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

Novo Nordisk A/S330 enrolled

Overview

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 Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Enrollment

330

Conditions

Diabetes Diabetes Mellitus, Type 1

Interventions

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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)

Locations (5)

Unnamed facility

Frankfurt, Germany

Unnamed facility

Skopje, North Macedonia

Unnamed facility

Moscow, Russia

Unnamed facility

Belgrade, Serbia and Montenegro

Unnamed facility

Cape Town, Western Cape, South Africa

Outcomes

Primary Outcomes

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.

Time frame: week 0, week 52

Secondary Outcomes

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.

Time frame: Weeks 0-52

Glycaemic Control Parameters (Change in HbA1c)

HbA1c (Glycosylated haemoglobin).

Time frame: week 0, week 52

Glycaemic Control Parameters (Change in Fasting Plasma Glucose [FPG])

Time frame: week 0, week 52

Glycaemic Control Parameters (9-point Self Measured Plasma Glucose [SMPG])

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

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: week 0, week 52

Clinical Laboratory Values (Change in Haematology - Eosinophils)

Time frame: Week 0, week 52

Clinical Laboratory Values (Change in Haematology - Haemoglobin)

Time frame: 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.

Time frame: Week 0, week 52

Clinical Laboratory Values (Change in Haematology - Monocytes)

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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

Time frame: 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)

Time frame: 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)

Time frame: 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

Time frame: 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)

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: Week 0, week 52

Adverse Events

Time frame: Weeks 0-52