Comparison of NN1250 Plus Insulin Aspart With Insulin Glargine Plus Insulin Aspart in Type 1 Diabetes (BEGIN™)
March 8, 2017 updated by: Novo Nordisk A/S
NN1250-3583: A 52 Week Randomised, Controlled, Open Label, Multicentre, Multinational, Parallel, 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 in Subjects With Type 1 Diabetes (BEGIN™: BB T1 LONG) / NN1250-3644: An Extension Trial to Trial NN1250-3583 Comparing Safety and Efficacy of NN1250 With Insulin Glargine, Both With Insulin Aspart as Meal-time Insulin, in Type 1 Diabetes (BEGIN™: T1)
This trial is conducted in Africa, Europe and the United States of America (USA).
The aim of the trial is to compare NN1250 (insulin degludec, soluble insulin basal analogue (SIBA)) plus insulin aspart with insulin glargine (IGlar) plus insulin aspart in patients with type 1 diabetes.
The main period is registered internally at Novo Nordisk as NN1250-3583 while the extension period is registered as NN1250-3644.
Study Overview
Status
Completed
Conditions
Intervention / Treatment
Study Type
Interventional
Enrollment (Actual)
629
Phase
- Phase 3
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
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Boisguillaume, France, 76233
- Novo Nordisk Investigational Site
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Brest, France, 29609
- Novo Nordisk Investigational Site
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Grenoble, France, 38043
- Novo Nordisk Investigational Site
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LA ROCHELLE cedex, France, 17019
- Novo Nordisk Investigational Site
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Montpellier, France
- Novo Nordisk Investigational Site
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Nice, France, 06002
- Novo Nordisk Investigational Site
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Paris, France, 75877
- Novo Nordisk Investigational Site
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Aschaffenburg, Germany, 63739
- Novo Nordisk Investigational Site
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Bad Kreuznach, Germany, 55545
- Novo Nordisk Investigational Site
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Dormagen, Germany, 41539
- Novo Nordisk Investigational Site
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Hamburg, Germany, 22607
- Novo Nordisk Investigational Site
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Hamburg, Germany, 21073
- Novo Nordisk Investigational Site
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St. Ingbert, Germany, 66386
- Novo Nordisk Investigational Site
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Moscow, Russian Federation, 117036
- Novo Nordisk Investigational Site
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Moscow, Russian Federation, 127486
- Novo Nordisk Investigational Site
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Moscow, Russian Federation, 119034
- Novo Nordisk Investigational Site
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Novosibirsk, Russian Federation, 630047
- Novo Nordisk Investigational Site
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Saint-Peterburg, Russian Federation, 190068
- Novo Nordisk Investigational Site
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Saint-Petersburg, Russian Federation, 194354
- Novo Nordisk Investigational Site
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Tumen, Russian Federation, 625023
- Novo Nordisk Investigational Site
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Yaroslavl, Russian Federation, 150062
- Novo Nordisk Investigational Site
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Gauteng
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Johannesburg, Gauteng, South Africa, 1724
- Novo Nordisk Investigational Site
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Western Cape
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Cape Town, Western Cape, South Africa, 7130
- Novo Nordisk Investigational Site
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Cape Town, Western Cape, South Africa, 7925
- Novo Nordisk Investigational Site
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Aberdeen, United Kingdom, AB25 1LD
- Novo Nordisk Investigational Site
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Birmingham, United Kingdom, B9 5SS
- Novo Nordisk Investigational Site
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Bradford, United Kingdom, BD9 6RJ
- Novo Nordisk Investigational Site
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Glasgow, United Kingdom, G21 3UW
- Novo Nordisk Investigational Site
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Guildford, United Kingdom, GU2 7XX
- Novo Nordisk Investigational Site
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Leeds, United Kingdom, LS9 7TF
- Novo Nordisk Investigational Site
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Llantrisant, United Kingdom, CF72 8XR
- Novo Nordisk Investigational Site
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Sheffield, United Kingdom, S5 7AU
- Novo Nordisk Investigational Site
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Alabama
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Birmingham, Alabama, United States, 35209
- Novo Nordisk Investigational Site
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Huntsville, Alabama, United States, 35801
- Novo Nordisk Investigational Site
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Arizona
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Peoria, Arizona, United States, 85381
- Novo Nordisk Investigational Site
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California
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Concord, California, United States, 94520
- Novo Nordisk Investigational Site
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Fresno, California, United States, 93720
- Novo Nordisk Investigational Site
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Greenbrae, California, United States, 94904
- Novo Nordisk Investigational Site
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Huntington Beach, California, United States, 92648
- Novo Nordisk Investigational Site
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La Mesa, California, United States, 91942
- Novo Nordisk Investigational Site
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Los Gatos, California, United States, 95032
- Novo Nordisk Investigational Site
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Santa Barbara, California, United States, 93105
- Novo Nordisk Investigational Site
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Tustin, California, United States, 92780
- Novo Nordisk Investigational Site
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Ventura, California, United States, 93003
- Novo Nordisk Investigational Site
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Walnut Creek, California, United States, 94598-3347
- Novo Nordisk Investigational Site
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Colorado
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Aurora, Colorado, United States, 80045
- Novo Nordisk Investigational Site
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Aurora, Colorado, United States, 80045-7402
- Novo Nordisk Investigational Site
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Florida
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Hollywood, Florida, United States, 33021
- Novo Nordisk Investigational Site
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Lake Mary, Florida, United States, 32746
- Novo Nordisk Investigational Site
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Miami, Florida, United States, 33136
- Novo Nordisk Investigational Site
