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 - Full Text View

Sponsor:	Sanofi-Aventis
Information provided by:	Sanofi-Aventis
ClinicalTrials.gov Identifier:	NCT00607087

Purpose

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

Condition	Intervention	Phase
Diabetes Mellitus, Type 1	Drug: Insulin glulisine Drug: Insulin lispro Drug: Insulin aspart	Phase IV

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

Resource links provided by NLM:

Genetics Home Reference related topics: 6q24-related transient neonatal diabetes mellitus

MedlinePlus related topics: Diabetes Medicines Diabetes Type 1

Drug Information available for: Insulin Insulin beef Insulin aspart Insulin lispro Insulin glulisine

U.S. FDA Resources

Further study details as provided by Sanofi-Aventis:

Primary Outcome 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 ] [ Designated as safety issue: No ]
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.

Secondary Outcome Measures:

Monthly Rate of Unexplained Hyperglycemia and/ or Confirmed Infusion Set Occlusion [ Time Frame: over 13 weeks of each treatment period ] [ Designated as safety issue: No ]
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.
Percentage of Patients With at Least One Unexplained Hyperglycemia [ Time Frame: over 13 weeks of each treatment period ] [ Designated as safety issue: No ]
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.
Monthly Rate of Unexplained Hyperglycemia [ Time Frame: over 13 weeks of each treatment period ] [ Designated as safety issue: No ]
Percentage of Patients With at Least One Confirmed Infusion Set Occlusion [ Time Frame: over 13 weeks of each treatment period ] [ Designated as safety issue: No ]
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.
Monthly Rate of Confirmed Infusion Set Occlusion [ Time Frame: over 13 weeks of each treatment period ] [ Designated as 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 ] [ Designated as safety issue: No ]
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
Monthly Rate of Episode of Significant Ketosis and/ or Risk Level for Impending Diabetic Ketoacidosis [ Time Frame: over 13 weeks of each treatment period ] [ Designated as safety issue: No ]
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
Rate of Symptomatic Hypoglycemia With a Plasma Glucose (PG) ≤ 70 mg/dL Per Patient-year [ Time Frame: over 13 weeks of each treatment period ] [ Designated as safety issue: No ]
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.
Rate of Severe Symptomatic Hypoglycemia Per Patient-year [ Time Frame: over 13 weeks of each treatment period ] [ Designated as safety issue: No ]
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.
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 ] [ Designated as safety issue: No ]
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.
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 ] [ Designated as safety issue: No ]
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.
Time Interval Between Infusion Set Changes: All Changes [ Time Frame: over 13 weeks of each treatment period ] [ Designated as safety issue: No ]
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.
Time Interval Between Infusion Set Changes in Routine [ Time Frame: over 13 weeks of each treatment period ] [ Designated as safety issue: No ]
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.
Glycosylated Hemoglobin: HbA1c [ Time Frame: over 13 weeks of each treatment period ] [ Designated as safety issue: No ]
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%
Total Daily Basal Insulin Infusion [ Time Frame: over 13 weeks of each treatment period ] [ Designated as safety issue: No ]
dose of the basal insulin regimen administered throughout the 24-hour period
Total Daily Bolus Insulin Dose [ Time Frame: over 13 weeks of each treatment period ] [ Designated as safety issue: No ]
dose of every increment administered for example before meals

Enrollment:	289
Study Start Date:	January 2008
Study Completion Date:	June 2009
Primary Completion Date:	June 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: sequence 1 sequence 1: insulin glulisine / insulin aspart / insulin lispro.	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
Experimental: Sequence 2 Sequence 2: insulin aspart / insulin lispro / insulin glulisine	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
Experimental: Sequence 3 Sequence 3: insulin lispro / insulin glulisine / insulin aspart	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

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

Ages Eligible for Study:	18 Years to 75 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00607087

Locations

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

Sponsors and Collaborators

Sanofi-Aventis

Investigators

Study Director:

Medical Affairs

Sanofi-Aventis

More Information

No publications provided by Sanofi-Aventis

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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. Epub 2011 Apr 2.

Responsible Party:	Medical Affairs Study Director, sanofi-aventis
ClinicalTrials.gov Identifier:	NCT00607087 History of Changes
Other Study ID Numbers:	APIDR_C_02083, 2007-003579-38
Study First Received:	January 23, 2008
Results First Received:	June 30, 2010
Last Updated:	August 26, 2010
Health Authority:	Sweden: Regional Ethical Review Board

Additional relevant MeSH terms:

Diabetes Mellitus
Diabetes Mellitus, Type 1
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Autoimmune Diseases
Immune System Diseases

Insulin aspart
Insulin LISPRO
Insulin glulisine
Insulin
Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on February 09, 2012