Comparison of NN1250 Plus Insulin Aspart With Insulin Glargine Plus Insulin Aspart in Type 1 Diabetes (BEGIN™)

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: Diabetes; Diabetes Mellitus, Type 1
• Intervention / Treatment: Drug: insulin degludec; Drug: insulin aspart; Drug: insulin glargine

• Study Type: Interventional
• Enrollment (Actual): 629
• Phase: Phase 3

Contacts and Locations

Study Locations

• France
  • Boisguillaume, France, 76233
    • Novo Nordisk Investigational Site
  • Brest, France, 29609
    • Novo Nordisk Investigational Site
  • Grenoble, France, 38043
    • Novo Nordisk Investigational Site
  • LA ROCHELLE cedex, France, 17019
    • Novo Nordisk Investigational Site
  • Montpellier, France
    • Novo Nordisk Investigational Site
  • Nice, France, 06002
    • Novo Nordisk Investigational Site
  • Paris, France, 75877
    • Novo Nordisk Investigational Site
• Germany
  • Aschaffenburg, Germany, 63739
    • Novo Nordisk Investigational Site
  • Bad Kreuznach, Germany, 55545
    • Novo Nordisk Investigational Site
  • Dormagen, Germany, 41539
    • Novo Nordisk Investigational Site
  • Hamburg, Germany, 22607
    • Novo Nordisk Investigational Site
  • Hamburg, Germany, 21073
    • Novo Nordisk Investigational Site
  • St. Ingbert, Germany, 66386
    • Novo Nordisk Investigational Site
• Russian Federation
  • Moscow, Russian Federation, 117036
    • Novo Nordisk Investigational Site
  • Moscow, Russian Federation, 127486
    • Novo Nordisk Investigational Site
  • Moscow, Russian Federation, 119034
    • Novo Nordisk Investigational Site
  • Novosibirsk, Russian Federation, 630047
    • Novo Nordisk Investigational Site
  • Saint-Peterburg, Russian Federation, 190068
    • Novo Nordisk Investigational Site
  • Saint-Petersburg, Russian Federation, 194354
    • Novo Nordisk Investigational Site
  • Tumen, Russian Federation, 625023
    • Novo Nordisk Investigational Site
  • Yaroslavl, Russian Federation, 150062
    • Novo Nordisk Investigational Site
• South Africa
  • Gauteng
    • Johannesburg, Gauteng, South Africa, 1724
      • Novo Nordisk Investigational Site
  • Western Cape
    • Cape Town, Western Cape, South Africa, 7130
      • Novo Nordisk Investigational Site
    • Cape Town, Western Cape, South Africa, 7925
      • Novo Nordisk Investigational Site
• United Kingdom
  • Aberdeen, United Kingdom, AB25 1LD
    • Novo Nordisk Investigational Site
  • Birmingham, United Kingdom, B9 5SS
    • Novo Nordisk Investigational Site
  • Bradford, United Kingdom, BD9 6RJ
    • Novo Nordisk Investigational Site
  • Glasgow, United Kingdom, G21 3UW
    • Novo Nordisk Investigational Site
  • Guildford, United Kingdom, GU2 7XX
    • Novo Nordisk Investigational Site
  • Leeds, United Kingdom, LS9 7TF
    • Novo Nordisk Investigational Site
  • Llantrisant, United Kingdom, CF72 8XR
    • Novo Nordisk Investigational Site
  • Sheffield, United Kingdom, S5 7AU
    • Novo Nordisk Investigational Site
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35209
      • Novo Nordisk Investigational Site
    • Huntsville, Alabama, United States, 35801
      • Novo Nordisk Investigational Site
  • Arizona
    • Peoria, Arizona, United States, 85381
      • Novo Nordisk Investigational Site
  • California
    • Concord, California, United States, 94520
      • Novo Nordisk Investigational Site
    • Fresno, California, United States, 93720
      • Novo Nordisk Investigational Site
    • Greenbrae, California, United States, 94904
      • Novo Nordisk Investigational Site
    • Huntington Beach, California, United States, 92648
      • Novo Nordisk Investigational Site
    • La Mesa, California, United States, 91942
      • Novo Nordisk Investigational Site
    • Los Gatos, California, United States, 95032
      • Novo Nordisk Investigational Site
    • Santa Barbara, California, United States, 93105
      • Novo Nordisk Investigational Site
    • Tustin, California, United States, 92780
      • Novo Nordisk Investigational Site
    • Ventura, California, United States, 93003
      • Novo Nordisk Investigational Site
    • Walnut Creek, California, United States, 94598-3347
      • Novo Nordisk Investigational Site
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Novo Nordisk Investigational Site
    • Aurora, Colorado, United States, 80045-7402
      • Novo Nordisk Investigational Site
  • Florida
    • Hollywood, Florida, United States, 33021
      • Novo Nordisk Investigational Site
    • Lake Mary, Florida, United States, 32746
      • Novo Nordisk Investigational Site
    • Miami, Florida, United States, 33136
      • Novo Nordisk Investigational Site
  • Georgia
    • Atlanta, Georgia, United States, 30318
      • Novo Nordisk Investigational Site
    • Lawrenceville, Georgia, United States, 30046
      • Novo Nordisk Investigational Site
  • Hawaii
    • Honolulu, Hawaii, United States, 96814
      • Novo Nordisk Investigational Site
  • Illinois
    • Chicago, Illinois, United States, 60611-2661
      • Novo Nordisk Investigational Site
  • Indiana
    • Vincennes, Indiana, United States, 47591-1029
      • Novo Nordisk Investigational Site
  • Kentucky
    • Lexington, Kentucky, United States, 40503
      • Novo Nordisk Investigational Site
    • Lexington, Kentucky, United States, 40536-0284
      • Novo Nordisk Investigational Site
  • Maine
    • Scarborough, Maine, United States, 04074-9302
      • Novo Nordisk Investigational Site
  • Maryland
    • Hyattsville, Maryland, United States, 20782
      • Novo Nordisk Investigational Site
    • Rockville, Maryland, United States, 20852
      • Novo Nordisk Investigational Site
  • Massachusetts
    • Brockton, Massachusetts, United States, 02301
      • Novo Nordisk Investigational Site
  • Michigan
    • Flint, Michigan, United States, 48503-5904
      • Novo Nordisk Investigational Site
    • Livonia, Michigan, United States, 48154
      • Novo Nordisk Investigational Site
  • Minnesota
    • Eagan, Minnesota, United States, 55123
      • Novo Nordisk Investigational Site
  • Missouri
    • Chesterfield, Missouri, United States, 63017
      • Novo Nordisk Investigational Site
    • Jefferson City, Missouri, United States, 65109
      • Novo Nordisk Investigational Site
    • St. Charles, Missouri, United States, 63303
      • Novo Nordisk Investigational Site
  • Montana
    • Great Falls, Montana, United States, 59405
      • Novo Nordisk Investigational Site
  • Nebraska
    • Omaha, Nebraska, United States, 68114
      • Novo Nordisk Investigational Site
    • Omaha, Nebraska, United States, 68124
      • Novo Nordisk Investigational Site
  • New Hampshire
    • Dover, New Hampshire, United States, 03820
      • Novo Nordisk Investigational Site
  • New Jersey
    • Lawrenceville, New Jersey, United States, 08648
      • Novo Nordisk Investigational Site
  • New York
    • Flushing, New York, United States, 11365
      • Novo Nordisk Investigational Site
    • Rochester, New York, United States, 14607
      • Novo Nordisk Investigational Site
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27517
      • Novo Nordisk Investigational Site
    • Raleigh, North Carolina, United States, 27609
      • Novo Nordisk Investigational Site
  • Ohio
    • Columbus, Ohio, United States, 43203
      • Novo Nordisk Investigational Site
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • Novo Nordisk Investigational Site
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15224-2215
      • Novo Nordisk Investigational Site
    • Pittsburgh, Pennsylvania, United States, 15212
      • Novo Nordisk Investigational Site
  • South Dakota
    • Rapid City, South Dakota, United States, 57701
      • Novo Nordisk Investigational Site
  • Tennessee
    • Chattanooga, Tennessee, United States, 37404
      • Novo Nordisk Investigational Site
    • Chattanooga, Tennessee, United States, 37411
      • Novo Nordisk Investigational Site
  • Texas
    • Dallas, Texas, United States, 75230
      • Novo Nordisk Investigational Site
    • Dallas, Texas, United States, 75231
      • Novo Nordisk Investigational Site
    • Dallas, Texas, United States, 75246
      • Novo Nordisk Investigational Site
    • Lubbock, Texas, United States, 79423
      • Novo Nordisk Investigational Site
    • Round Rock, Texas, United States, 78681
      • Novo Nordisk Investigational Site
  • Utah
    • St. George, Utah, United States, 84790
      • Novo Nordisk Investigational Site
  • Washington
    • Renton, Washington, United States, 98057
      • Novo Nordisk Investigational Site
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53209
      • Novo Nordisk Investigational Site