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Georgia
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Atlanta, Georgia, United States, 30318
- Novo Nordisk Investigational Site
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Lawrenceville, Georgia, United States, 30046
- Novo Nordisk Investigational Site
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Hawaii
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Honolulu, Hawaii, United States, 96814
- Novo Nordisk Investigational Site
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Illinois
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Chicago, Illinois, United States, 60611-2661
- Novo Nordisk Investigational Site
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Indiana
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Vincennes, Indiana, United States, 47591-1029
- Novo Nordisk Investigational Site
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Kentucky
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Lexington, Kentucky, United States, 40503
- Novo Nordisk Investigational Site
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Lexington, Kentucky, United States, 40536-0284
- Novo Nordisk Investigational Site
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Maine
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Scarborough, Maine, United States, 04074-9302
- Novo Nordisk Investigational Site
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Maryland
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Hyattsville, Maryland, United States, 20782
- Novo Nordisk Investigational Site
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Rockville, Maryland, United States, 20852
- Novo Nordisk Investigational Site
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Massachusetts
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Brockton, Massachusetts, United States, 02301
- Novo Nordisk Investigational Site
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Michigan
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Flint, Michigan, United States, 48503-5904
- Novo Nordisk Investigational Site
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Livonia, Michigan, United States, 48154
- Novo Nordisk Investigational Site
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Minnesota
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Eagan, Minnesota, United States, 55123
- Novo Nordisk Investigational Site
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Missouri
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Chesterfield, Missouri, United States, 63017
- Novo Nordisk Investigational Site
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Jefferson City, Missouri, United States, 65109
- Novo Nordisk Investigational Site
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St. Charles, Missouri, United States, 63303
- Novo Nordisk Investigational Site
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Montana
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Great Falls, Montana, United States, 59405
- Novo Nordisk Investigational Site
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Nebraska
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Omaha, Nebraska, United States, 68114
- Novo Nordisk Investigational Site
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Omaha, Nebraska, United States, 68124
- Novo Nordisk Investigational Site
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New Hampshire
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Dover, New Hampshire, United States, 03820
- Novo Nordisk Investigational Site
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New Jersey
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Lawrenceville, New Jersey, United States, 08648
- Novo Nordisk Investigational Site
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New York
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Flushing, New York, United States, 11365
- Novo Nordisk Investigational Site
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Rochester, New York, United States, 14607
- Novo Nordisk Investigational Site
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North Carolina
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Chapel Hill, North Carolina, United States, 27517
- Novo Nordisk Investigational Site
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Raleigh, North Carolina, United States, 27609
- Novo Nordisk Investigational Site
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Ohio
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Columbus, Ohio, United States, 43203
- Novo Nordisk Investigational Site
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Oklahoma
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Oklahoma City, Oklahoma, United States, 73104
- Novo Nordisk Investigational Site
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Pennsylvania
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Pittsburgh, Pennsylvania, United States, 15224-2215
- Novo Nordisk Investigational Site
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Pittsburgh, Pennsylvania, United States, 15212
- Novo Nordisk Investigational Site
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South Dakota
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Rapid City, South Dakota, United States, 57701
- Novo Nordisk Investigational Site
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Tennessee
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Chattanooga, Tennessee, United States, 37404
- Novo Nordisk Investigational Site
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Chattanooga, Tennessee, United States, 37411
- Novo Nordisk Investigational Site
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Texas
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Dallas, Texas, United States, 75230
- Novo Nordisk Investigational Site
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Dallas, Texas, United States, 75231
- Novo Nordisk Investigational Site
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Dallas, Texas, United States, 75246
- Novo Nordisk Investigational Site
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Lubbock, Texas, United States, 79423
- Novo Nordisk Investigational Site
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Round Rock, Texas, United States, 78681
- Novo Nordisk Investigational Site
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Utah
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St. George, Utah, United States, 84790
- Novo Nordisk Investigational Site
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Washington
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Renton, Washington, United States, 98057
- Novo Nordisk Investigational Site
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Wisconsin
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Milwaukee, Wisconsin, United States, 53209
- Novo Nordisk Investigational Site
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years and older (ADULT, OLDER_ADULT)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
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%
- BMI (Body Mass Index) below or equal to 35.0 kg/m^2
- For the extension trial only: Completion of the 52 week treatment period in trial NN1250-3583 (NCT00982228)
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 according to local requirements
- Cancer and medical history of cancer
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: TREATMENT
- Allocation: RANDOMIZED
- Interventional Model: PARALLEL
- Masking: NONE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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ACTIVE_COMPARATOR: IGlar OD
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Injected subcutaneously as mealtime insulin.
