Comparison of NN1250 With Insulin Glargine in Type 1 Diabetes

Study Overview
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Brief Summary
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This trial is conducted in Europe and in the United States of America (USA). The aim of this trial is to investigate the efficacy and safety of NN1250 (insulin degludec) in subjects with type 1 diabetes.

Official Title
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A 26-week Trial Investigating the Dosing Flexibility, Efficacy and Safety of NN1250 in Subjects With Type 1 Diabetes With a 26-week Extension (Begin™: Flex T1)

Conditions
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Diabetes, Diabetes Mellitus, Type 1

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: Type 1 diabetes for 12 months or longer, hereof the last 3 months with injection based therapies Current treatment with any basal insulin (e.g. insulin glargine, insulin detemir, NPH insulin) using one or two daily injections and with three or more daily meal-time insulin injections (e.g. insulin aspart, insulin lispro, insulin glulisine, human insulin) used as bolus insulin therapy HbA1c maximum 10.0 % by central laboratory analysis Body Mass Index (BMI) below or equal to 35.0 kg/m^2 Ability to self-manage insulin therapy as assessed by confirmation (verbal confirmation at screening visit) of a changed insulin dose in the preceding two months prior to screening Ability and willingness to adhere to the protocol including performance of self measured plasma glucose (SMPG) profiles and self adjustment of insulin doses Exclusion Criteria: Use within the last 3 months prior to Visit 1 of any antidiabetic glucose lowering drug other than insulin Cardiovascular disease, within the last 6 months prior to visit 1, defined as: stroke; decompensated heart failure New York Heart Association (NYHA) class III or IV; myocardial infarction; unstable angina pectoris; or coronary arterial bypass graft or angioplasty Uncontrolled treated/ untreated severe hypertension (systolic blood pressure above or equal to 180 millimetre (mm) mercury (Hg) and/or diastolic blood pressure above or equal to 100 mmHg) Pregnancy, breast-feeding, the intention of becoming pregnant or not using adequate contraceptive measures according to local requirements Cancer and medical history of cancer (except basal cell skin cancer or squamous cell skin 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: Flex + insulin aspart<br> | Drug: insulin degludec<br>* Injected subcutaneously (under the skin) once daily<br>Drug: insulin aspart<br>* At least three daily doses at meal-time<br>|
| Experimental: Fixed + insulin aspart<br> | Drug: insulin degludec<br>* Injected subcutaneously (under the skin) once daily<br>Drug: insulin aspart<br>* At least three daily doses at meal-time<br>|
| Active Comparator: IGlar + insulin aspart<br> | Drug: insulin glargine<br>* Insulin glargine injected subcutaneously (under the skin) once daily<br>Drug: insulin aspart<br>* At least three daily doses at meal-time<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 52 + 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 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): 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 |