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

Phase 3

Completed

• Conditions: Diabetes; Diabetes Mellitus, Type 1
• Interventions: Drug: insulin aspart; Drug: insulin detemir

• Registration Number: NCT00447382
• Lead Sponsor: Novo Nordisk A/S

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2007-03
• Study First Submitted: 2007-03-13
• Study First Submitted QC: 2007-03-13
• Study First Posted: 2007-03-14
• Primary Completion: 2008-07
• Study Completion: 2008-07
• Disposition First Submitted: 2010-10-29
• Disposition First Submitted QC: 2010-10-29
• Disposition First Posted: 2010-11-02
• Results First Submitted: 2010-11-24
• Results First Submitted QC: 2011-05-11
• Results First Posted: 2011-05-12
• Status Verified: 2023-12
• Last Update Submitted: 2023-12-29
• Last Update Posted: 2024-01-02

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 330

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
NN729	insulin aspart	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
NN304	insulin aspart	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
NN304	insulin detemir	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
NN729	insulin detemir	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

Primary Outcome Measures

Name	Time	Method
Change From Baseline in Insulin Detemir - Human Insulin Cross-reacting Antibodies	week 0, week 52	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

Name	Time	Method
Glycaemic Control Parameters (Change in HbA1c)	week 0, week 52	HbA1c (Glycosylated haemoglobin).
Clinical Laboratory Values (Change in Biochemistry - Albumin)	Week 0, week 52	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)	Week 0, week 52	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)	Week 0, week 52	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)	Week 0, week 52	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 - Potassium)	Week 0, week 52	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
Glycaemic Control Parameters (Change in Fasting Plasma Glucose [FPG])	week 0, week 52
Change From Baseline in Detemir Specific Antibodies	Week 0, week 52	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	Week 0, week 52	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 - Leucocytes)	Week 0, week 52	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])	Week 0, week 52	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])	Week 0, week 52	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)	Week 0, week 52	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
Hypoglycaemic Episodes	Weeks 0-52	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.
Clinical Laboratory Values (Change in Haematology - Eosinophils)	Week 0, week 52	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)	Week 0, week 52	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])	Week 0, week 52	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 - Total Protein)	Week 0, week 52	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
Glycaemic Control Parameters (9-point Self Measured Plasma Glucose [SMPG])	week 0, 26 and 52	1. point is Before Breakfast; 2. point is 120 minutes after Breakfast; 3. point is Before Lunch; 4. point is 120 minutes after Lunch; 5. point is Before Dinner; 6. point is 120 minutes after Dinner; 7. point is at Bedtime; 8. point is At 03:00 A.M.; 9. point is Before Breakfast the Following Day
Clinical Laboratory Values (Change in Haematology - Basophilis)	week 0, week 52	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)	Week 0, week 52	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	Weeks 0-52
Clinical Laboratory Values (Change in Biochemistry - Sodium)	Week 0, week 52	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