Efficacy and Safety of FIAsp in a Basal-bolus Regimen Versus Basal Insulin Therapy, Both in Combination With Metformin in Adult Subjects With Type 2 Diabetes

Study Overview
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Brief Summary
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This trial is conducted in Asia, Europe, South America, and the United States of America (USA). The aim of the trial is to investigate efficacy and safety of FIAsp in a basal-bolus regimen versus basal insulin therapy, both in combination with metformin in adult subjects with type 2 diabetes.

Official Title
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Efficacy and Safety of FIAsp in a Basal-bolus Regimen Versus Basal Insulin Therapy, Both in Combination With Metformin in Adult Subjects With Type 2 Diabetes

Conditions
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Diabetes, Diabetes Mellitus, Type 2

Intervention / Treatment
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* Drug: Faster-acting insulin aspart
* Drug: basal insulin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Type 2 diabetes (diagnosed clinically) for at least 6 months prior to the screening visit (Visit 1) Current treatment with once daily insulin detemir, insulin glargine or human isophane insulin, NPH for at least 3 months prior to the screening visit (Visit 1) Current treatment with a) metformin with unchanged dosing for at least 3 months prior to screening (visit 1). The metformin dose must be at least 1000 mg or b) metformin in combination with sulfonylurea (SU) or glinide or Dipeptidyl peptidase-IV inhibitors and/or alpha-glucosidase inhibitors (AGI) with unchanged dosing for at least 3 months prior to screening (visit 1). The metformin dose must be at least 1000 mg HbA1c by central laboratory a) 7.5-9.5% (58 - 80 mmol/mol) (both inclusive) in the metformin group at the screening visit (Visit 1) or b) 7.5-9.0% (58 - 75 mmol/mol) (both inclusive) in the metformin + other oral antidiabetic drug (OAD) (sulphonylurea (SU), glinide, dipeptidyl peptidase-IV (DDP-IV) inhibitors, alpha-glucosidase inhibitors (AGI) combination group at the screening visit (Visit 1) Body mass index (BMI) equal or less than 40.0 kg/m^2 Exclusion Criteria: Any use of bolus insulin, except short-term use due to intermittent illness (no longer than 14 days of consecutive treatment) and not within 3 months prior to the screening visit (Visit 1) Use of Glucagon-like peptide-1 (GLP-1) agonists and/or Thiazolidinediones (TZD) within the last 3 months prior to screening (visit 1) Recurrent severe hypoglycaemia (more than one severe hypoglycaemic event during the last 12 months) or hypoglycaemic unawareness as judged by the Investigator, or hospitalisation for diabetic ketoacidosis during the previous 6 months prior to screening (Visit 1)

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: FIAsp and basal insulin + metformin<br>Subjects will receive FIAsp combined with their pre-trial basal insulin (insulin human, insulin detemir or insulin glargine) treatment in combination with their pre-trial metformin. | Drug: Faster-acting insulin aspart<br>* Administrated subcutaneously (s.c., under the skin) at each main meal.<br>* Other names: NN1218;Drug: basal insulin<br>* Administrated subcutaneously (s.c., under the skin) once daily.<br>|
| Active Comparator: Basal insulin + metformin<br>Subjects will continue their pre-trial basal insulin (insulin human, insulin detemir or insulin glargine) treatment in combination with their pre-trial metformin. | Drug: basal insulin<br>* Administrated subcutaneously (s.c., under the skin) once daily.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in HbA1c | For this endpoint, baseline (week 0) and week 18 data are presented, where week 18 data are the end of trial data containing last available measurements. | Week 0, week 18 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Self-measured Plasma Glucose (SMPG) 7-point Profile: Post Prandial Plasma Glucose (PPG), Overall 2-hour Mean (of Breakfast, Lunch, Main Evening Meal) | For this endpoint the end of trial data containing last available measurements are presented. PPG measurements were recorded by the subjects at 2 hours after each meal (breakfast, lunch and main evening meal) as part of three 7-point profiles (SMPG) prior to the visits. Individual mean meal PPG (post-breakfast, post-lunch, post-main evening meal) was derived from the three measurements. | After 18 weeks of randomised treatment | 
| Self-measured Plasma Glucose (SMPG) 7-point Profile: Prandial Plasma Glucose (PG) Increment, Overall 2-hour Mean (of Breakfast, Lunch, Main Evening Meal) | For this endpoint the end of trial data containing last available measurements are presented. Prandial PG increment for each meal (breakfast, lunch, main evening meal) was derived from the 7-point profiles (SMPG) as the difference between the PPG value 2 hours after each meal and the PG value before each meal. Individual mean meal PPG (post-breakfast, post-lunch, post-main evening meal) was derived from the three measurements. | After 18 weeks of randomised treatment | 
| Change From Baseline in Body Weight | For this endpoint, baseline (week 0) and week 18 data are presented, where week 18 data are the end of trial data containing last available measurements. | Week 0, week 18 | 
| Number of Treatment Emergent Hypoglycaemic Episodes | Plasma glucose (PG) was measured and recorded when a hypoglycaemic episode was suspected. All PG values ≤3.9 mmol/L (70 mg/dL) or >3.9 mmol/L (70 mg/dL) when they occurred in conjunction with hypoglycaemic symptoms were recorded by the subject. Numbers of treatment emergent hypoglycaemic episodes were recorded during 18 weeks of treatment. | Weeks 0-18 | 
| Number of Adverse Events | All adverse events (AEs) described here refer to treatment emergent adverse events (TEAE). A TEAE was defined as an event that had onset date on or after the first day of exposure to randomised treatment and no later than 7 days after the last day of randomised treatment, week 18. | Weeks 0-18 |