Efficacy and Safety of Insulin Degludec/Insulin Aspart in Insulin-naïve Subjects With Type 2 Diabetes Using Two Dosing Regimens

Study Overview
=================
Brief Summary
-----------------
This trial is conducted in Asia and North America. The aim of this trial is to compare the efficacy and safety of insulin degludec/insulin aspart (IDegAsp) once daily in insulin-naïve subjects with type 2 diabetes mellitus when using two different titration algorithms (dose individually adjusted) as add-on to subject's ongoing treatment with metformin.

Official Title
-----------------
A Trial Comparing the Efficacy and Safety of Insulin Degludec/Insulin Aspart Once Daily in Insulin-naïve Subjects With Type 2 Diabetes Mellitus When Using Two Different Titration Algorithms (BOOST™: SIMPLE USE)

Conditions
-----------------
Diabetes, Diabetes Mellitus, Type 2

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


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Type 2 diabetes (diagnosed clinically) for 24 weeks or longer prior to randomisation (visit 2) Insulin naïve subjects (Allowed are: Previous short term insulin treatment no longer than or equal to 14 days in total; Treatment during hospitalisation or during gestational diabetes is allowed for periods longer than 14 days in total) Current treatment: Metformin alone or metformin in any combination of 1 or 2 additional OADs (oral anti-diabetic drug) including an insulin secretagogue (sulfonylurea or glinide), dipeptidyl peptidase IV (DPP-IV) inhibitors, alpha-glucosidase inhibitors or thiazolidinediones (TZDs) - all with unchanged dosing for at least 12 weeks prior to randomisation (visit 2). Metformin dose, alone or in combination (including fixed combination), must be at least 1000 mg daily HbA1c (glycosylated haemoglobin) 7.0-10.0% (both inclusive) BMI (Body Mass Index) below or equal to 45 kg/m^2 Ability and willingness to adhere to the protocol including self measurement of plasma glucose Exclusion Criteria: Treatment with GLP-1 (glucagon like peptide) receptor agonists within the last 12 weeks prior to randomisation (visit 2) Recurrent severe hypoglycaemia (more than one severe hypoglycaemic event during the last 12 months) or hypoglycaemic unawareness as judged by the Investigator (trial physician) Previous participation in this trial. Participation is defined as randomised. Re-screening is allowed once during the recruitment period Known or suspected hypersensitivity to trial products or related products The receipt of any investigational drug within 4 weeks prior to randomisation (visit 2) Anticipated significant lifestyle changes during the study, e.g. shift work (including permanent night/evening shift workers) as well as highly variable eating habits

Ages Eligible for Study
-----------------
Minimum Age: 18 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: IDegAsp Simple<br> | Drug: insulin degludec/insulin aspart<br>* Insulin degludec/insulin aspart injected subcutaneously (under the skin) once daily. Dose individually adjusted.<br>* Other names: IDegAsp;|
| Experimental: IDegAsp Step wise<br> | Drug: insulin degludec/insulin aspart<br>* Insulin degludec/insulin aspart injected subcutaneously (under the skin) once daily. Dose individually adjusted.<br>* Other names: IDegAsp;|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Glycosylated Haemoglobin (HbA1c) | Change from baseline in HbA1c after 26 weeks of treatment. | Week 0, week 26 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Fasting Plasma Glucose (FPG) | Change from baseline in FPG after 26 weeks of treatment. | Week 0, week 26 | 
| Rate of Treatment Emergent Adverse Events (AEs) | Corresponds to rate of AEs per 100 patient years of exposure. Severity assessed by investigator. Mild: no or transient symptoms, no interference with subject's daily activities. Moderate: marked symptoms, moderate interference with subject's daily activities. Severe: considerable interference with subject's daily activities, unacceptable. Serious AE: AE that at any dose results in any of the following: death, a life-threatening experience, in-subject hospitalization/prolongation of existing hospitalisation, persistent/significant disability/incapacity/congenital anomaly/birth defect. | Week 0 to Week 26 + 7 days follow up | 
| Rate of Confirmed Hypoglycaemic Episodes | Rate of confirmed hypoglycaemic episodes per 100 patient years of exposure (PYE). Confirmed hypoglycaemic episodes consisted of severe hypoglycaemia as well as minor hypoglycaemic episodes. Severe hypoglycaemic episodes were defined as requiring assistance to administer carbohydrate, glucagon, or other resuscitative actions. Minor hypoglycaemic episodes were defined as able to treat her/himself and plasma glucose below 3.1 mmol/L. | Week 0 to Week 26 + 7 days follow up | 
| Rate of Nocturnal Confirmed Hypoglycaemic Episodes | Rate of nocturnal confirmed hypoglycaemic episodes per 100 patient years of exposure (PYE). Confirmed hypoglycaemic episodes consisted of severe hypoglycaemia as well as minor hypoglycaemic episodes. Severe hypoglycaemic episodes were defined as requiring assistance to administer carbohydrate, glucagon, or other resuscitative actions. Minor hypoglycaemic episodes were defined as able to treat her/himself and plasma glucose below 3.1 mmol/L. Nocturnal hypoglycaemic episodes were defined as occurring between 00:01 and 05:59 a.m. | Week 0 to Week 26 + 7 days follow up |