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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Novo Nordisk A/S
ClinicalTrials.gov Identifier:
NCT00447382
First received: March 13, 2007
Last updated: October 8, 2014
Last verified: October 2014
  Purpose

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.


Condition Intervention Phase
Diabetes
Diabetes Mellitus, Type 1
Drug: insulin detemir
Drug: insulin aspart
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Novo Nordisk A/S:

Primary Outcome Measures:
  • Change From Baseline in Insulin Detemir - Human Insulin Cross-reacting Antibodies [ Time Frame: week 0, week 52 ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: Weeks 0-52 ] [ Designated as safety issue: Yes ]
    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) [ Time Frame: week 0, week 52 ] [ Designated as safety issue: No ]
    HbA1c (Glycosylated haemoglobin).

  • Glycaemic Control Parameters (Change in Fasting Plasma Glucose [FPG]) [ Time Frame: week 0, week 52 ] [ Designated as safety issue: No ]
  • Glycaemic Control Parameters (9-point Self Measured Plasma Glucose [SMPG]) [ Time Frame: week 0, 26 and 52 ] [ Designated as safety issue: No ]
    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

  • Change From Baseline in Detemir Specific Antibodies [ Time Frame: Week 0, week 52 ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: Week 0, week 52 ] [ Designated as safety issue: Yes ]
    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) [ Time Frame: week 0, week 52 ] [ Designated as safety issue: Yes ]

    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) [ Time Frame: Week 0, week 52 ] [ Designated as safety issue: Yes ]
    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) [ Time Frame: Week 0, week 52 ] [ Designated as safety issue: Yes ]
    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) [ Time Frame: Week 0, week 52 ] [ Designated as safety issue: Yes ]

    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) [ Time Frame: Week 0, week 52 ] [ Designated as safety issue: Yes ]

    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) [ Time Frame: Week 0, week 52 ] [ Designated as safety issue: Yes ]

    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) [ Time Frame: Week 0, week 52 ] [ Designated as safety issue: Yes ]
    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) [ Time Frame: Week 0, week 52 ] [ Designated as safety issue: Yes ]

    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) [ Time Frame: Week 0, week 52 ] [ Designated as safety issue: Yes ]
    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]) [ Time Frame: Week 0, week 52 ] [ Designated as safety issue: Yes ]

    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]) [ Time Frame: Week 0, week 52 ] [ Designated as safety issue: Yes ]

    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) [ Time Frame: Week 0, week 52 ] [ Designated as safety issue: Yes ]
    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]) [ Time Frame: Week 0, week 52 ] [ Designated as safety issue: Yes ]
    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) [ Time Frame: Week 0, week 52 ] [ Designated as safety issue: Yes ]
    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) [ Time Frame: Week 0, week 52 ] [ Designated as safety issue: Yes ]
    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) [ Time Frame: Week 0, week 52 ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: Weeks 0-52 ] [ Designated as safety issue: Yes ]

Enrollment: 330
Study Start Date: March 2007
Study Completion Date: July 2008
Primary Completion Date: July 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
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 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

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00447382

Locations
Former Serbia and Montenegro
Belgrade, Former Serbia and Montenegro, 11000
Germany
Frankfurt, Germany, 60590
Macedonia, The Former Yugoslav Republic of
Skopje, Macedonia, The Former Yugoslav Republic of, 1000
Russian Federation
Moscow, Russian Federation, 119034
South Africa
Cape Town, Western Cape, South Africa, 7925
Sponsors and Collaborators
Novo Nordisk A/S
Investigators
Study Director: Global Clinical Registry (GCR, 1452) Novo Nordisk A/S
  More Information

Additional Information:
No publications provided

Responsible Party: Novo Nordisk A/S
ClinicalTrials.gov Identifier: NCT00447382     History of Changes
Other Study ID Numbers: EX1729-1778, 2006-004733-15
Study First Received: March 13, 2007
Results First Received: November 24, 2010
Last Updated: October 8, 2014
Health Authority: Russia: Federal Service for Control of Health Care and Social Development
South Africa: Medicines Control Council
Macedonia, The Former Yugoslav Republic of: Drug Agency, Ministry of Health
Germany: Federal Institute for Drugs and Medical Devices
Serbia: Medicines and Medical Devices Agency of Serbia

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 1
Autoimmune Diseases
Endocrine System Diseases
Glucose Metabolism Disorders
Immune System Diseases
Metabolic Diseases
Insulin
Insulin Aspart
Insulin, Globin Zinc
Insulin, Long-Acting
Hypoglycemic Agents
Pharmacologic Actions
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on November 25, 2014