Comparison of NN1250 With Insulin Glargine Plus Insulin Aspart With/Without Metformin and With/Without Pioglitazone in Type 2 Diabetes

Study Overview
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Brief Summary
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This trial is conducted in Africa, Asia, Europe, and the United States of America (USA). The aim of this clinical trial is to compare NN1250 (insulin degludec (IDeg)) with insulin glargine (IGlar) plus insulin aspart (IAsp) with/without metformin and with/without pioglitazone in subjects with type 2 diabetes (main period) followed by investigating the long-term safety in terms of comparing NN1250 with insulin glargine plus insulin aspart with or without metformin and with or without pioglitazone in subjects with type 2 diabetes. All oral anti-diabetic drug (OAD) treatment will be discontinued, if applicable, when trial participant enters the trial (NN1250-3582) with the exception of metformin and pioglitazone. Subjects who consent to participate in the extension trial (NN1250-3667) will continue to receive the treatment to which they were randomly allocated in the 52 week trial NN1250-3582. The main period is registered internally at Novo Nordisk as NN1250-3582 while the extension period is registered as NN1250-3667.

Official Title
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NN1250-3582: A 52-week Randomised, Controlled, Open Label, Multicentre, Multinational Treat-to-target Trial Comparing Efficacy and Safety of SIBA and Insulin Glargine Both Administered Once Daily in a Basal-bolus Regimen With Insulin Aspart as Mealtime Insulin ± Treatment With Metformin, ± Pioglitazone in Subjects With Type 2 Diabetes Currently Treated With Insulin Qualifying for Intensified Treatment/NN1250-3667: An Extension Trial to NN1250-3582 Comparing Safety and Efficacy of NN1250 and Insulin Glargine, Both With Insulin Aspart as Meal-time Insulin ± OADs in Type 2 Diabetes (BEGIN™: BB)

Conditions
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Diabetes, Diabetes Mellitus, Type 2

Intervention / Treatment
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* Drug: insulin degludec
* Drug: insulin glargine
* Drug: insulin aspart


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: For MAIN period (NN1250-3582): Type 2 diabetes mellitus for at least 6 months Ongoing daily treatment with insulin (premix, self-mix, basal only, basal bolus) for at least 3 months with/without oral anti-diabetics drug (OAD) prior to trial start HbA1c 7.0-10.0 % (both inclusive) Body Mass Index (BMI) below or equal to 40.0 kg/m^2 For EXTENSION period (NN1250-3667): Completion of the 52 week treatment period in NN1250-3582 Exclusion Criteria: For MAIN period (NN1250-3582): Treatment with other insulin regimens than premix, self-mix, basal only, basal bolus within 3 months Cardiovascular disease within the last 6 months Uncontrolled treated/untreated severe hypertension Pregnancy, breast-feeding, the intention of becoming pregnant or not using adequate contraceptive measures Cancer and medical history of cancer