Dose was individually adjusted.
Injected subcutaneously once daily.
Dose individually adjusted.
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EXPERIMENTAL: IDeg OD
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Injected subcutaneously once daily.
Dose was individually adjusted.
Injected subcutaneously as mealtime insulin.
Dose was individually adjusted.
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Main Trial (Primary Endpoint): Change in Glycosylated Haemoglobin (HbA1c) After 52 Weeks of Treatment
Time Frame: Week 0, Week 52
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Change from baseline in HbA1c after 52 weeks of treatment
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Week 0, Week 52
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Extension Trial (Primary Endpoint): Rate of Treatment Emergent Adverse Events (AEs)
Time Frame: Week 0 to Week 104 + 7 days follow up
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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.
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Week 0 to Week 104 + 7 days follow up
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Extension Trial (Primary Endpoint): Rate of Confirmed Hypoglycaemic Episodes
Time Frame: Week 0 to Week 104 + 7 days follow up
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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.
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Week 0 to Week 104 + 7 days follow up
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Extension Trial (Primary Endpoint): Cross-reacting Antibodies to Human Insulin
Time Frame: Week 0, Week 106
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The unit for measuring antibody levels is amount of tracer bound to the antibodies in the precipitate (B) expressed in percentage of the total amount of tracer (T) added to the mixture (%B/T).
Samples were taken before 1st dosing and after a 1-week wash-out period.
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Week 0, Week 106
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Main Trial (Secondary Endpoint): Rate of Confirmed Hypoglycaemic Episodes
Time Frame: Week 0 to Week 52 + 7 days follow up
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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.
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Week 0 to Week 52 + 7 days follow up
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Extension Trial (Primary Endpoint): Rate of Nocturnal Confirmed Hypoglycaemic Episodes
Time Frame: Week 0 to Week 104 + 7 days follow up
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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 occuring between 00:01 and 05:59 a.m.
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Week 0 to Week 104 + 7 days follow up
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Extension Trial (Secondary Endpoint): Change in Glycosylated Haemoglobin (HbA1c) After 104 Weeks of Treatment
Time Frame: Week 0, Week 104
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Change from baseline in HbA1c after 104 weeks of treatment
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Week 0, Week 104
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Extension Trial (Secondary Endpoint): Mean of 9-point Self Measured Plasma Glucose Profile (SMPG) at Week 104 of Treatment
Time Frame: Treatment week 104
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Mean of 9-point self-measured plasma glucose profile (SMPG) after 104 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.
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Treatment week 104
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Main Trial (Secondary Endpoint): Rate of Nocturnal Confirmed Hypoglycaemic Episodes
Time Frame: Week 0 to Week 52 + 7 days follow up
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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 occuring between 00:01 and 05:59 a.m.
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Week 0 to Week 52 + 7 days follow up
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Main Trial (Secondary Endpoint): Mean of 9-point Self Measured Plasma Glucose Profile (SMPG) at Week 52
Time Frame: Week 52
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Mean of 9-point self-measured plasma glucose profile (SMPG) after 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.
