Comparison of Two NN5401 Formulations Versus Biphasic Insulin Aspart 30, All in Combination With Metformin in Subjects With Type 2 Diabetes

Study Overview
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Brief Summary
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This trial is conducted in Europe. The aim of this trial is to compare two NN5401 (Soluble Insulin Analogue Combination [SIAC], insulin degludec/insulin aspart) formulations with each other and with biphasic insulin aspart 30, all in combination with metformin in insulin naive subjects with type 2 diabetes.

Official Title
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A 16 Week Randomised, Open Labelled, 3-armed, Parallel Group, Treat-to-target Trial Comparing Twice Daily (BID) Injections of SIAC 30 (B), SIAC 45 (B) and NovoMix®30, All in Combination With Metformin in Subjects With Type 2 Diabetes Failing on OAD Treatment

Conditions
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Diabetes, Diabetes Mellitus, Type 2

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


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 procedure that would not have been performed during normal management of the subject.) Insulin naïve type 2 diabetes subjects (as diagnosed clinically) for at least 3 months (no previous insulin treatment or previous short term insulin treatment maximum 14 days within the last 3 months) Treatment with one or two oral anti-diabetic drugs (OADs): metformin, sulfonylurea, other insulin secretagogue (e.g. repaglinide, nateglinide), alpha-glucosidase inhibitors for at least 2 months at a stable maximally tolerated dose or at least half maximally allowed dose according to locally approved summary of product characteristics (SPC) HbA1c, 7.0-11.0 % (both inclusive) Body Mass Index (BMI), 25.0-37.0 kg/m^2 (both inclusive) Exclusion Criteria: Metformin contraindication according to local practice Thiazolidinedione (TZD) treatment within previous 3 months prior to Visit 1 Any systemic treatment with products, which in the investigator's opinion could interfere with glucose or lipid metabolism (e.g. systemic corticosteroids) within 3 months prior to randomisation Subject has a clinically significant, active (during the past 12 months) disease of the gastrointestinal, pulmonary, neurological, genitourinary, or haematological system (except for conditions associated with type 2 diabetes) that, in the opinion of the investigator, may confound the results of the trial or pose additional risk in administering trial product

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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: SIAC 30 (B)<br> | Drug: insulin degludec/insulin aspart<br>* Formulation B: Treat-to-target dose titration scheme, injection s.c., twice daily<br>Drug: metformin<br>* Tablets, 1500-2000 mg/daily<br>|
| Experimental: SIAC 45 (B)<br> | Drug: insulin degludec/insulin aspart<br>* Formulation B: Treat-to-target dose titration scheme, injection s.c., twice daily<br>Drug: metformin<br>* Tablets, 1500-2000 mg/daily<br>|
| Active Comparator: BIAsp 30<br> | Drug: biphasic insulin aspart<br>* Treat-to-target dose titration scheme, injection s.c., twice daily<br>Drug: metformin<br>* Tablets, 1500-2000 mg/daily<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Glycosylated Haemoglobin (HbA1c) | Change from baseline in HbA1c after 16 weeks of treatment | Week 0, Week 16 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean of 9-point Self Measured Plasma Glucose Profile (SMPG) | Estimate of the overall mean of SMPG after 16 weeks of treatment. Plasma glucose measured: before breakfast, 120 minutes after start of breakfast, before lunch, 120 minutes after start of lunch, before dinner, 120 minutes after start of dinner, before bedtime, at 4 am and before breakfast. | Week 16 | 
| Rate of Major and Minor Hypoglycaemic Episodes | Observed rate of major and minor hypoglycaemic episodes per 100 patient years of exposure (PYE). Major if unable to treat her/himself. Minor if able to treat her/himself and plasma glucose below 3.1 mmol/L. | Week 0 to Week 16 + 5 days follow up | 
| Rate of Nocturnal Major and Minor Hypoglycaemic Episodes | Rate of nocturnal major and minor hypoglycaemic episodes per 100 patient years of exposure (PYE). Major if unable to treat her/himself. Minor if able to treat her/himself and plasma glucose below 3.1 mmol/L. Episodes were defined as nocturnal if the time of onset was between 23:00 (included) and 05:59 (included). | Week 0 to Week 16 + 5 days follow up | 
| 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 16 + 5 days follow up | 
| Laboratory Safety Parameters (Biochemistry): Alanine Aminotransferase (ALAT) | Laboratory values at screening (Week -4) and at Week 16 | Week -4, Week 16 | 
| Laboratory Safety Parameters (Biochemistry): Aspartate Aminotransferase (ASAT) | Laboratory values at screening (Week -4) and at Week 16 | Week -4, Week 16 | 
| Laboratory Safety Parameters (Biochemistry): Serum Creatinine | Laboratory values at screening (Week -4) and at Week 16 | Week -4, Week 16 | 
| Vital Signs: Diastolic Blood Pressure (BP) | Values at baseline (Week 0) and at Week 16 | Week 0, Week 16 | 
| Vital Signs: Systolic Blood Pressure (BP) | Values at baseline (Week 0) and at Week 16 | Week 0, Week 16 | 
| Vital Signs: Pulse | Values at baseline (Week 0) and at Week 16 | Week 0, Week 16 | 
| Physical Examination | Physical examination was performed at screening (week -4), and after 8 and 16 weeks of treatment. If any new findings or deterioration in previous findings were observed during the trial, these were recorded as AEs and are therefore not presented separately as no analysis was performed. | Week -4, Week 8, Week 16 |