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

• Sponsor: Novo Nordisk A/S (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00982228
• Collaborator: (none)
• Enrollment: 629
• Locations: 91
• Arms: 2
• Actual Duration (Months): 14.2
• Patients Per Site: 6.9
• Patients Per Site Per Month: 0.5

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Diabetes; Diabetes Mellitus, Type 1	Drug: insulin degludec; Drug: insulin glargine; Drug: insulin aspart	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 629 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: 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)
• Actual Study Start Date: Sep 1, 2009
• Actual Primary Completion Date: Nov 8, 2010
• Actual Study Completion Date: Nov 8, 2010

Arms and Interventions

Arm	Intervention/Treatment
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.
Active Comparator: IGlar OD	Drug: insulin glargine; Injected subcutaneously once daily. Dose individually adjusted.; Drug: insulin aspart; Injected subcutaneously as mealtime insulin. Dose was individually adjusted.

Outcome Measures

Primary Outcome Measures

1. Main Trial (Primary Endpoint): Change in Glycosylated Haemoglobin (HbA1c) After 52 Weeks of Treatment [Week 0, Week 52]

   Change from baseline in HbA1c after 52 weeks of treatment

2. Extension Trial (Primary Endpoint): Rate of Treatment Emergent Adverse Events (AEs) [Week 0 to Week 104 + 7 days follow up]

   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.

3. Extension Trial (Primary Endpoint): Rate of Confirmed Hypoglycaemic Episodes [Week 0 to Week 104 + 7 days follow up]

   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.

4. Extension Trial (Primary Endpoint): Cross-reacting Antibodies to Human Insulin [Week 0, Week 106]

   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.

Secondary Outcome Measures

1. Extension Trial (Primary Endpoint): Rate of Nocturnal Confirmed Hypoglycaemic Episodes [Week 0 to Week 104 + 7 days follow up]

   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.

2. Extension Trial (Secondary Endpoint): Change in Glycosylated Haemoglobin (HbA1c) After 104 Weeks of Treatment [Week 0, Week 104]

   Change from baseline in HbA1c after 104 weeks of treatment

3. Extension Trial (Secondary Endpoint): Mean of 9-point Self Measured Plasma Glucose Profile (SMPG) at Week 104 of Treatment [Treatment week 104]

   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.

4. Main Trial (Secondary Endpoint): Rate of Confirmed Hypoglycaemic Episodes [Week 0 to Week 52 + 7 days follow up]

   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.

5. Main Trial (Secondary Endpoint): Rate of Nocturnal Confirmed Hypoglycaemic Episodes [Week 0 to Week 52 + 7 days follow up]

   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.

