Comparison of Two NN1250 Formulations Versus Insulin Glargine, 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 Africa, Asia and North America. The aim of this trial is to compare two insulin degludec (NN1250, SIBA) formulations with each other and with insulin glargine, 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, Four-armed, Treat-to-target, Parallel-group Trial Comparing SIBA D Once Daily, SIBA E Once Daily, SIBA D Monday, Wednesday and Friday and Insulin Glargine Once Daily, 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 glargine
* Drug: insulin degludec
* Drug: insulin degludec
* Drug: insulin degludec
* 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 maximeum 14 days within the last 3 months) Treatment with one or two oral anti-diabetic drug (OADs): metformin, sulphonylurea (SU) (or 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 the summary of product characteristics (SPC) or locally approved PI HbA1c 7.0-11.0 % (both inclusive) Body Mass Index (BMI) 23-42 kg/m^2 [lb/in^2 x 703] (both inclusive) Exclusion Criteria: Metformin contraindication according to local practice Thiazolidinedione (TZD) treatment within previous three 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) three 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 drug

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: SIBA (D)<br> | Drug: insulin degludec<br>* Formulation D: Treat-to-target dose titration scheme, s.c. injection, once daily<br>Drug: metformin<br>* Tablets, 1500-2000 mg/day<br>|
| Experimental: SIBA (E)<br> | Drug: insulin degludec<br>* Formulation E: Treat-to-target dose titration scheme, s.c. injection, once daily<br>Drug: metformin<br>* Tablets, 1500-2000 mg/day<br>|
| Experimental: SIBA (D) M, W, F<br> | Drug: insulin degludec<br>* Formulation D: Treat-to-target dose titration scheme, s.c. injection, 3 times weekly<br>Drug: metformin<br>* Tablets, 1500-2000 mg/day<br>|
| Active Comparator: IGlar<br> | Drug: insulin glargine<br>* Treat-to-target dose titration scheme, s.c. injection.<br>Drug: metformin<br>* Tablets, 1500-2000 mg/day<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) | 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 | 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) | Mean values at Week -4 and at Week 16 | Week -4, Week 16 | 
| Laboratory Safety Parameters (Biochemistry): Aspartate Aminotransferase (ASAT) | Mean values at Week -4 and at Week 16 | Week -4, Week 16 | 
| Laboratory Safety Parameters (Biochemistry): Serum Creatinine | Mean values at Week -4 and at Week 16 | Week -4, Week 16 | 
| Vital Signs: Diastolic Blood Pressure (BP) | Mean values at baseline (Week 0) and at Week 16 | Week 0, Week 16 | 
| Vital Signs: Systolic Blood Pressure (BP) | Mean values at baseline (Week 0) and at Week 16 | Week 0, Week 16 | 
| Vital Signs: Pulse | Mean values at baseline (Week 0) and at Week 16 | Week 0, Week 16 | 
| Physical Examination | Physical examination was performed at screening (Week -4), randomisation (Week 0) 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 0, Week 8, Week 16 |