Comparison of NN5401 Versus Insulin Glargine, Both Combined With Metformin Treatment, in Subjects With Type 2 Diabetes

Study Overview
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Brief Summary
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This trial is conducted in Asia, Europe and the United States of America (USA). The aim of this trial is to compare the efficacy and safety of NN5401 (insulin degludec/insulin aspart (IDegAsp)) with insulin glargine (IGlar), both as add-on to subject's ongoing treatment with metformin + at least one OAD (oral anti-diabetic drug). The main period is registered internally at Novo Nordisk as NN5401-3590 while the extension period is registered as NN5401-3726.

Official Title
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NN5401-3590: A Trial Comparing Efficacy and Safety of NN5401 With Insulin Glargine in Insulin Naive Subjects With Type 2 Diabetes (BOOST™ : START 1) / NN5401-3726: An Extension Trial Comparing Safety and Efficacy of NN5401 With Insulin Glargine in Subjects With Type 2 Diabetes (BOOST™: START 1)

Conditions
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Diabetes, Diabetes Mellitus, Type 2

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


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: For MAIN period (NN5401-3590): Diagnosis of type 2 diabetes mellitus for at least 6 months Insulin naïve subjects Treatment with metformin and at least one other oral antidiabetic drug for at least 3 months before trial start Glycosylated haemoglobin (HbA1c) between 7.5 - 11.0% (both inclusive) Body Mass Index (BMI) no higher than 40.0 kg/m^2 For EXTENSION period (NN5401-3726): Informed consent obtained before any trial-related activities Must have completed the 26-week treatment period (visit 28) in trial NN5401-3590 Exclusion Criteria: For MAIN period (NN5401-3590): Treatment with glucagon like peptide-1 (GLP-1) receptor agonists and/or thiazolidinedione(s) within the last 3 months prior to trial start Cardiovascular disease diagnosed within 6 months before trial start For EXTENSION period (NN5401-3726): Anticipated change in concomitant medication known to interfere significantly with glucose metabolism, such as systemic corticosteroids, beta-blockers, Monoamine oxidase (MAO) inhibitors Anticipated significant lifestyle changes during the trial, e.g. shift work (including permanent night/evening shift workers), as well as highly variable eating habits as judged by the physician) Pregnancy, breast-feeding, the intention of becoming pregnant or not using adequate contraceptive measures according to local requirements

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: IDegAsp OD<br> | Drug: insulin degludec/insulin aspart<br>* Injected s.c. (under the skin) once daily with the breakfast meal. Dose was individually adjusted.<br>|
| Experimental: IGlar OD<br> | Drug: insulin glargine<br>* Injected s.c. (under the skin) once daily. 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 26 Weeks of Treatment | Change from baseline in HbA1c after 26 weeks of treatment. | Week 0, Week 26 | 
| 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 53 + 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 53 + 7 days follow up | 
| Extension Trial (Primary Endpoint): 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 the subject's daily activities. Moderate: marked symptoms, moderate interference with the subject's daily activities. Severe: considerable interference with the 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 hospitalisation/prolongation of existing hospitalisation, persistent/significant disability/incapacity/congenital anomaly/birth defect | Week 0 to Week 53 + 7 days follow up | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Extension Trial (Secondary Endpoint): Change in Glycosylated Haemoglobin (HbA1c) After 52 Weeks of Treatment | Change from baseline in HbA1c after 52 weeks of treatment. | Week 0, Week 53 | 
| Main Trial (Secondary Endpoint): Mean of 9-point Self Measured Plasma Glucose Profile (SMPG) at Week 26 | Mean of SMPG at 26 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 26 |