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: IDeg OD<br> | Drug: insulin degludec<br>* Injected subcutaneously (under the skin) with main evening meal. Dose was individually adjusted.<br>Drug: insulin aspart<br>* Injected subcutaneously (under the skin) at each main meal. Dose was individually adjusted.<br>|
| Active Comparator: IGlar OD<br> | Drug: insulin glargine<br>* Injected subcutanoeusly (under the skin) according to approved label. Dose was individually adjusted.<br>Drug: insulin aspart<br>* Injected subcutaneously (under the skin) at each main meal. Dose was individually adjusted.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Main Trial (Primary Endpoint): Change in Glycosylated Haemoglobin (HbA1c) After 52 Weeks of Treatment | Change from baseline in HbA1c after 52 weeks of treatment | Week 0, Week 52 | 
| Extension Trial (Primary Endpoint): Rate of Confirmed Hypoglycaemic Episodes | Rate of confirmed hypoglycaemic episodes per 100 patient years of exposure (PYE). Confirmed hypoglycaemic episodes consisted of severe hypoglycaemia as well as minor hypoglycaemic episodes. Severe hypoglycaemic episodes are defined as requiring assistance to administer carbohydrate, glucagon, or other resuscitative actions. Minor hypoglycaemic episodes are defined as able to treat her/himself and plasma glucose below 3.1 mmol/L. | Week 0 to Week 78 + 7 days follow up | 
| Extension Trial (Primary Endpoint): Rate of Nocturnal Confirmed Hypoglycaemic Episodes | Rate of confirmed hypoglycaemic episodes per 100 patient years of exposure (PYE). Confirmed hypoglycaemic episodes consisted of severe hypoglycaemia as well as minor hypoglycaemic episodes. Severe hypoglycaemic episodes are defined as requiring assistance to administer carbohydrate, glucagon, or other resuscitative actions. Minor hypoglycaemic episodes are defined as able to treat her/himself and plasma glucose below 3.1 mmol/L. Nocturnal hypoglycaemic episodes are defined as occurring between 00:01 and 05:59 a.m. | Week 0 to Week 78 + 7 days follow up | 
| Rate of Treatment Emergent Adverse Events (AEs) | Corresponds to rate of AEs per 100 patient years of exposure. Mild AEs: no or transient symptoms, no interference with subject's daily activities. Moderate AEs: marked symptoms, moderate interference with subject's daily activities. Severe AEs: considerable interference with subject's daily activities, unacceptable. Serious adverse event (SAE): 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 78 + 7 days follow up | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Extension Trial (Secondary Endpoint): Change in Glycosylated Haemoglobin (HbA1c) After 78 Weeks of Treatment | Change from baseline in HbA1c after 78 weeks of treatment | Week 0, Week 78 | 
| Main Trial (Secondary Endpoint): Mean of 9-point Self Measured Plasma Glucose Profile (SMPG) at Week 52 | Mean of 9-point SMPG at 52 weeks of treatment. Plasma glucose measured: before breakfast, 90 minutes after start of breakfast, before lunch, 90 minutes after start of lunch, before dinner, 90 minutes after start of dinner, bedtime, at 4 am and before breakfast. | Week 52 | 
| Extension Trial (Secondary Endpoint): Mean of 9-point Self Measured Plasma Glucose Profile (SMPG) at Week 78 | Mean of the SMPG at 78 weeks of treatment. Plasma glucose measured: before breakfast, 90 minutes after start of breakfast, before lunch, 90 minutes after start of lunch, before dinner, 90 minutes after start of dinner, bedtime, at 4 am, before breakfast. | Week 78 | 
| Main Trial (Secondary Endpoint): Rate of Confirmed Hypoglycaemic Episodes | Rate of confirmed hypoglycaemic episodes per 100 patient years of exposure (PYE). Confirmed hypoglycaemic episodes consisted of severe hypoglycaemia as well as minor hypoglycaemic episodes. Severe hypoglycaemic episodes are defined as requiring assistance to administer carbohydrate, glucagon, or other resuscitative actions. Minor hypoglycaemic episodes are defined as able to treat her/himself and plasma glucose below 3.1 mmol/L. | Week 0 to Week 52 + 7 days follow up | 
| Main Trial (Secondary Endpoint): Rate of Nocturnal Confirmed Hypoglycaemic Episodes | Rate of confirmed hypoglycaemic episodes per 100 patient years of exposure (PYE). Confirmed hypoglycaemic episodes consisted of severe hypoglycaemia as well as minor hypoglycaemic episodes. Severe hypoglycaemic episodes are defined as requiring assistance to administer carbohydrate, glucagon, or other resuscitative actions. Minor hypoglycaemic episodes are defined as able to treat her/himself and plasma glucose below 3.1 mmol/L. Nocturnal hypoglycaemic episodes are defined as occurring between 00:01 and 05:59 a.m. | Week 0 to Week 52 + 7 days follow up |