Comparison of NN5401 Plus Insulin Aspart With Insulin Detemir Plus Insulin Aspart in Type 1 Diabetes

Study Overview
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Brief Summary
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This trial is conducted in Europe, Oceania, and the United States of America (USA). The aim of this clinical trial is to compare NN5401 (insulin degludec/insulin aspart (IDegAsp)) with insulin detemir (IDet) plus insulin aspart in patients with type 1 diabetes (main period) followed by the extension period comparing the long-term safety of NN5401 plus insulin aspart with insulin detemir plus insulin aspart. The main period is registered internally at Novo Nordisk as NN5401-3594 while the extension period is registered as NN5401-3645.

Official Title
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NN5401-3594: A 26-week, Open-labelled, Two-arm, Parallel, Randomised Trial Comparing Efficacy and Safety of NN5401 Once Daily Plus Insulin Aspart vs. Basal-bolus Treatment With Insulin Detemir Plus Insulin Aspart in Subjects With Type 1 Diabetes / NN5401-3645: An Extension Trial Comparing Safety and Efficacy of NN5401 Plus Meal-time Insulin Aspart for the Remaining Meals With Insulin Detemir Plus Meal-time Insulin Aspart in Type 1 Diabetes (BOOST™: T1)

Conditions
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Diabetes, Diabetes Mellitus, Type 1

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


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: FOR THE MAIN TRIAL, NN5401-3594: Type 1 diabetes mellitus for at least 12 months Ongoing daily treatment with insulin (in a basal bolus regimen, premix insulin regimen, self mix regimen) for at least 12 months HbA1c 7.0-10.0% (both inclusive) BMI (Body Mass Index) below or equal to 35.0 kg/m^2 FOR THE EXTENSION TRIAL, NN5401-3645: The subject must have completed the six-month treatment period in trial NN5401-3594 Exclusion Criteria: FOR THE MAIN TRIAL, NN5401-3594: Treatment with other insulin regimens than insulin in a basal bolus regimen/premix insulin regimen/self mix regimen 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 according to local requirements Cancer and medical history of cancer FOR THE EXTENSION TRIAL, NN5401-3645: Anticipated significant lifestyle changes during the trial Pregnancy, breast-feeding, the intention of becoming pregnant or not using adequate contraceptive measures

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 subcutaneously (under the skin) once daily with a meal. Dose was individually adjusted.<br>Drug: insulin aspart<br>* Injected subcutaneously (under the skin) at the remaining meals. Dose was individually adjusted.<br>|
| Active Comparator: IDet<br> | Drug: insulin detemir<br>* Injected subcutaneously (under the skin) once daily or twice daily. Dose was individually adjusted.<br>Drug: insulin aspart<br>* Injected subcutaneously (under the skin) as meal time insulin. 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 were defined as requiring assistance to administer carbohydrate, glucagon, or other resuscitative actions. Minor hypoglycaemic episodes were 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 were defined as requiring assistance to administer carbohydrate, glucagon, or other resuscitative actions. Minor hypoglycaemic episodes were defined as able to treat her/himself and plasma glucose below 3.1 mmol/L. Nocturnal hypoglycaemic episodes were 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 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 53 + 7 days of follow up | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 were defined as requiring assistance to administer carbohydrate, glucagon, or other resuscitative actions. Minor hypoglycaemic episodes were defined as able to treat her/himself and plasma glucose below 3.1 mmol/L. | Week 0 to Week 26 + 7 days follow up | 
| Main Trial (Secondary Endpoint): Mean of 9-point Self Measured Plasma Glucose Profile (SMPG) at Week 26 | Overall mean of 9-point 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 | 
| 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): 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 were defined as requiring assistance to administer carbohydrate, glucagon, or other resuscitative actions. Minor hypoglycaemic episodes were defined as able to treat her/himself and plasma glucose below 3.1 mmol/L. Nocturnal hypoglycaemic episodes were defined as occurring between 00:01 and 05:59 a.m. | Week 0 to Week 26 + 7 days follow up | 
| Extension Trial (Secondary Endpoint): Change in Fasting Plasma Glucose (FPG) After 52 Weeks of Treatment | Change from baseline in FPG after 52 weeks of treatment. | Week 0, Week 53 |