Safety of Insulin Detemir Produced by a New Process as Measured by Antibody Formation in Subjects With Type 1 Diabetes

A 12-months Multi-national, Multi-centre, Double Blind, Randomised, Parallel Safety and Efficacy Comparison of Insulin Detemir Produced by the Current Process and Insulin Detemir Produced by the NN729 Process in Subjects With Type 1 Diabetes on a Basal-bolus Regimen With Insulin Aspart as the Bolus Insulin

The trial was conducted in Germany, The Republic of Macedonia, Russian Federation, Serbia and South Africa. The aim of this trial was to make a safety comparison of insulin detemir produced by a new production method (NN729) with insulin detemir made by the previous production method (NN304). Subjects were treated with NN729 or NN304 for a period of 52 weeks at the same total daily dose and frequency of administration as their own pre-trial basal insulin . During the trial doses were individualised based on subject's plasma glucose measurements.

Study Overview

• Status: Completed
• Conditions: Diabetes; Diabetes Mellitus, Type 1
• Intervention / Treatment: Drug: insulin detemir; Drug: insulin aspart; Drug: insulin detemir

• Study Type: Interventional
• Enrollment (Actual): 330
• Phase: Phase 3

Contacts and Locations

Study Locations

• Former Serbia and Montenegro
  • Belgrade, Former Serbia and Montenegro, 11000
• Germany
  • Frankfurt, Germany, 60590
• North Macedonia
  • Skopje, North Macedonia, 1000
• Russian Federation
  • Moscow, Russian Federation, 119034
• South Africa
  • Western Cape
    • Cape Town, Western Cape, South Africa, 7925

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Type 1 diabetes for at least 12 months
• Basal-bolus treatment for at least 3 months
• Body Mass Index (BMI) less than or equal to 35.0 kg/m^2
• HbA1c (glycosylated haemoglobin) less than or equal to 12.0%

Exclusion Criteria:

• Known or suspected allergy to trial products or related products
• Pregnancy, breast-feeding or the intention to become pregnant or not using adequate contraceptive measures
• Receipt of any trial drug within 1 month prior to this trial
• Mental incapacity, unwillingness or language barriers precluding adequate understanding or cooperation
• Conditions that may interfere with trial participation as judged by Investigator: proliferative retinopathy or maculopathy requiring acute treatment within the last six months, recurrent major hypoglycaemia, impaired hepatic or renal function, cardiac problems, uncontrolled hypertension (treated and untreated)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: NN304; Individually adjusted dosage of insulin detemir produced by the NN304 process, administered sub-cutaneously (s.c.) 1-2 times daily + Individually adjusted dosage of insulin aspart, administered sub-cutaneously (s.c.) at meals for 52 weeks	Drug: insulin detemir; NN304 injected s.c. (under the skin). Given as basal insulin.; Drug: insulin aspart; Injected s.c. (under the skin). Given as bolus insulin.; Drug: insulin detemir; NN729 injected s.c. (under the skin). Given as basal insulin
Experimental: NN729; Individually adjusted dosage of insulin detemir produced by the NN729 process, administered sub-cutaneously (s.c.) 1-2 times daily + Individually adjusted dosage of insulin aspart, administered sub-cutaneously (s.c.) at meals for 52 weeks	Drug: insulin detemir; NN304 injected s.c. (under the skin). Given as basal insulin.; Drug: insulin aspart; Injected s.c. (under the skin). Given as bolus insulin.; Drug: insulin detemir; NN729 injected s.c. (under the skin). Given as basal insulin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Insulin Detemir - Human Insulin Cross-reacting Antibodies	Measured change in concentrations of insulin detemir cross-reacting antibodies and the change ratio from baseline to end of trial was calculated. The unit for measuring antibody levels is %B/T (amount of tracer bound to the antibodies in the precipitate (B) expressed in percentage of the total amount of tracer (T) added to the mixture). The change ratio does not have any unit as it is a ratio.	week 0, week 52

