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

Primary Purpose

Diabetes, Diabetes Mellitus, Type 1

Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
insulin detemir
insulin aspart
insulin detemir
Sponsored by
Novo Nordisk A/S
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Diabetes

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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)

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Experimental

Arm Label

NN304

NN729

Arm Description

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

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

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.
Glycaemic Control Parameters (Change in HbA1c)
HbA1c (Glycosylated haemoglobin).
Glycaemic Control Parameters (Change in Fasting Plasma Glucose [FPG])
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
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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
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)
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)
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
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)
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
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
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
Adverse Events

Full Information

First Posted
March 13, 2007
Last Updated
October 8, 2014
Sponsor
Novo Nordisk A/S
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1. Study Identification

Unique Protocol Identification Number
NCT00447382
Brief Title
Safety of Insulin Detemir Produced by a New Process as Measured by Antibody Formation in Subjects With Type 1 Diabetes
Official Title
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
Study Type
Interventional

2. Study Status

Record Verification Date
October 2014
Overall Recruitment Status
Completed
Study Start Date
March 2007 (undefined)
Primary Completion Date
July 2008 (Actual)
Study Completion Date
July 2008 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Novo Nordisk A/S

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Diabetes, Diabetes Mellitus, Type 1

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
330 (Actual)

8. Arms, Groups, and Interventions

Arm Title
NN304
Arm Type
Active Comparator
Arm Description
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
Arm Title
NN729
Arm Type
Experimental
Arm Description
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
Intervention Type
Drug
Intervention Name(s)
insulin detemir
Intervention Description
NN304 injected s.c. (under the skin). Given as basal insulin.
Intervention Type
Drug
Intervention Name(s)
insulin aspart
Intervention Description
Injected s.c. (under the skin). Given as bolus insulin.
Intervention Type
Drug
Intervention Name(s)
insulin detemir
Intervention Description
NN729 injected s.c. (under the skin). Given as basal insulin
Primary Outcome Measure Information:
Title
Change From Baseline in Insulin Detemir - Human Insulin Cross-reacting Antibodies
Description
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.
Time Frame
week 0, week 52
Secondary Outcome Measure Information:
Title
Hypoglycaemic Episodes
Description
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.
Time Frame
Weeks 0-52
Title
Glycaemic Control Parameters (Change in HbA1c)
Description
HbA1c (Glycosylated haemoglobin).
Time Frame
week 0, week 52
Title
Glycaemic Control Parameters (Change in Fasting Plasma Glucose [FPG])
Time Frame
week 0, week 52
Title
Glycaemic Control Parameters (9-point Self Measured Plasma Glucose [SMPG])
Description
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
Time Frame
week 0, 26 and 52
Title
Change From Baseline in Detemir Specific Antibodies
Description
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.
Time Frame
Week 0, week 52
Title
Change From Baseline in Total Antibodies
Description
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.
Time Frame
Week 0, week 52
Title
Clinical Laboratory Values (Change in Haematology - Basophilis)
Description
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.
Time Frame
week 0, week 52
Title
Clinical Laboratory Values (Change in Haematology - Eosinophils)
Description
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.
Time Frame
Week 0, week 52
Title
Clinical Laboratory Values (Change in Haematology - Haemoglobin)
Description
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.
Time Frame
Week 0, week 52
Title
Clinical Laboratory Values (Change in Haematology - Lymphocytes)
Description
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.
Time Frame
Week 0, week 52
Title
Clinical Laboratory Values (Change in Haematology - Monocytes)
Description
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.
Time Frame
Week 0, week 52
Title
Clinical Laboratory Values (Change in Haematology - Neutrophils)
Description
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.
Time Frame
Week 0, week 52
Title
Clinical Laboratory Values (Change in Haematology - Thrombocytes)
Description
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.
Time Frame
Week 0, week 52
Title
Clinical Laboratory Values (Change in Haematology - Leucocytes)
Description
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.
Time Frame
Week 0, week 52
Title
Clinical Laboratory Values (Change in Biochemistry - Albumin)
Description
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
Time Frame
Week 0, week 52
Title
Clinical Laboratory Values (Change in Biochemistry - Alanine Aminotransferase [ALAT])
Description
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)
Time Frame
Week 0, week 52
Title
Clinical Laboratory Values (Change in Biochemistry - Alkaline Phosphatase [ALP])
Description
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)
Time Frame
Week 0, week 52
Title
Clinical Laboratory Values (Change in Biochemistry - Creatinine)
Description
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
Time Frame
Week 0, week 52
Title
Clinical Laboratory Values (Change in Biochemistry - Lactate Dehydrogenase [LDH])
Description
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)
Time Frame
Week 0, week 52
Title
Clinical Laboratory Values (Change in Biochemistry - Potassium)
Description
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
Time Frame
Week 0, week 52
Title
Clinical Laboratory Values (Change in Biochemistry - Sodium)
Description
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
Time Frame
Week 0, week 52
Title
Clinical Laboratory Values (Change in Biochemistry - Total Protein)
Description
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
Time Frame
Week 0, week 52
Title
Adverse Events
Time Frame
Weeks 0-52

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Global Clinical Registry (GCR, 1452)
Organizational Affiliation
Novo Nordisk A/S
Official's Role
Study Director
Facility Information:
City
Belgrade
ZIP/Postal Code
11000
Country
Former Serbia and Montenegro
City
Frankfurt
ZIP/Postal Code
60590
Country
Germany
City
Skopje
ZIP/Postal Code
1000
Country
Macedonia, The Former Yugoslav Republic of
City
Moscow
ZIP/Postal Code
119034
Country
Russian Federation
City
Cape Town
State/Province
Western Cape
ZIP/Postal Code
7925
Country
South Africa

12. IPD Sharing Statement

Links:
URL
http://novonordisk-trials.com
Description
Clinical Trials at Novo Nordisk

Learn more about this trial

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

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