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

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)

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.

Study Overview

• Status: Completed
• Conditions: Diabetes; Diabetes Mellitus, Type 1
• Intervention / Treatment: Drug: insulin degludec; Drug: insulin aspart; Drug: insulin detemir

• Study Type: Interventional
• Enrollment (Actual): 456
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Caba, Argentina, C1440AAD
    • Novo Nordisk Investigational Site
  • Ciudad Autónoma de Bs As, Argentina, C1426ABP
    • Novo Nordisk Investigational Site
  • Mar del Plata, Argentina, B7600FZN
    • Novo Nordisk Investigational Site
  • Rosario, Argentina, 2000
    • Novo Nordisk Investigational Site
• Brazil
  • Marília, Brazil, 17519-000
    • Novo Nordisk Investigational Site
  • Porto Alegre, Brazil, 90035-170
    • Novo Nordisk Investigational Site
  • Sao Paulo, Brazil, 04022-001
    • Novo Nordisk Investigational Site
  • Rio Grande do Sul
    • Porto Alegre, Rio Grande do Sul, Brazil, 91350-250
      • Novo Nordisk Investigational Site
  • Sao Paulo
    • São Paulo, Sao Paulo, Brazil, 01244-030
      • Novo Nordisk Investigational Site
• Finland
  • Helsinki, Finland, 00250
    • Novo Nordisk Investigational Site
  • Helsinki, Finland, 00260
    • Novo Nordisk Investigational Site
  • Hämeenlinna, Finland, 13530
    • Novo Nordisk Investigational Site
  • Kuopio, Finland, 70210
    • Novo Nordisk Investigational Site
  • Lahti, Finland, 15110
    • Novo Nordisk Investigational Site
  • Seinäjoki, Finland, 60220
    • Novo Nordisk Investigational Site
  • Tampere, Finland, 33520
    • Novo Nordisk Investigational Site
  • Turku, Finland, FI-20520
    • Novo Nordisk Investigational Site
• India
  • Ahmedabad, India, 380015
    • Novo Nordisk Investigational Site
  • Bilaspur, India, 495001
    • Novo Nordisk Investigational Site
  • Dhantoli, Nagpur, India, 440012
    • Novo Nordisk Investigational Site
  • Hyderabad, India, 500034
    • Novo Nordisk Investigational Site
  • New Dehli, India, 110029
    • Novo Nordisk Investigational Site
  • Ramdaspeth / Nagpur, India, 440010
    • Novo Nordisk Investigational Site
  • Thriruvananthapuram, India, 695 032
    • Novo Nordisk Investigational Site
  • Karnataka
    • Bangalore, Karnataka, India, 560034
      • Novo Nordisk Investigational Site
  • Tamil Nadu
    • Chennai, Tamil Nadu, India, 600086
      • Novo Nordisk Investigational Site
    • Chennai, Tamil Nadu, India, 600029
      • Novo Nordisk Investigational Site
• Italy
  • Bari, Italy, 70124
    • Novo Nordisk Investigational Site
  • Forlì, Italy, 47100
    • Novo Nordisk Investigational Site
  • Gazi, Italy, 98124
    • Novo Nordisk Investigational Site
  • Milano, Italy, 20162
    • Novo Nordisk Investigational Site
  • Milano, Italy, 200122
    • Novo Nordisk Investigational Site
  • Olbia, Italy, 07026
    • Novo Nordisk Investigational Site
  • Palermo, Italy, 90127
    • Novo Nordisk Investigational Site
  • Partinico, Italy, 90047
    • Novo Nordisk Investigational Site
  • Roma, Italy, 00168
    • Novo Nordisk Investigational Site
  • Torino, Italy, 10126
    • Novo Nordisk Investigational Site
  • Treviglio, Italy, 24047
    • Novo Nordisk Investigational Site
  • Treviso, Italy, 31100
    • Novo Nordisk Investigational Site
• Japan
  • Chuo-ku, Tokyo, Japan, 103 0002
    • Novo Nordisk Investigational Site
  • Ebina-shi, Japan, 243 0432
    • Novo Nordisk Investigational Site
  • Imizu-shi, Japan, 939 0363
    • Novo Nordisk Investigational Site
  • Izumisano-shi, Japan, 598 0048
    • Novo Nordisk Investigational Site
  • Koriyama-shi, Fukushima, Japan, 963 8851
    • Novo Nordisk Investigational Site
  • Kumamoto-shi,Kumamoto, Japan, 862 0976
    • Novo Nordisk Investigational Site
  • Miyazaki-shi, Japan, 880 0034
    • Novo Nordisk Investigational Site
  • Naka-shi, Ibaraki, Japan, 311 0113
    • Novo Nordisk Investigational Site
  • Nishinomiya-shi, Hygo, Japan, 662 0971
    • Novo Nordisk Investigational Site
  • Oita-shi, Japan, 870 0039
    • Novo Nordisk Investigational Site
  • Ota-ku, Tokyo, Japan, 144 0035
    • Novo Nordisk Investigational Site
  • Sapporo-shi, Hokkaido, Japan, 060 0062
    • Novo Nordisk Investigational Site
  • Sapporo-shi, Hokkaido, Japan, 060-0001
    • Novo Nordisk Investigational Site
  • Sapporo-shi, Hokkaido, Japan, 062 0007
    • Novo Nordisk Investigational Site
  • Yokohama-shi, Japan, 235 0045
    • Novo Nordisk Investigational Site
• Macedonia, The Former Yugoslav Republic of
  • Skopje, Macedonia, The Former Yugoslav Republic of, 1000
    • Novo Nordisk Investigational Site
• United Kingdom
  • Bath, United Kingdom, BA1 3NG
    • Novo Nordisk Investigational Site
  • Blackburn, United Kingdom, BB2 3HH
    • Novo Nordisk Investigational Site
  • Carmarthen, United Kingdom, SA31 2AF
    • Novo Nordisk Investigational Site
  • Edinburgh, United Kingdom, EH4 2XU
    • Novo Nordisk Investigational Site
  • Leicester, United Kingdom, LE1 5WW
    • Novo Nordisk Investigational Site
  • Manchester, United Kingdom, M8 5RB
    • Novo Nordisk Investigational Site
  • Middlesbrough, United Kingdom, TS4 3BW
    • Novo Nordisk Investigational Site
  • Northampton, United Kingdom, NN1 5BD
    • Novo Nordisk Investigational Site
  • Nottingham, United Kingdom, NG7 2UH
    • Novo Nordisk Investigational Site
  • Penarth, United Kingdom, CF64 2XX
    • Novo Nordisk Investigational Site
  • Plymouth, United Kingdom, PL6 8BQ
    • Novo Nordisk Investigational Site
  • Sheffield, United Kingdom, S5 7AU
    • Novo Nordisk Investigational Site
  • Torquay, United Kingdom, TQ2 7AA
    • Novo Nordisk Investigational Site
  • Wirral, Merseyside, United Kingdom, CH63 4JY
    • 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%
• 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: IDeg OD	Drug: insulin degludec; Injected s.c. (under the skin) once daily. Dose was individually adjusted.; Drug: insulin aspart; Injected s.c. (under the skin) as mealtime insulin. Dose was individually adjusted.
Active Comparator: IDet	Drug: insulin aspart; Injected s.c. (under the skin) as mealtime insulin. Dose was individually adjusted.; Drug: insulin detemir; Injected s.c. (under the skin) once daily or twice daily (BID). 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 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

