A Study to Compare Insulin Intensification of Biphasic Insulin Aspart 30 and Insulin Analogues (Insulin Glargine and Insulin Aspart) in Insulin naïve Type 2 Diabetic Patients

Study Overview
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Brief Summary
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This trial is conducted globally. The aim of this trial is to compare stepwise insulin intensification of biphasic insulin aspart (BIAsp) 30 and basal-bolus therapy with insulin glargine and insulin aspart in insulin naïve type 2 diabetic patients inadequately controlled on oral anti-diabetic therapy.

Official Title
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A 32-week Randomised, Multinational, Treat-to-target, Open Label, Parallel Group Comparison of Stepwise Insulin Intensification of Biphasic Insulin Aspart (BIAsp) 30 and Basal-bolus Therapy With Insulin Glargine and Insulin Aspart in Insulin naïve Type 2 Diabetic Patients Inadequately Controlled on Oral Anti-diabetic Therapy

Conditions
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Diabetes, Diabetes Mellitus, Type 2

Intervention / Treatment
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* Drug: biphasic insulin aspart 30
* Drug: insulin glargine
* Drug: insulin aspart


Participation Criteria
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Eligibility Criteria
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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 Male or female, age at least 18 years at the time of signing informed consent Type 2 diabetes subjects clinically diagnosed at least 6 months prior to screening Treatment with stable daily dose (for at least 90 days prior to screening) of: - Metformin (equal or above 1000 mg or maximum tolerated dose documented in the patient medical record) and - Sulfonylurea - and willing to discontinue any other oral antidiabetic drugs containing insulin secretagogues, DPP4i (dipeptidyl peptidase-4 inhibitor), SGLT2 (sodium glucose co-transporter 2), colesevelam, bromocriptin and/or combination products at randomisation Insulin-naïve. Short term insulin treatment for acute illnesses for a total of 14 days or less is allowed as is prior insulin treatment for gestational diabetes HbA1c (glycosylated haemoglobin) 7.0-9.5 % (both inclusive) analysed by central laboratory Willing to consume 3 main meals daily (morning, mid-day and evening) throughout the entire trial. The definition for 'main meal' will be according to the investigator's discretion Exclusion Criteria: Anticipated initiation or change in concomitant medications known to affect weight or glucose metabolism, in excess of 14 days (i.e. sibutramine, orlistat, thyroid hormones, systemic corticosteroids and other weight loss/modifying agents) Impaired liver function, defined as ALT (alanine aminotransferase) at least 2.5 times upper limit of normal (central laboratory value measured at screening visit) Inadequately treated high blood pressure defined as Class 2 hypertension or higher (i.e. systolic blood pressure equal to or above 160 mm Hg or diastolic equal to or above 100 mm Hg) in accordance with the National High Blood Pressure Education Program, 7th Joint National Committee1 and ESH/ESC 2013 Guidelines2 Within the past 180 days prior to randomisation, any of the following: Myocardial Infarction, stroke or hospitalization for unstable angina and /or transient ischemic attack

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: BIAsp<br> | Drug: biphasic insulin aspart 30<br>* Injected s.c./subcutaneously once daily with the largest meal Subjects should continue their pre-trial metformin and sulfonylurea dosages all throughout the trial while other oral antidiabetic drugs will be discontinued.<br>|
| Active Comparator: IGlar + IAsp<br> | Drug: insulin glargine<br>* Injected s.c./subcutaneously once daily at the same time every day, with the possibility of treatment intensification with insulin aspart (Basal-bolus arm) Subjects should continue their pre-trial metformin and sulfonylurea dosages all throughout the trial while other oral antidiabetic drugs will be discontinued.<br>Drug: insulin aspart<br>* Injected s.c./subcutaneously once daily.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in HbA1c (Glycosylated Haemoglobin) | Change in HbA1c from baseline (week 0) to week 32. | Week 0, week 32 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| HbA1c Below 7.0% Without Severe Hypoglycaemic Episodes | Percentage of subjects with HbA1c below 7.0% after 32 weeks of randomised treatment without treatment emergent severe hypoglycaemic episodes during the last 12 weeks of treatment. Subjects withdrawn before 32 weeks were handled as non-responders. Severe hypoglycaemic episode was defined as an episode requiring assistance of another person to actively administer carbohydrate, glucagon, or take other corrective actions. Plasma glucose (PG) concentrations may not be available during an event, but neurological recovery following the return of PG to normal is considered sufficient evidence that the event was induced by a low PG concentration. | After 32 weeks of treatment (yes/no) | 
| Number of Treatment Emergent Hypoglycaemic Episodes Classified According to the American Diabetes Association (ADA) and the Novo Nordisk Definitions | Hypoglycaemic episodes were classified as severe, Asymptomatic, Documented symptomatic, Pseudo, and Probable symptomatic as per ADA classification. As symptoms of hypoglycaemia occur below a PG level of 3.1 mmol/L, (56 mg/dL) Novo Nordisk classification included hypoglycaemia with plasma glucose (PG) levels below 3.1 mmol/L (56 mg/dL) in the definition of blood glucose confirmed hypoglycaemia. Hence, Novo Nordisk classification included following types of hypoglycaemia in addition to ADA classification: Severe hypoglycaemia, Symptomatic blood glucose confirmed hypoglycaemia, Asymptomatic blood glucose confirmed hypoglycaemia, Severe or blood glucose confirmed symptomatic hypoglycaemia, Blood glucose confirmed hypoglycaemia, and Severe or blood glucose confirmed hypoglycaemia. Reported data represents total of all hypoglycaemic episodes. | Weeks 0-32 | 
| Total Daily Insulin Dose | Total daily insulin dose in the basal bolus treatment group and in BIAsp 30 treatment group at each week of each treatment. | Weeks 0-32 |