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

Diabetes Mellitus, Type 1 Clinical Trial

— PUMP  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00607087
• Other study ID #: APIDR_C_02083
• Secondary ID: 2007-003579-38
• Status: Completed
• Phase: Phase 4
• First received: January 23, 2008
• Last updated: August 26, 2010
• Start date: January 2008
• Est. completion date: June 2009

Study information

• Verified date: August 2010
• Source: Sanofi
• Contact: n/a
• Is FDA regulated: No
• Health authority: Sweden: Regional Ethical Review Board
• Study type: Interventional

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 289
• Est. completion date: June 2009
• Est. primary completion date: June 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 75 Years

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Crossover Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 1

Intervention

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

Locations

Country	Name	City	State
Australia	Sanofi-Aventis Administrative Office	Macquarie Park
Austria	Sanofi-Aventis Administrative Office	Vienna
France	Sanofi-Aventis Administrative Office	Paris
Hungary	Sanofi-Aventis Administrative Office	Budapest
Israel	Sanofi-Aventis Administrative Office	Natanya
Italy	Sanofi-Aventis Administrative Office	Milan
Korea, Republic of	Sanofi-Aventis Administrative Office	Seoul
Netherlands	Sanofi-Aventis Administrative Office	PE Gouda
Spain	Sanofi-Aventis Administrative Office	Barcelona
Sweden	Sanofi-Aventis Administrative Office	Bromma
United Kingdom	Sanofi-Aventis Administrative Office	Guildford Surrey
United States	Sanofi-Aventis Administrative Office	Bridgewater	New Jersey

Sponsors (1)