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hypoglycaemic Episodes	Number of hypoglycaemic episodes from Week 0 to Week 52, defined as major, minor, or symptoms only. Major if unable to treat her/himself. Minor if able to treat her/himself and plasma glucose below 3.1 mmol/L. Symptoms only if able to treat her/himself and no plasma glucose measurement or plasma glucose higher than or equal to 3.1 mmol/L. Hypoglycaemic episodes occurring in the time frame between 23:00 hours (included) and 06:00 hours (excluded) were defined as nocturnal.	Weeks 0-52
Glycaemic Control Parameters (Change in HbA1c)	HbA1c (Glycosylated haemoglobin).	week 0, week 52
Glycaemic Control Parameters (Change in Fasting Plasma Glucose [FPG])		week 0, week 52
Glycaemic Control Parameters (9-point Self Measured Plasma Glucose [SMPG])	point is Before Breakfast; point is 120 minutes after Breakfast; point is Before Lunch; point is 120 minutes after Lunch; point is Before Dinner; point is 120 minutes after Dinner; point is at Bedtime; point is At 03:00 A.M.; point is Before Breakfast the Following Day	week 0, 26 and 52
Change From Baseline in Detemir Specific Antibodies	Measured change in concentrations of antibody values for insulin detemir specific antibodies and the change ratio from the baseline to end of trial was calculated. The unit for measuring antibody levels is %B/T (amount of tracer bound to the antibodies in the precipitate (B) expressed in percentage of the total amount of tracer (T) added to the mixture). The change ratio does not have any unit as it is a ratio.	Week 0, week 52
Change From Baseline in Total Antibodies	Measured change in concentrations of total insulin antibodies values (the sum of insulin detemir specific and insulin detemir - human insulin cross-reacting antibodies) and the change ratio from baseline to end of trial was calculated. The unit for measuring antibody levels is %B/T (amount of tracer bound to the antibodies in the precipitate (B) expressed in percentage of the total amount of tracer (T) added to the mixture). The change ratio does not have any unit as it is a ratio.	Week 0, week 52
Clinical Laboratory Values (Change in Haematology - Basophilis)	Change from Baseline to Week 52 is calculated from the change in percentage ((Week 52 %) - (Baseline %)) per participant, averaged across all participants. Measured in serum at baseline and week 52. Serum samples were analysed at a central laboratory.	week 0, week 52
Clinical Laboratory Values (Change in Haematology - Eosinophils)	Change from Baseline to Week 52 is calculated from the change in percentage ((Week 52 %) - (Baseline %)) per participant, averaged across all participants. Measured in serum at baseline and week 52. Serum samples were analysed at a central laboratory.	Week 0, week 52
Clinical Laboratory Values (Change in Haematology - Haemoglobin)	Change from Baseline to Week 52 is calculated from the change in percentage ((Week 52 %) - (Baseline %)) per participant, averaged across all participants. Measured in serum at baseline and week 52. Serum samples were analysed at a central laboratory.	Week 0, week 52
Clinical Laboratory Values (Change in Haematology - Lymphocytes)	Change from Baseline to Week 52 is calculated from the change in percentage((Week 52 %) - (Baseline %)) per participant, averaged across all participants. Measured in serum at baseline and week 52. Serum samples were analysed at a central laboratory.	Week 0, week 52
Clinical Laboratory Values (Change in Haematology - Monocytes)	Change from Baseline to Week 52 is calculated from the change in percentage ((Week 52 %) - (Baseline %)) per participant, averaged across all participants. Measured in serum at baseline and week 52. Serum samples were analysed at a central laboratory.	Week 0, week 52
Clinical Laboratory Values (Change in Haematology - Neutrophils)	Change from Baseline to Week 52 is calculated from the change in percentage((Week 52 %) - (Baseline %)) per participant, averaged across all participants. Measured in serum at baseline and week 52. Serum samples were analysed at a central laboratory.	Week 0, week 52
Clinical Laboratory Values (Change in Haematology - Thrombocytes)	Change from Baseline to Week 52 is calculated from the change in percentage((Week 52 %) - (Baseline %)) per participant, averaged across all participants. Measured in serum at baseline and week 52. Serum samples were analysed at a central laboratory.	Week 0, week 52
