Efficacy and Safety of Basal-bolus Therapy, Comparing Stepwise Addition of Insulin Aspart Versus Complete Basal-bolus Regimen

Study Overview
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Brief Summary
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This trial is conducted in Europe, and North and South America. The aim of this clinical trial is to investigate if the two treatments are equally effective.

Official Title
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A Randomised, Controlled, Open Label, Multicentre, Multinational, Treat-to-target Trial Investigating the Efficacy and Safety of Intensification With Addition of Bolus Insulin Aspart in Subjects With Type 2 Diabetes Inadequately Controlled on Basal Insulin With or Without Oral Anti-diabetic Drugs: Step-wise Addition Versus Complete Basal-bolus Therapy

Conditions
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Diabetes Mellitus, Type 2, Diabetes

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


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Type 2 diabetes (diagnosed clinically) for at least 12 months Basal insulin treatment (NPH once or twice daily, insulin glargine once daily or insulin detemir once daily) for at least 6 months HbA1c: 7.0-9.0 % (both inclusive) by central laboratory analysis (one retest analysed at the central laboratory within a week is permitted with the result of the last sample being conclusive) BMI (Body Mass Index) less than 40.0 kg/m^2 Exclusion Criteria: Previous use of pre-mix or bolus insulin (allowed is previous use of bolus insulin only in case of a hospitalisation or a severe condition requiring intermittent use of bolus insulin for less than 14 consecutive days, but not during the last 6 months prior to screening visit (Visit 1) Use of GLP-1 (Glucagon-like peptide-1) receptor agonists or pramlintide within the last 6 months prior to prior to screening visit (Visit 1) Anticipated change in concomitant medication known to interfere significantly with glucose metabolism (e.g. systemic corticosteroids, beta-blockers, MAO (Monoamine oxidase) inhibitors, etc.) Cardiovascular disease, within the last 12 months prior to screening visit (Visit 1), defined as: stroke; decompensated heart failure New York Heart Association (NYHA) class III or IV; myocardial infarction; unstable angina pectoris; or coronary arterial bypass graft or angioplasty Uncontrolled treated/untreated severe hypertension (systolic blood pressure sitting at least 180 millimetre (mm) mercury (Hg) and/or diastolic blood pressure at least 100 mmHg). For Argentina: systolic blood pressure sitting at least 150 mmHg and/or diastolic blood pressure at least 90 mmHg Impaired liver function, defined as ALAT (Alanine aminotransferase) at least 2.5 times upper limit of normal (one retest analysed at the central laboratory within a week is permitted with the result of the last sample being conclusive) Impaired renal function defined as serum creatinine above 135 micromol/L (above 1.5 mg/dL) for males and above 110 micromol/L (above 1.2 mg/dL) for females; and, if required by the locally applicable metformin label, glomerular filtration rate below 60 ml/min, calculated by the Cockroft & Gault formula). One retest within a week is permitted with the result of the last sample being conclusive Recurrent severe hypoglycaemia (more than 1 severe hypoglycaemic episode, during the last 12 months) or hypoglycaemic unawareness as judged by the Investigator or hospitalisation for diabetic ketoacidosis during the previous 6 months Proliferative retinopathy or maculopathy requiring treatment according to the Investigator Treatment with OADs (Oral anti-diabetic drug) contraindicated or unapproved for combination treatment with insulin (according to local OAD label)

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: Step-wise<br> | Drug: insulin aspart<br>* Insulin aspart added stepwise according to the largest meal following an evaluation of HbA1c. Doses individually adjusted.<br>Drug: insulin detemir<br>* Insulin detemir as basal insulin, adminstered once daily. Doses individually adjusted.<br>|
| Active Comparator: Basal-bolus<br> | Drug: insulin aspart<br>* Insulin aspart added before each main meal. Doses individually adjusted.<br>Drug: insulin detemir<br>* Insulin detemir as basal insulin, adminstered once daily. Doses individually adjusted.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Glycosylated Haemoglobin (HbA1c) From Baseline to Week 32 | Estimated mean change from baseline in HbA1c after 32 Weeks of treatment | Week 0, Week 32 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Glycosylated Haemoglobin (HbA1c) From Baseline to Week 10 | Estimated mean change from baseline in HbA1c after 10 Weeks of treatment | Week 0, Week 10 | 
| Change in Glycosylated Haemoglobin (HbA1c) From Baseline to Week 21 | Estimated mean change from baseline in HbA1c after 21 Weeks of treatment | Week 0, Week 21 | 
| Proportion of Subjects Reaching Glycosylated Haemoglobin (HbA1c) Below 7.0% at Week 10 | Proportion of subjects reaching HbA1c below 7.0% at Week 10 | Week 10 | 
| Proportion of Subjects Reaching Glycosylated Haemoglobin (HbA1c) Below 7.0% at Week 21 | Proportion of subjects reaching HbA1c below 7.0% at Week 21 | Week 21 | 
| Proportion of Subjects Reaching Glycosylated Haemoglobin (HbA1c) Below 7.0% at Week 32 | Proportion of subjects reaching HbA1c below 7.0% at Week 32 | Week 32 | 
| Fasting Plasma Glucose (FPG) at Week 10 | Mean FPG at Week 10 | Week 10 | 
| Fasting Plasma Glucose (FPG) at Week 21 | Mean FPG at Week 21 | Week 21 | 
| Fasting Plasma Glucose (FPG) at Week 32 | Estimated Mean FPG at Week 32 | Week 32 | 
| Mean Plasma Glucose Increment Over 3 Meals (Breakfast, Lunch and Dinner) at Week 10 | Mean plasma glucose increment over 3 meals (breakfast, lunch and dinner) at Week 10 | Week 10 | 
| Mean Plasma Glucose Increment Over 3 Meals (Breakfast, Lunch and Dinner) at Week 21 | Mean plasma glucose increment over 3 meals (breakfast, lunch and dinner) at Week 21 | Week 21 | 
| Mean Plasma Glucose Increment Over 3 Meals (Breakfast, Lunch and Dinner) at Week 32 | Estimated mean plasma glucose increment over 3 meals (breakfast, lunch and dinner) at Week 32 | Week 32 | 
| Body Weight at Week 32 | Estimated mean body weight after 32 Weeks of treatment | Week 32 | 
| Body Mass Index (BMI) at Week 32 | Estimated mean BMI after 32 Weeks of treatment | Week 32 | 
| Hypoglycaemic Episodes (Rate of All Treatment Emergent Hypoglycaemia Episodes) | A hypoglycaemic episode was defined as treatment emergent if the onset of the episode was on or after the first day of exposure to randomised treatment and no later than 1 day after the last day of randomised treatment. | Week 0 to Week 32 |