Participation Criteria

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

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: IGlar OD	Drug: insulin aspart; Injected subcutaneously as mealtime insulin. Dose was individually adjusted.; Drug: insulin glargine; Injected subcutaneously once daily. Dose individually adjusted.
EXPERIMENTAL: IDeg OD	Drug: insulin degludec; Injected subcutaneously once daily. Dose was individually adjusted.; Drug: insulin aspart; Injected subcutaneously as mealtime insulin. Dose was individually adjusted.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Main Trial (Primary 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
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 104 + 7 days follow up
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 104 + 7 days follow up
Extension Trial (Primary Endpoint): Cross-reacting Antibodies to Human Insulin	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.	Week 0, Week 106

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 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 occuring between 00:01 and 05:59 a.m.	Week 0 to Week 104 + 7 days follow up
Extension Trial (Secondary Endpoint): Change in Glycosylated Haemoglobin (HbA1c) After 104 Weeks of Treatment	Change from baseline in HbA1c after 104 weeks of treatment	Week 0, Week 104
Extension Trial (Secondary Endpoint): Mean of 9-point Self Measured Plasma Glucose Profile (SMPG) at Week 104 of Treatment	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.	Treatment week 104
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 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.	Week 0 to Week 52 + 7 days follow up
Main 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) 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.	Week 52

Collaborators and Investigators

• Sponsor: Novo Nordisk A/S

Publications and helpful links

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

• Clinical Trials at Novo Nordisk

Study record dates

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: Glucose Metabolism Disorders; Metabolic Diseases; Immune System Diseases; Autoimmune Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 1; Hypoglycemic Agents; Physiological Effects of Drugs; Insulin; Insulin, Globin Zinc; Insulin Aspart; Insulin Glargine
• 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)