Clinical Laboratory Values (Change in Haematology - Leucocytes)	Change from Baseline to Week 52 is calculated from the change in percentage((Week 52 %) - (Baseline %)) per participant, averaged across all participants. Measured in serum at baseline and week 52. Serum samples were analysed at a central laboratory.	Week 0, week 52
Clinical Laboratory Values (Change in Biochemistry - Albumin)	Change from Baseline to Week 52 is calculated from the change in percentage((Week 52 %) - (Baseline %)) per participant, averaged across all participants. Measured in serum at baseline and week 52. Serum samples were analysed at a central laboratory	Week 0, week 52
Clinical Laboratory Values (Change in Biochemistry - Alanine Aminotransferase [ALAT])	Change from Baseline to Week 52 is calculated from the change in percentage((Week 52 %) - (Baseline %)) per participant, averaged across all participants. Measured in serum at baseline and week 52. Serum samples were analysed at a central laboratory. (ALAT = alanine aminotransferase)	Week 0, week 52
Clinical Laboratory Values (Change in Biochemistry - Alkaline Phosphatase [ALP])	Change from Baseline to Week 52 is calculated from the change in percentage((Week 52 %) - (Baseline %)) per participant, averaged across all participants. Measured in serum at baseline and week 52. Serum samples were analysed at a central laboratory. (ALP = alkaline phosphatase)	Week 0, week 52
Clinical Laboratory Values (Change in Biochemistry - Creatinine)	Change from Baseline to Week 52 is calculated from the change in percentage((Week 52 %) - (Baseline %)) per participant, averaged across all participants. Measured in serum at baseline and week 52. Serum samples were analysed at a central laboratory	Week 0, week 52
Clinical Laboratory Values (Change in Biochemistry - Lactate Dehydrogenase [LDH])	Change from Baseline to Week 52 is calculated from the change in percentage((Week 52 %) - (Baseline %)) per participant, averaged across all participants. Measured in serum at baseline and week 52. Serum samples were analysed at a central laboratory (LDH = lactate dehydrogenase)	Week 0, week 52
Clinical Laboratory Values (Change in Biochemistry - Potassium)	Change from Baseline to Week 52 is calculated from the change in percentage((Week 52 %) - (Baseline %)) per participant, averaged across all participants. Measured in serum at baseline and week 52. Serum samples were analysed at a central laboratory	Week 0, week 52
Clinical Laboratory Values (Change in Biochemistry - Sodium)	Change from Baseline to Week 52 is calculated from the change in percentage((Week 52 %) - (Baseline %)) per participant, averaged across all participants. Measured in serum at baseline and week 52. Serum samples were analysed at a central laboratory	Week 0, week 52
Clinical Laboratory Values (Change in Biochemistry - Total Protein)	Change from Baseline to Week 52 is calculated from the change in percentage((Week 52 %) - (Baseline %)) per participant, averaged across all participants. Measured in serum at baseline and week 52. Serum samples were analysed at a central laboratory	Week 0, week 52
Adverse Events		Weeks 0-52

Collaborators and Investigators

• Sponsor: Novo Nordisk A/S
• Investigators: Study Director: Global Clinical Registry (GCR, 1452), Novo Nordisk A/S

Publications and helpful links

Helpful Links

• Clinical Trials at Novo Nordisk

Study record dates

Study Major Dates

• Study Start: March 1, 2007
• Primary Completion (Actual): July 1, 2008
• Study Completion (Actual): July 1, 2008

Study Registration Dates

• First Submitted: March 13, 2007
• First Submitted That Met QC Criteria: March 13, 2007
• First Posted (Estimated): March 14, 2007

Study Record Updates

• Last Update Posted (Estimated): January 1, 2024
• Last Update Submitted That Met QC Criteria: December 29, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Immune System Diseases; Autoimmune Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 1; Hypoglycemic Agents; Physiological Effects of Drugs; Insulin; Insulin, Globin Zinc; Insulin Aspart; Insulin Detemir
• Other Study ID Numbers: EX1729-1778; 2006-004733-15 (EudraCT Number)