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 (PUMP)

Sanofi

Status and phase: Completed; Phase 4

Conditions: Diabetes Mellitus, Type 1

Treatments: Drug: Insulin aspart; Drug: Insulin glulisine; Drug: Insulin lispro

Study type: Interventional

Funder types: Industry

Identifiers

NCT00607087

2007-003579-38 (EudraCT Number)

APIDR_C_02083

Details and patient eligibility

About

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

Full 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.

Enrollment: 289 patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: None (Open label)

---

289 participants in 3 patient groups

sequence 1

Experimental group

Description:

sequence 1: insulin glulisine / insulin aspart / insulin lispro.

Treatment:

Drug: Insulin glulisine

Drug: Insulin lispro

Drug: Insulin aspart

Sequence 2

Experimental group

Description:

Sequence 2: insulin aspart / insulin lispro / insulin glulisine

Treatment:

Drug: Insulin glulisine

Drug: Insulin lispro

Drug: Insulin aspart

Sequence 3

Experimental group

Description:

Sequence 3: insulin lispro / insulin glulisine / insulin aspart

Treatment:

Drug: Insulin glulisine

Drug: Insulin lispro

Drug: Insulin aspart