Lead Sponsor	Collaborator
Sanofi

Countries where clinical trial is conducted

United States,  Australia,  Austria,  France,  Hungary,  Israel,  Italy,  Korea, Republic of,  Netherlands,  Spain,  Sweden,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Patients With at Least One Unexplained Hyperglycemia and/ or Confirmed Infusion Set Occlusion	Unexplained hyperglycemia defined as blood glucose value above 300 mg/dL (16.7 mmol/L) with no apparent medical dietary, insulin dosage or pump failure reason.; Pump infusion set occlusion defined by at least one of the following items: pump occlusion alarm,; patient observation of an occlusion, spontaneously or because of elevated blood glucose value.	over 13 weeks of each treatment period	No
Secondary	Monthly Rate of Unexplained Hyperglycemia and/ or Confirmed Infusion Set Occlusion	Unexplained hyperglycemia defined as blood glucose value above 300 mg/dL (16.7 mmol/L) with no apparent medical dietary, insulin dosage or pump failure reason.; Pump infusion set occlusion defined by at least one of the following items: pump occlusion alarm,; patient observation of an occlusion, spontaneously or because of elevated blood glucose value.	over 13 weeks of each treatment period	No
Secondary	Percentage of Patients With at Least One Unexplained Hyperglycemia	Unexplained hyperglycemia defined as blood glucose value above 300 mg/dL (16.7 mmol/L) with no apparent medical dietary, insulin dosage or pump failure reason.	over 13 weeks of each treatment period	No
Secondary	Monthly Rate of Unexplained Hyperglycemia		over 13 weeks of each treatment period	No
Secondary	Percentage of Patients With at Least One Confirmed Infusion Set Occlusion	Pump infusion set occlusion defined by at least one of the following items: pump occlusion alarm,; patient observation of an occlusion, spontaneously or because of elevated blood glucose value.	over 13 weeks of each treatment period	No
Secondary	Monthly Rate of Confirmed Infusion Set Occlusion		over 13 weeks of each treatment period	No
Secondary	Percentage of Patients With at Least One Episode of Significant Ketosis and/ or Risk Level for Impending Diabetic Ketoacidosis	Diabetic ketoacidosis (DKA) is preceded by an increase in ketone production, resulting in blood ketone value increase (hyperketonemia) and later in ketone urine value (hyperketonuria).; Significant hyperketonemia and risk level for impending diabetic ketoacidosis (DKA) are reported respectively as a blood ketone value from 0.6 to 1.5 mmol/L and >1.5 mmol/l	over 13 weeks of each treatment period	No
Secondary	Monthly Rate of Episode of Significant Ketosis and/ or Risk Level for Impending Diabetic Ketoacidosis	Diabetic ketoacidosis (DKA) is preceded by an increase in ketone production, resulting in blood ketone value increase (hyperketonemia) and later in ketone urine value (hyperketonuria).; Significant hyperketonemia and risk level for impending diabetic ketoacidosis (DKA) are reported respectively as a blood ketone value from 0.6 to 1.5 mmol/L and >1.5 mmol/l	over 13 weeks of each treatment period	No
Secondary	Rate of Symptomatic Hypoglycemia With a Plasma Glucose (PG) = 70 mg/dL Per Patient-year	Symptomatic hypoglycemia is defined as an event with clinical symptoms that are considered to results from hypoglycemia (confirmed or not by a glucose measurement) and associated with prompt recovery after oral carbohydrate administration.	over 13 weeks of each treatment period	No
Secondary	Rate of Severe Symptomatic Hypoglycemia Per Patient-year	Severe symptomatic hypoglycemia is defined as an event with clinical symptoms that are considered to results from hypoglycemia in which the patient required assistance of another person and one of the following: the event was associated with a measured blood glucose level below 36 mg/dL; or event was associated with prompt recovery after oral carbohydrate, intravenous glucose, or glucagon administration.	over 13 weeks of each treatment period	No
Secondary	Rate of Nocturnal Symptomatic Hypoglycemia With a Plasma Glucose (PG) =70 mg/dL Per Patient-year	Nocturnal Symptomatic hypoglycemia was defined as an event with clinical symptoms that are considered to result from hypoglycemia (confirmed or not by a glucose measurement) and associated with prompt recovery after oral carbohydrate administration which occurs while the patient is asleep, after bedtime and before getting up in the morning.	over 13 weeks of each treatment period	No
Secondary	Patients With at Least One Site Infection, Site Inflammation/Erythema, Pruritus or Isolated Pain at Injection Site	Infection: local reaction at the infusion site requiring local or systemic antibiotherapy, or local drainage as per Investigator judgment.; Site inflammation or erythema: local reaction at the infusion site with no need for local or systemic antibiotherapy as per Investigator judgment.; Pruritis at injection site: presence of pruritis at the infusion site without any symptom of inflammation or erythema and/or infection.; Isolated pain at injection site: presence of pain at the infusion site without any symptom of inflammation or erythema and/or infection.	over 13 weeks of each treatment period	No
Secondary	Time Interval Between Infusion Set Changes: All Changes	Patients treated with insulin pump have to change their infusion set regularly (i.e.change was recommended every 48h). The patients were asked to report any change of their infusion set and the reason for change (routine basis or because of occurrence of a specific event such as occlusion, unexplained hyperglycemia or adverse event).; "All changes" include all the changes whatever the reason such as routine or requested by occurrence of events.	over 13 weeks of each treatment period	No
Secondary	Time Interval Between Infusion Set Changes in Routine	Patients treated with insulin pump have to change their infusion set regularly (i.e.change was recommended every 48h). The patients were asked to report any change of their infusion set and the reason for change (routine basis or because of occurrence of a specific event such as occlusion, unexplained hyperglycemia or adverse event).; Changes in routine correspond to interval between changes according to patient use.	over 13 weeks of each treatment period	No
Secondary	Glycosylated Hemoglobin: HbA1c	Glycolysated Haemoglobin (HbA1c) is a biological parameter that reflects the blood glucose concentration over a long period of time. It is the standard parameter for glycemic control follow-up in diabetic patients. This parameter is expressed in percentage (%) and the target in diabetes management is to reach a HbA1c <7%	over 13 weeks of each treatment period	No
Secondary	Total Daily Basal Insulin Infusion	dose of the basal insulin regimen administered throughout the 24-hour period	over 13 weeks of each treatment period	No
Secondary	Total Daily Bolus Insulin Dose	dose of every increment administered for example before meals	over 13 weeks of each treatment period	No