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Week 52
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
General Publications
- Ratner RE, Gough SC, Mathieu C, Del Prato S, Bode B, Mersebach H, Endahl L, Zinman B. Hypoglycaemia risk with insulin degludec compared with insulin glargine in type 2 and type 1 diabetes: a pre-planned meta-analysis of phase 3 trials. Diabetes Obes Metab. 2013 Feb;15(2):175-84. doi: 10.1111/dom.12032. Epub 2012 Dec 3.
- Heller S, Mathieu C, Kapur R, Wolden ML, Zinman B. A meta-analysis of rate ratios for nocturnal confirmed hypoglycaemia with insulin degludec vs. insulin glargine using different definitions for hypoglycaemia. Diabet Med. 2016 Apr;33(4):478-87. doi: 10.1111/dme.13002. Epub 2015 Dec 13.
- Sorli C, Warren M, Oyer D, Mersebach H, Johansen T, Gough SC. Elderly patients with diabetes experience a lower rate of nocturnal hypoglycaemia with insulin degludec than with insulin glargine: a meta-analysis of phase IIIa trials. Drugs Aging. 2013 Dec;30(12):1009-18. doi: 10.1007/s40266-013-0128-2.
- Einhorn D, Handelsman Y, Bode BW, Endahl LA, Mersebach H, King AB. PATIENTS ACHIEVING GOOD GLYCEMIC CONTROL (HBA1c <7%) EXPERIENCE A LOWER RATE OF HYPOGLYCEMIA WITH INSULIN DEGLUDEC THAN WITH INSULIN GLARGINE: A META-ANALYSIS OF PHASE 3A TRIALS. Endocr Pract. 2015 Aug;21(8):917-26. doi: 10.4158/EP14523.OR. Epub 2015 Jun 29.
- Russell-Jones D, Gall MA, Niemeyer M, Diamant M, Del Prato S. Insulin degludec results in lower rates of nocturnal hypoglycaemia and fasting plasma glucose vs. insulin glargine: A meta-analysis of seven clinical trials. Nutr Metab Cardiovasc Dis. 2015 Oct;25(10):898-905. doi: 10.1016/j.numecd.2015.06.005. Epub 2015 Jun 18.
- Vora J, Christensen T, Rana A, Bain SC. Insulin degludec versus insulin glargine in type 1 and type 2 diabetes mellitus: a meta-analysis of endpoints in phase 3a trials. Diabetes Ther. 2014 Dec;5(2):435-46. doi: 10.1007/s13300-014-0076-9. Epub 2014 Aug 1.
- Aye MM, Atkin SL. Patient safety and minimizing risk with insulin administration - role of insulin degludec. Drug Healthc Patient Saf. 2014 Apr 30;6:55-67. doi: 10.2147/DHPS.S59566. eCollection 2014.
- Evans M, Chubb B, Gundgaard J. Cost-effectiveness of Insulin Degludec Versus Insulin Glargine in Adults with Type 1 and Type 2 Diabetes Mellitus. Diabetes Ther. 2017 Apr;8(2):275-291. doi: 10.1007/s13300-017-0236-9. Epub 2017 Feb 16.
- Heller S, Buse J, Fisher M, Garg S, Marre M, Merker L, Renard E, Russell-Jones D, Philotheou A, Francisco AM, Pei H, Bode B; BEGIN Basal-Bolus Type 1 Trial Investigators. Insulin degludec, an ultra-longacting basal insulin, versus insulin glargine in basal-bolus treatment with mealtime insulin aspart in type 1 diabetes (BEGIN Basal-Bolus Type 1): a phase 3, randomised, open-label, treat-to-target non-inferiority trial. Lancet. 2012 Apr 21;379(9825):1489-97. doi: 10.1016/S0140-6736(12)60204-9.
Helpful Links
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (ACTUAL)
September 1, 2009
Primary Completion (ACTUAL)
November 8, 2010
Study Completion (ACTUAL)
November 8, 2010
Study Registration Dates
First Submitted
September 22, 2009
First Submitted That Met QC Criteria
September 22, 2009
First Posted (ESTIMATE)
September 23, 2009
Study Record Updates
Last Update Posted (ACTUAL)
April 6, 2017
Last Update Submitted That Met QC Criteria
March 8, 2017
Last Verified
March 1, 2017
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- NN1250-3583
- 2008-005774-13 (EUDRACT_NUMBER)
- U1111-1111-8789 (OTHER: WHO)
- 2009-015755-24 (EUDRACT_NUMBER)
- U1111-1116-1578 (OTHER: WHO)
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.