Comparison of NN1250 Plus Insulin Aspart With Insulin Detemir Plus Insulin Aspart in Type 1 Diabetes

Study Overview
=================
Brief Summary
-----------------
This trial is conducted in Asia, Europe, Japan and South America. The aim of the trial is to compare the efficacy, safety and tolerability of NN1250 (insulin degludec ([Deg]) with insulin detemir (IDet), both combined with insulin aspart. The main period is registered internally at Novo Nordisk as NN1250-3585 while the extension period is registered as NN1250-3725.

Official Title
-----------------
NN1250-3585: A Trial Investigating the Efficacy and Safety of NN1250 Compared to Insulin Detemir in Subjects With Type 1 Diabetes Mellitus in a Basal/Bolus Treatment Regimen / NN1250-3725: An Extension Trial to NN1250-3585 Investigating Safety and Efficacy of NN1250 Compared to Insulin Detemir in Subjects With Type 1 Diabetes Mellitus in a Basal/Bolus Treatment Regimen (BEGIN™: BB T1)

Conditions
-----------------
Diabetes, Diabetes Mellitus, Type 1

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


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Type 1 diabetes mellitus for at least 12 months Current treatment with any basal bolus insulin for at least 12 months HbA1c below or equal to 10.0% Body Mass Index (BMI) below or equal to 35.0 kg/m^2 For Japan only: Minimum age is 20 years For the extension trial only: Completed the six-month treatment period in trial NN1250-3585 (NCT01074268) Exclusion Criteria: Use of any other antidiabetic drug than insulin within the last 3 months Cardiovascular disease within the last 6 months Uncontrolled treated/untreated severe hypertension Recurrent severe hypoglycemia or hypoglycemic unawareness or hospitalisation for diabetic ketoacidosis during the previous 6 months Pregnancy, breast-feeding, the intention of becoming pregnant or not using adequate contraceptive measures Cancer and medical history of cancer

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

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 s.c. (under the skin) once daily. Dose was individually adjusted.<br>Drug: insulin aspart<br>* Injected s.c. (under the skin) as mealtime insulin. Dose was individually adjusted.<br>|
| Active Comparator: IDet<br> | Drug: insulin detemir<br>* Injected s.c. (under the skin) once daily or twice daily (BID). Dose was individually adjusted.<br>Drug: insulin aspart<br>* Injected s.c. (under the skin) as mealtime insulin. Dose was individually adjusted.<br>|

What is the study measuring?
-----------------
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 Treatment Emergent Adverse Events (AEs) | Rate of AEs per 100 patient years of exposure. Severity assessed by investigator. Mild: no/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 or important medical issues | Week 0 to Week 52 + 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 52 | 
| Main Trial (Secondary Endpoint): Mean of 9-point Self Measured Plasma Glucose Profile (SMPG) at Week 26 | Mean of 9-point self-measured plasma glucose profile (SMPG) after week 26. Plasma glucose was measured before breakfast, 90 minutes after the start of breakfast, before lunch, 90 minutes after the start of lunch, before main evening meal, 90 minutes after the start of main evening meal, before bedtime, at 04:00 AM and before breakfast on the following day. | Week 26 | 
| Extension Trial (Secondary Endpoint): Mean of 9-point Self Measured Plasma Glucose Profile (SMPG) at Week 52 | Mean of 9-point self-measured plasma glucose profile (SMPG) at week 52. Plasma glucose was measured before breakfast, 90 minutes after the start of breakfast, before lunch, 90 minutes after the start of lunch, before main evening meal, 90 minutes after the start of main evening meal, before bedtime, at 04:00 AM and before breakfast on the following day. | Week 52 | 
| Main Trial (Secondary Endpoint): Change in Fasting Plasma Glucose (FPG) After 26 Weeks of Treatment | Change from baseline in FPG after 26 weeks of treatment | Week 0, Week 26 | 
| 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 52 | 
| 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: episodes requiring active assistance of another person to administer carbohydrate, glucagon, or other resuscitative actions. Minor hypoglycaemic episodes: episodes where the subject was able to treat her/himself and plasma glucose below 3.1 mmol/L, with or without symptoms. | Week 0 to Week 26 + 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: episodes requiring active assistance of another person to administer carbohydrate, glucagon, or other resuscitative actions. Minor hypoglycaemic episodes: episodes where subject was able to treat her/himself and plasma glucose below 3.1 mmol/L, with or without symptoms. Nocturnal hypoglycaemic episodes are defined as occuring between 00:01 and 05:59 a.m. | Week 0 to Week 26 + 7 days follow up | 
| Extension 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: episodes requiring active assistance of another person to administer carbohydrate, glucagon, or other resuscitative actions. Minor hypoglycaemic episodes: episodes where the subject was able to treat her/himself and plasma glucose below 3.1 mmol/L with or without symptoms | Week 0 to Week 52 + 7 days follow up | 
| Extension 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: episodes requiring active assistance of another person to administer carbohydrate, glucagon, or other resuscitative actions. Minor hypoglycaemic episodes: episodes where subject was able to treat her/himself and plasma glucose below 3.1 mmol/L, with or without symptoms. Nocturnal hypoglycaemic episodes are defined as occuring between 00:01 and 05:59 a.m. | Week 0 to Week 52 + 7 days follow up |