame: over 13 weeks of each treatment period
measure: Percentage of Patients With at Least One Episode of Significant Ketosis and/ or Risk Level for Impending Diabetic Ketoacidosis
timeFrame: over 13 weeks of each treatment period
measure: Monthly Rate of Episode of Significant Ketosis and/ or Risk Level for Impending Diabetic Ketoacidosis
timeFrame: over 13 weeks of each treatment period
measure: Rate of Symptomatic Hypoglycemia With a Plasma Glucose (PG) ≤ 70 mg/dL Per Patient-year
timeFrame: over 13 weeks of each treatment period
measure: Rate of Severe Symptomatic Hypoglycemia Per Patient-year
timeFrame: over 13 weeks of each treatment period
measure: Rate of Nocturnal Symptomatic Hypoglycemia With a Plasma Glucose (PG) ≤70 mg/dL Per Patient-year
timeFrame: over 13 weeks of each treatment period
measure: Patients With at Least One Site Infection, Site Inflammation/Erythema, Pruritus or Isolated Pain at Injection Site
timeFrame: over 13 weeks of each treatment period
measure: Time Interval Between Infusion Set Changes: All Changes
timeFrame: over 13 weeks of each treatment period
measure: Time Interval Between Infusion Set Changes in Routine
timeFrame: over 13 weeks of each treatment period
measure: Glycosylated Hemoglobin: HbA1c
timeFrame: over 13 weeks of each treatment period
measure: Total Daily Basal Insulin Infusion
timeFrame: over 13 weeks of each treatment period
measure: Total Daily Bolus Insulin Dose
timeFrame: over 13 weeks of each treatment period
Other outcomes:
Locations:
city: Bridgewater
country: United States
facility: Sanofi-Aventis Administrative Office
state: New Jersey
city: Macquarie Park
country: Australia
facility: Sanofi-Aventis Administrative Office
city: Vienna
country: Austria
facility: Sanofi-Aventis Administrative Office
city: Paris
country: France
facility: Sanofi-Aventis Administrative Office
city: Budapest
country: Hungary
facility: Sanofi-Aventis Administrative Office
city: Natanya
country: Israel
facility: Sanofi-Aventis Administrative Office
city: Milan
country: Italy
facility: Sanofi-Aventis Administrative Office
city: Seoul
country: Korea, Republic of
facility: Sanofi-Aventis Administrative Office
city: PE Gouda
country: Netherlands
facility: Sanofi-Aventis Administrative Office
city: Barcelona
country: Spain
facility: Sanofi-Aventis Administrative Office
city: Bromma
country: Sweden
facility: Sanofi-Aventis Administrative Office
city: Guildford Surrey
country: United Kingdom
facility: Sanofi-Aventis Administrative Office
Study officials:
affiliation: Sanofi
name: Medical Affairs
role: STUDY_DIRECTOR
References:
citation: van Bon AC, Bode BW, Sert-Langeron C, DeVries JH, Charpentier G. Insulin glulisine compared to insulin aspart and to insulin lispro administered by continuous subcutaneous insulin infusion in patients with type 1 diabetes: a randomized controlled trial. Diabetes Technol Ther. 2011 Jun;13(6):607-14. doi: 10.1089/dia.2010.0224. Epub 2011 Apr 2.