Safety Follow-up on Children and Adolescents With Type 1 Diabetes Treated With Insulin Detemir. An Extension to Trial NN304-1689

Study Overview
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Brief Summary
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This trial is conducted in Europe. The aim of this research is to assess the safety of continuous treatment with insulin detemir following participation in trial NN304-1689 (NCT00435019) on antibody development.

Official Title
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A 52-Week, Multinational, Multi-Centre, Open-Labelled Extension Trial of Insulin Detemir in Children and Adolescents 3-17 Years With Type 1 Diabetes on a Basal-Bolus Regimen With Insulin Aspart as Bolus Insulin

Conditions
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Diabetes, Diabetes Mellitus, Type 1

Intervention / Treatment
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* Drug: insulin detemir
* Drug: insulin aspart


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Informed Consent obtained before any trial-related activities. (Trial-related activities are any procedure that would not have been performed during normal management of the subject). The parents or legal representative of the subject must sign and date the Informed Consent Form. Finalised 52 weeks of treatment with insulin detemir in trial NN304-1689. Fertile females (girls who have had their first menstrual period) must use adequate contraception (barrier methods, contraceptive pills or intrauterine device (IUD)) if there is any risk of pregnancy in the opinion of the Investigator. For Denmark and France only contraceptive pills or intrauterine device are considered as adequate contraceptive methods. Exclusion Criteria: Significant concomitant disease such as endocrine, hepatic, renal, cardiac, respiratory, neurological, gastrointestinal, malignant or pancreatic diseases as judged by the Investigator. Pregnant or the intention of becoming pregnant. Previous participation in this trial (defined as enrolment).

Ages Eligible for Study
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Minimum Age: 3 Years
Maximum Age: 17 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: insulin detemir<br>Insulin detemir up to twice daily plus insulin aspart at larger meals, doses are adjusted individually (treatment up to 104 weeks) | Drug: insulin detemir<br>* Treat-to-target dose titration scheme (individually adjusted), injection s.c. (under the skin), once or twice daily.<br>Drug: insulin aspart<br>* Treat-to target dose titration scheme (individually adjusted), injection s.c. (under the skin), at larger meals.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Insulin Detemir-insulin Aspart Cross-reacting Antibodies | Estimated amount of bound antibodies in percent of total antibodies. The primary analysis of cross-reacting antibodies included results from blood samples taken before insulin detemir and less than 3 hours after insulin aspart injection. In addition, an analysis was done including results from samples taken before insulin detemir and less than 2.5 hours after insulin aspart injection. | week 0, 52 and 104 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Development of Insulin Detemir Specific Antibodies and Insulin Aspart Specific Antibodies | Amount of Insulin Detemir and Insulin Aspart specific antibodies in percent of total antibodies after 0, 52 and 104 weeks. | At 0, 52 and 104 weeks | 
| Glycosylated Haemoglobin A1c (HbA1c) | Glycosylated Haemoglobin A1c (HbA1c) measured after 104 weeks. | At 104 weeks | 
| Fasting Plasma Glucose Values | FPG (Fasting Plasma Glucose) values after 104 weeks. | At 104 weeks | 
| Hypoglycaemic Episodes | Mild: signs/symptoms but able to treat him/herself. Moderate: signs/symptoms not able to treat him/herself. Responds to oral treatment. Severe: signs/symptoms and unable to treat him/herself. semiconscious/unconscious/in coma +/- convulsion and may require parenteral treatment. | Weeks 0-104 | 
| BMI (Body Mass Index) | BMI (Body Mass Index) after 104 weeks. | At 104 weeks | 
| SD-score (Z-score) for Body Weight | Standard deviation-score (SD-score) after 104 weeks. The SD-score for weight was calculated based on a British reference population from 1990. To estimate the growth of children, standardised mean weight values were calculated for each month of age and for each sex. Thus, a child with a weight equal to the mean value for its age and sex has an SD score of 0, while a child with a weight 2 SDs above the mean value for its age and sex has an SD score of +2. | At 104 weeks | 
| Diabetic Ketoacidosis | Diabetic ketoacidosis requiring hospitalisation | At 104 weeks | 
| Insulin Dose | Daily insulin doses (basal (Insulin Detemir) and bolus (Insulin Aspart)) at week 104. | At 104 weeks | 
| Laboratory Values: Albumin Serum and Total Protein Serum (g/dL) | Albumin Serum and Total Protein Serum after 104 weeks. | At 104 weeks | 
| Laboratory Values: Creatine Serum Umol/L | Creatine serum after 104 weeks. | At 104 weeks | 
| Laboratory Values: Sodium Serum, Potassium Serum and Haemoglobin (mmol/L) | Sodium Serum, Potassium Serum and Haemoglobin after 104 weeks. | At 104 weeks | 
| Laboratory Values: Alkaline Phosphatase Serum, Alanine Aminotransferase Serum and Lactate Dehydrogenase Serum (U/L) | Alkaline phosphatase serum, Alanine Aminotransferase serum and Lactate Dehydrogenase serum after 104 weeks. | At 104 weeks | 
| Laboratory Values: Leukocytes and Thrombocytes | Leukocytes and Thrombocytes after 104 weeks. | At 104 weeks | 
| Fundoscopy/Fundus Photography | Fundoscopy after 104 weeks. Abn. CS = Abnormal, clinically significant Abn. NCS = Abnormal, Not clinically significant Abn. CS = Abnormal, clinically significant Abn. NCS = Abnormal, Not clinically significant | at 52 weeks and at 104 weeks | 
| Vital Signs: Blood Pressure | Blood pressure (Systolic and Diastolic) after 104 weeks. | At 104 weeks | 
| Vital Signs: Pulse | Pulse at week 104 | At 104 weeks |