A Randomised Trial Comparing Efficacy and Safety After Intensification With Either Insulin Aspart Once Daily as add-on or Changing to Basal Bolus Treatment With Insulin Degludec and Insulin Aspart in Subjects With Type 2 Diabetes Previously Treated With Insulin Degludec/Insulin Aspart Twice Daily

Study Overview
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Brief Summary
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This trial is conducted globally. The aim of the trial is to compare efficacy of insulin degludec/insulin aspart (IDegAsp) twice daily (BID) + insulin aspart (IAsp) once daily (OD) versus basal bolus with insulin degludec (IDeg) OD + IAsp three times a day (TID) in controlling glycaemia by evaluating glycosylated haemoglobin (HbA1c). The trial is an extension to trial NN5401-3941 (NCT01680341).

Official Title
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A Randomised Trial Comparing Efficacy and Safety After Intensification With Either Insulin Aspart Once Daily as add-on or Changing to Basal Bolus Treatment With Insulin Degludec and Insulin Aspart in Subjects With Type 2 Diabetes Previously Treated With Insulin Degludec/Insulin Aspart Twice Daily (BOOST®: INTENSIFY BID)

Conditions
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Diabetes, Diabetes Mellitus, Type 2

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


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: HbA1c equal to or above 7.0% measured after 26 weeks of treatment in NN5401-3941 (NCT01680341), by central laboratory Exclusion Criteria: Uncontrolled or untreated severe hypertension defined as systolic blood pressure equal to or above 180 mmHg and/or diastolic blood pressure equal to or above 100 mmHg Impaired liver function, defined as alanine aminotransferase (ALAT) or aspartate aminotransferase (ASAT) equal to or above 2.5 times upper limit of normal Impaired renal function defined as serum-creatinine equal to or above 125 micromol/L (equal to or above 1.4 mg/dL) for males and equal to or above 110 micromol/L (equal to or above 1.3 mg/dL) for females

Ages Eligible for Study
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Minimum 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: IDegAsp BID + IAsp OD<br> | Drug: insulin degludec/insulin aspart<br>* For subcutaneous (s.c., under the skin) administration twice daily in combination with up to 2 oral antidiabetic drugs (OADs- dose and dosing frequency of OAD should remain unchanged).<br>Drug: insulin aspart<br>* For subcutaneous (s.c., under the skin) administration once daily. Dose of IDegAsp and IAsp are individually adjusted.<br>|
| Experimental: IDeg OD + IAsp TID<br> | Drug: insulin degludec<br>* For subcutaneous (s.c., under the skin) administration once daily in combination with up to 2 oral antidiabetic drugs (OADs- dose and dosing frequency of OAD should remain unchanged).<br>Drug: insulin aspart<br>* For subcutaneous (s.c., under the skin) administration three times a day. Dose of IDeg and IAsp are 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) | Change from baseline in HbA1c after 26 weeks of treatment | Week 0, week 26 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Treatment Emergent Adverse Events (TEAEs) | A treatment emergent adverse event was defined as an event that had onset date on or after the first day of trial product administration, and no later than 7 days after the last dose of the trial product. | During 26 weeks of treatment | 
| Number of Treatment Emergent Hypoglycaemic Episodes | Confirmed hypoglycaemic episodes were defined as episodes that are either: severe (i.e., an episode requiring assistance of another person to actively administer carbohydrate, glucagon, or other resuscitative actions) or biochemically confirmed by a PG value of <3.1 mmol/L (56 mg/dL), with or without symptoms consistent with hypoglycaemia. | During 26 weeks of treatment | 
| Number of Treatment Emergent Nocturnal (00:01-05:59) Confirmed Hypoglycaemic Episodes | Hypoglycaemic episodes were defined as nocturnal if the time of onset was between 00:01 and 05:59 hours inclusive. Confirmed hypoglycaemic episodes were defined as severe hypoglycaemic episodes and/or a measured PG below 3.1 mmol/L (below 56 mg/dL). | During 26 weeks of treatment | 
| Change From Baseline in Fasting Plasma Glucose (FPG) | Change from baseline in FPG after 26 weeks of treatment. FPG was analysed on blood samples from fasting subjects which were analysed centrally. | Week 0, week 26 |