A Trial Investigating the Efficacy and Safety of Insulin Detemir Versus Insulin NPH in Combination With Metformin and Diet/Exercise in Children and Adolescents With Type 2 Diabetes Insufficiently Controlled on Metformin With or Without Other Oral Antidiabetic Drug(s) With or Without Basal Insulin

Study Overview
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Brief Summary
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This trial is conducted globally. The aim of the trial is to investigate the efficacy and safety of insulin detemir versus insulin Neutral Protamine Hagedorn (NPH) in combination with the maximum tolerated dose of metformin and diet/exercise on glycaemic control in children and adolescents with type 2 diabetes insufficiently controlled on the maximum tolerated dose of metformin with or without other oral antidiabetic drug(s) with or without basal insulin.

Official Title
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A 26-week Open Label, Randomised, 2-armed, Parallel Group, Multi-centre Trial Investigating Efficacy and Safety of Insulin Detemir Versus Insulin Neutral Protamine Hagedorn in Combination With the Maximum Tolerated Dose of Metformin and Diet/Exercise on Glycaemic Control in Children and Adolescents With Type 2 Diabetes Insufficiently Controlled on the Maximum Tolerated Dose of Metformin ± Other Oral Antidiabetic Drug(s) ± Basal Insulin

Conditions
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Diabetes, Diabetes Mellitus, Type 2

Intervention / Treatment
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* Drug: Insulin detemir
* Drug: Insulin NPH
* Behavioral: Diet/exercise


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Informed consent from the subject or a legally acceptable representative (LAR) and child assent from the subject 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 Male or female, above or equal to 10 years and below or equal to 17 years at the time of signing informed consent/assent Diagnosis of type 2 diabetes mellitus at least 3 months prior to screening Treated with the maximum tolerated stable dose of metformin for at least 3 months prior to screening or have documented complete metformin intolerance HbA1c (glycosylated haemoglobin) above or equal to 7.0% and below or equal to 10.5% (above or equal to 53 mmol/mol and below or equal to 91 mmol/mol) at screening Exclusion Criteria: Maturity onset diabetes of the young (MODY) Fasting C-peptide at screening below 0.6 ng/mL Impaired liver function defined as alanine aminotransferase (ALT) above or equal to 2.5 times upper normal limit Known proliferative retinopathy or maculopathy requiring acute treatment as judged by the investigator Treatment with any medication for the indication of diabetes or obesity other than stated in the inclusion criteria in a period of 3 months before the day of screening

Ages Eligible for Study
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Minimum Age: 10 Years
Maximum Age: 18 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 detemir and diet/exercise<br>Current OADs i.e. metformin or other OADs are continued unchanged | Drug: Insulin NPH<br>* Administered subcutaneously (s.c., under the skin) once or twice daily. The subjects' pre-trial OADs i.e. metformin treatment should continue unchanged during the treatment period.<br>Behavioral: Diet/exercise<br>* Intervention will be performed through family based changes in eating and activity behaviours.<br>|
| Active Comparator: Insulin NPH and diet/exercise<br>Current OADs i.e. metformin or other OADs are continued unchanged | Drug: Insulin detemir<br>* Administered subcutaneously (s.c., under the skin) once or twice daily. The subjects' pre-trial OAD's i.e. metformin treatment should continue unchanged during the treatment period.<br>Behavioral: Diet/exercise<br>* Intervention will be performed through family based changes in eating and activity behaviours.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in HbA1c (Glycosylated Haemoglobin) | Estimated mean change in HbA1c (glycosylated haemoglobin) from baseline to week 26. | week 0, week 26 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Body Weight Standard Deviation Score (SDS) | Change in body weight standard deviation score (SDS) from baseline to week 26. In order to reduce the variability in body weight measurements, SDS were calculated. SDS for weight was derived by comparing the actual measurements with standard growth charts for the United States. Standard values provided by the standard growth charts according to the subject's sex and age at the time of the measurement were used to calculate the SDS. | week 0, week 26 | 
| Proportion of Subjects Achieving HbA1c Below 7.0%, Who Have Not Experienced Any Treatment Emergent Severe Hypoglycaemic Episodes Within the Last 14 Weeks of Treatment. | Proportion of subjects achieving HbA1c <7.0% is presented as percentage of subjects achieving HbA1c <7.0%, who have not experienced any treatment emergent severe hypoglycaemic episodes (an episode requiring assistance of another person to actively administer carbohydrate, glucagon, or take other corrective actions) within the last 14 weeks of treatment. | At week 26 | 
| Proportion of Subjects Achieving HbA1c Below 7.5%, Who Have Not Experienced Any Treatment Emergent Severe Hypoglycaemic Episodes Within the Last 14 Weeks of Treatment | Proportion of subjects achieving HbA1c below 7.5% is presented as percentage of subjects achieving HbA1c <7.5%, who have not experienced any treatment emergent severe hypoglycaemic episodes (an episode requiring assistance of another person to actively administer carbohydrate, glucagon, or take other corrective actions) within the last 14 weeks of treatment. | At week 26 | 
| Total Number of Treatment Emergent Nocturnal (23:00-06:59) Severe or Blood Glucose (BG) Confirmed Symptomatic Hypoglycaemic Episodes | The total number of blood glucose confirmed symptomatic nocturnal (time of onset between 23:00 and 06.59 both inclusive) severe (an episode requiring assistance of another person to actively administer carbohydrate, glucagon, or take other corrective actions) or blood glucose confirmed symptomatic hypoglycaemic episodes (plasma glucose value <3.1 mmol/L [56 mg/dL] with symptoms consistent with hypoglycaemia) experienced by the subjects during the trial. | Weeks 0 - 26 | 
| Total Number of Treatment Emergent Severe or BG Confirmed Symptomatic Hypoglycaemic Episodes | Total number of treatment emergent severe (an episode requiring assistance of another person to actively administer carbohydrate, glucagon, or take other corrective actions) or blood glucose confirmed symptomatic hypoglycaemic episodes (plasma glucose value <3.1 mmol/L [56 mg/dL] with symptoms consistent with hypoglycaemia) experienced by the subjects during the trial. | Weeks 0 - 26 | 
| Incidence of Adverse Events (AEs) | The total number of treatment emergent adverse events (the onset of the adverse event is on or after the first day of trial product administration, and no later than 7 days after the last day of trial product administration) reported during the 26 weeks of treatment. | weeks 0 - 26 |