Collaborators and Investigators

• Sponsor: Novo Nordisk A/S

Publications and helpful links

General Publications

• Davies MJ, Gross JL, Ono Y, Sasaki T, Bantwal G, Gall MA, Niemeyer M, Seino H; BEGIN BB T1 Study Group. Efficacy and safety of insulin degludec given as part of basal-bolus treatment with mealtime insulin aspart in type 1 diabetes: a 26-week randomized, open-label, treat-to-target non-inferiority trial. Diabetes Obes Metab. 2014 Oct;16(10):922-30. doi: 10.1111/dom.12298. Epub 2014 May 8.
• Davies M, Sasaki T, Gross JL, Bantwal G, Ono Y, Nishida T, Tojjar D, Seino H. Comparison of insulin degludec with insulin detemir in type 1 diabetes: a 1-year treat-to-target trial. Diabetes Obes Metab. 2016 Jan;18(1):96-9. doi: 10.1111/dom.12573. Epub 2015 Oct 19.

Helpful Links

• Clinical Trials at Novo Nordisk

Study record dates

Study Major Dates

• Study Start: February 1, 2010
• Primary Completion (Actual): December 1, 2010
• Study Completion (Actual): December 1, 2010

Study Registration Dates

• First Submitted: February 22, 2010
• First Submitted That Met QC Criteria: February 22, 2010
• First Posted (Estimate): February 24, 2010

Study Record Updates

• Last Update Posted (Actual): March 6, 2017
• Last Update Submitted That Met QC Criteria: January 20, 2017
• Last Verified: January 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 Detemir
• Other Study ID Numbers: NN1250-3585; 2009-011672-29 (EudraCT Number); U1111-1111-7249 (Other Identifier: WHO); JapicCTI-101067 (Registry Identifier: JAPIC); 2009-015721-36 (EudraCT Number); U1111-1114-9479 (Other Identifier: WHO); JapicCTI-22-0677 (Registry Identifier: JAPIC)