Insulin Glulisine in Type 1 Diabetes Mellitus

Type 1 Diabetes Mellitus Clinical Trial

Official title:

A Single-center, Randomized, Double-blind, 3-period Cross-over Trial to Compare the Effect of Insulin Glulisine, Insulin Lispro and Unmodified Human Insulin on the Endogenous Glucose Production in Type 1 Diabetic Patients.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00297583
• Other study ID #: HMR1964A_1501
• Status: Completed
• Phase: Phase 1
• First received: February 20, 2006
• Last updated: December 4, 2009
• Start date: April 2004

Study information

• Verified date: December 2009
• Source: Sanofi
• Contact: n/a
• Is FDA regulated: No
• Health authority: Austria: Federal Ministry for Health and Women
• Study type: Interventional

Clinical Trial Summary

The primary objective of the study was to compare the effect of insulin glulisine, insulin lispro and unmodified human insulin on endogenous glucose production during euglycemic glucose clamps using stable labeled glucose in type 1 diabetic subjects.

The secondary objectives of the study were to assess:

• the effect of insulin glulisine, insulin lispro and unmodified human insulin on plasma nonesterified free fatty acids (NEFA) and glycerol levels

• the effect of insulin glulisine, insulin lispro and unmodified human insulin on plasma lactate levels

• the safety and tolerability of insulin glulisine in comparison to insulin lispro and unmodified human insulin.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 0
• Est. primary completion date: May 2004
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 70 Years

Eligibility

Inclusion criteria

• Type 1 diabetes (as defined by the World Health Organization) for at least 2 years

• HbA1c = 10.0 %

• C-peptide < 0.05 nmol/L, based on fasting C-peptide level

• Body mass index (BMI) = 30 kg/m²

• Treatment with intensified insulin therapy: short acting insulin before meals (breakfast, lunch,dinner) with neutral protamine Hagedorn (NPH) insulin, or continuous subcutaneous insulin infusion (CSII) for at least 3 months.Insulin glargine, or other basal insulin than NPH, had to be replaced by NPH insulin at the screening visit.

• Women not of childbearing potential (surgically sterile, or postmenopausal for more than 2 years) or not pregnant and agreed to use a reliable contraceptive measure for the duration of the study.

• Able and willing to perform self-monitoring of blood glucose

Exclusion criteria

• Contraindications from:

• The medical history and physical examination

• Laboratory tests (hematology, clinical chemistry and urinalysis)

• 12-lead electrocardiogram (ECG)

• Blood pressure and pulse rate

• Hepatitis screen

• Pregnancy, breast-feeding or intention to become pregnant

• History of drug or alcohol abuse

• Receipt of any investigational drug within the last 30 days prior to this trial

• Experienced recurrent severe hypoglycemia or hypoglycemic unawareness (as judged by the investigator)

• Total daily insulin dose = 1.4 IU/kg

• Serum insulin antibody level > 20 U/mL determined at screening visit

• Smokers > 10 cigarettes per day or equivalent

• Pre-planned surgery during the study

• Currently being treated with systemic corticosteroids or any other drugs affecting blood glucose, or immunosuppressives

• Known diabetic gastroparesis or lipodystrophia

• Active proliferative diabetic retinopathy, as defined by the application of focal or panretinal photocoagulation or vitrectomy, in the 6 months prior to visit 1, or any other unstable (rapidly progressing) retinopathy that may require surgical treatment (including laser photocoagulation) during the study

• Cardiac problems:

• New York Heart Association (NYHA) Functional Capacity Class III and IV

• Diagnosis of unstable angina pectoris

• Myocardial infarction within the last 12 months

• Biochemical signs of hepatic or renal diseases as indicated by alanine aminotransferase and/or alkaline phosphatase = 2 times and/or creatinine = 1.5 times the upper limit of the normal reference range for the age group or current renal dialysis

• Anemia as indicated by hemoglobin < 6.2 mmol/L or clinically relevant iron deficiency as indicated by low ferritin levels in men (< 34 ng/mL) and women (premenopausal < 22 ng/mL, menopausal < 13 ng/mL)

• Any other clinically significant major organ system disease such as relevant cardiovascular (e.g. uncontrolled hypertension), gastrointestinal, hepatic, neurologic, endocrine (e.g.pancreatic), hematologic, malignant or other major systemic diseases making implementation of the protocol or interpretation of the study results difficult

• Significant endogenous insulin secretion indicated by fasting C-peptide

• History of hypersensitivity to insulin or insulin analogues or any of the excipients in the HMR

• Donation of blood (>500 mL) during the previous 3 months prior to the screening visit or during the duration of the study

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Crossover Assignment, Masking: Double-Blind, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 1
• Type 1 Diabetes Mellitus

Intervention

Drug:
• Insulin Glulisine

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Sanofi

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	serum insulin concentrations		During the Study Conduct	No
Secondary	glucose infusion rates		During the study conduct	No
Secondary	blood glucose concentrations		During the study conduct	No
Secondary	Adverse events and hypoglycemic episodes collection		from the inform consnet signed up to the end of the study	No