A Trial Investigating the Efficacy and Safety of Insulin Degludec in Children and Adolescents With Type 1 Diabetes Mellitus

Study Overview
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Brief Summary
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This trial is conducted in Africa, Asia, Europe and the United States of America (USA). The aim of this trial is to investigate the efficacy and safety of insulin degludec in children and adolescents with type 1 diabetes mellitus.

Official Title
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A 26-week, Multinational, Multi-centre, Open-Labelled, Randomised, Parallel, Efficacy and Safety Comparison of Insulin Degludec and Insulin Detemir in Children and Adolescents 1 to Less Than 18 Years With Type 1 Diabetes Mellitus on a Basal-bolus Regimen With Insulin Aspart as Bolus Insulin, Followed by a 26-week Extension Investigating Long Term Safety (BEGIN™: Young 1)

Conditions
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Diabetes, Diabetes Mellitus, Type 1

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


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Informed consent, and child assent as age-appropriate, 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 child must sign and date the Informed Consent Form according to local requirements. The child, if possible, parents or legal representative of the child must sign and date the Child Assent Form according to local requirements Male or female diagnosed with type 1 diabetes mellitus (T1DM) (based on clinical judgement and supported by laboratory analysis as per local guidelines) Ongoing daily treatment with insulin (any regimen) for at least 3 months prior to Visit 1 (screening). No OADs (oral anti-diabetic drugs) are allowed HbA1c (glycosylated haemoglobin) maximum 11% Exclusion Criteria: Known or suspected hypersensitivity to trial product(s) or related products Previous participation in this trial. Participation is defined as randomisation Girls who are pregnant, breastfeeding or intend to become pregnant Girls who have had menarche and are not using adequate contraceptive measures according to local requirements Known hypoglycaemic unawareness or recurrent severe hypoglycaemic events as judged by the Investigator (trial physician) More than 1 diabetic ketoacidosis requiring hospitalisation within the last 3 months prior to Visit 1 Significant concomitant disease, except for conditions associated with type 1 diabetes mellitus, which in the Investigator's opinion could interfere with the trial The receipt of any investigational drug within 1 month prior to Visit 1

Ages Eligible for Study
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Minimum Age: 1 Year
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: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Insulin Degludec + Insulin Aspart<br> | Drug: insulin degludec<br>* Injected subcutaneously (under the skin) once daily. Dose individually adjusted.<br>Drug: insulin aspart<br>* Injected subcutaneously (under the skin) as mealtime bolus insulin. Dose individually adjusted.<br>|
| Experimental: Insulin Detemir +Insulin Aspart<br> | Drug: insulin detemir<br>* Injected subcutaneously (under the skin) once or twice daily. Dose individually adjusted.<br>Drug: insulin aspart<br>* Injected subcutaneously (under the skin) as mealtime bolus insulin. Dose individually adjusted.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in HbA1c (Glycosylated Haemoglobin) (%) at 26 Weeks (Analysed by Central Laboratory) | Change from baseline in HbA1c (%) after 26 weeks of treatment. | Week 0, week 26 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in HbA1c (%) at 52 Weeks (Analysed by Central Laboratory) | Change from baseline in HbA1c (%) after 52 weeks of treatments. | Week 0, week 52 | 
| Change From Baseline in Fasting Blood Glucose (FPG) at 26 Weeks (Analysed by Central Laboratory) | Change from baseline in FPG after 26 weeks of treatment. | Week 0, week 26 | 
| Change From Baseline in Fasting Blood Glucose (FPG) at 52 Weeks (Analysed by Central Laboratory) | Change from baseline in FPG after 52 weeks of treatment. | Week 0, week 52 | 
| Number of Treatment Emergent Adverse Events (TEAEs) | TEAE is defined as an event that has onset date on or after the first day of exposure to randomised treatment and no later than 7 days after the last day of randomised treatment. | After 26 weeks and 52 weeks of treatment | 
| Number of Hypoglycaemic Episodes | Number of hypoglycaemic episodes (severe episodes or episodes with plasma glucose (PG) below or equal to 3.9 mmol/L (70 mg/dL) with or without symptoms of hypoglycaemia) during the trial; nocturnal [11 p.m. - 7 a.m./23:00 - 07:00] and over the entire day (24 hours) | After 26 weeks and 52 weeks of treatment | 
| Number of Self-measured Hyperglycaemia (Episodes of PG Above 11.1 mmol/L (200 mg/dL)) | Episodes of PG >11.1mmol/L (200mg/dL) | After 26 weeks and 52 weeks of treatment | 
| Number of Episodes With Self Monitored Blood Ketones Above 1.5 mmol (Capillary Blood Ketone Measurement to be Performed if Self-measured Plasma Glucose (SMPG) Exceeds 14.0 mmol/l (250 mg/dL)) | Blood ketones > 1.5mmol/L (Capillary blood ketone measurement to be performed if SMPG exceeds 14.0mmol/L (250mg/dL) )after 26 and 52 weeks of treatment | After 26 weeks and 52 weeks of treatment | 
| Steady-state Plasma Concentrations of Insulin Degludec and Insulin Detemir on Three Different Visits (Three Different Weeks) During the First 26 Weeks of Treatment | Steady state plasma concentrations of insulin degludec and insulin detemir on three different visits (three different weeks) during the trial. | Between week 1 and week 26 | 
| Insulin Antibodies (Insulin Degludec Specific, Insulin Detemir Specific, Insulin Aspart Specific and Antibodies Cross-reacting to Human Insulin) | Antibody measurements : the values presented are week 52 (LOCF). The measurement of insulin antibodies after 26 and 52 weeks of treatment was done to fulfil the requirement of monitoring the long term immunogenicity. The unit of measure is percentage bound/total (%B/T) for these antibodies. The Antibodies cross reacting to Human Insulin is abbreviated as X-reacting AB Hu Insulin below) | After 52 weeks of treatment |