A Trial Investigating the Efficacy and Safety of Insulin Degludec/Insulin Aspart Once Daily Plus Insulin Aspart for the Remaining Meals Versus Insulin Detemir Once or Twice Daily Plus Meal Time Insulin Aspart in Children and Adolescents With Type 1 Diabetes Mellitus

Study Overview
=================
Brief Summary
-----------------
This trial is conducted in Asia, Europe and North and South America. The aim of the trial is to investigate the efficacy and safety of insulin degludec/insulin aspart once daily plus insulin aspart for the remaining meals in children and adolescents with type 1 diabetes mellitus.

Official Title
-----------------
A Trial Investigating the Efficacy and Safety of Insulin Degludec/Insulin Aspart Once Daily Plus Insulin Aspart for the Remaining Meals Versus Insulin Detemir Once or Twice Daily Plus Meal Time Insulin Aspart in Children and Adolescents With Type 1 Diabetes Mellitus

Conditions
-----------------
Diabetes, Diabetes Mellitus, Type 1

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


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: - Informed consent obtained before any trial related activities. Trial related activities are any procedures that are carried out as part of the trial, including activities to determine suitability for the trial - Subjects diagnosed with type 1 diabetes mellitus - HbA1c below or equal to 11.0% Exclusion Criteria: - Known hypoglycaemic unawareness or recurrent severe hypoglycaemic events as judged by the investigator - More than 1 episode of diabetic ketoacidosis requiring hospitalisation within the last 3 months prior to Visit 1 (Screening) - Any chronic disorder or significant concomitant disease, which in the investigator's opinion might jeopardise the subject's safety or compliance with the protocol

Ages Eligible for Study
-----------------
Minimum Age: 1 Year
Maximum Age: 17 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

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/insulin aspart<br>* Administered subcutaneously (s.c., under the skin) once daily with a main meal. Dose individually adjusted.<br>Drug: insulin aspart<br>* Administered s.c. with the remaining meals. Dose individually adjusted.<br>|
| Active Comparator: Insulin detemir<br> | Drug: insulin detemir<br>* Administered s.c. once or twice daily. Dose individually adjusted. Subjects will continue with their pre-trial dosing scheme (once (OD) or twice daily (BID)) and will be allowed to switch from OD to BID dosing.<br>Drug: insulin aspart<br>* Administered s.c. at meal-times. Dose individually adjusted.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in HbA1c (Glycosylated Haemoglobin) (%) | Percentage point change in glycosylated haemoglobin A1c (HbA1c) from baseline (week 0) to 16 Weeks. Change from baseline summary statistics at week 16 contains only those who had both baseline and week 16 assesment. | Week 0 to week 16 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Fasting Plasma Glucose | Change from baseline in FPG after 16 weeks of treatment. Change from baseline summary statistics at week 16 contains only those who had both baseline and week 16 assesment. | week 0, week 16 | 
| Incidence of Treatment Emergent Adverse Events (TEAEs) | A Treatment Emergent Adverse Event (TEAE) was defined as an event with onset date on or after the first day of exposure to randomised treatment and no later than 7 days after the last day on randomised treatment. | After 16 weeks of treatment | 
| Number of Treatment Emergent Confirmed Hypoglycaemic Episodes (Plasma Glucose (PG) Below 3.1mmol/L (56mg/dL) or Severe Hypoglycaemia) | Treatment emergent hypoglycaemic episodes (PG < 3.1 mmol/L (56 mg/dL) or severe hypoglycaemia). Confirmed hypoglycaemic episodes were defined as episodes that were either: Severe (i.e. the child is having altered mental status and cannot assist in their care, is semiconscious or unconscious or in coma with or without convulsions and may require parenteral therapy (glucagon or i.v. glucose), or An episode biochemically confirmed by PG value of <3.1 mmol/L (56 mg/dL), with or without symptoms consistent with hypoglycaemia. | After 16 weeks of treatment | 
| Number of Treatment Emergent Nocturnal Confirmed Hypoglycaemic Episodes | The confirmed hypoglycaemic episodes occurring between 23:00 and 07:00 were considered for this endpoint | After 16 weeks of treatment | 
| Number of Hyperglycaemic Episodes (PG Above 14.0 mmol/L (250 mg/dL) Where Subject Looks/Feels Ill | The episode of hyperglycaemia was noted when the glucose measurement was 14.0mmol/L or above and the subject looked /felt ill. | After 16 weeks of treatment | 
| Number of Hyperglycaemic Episodes (PG Above 14.0 mmol/L (250 mg/dL) Where Subject Looks/Feels Ill With Ketosis (Blood Ketones Above 1.5 mmol/L) | The episode of hyperglycaemia was noted when the glucose measurement was 14.0mmol/L or above and the subject looked /felt ill. The ketone meaurement involved an additional finger prick and ketosis was considered present if blood ketones were higher than 1.5mmol/L | After 16 weeks of treatment |