6. Main Trial (Secondary Endpoint): Mean of 9-point Self Measured Plasma Glucose Profile (SMPG) at Week 52 [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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Novo Nordisk Investigational Site	Birmingham	Alabama	United States	35209
2	Novo Nordisk Investigational Site	Huntsville	Alabama	United States	35801
3	Novo Nordisk Investigational Site	Peoria	Arizona	United States	85381
4	Novo Nordisk Investigational Site	Concord	California	United States	94520
5	Novo Nordisk Investigational Site	Fresno	California	United States	93720
6	Novo Nordisk Investigational Site	Greenbrae	California	United States	94904
7	Novo Nordisk Investigational Site	Huntington Beach	California	United States	92648
8	Novo Nordisk Investigational Site	La Mesa	California	United States	91942
9	Novo Nordisk Investigational Site	Los Gatos	California	United States	95032
10	Novo Nordisk Investigational Site	Santa Barbara	California	United States	93105
11	Novo Nordisk Investigational Site	Tustin	California	United States	92780
12	Novo Nordisk Investigational Site	Ventura	California	United States	93003
13	Novo Nordisk Investigational Site	Walnut Creek	California	United States	94598-3347
14	Novo Nordisk Investigational Site	Aurora	Colorado	United States	80045-7402
15	Novo Nordisk Investigational Site	Aurora	Colorado	United States	80045
16	Novo Nordisk Investigational Site	Hollywood	Florida	United States	33021
17	Novo Nordisk Investigational Site	Lake Mary	Florida	United States	32746
18	Novo Nordisk Investigational Site	Miami	Florida	United States	33136
19	Novo Nordisk Investigational Site	Atlanta	Georgia	United States	30318
20	Novo Nordisk Investigational Site	Lawrenceville	Georgia	United States	30046
21	Novo Nordisk Investigational Site	Honolulu	Hawaii	United States	96814
22	Novo Nordisk Investigational Site	Chicago	Illinois	United States	60611-2661
23	Novo Nordisk Investigational Site	Vincennes	Indiana	United States	47591-1029
24	Novo Nordisk Investigational Site	Lexington	Kentucky	United States	40503
25	Novo Nordisk Investigational Site	Lexington	Kentucky	United States	40536-0284
26	Novo Nordisk Investigational Site	Scarborough	Maine	United States	04074-9302
27	Novo Nordisk Investigational Site	Hyattsville	Maryland	United States	20782
28	Novo Nordisk Investigational Site	Rockville	Maryland	United States	20852
29	Novo Nordisk Investigational Site	Brockton	Massachusetts	United States	02301
30	Novo Nordisk Investigational Site	Flint	Michigan	United States	48503-5904
31	Novo Nordisk Investigational Site	Livonia	Michigan	United States	48154
32	Novo Nordisk Investigational Site	Eagan	Minnesota	United States	55123
33	Novo Nordisk Investigational Site	Chesterfield	Missouri	United States	63017
34	Novo Nordisk Investigational Site	Jefferson City	Missouri	United States	65109
35	Novo Nordisk Investigational Site	St. Charles	Missouri	United States	63303
36	Novo Nordisk Investigational Site	Great Falls	Montana	United States	59405
37	Novo Nordisk Investigational Site	Omaha	Nebraska	United States	68114
38	Novo Nordisk Investigational Site	Omaha	Nebraska	United States	68124
39	Novo Nordisk Investigational Site	Dover	New Hampshire	United States	03820
40	Novo Nordisk Investigational Site	Lawrenceville	New Jersey	United States	08648
41	Novo Nordisk Investigational Site	Flushing	New York	United States	11365
42	Novo Nordisk Investigational Site	Rochester	New York	United States	14607
43	Novo Nordisk Investigational Site	Chapel Hill	North Carolina	United States	27517
44	Novo Nordisk Investigational Site	Raleigh	North Carolina	United States	27609
45	Novo Nordisk Investigational Site	Columbus	Ohio	United States	43203
46	Novo Nordisk Investigational Site	Oklahoma City	Oklahoma	United States	73104
47	Novo Nordisk Investigational Site	Pittsburgh	Pennsylvania	United States	15212
48	Novo Nordisk Investigational Site	Pittsburgh	Pennsylvania	United States	15224-2215
49	Novo Nordisk Investigational Site	Rapid City	South Dakota	United States	57701
50	Novo Nordisk Investigational Site	Chattanooga	Tennessee	United States	37404
51	Novo Nordisk Investigational Site	Chattanooga	Tennessee	United States	37411
52	Novo Nordisk Investigational Site	Dallas	Texas	United States	75230
53	Novo Nordisk Investigational Site	Dallas	Texas	United States	75231
54	Novo Nordisk Investigational Site	Dallas	Texas	United States	75246
55	Novo Nordisk Investigational Site	Lubbock	Texas	United States	79423
56	Novo Nordisk Investigational Site	Round Rock	Texas	United States	78681
57	Novo Nordisk Investigational Site	St. George	Utah	United States	84790
58	Novo Nordisk Investigational Site	Renton	Washington	United States	98057
59	Novo Nordisk Investigational Site	Milwaukee	Wisconsin	United States	53209
60	Novo Nordisk Investigational Site	Boisguillaume		France	76233
61	Novo Nordisk Investigational Site	Brest		France	29609
62	Novo Nordisk Investigational Site	Grenoble		France	38043
63	Novo Nordisk Investigational Site	LA ROCHELLE cedex		France	17019
64	Novo Nordisk Investigational Site	Montpellier		France
65	Novo Nordisk Investigational Site	Nice		France	06002
66	Novo Nordisk Investigational Site	Paris		France	75877
67	Novo Nordisk Investigational Site	Aschaffenburg		Germany	63739
68	Novo Nordisk Investigational Site	Bad Kreuznach		Germany	55545
69	Novo Nordisk Investigational Site	Dormagen		Germany	41539
70	Novo Nordisk Investigational Site	Hamburg		Germany	21073
71	Novo Nordisk Investigational Site	Hamburg		Germany	22607
72	Novo Nordisk Investigational Site	St. Ingbert		Germany	66386
73	Novo Nordisk Investigational Site	Moscow		Russian Federation	117036
74	Novo Nordisk Investigational Site	Moscow		Russian Federation	119034
75	Novo Nordisk Investigational Site	Moscow		Russian Federation	127486
76	Novo Nordisk Investigational Site	Novosibirsk		Russian Federation	630047
77	Novo Nordisk Investigational Site	Saint-Peterburg		Russian Federation	190068
78	Novo Nordisk Investigational Site	Saint-Petersburg		Russian Federation	194354
79	Novo Nordisk Investigational Site	Tumen		Russian Federation	625023
80	Novo Nordisk Investigational Site	Yaroslavl		Russian Federation	150062
81	Novo Nordisk Investigational Site	Johannesburg	Gauteng	South Africa	1724
82	Novo Nordisk Investigational Site	Cape Town	Western Cape	South Africa	7130
83	Novo Nordisk Investigational Site	Cape Town	Western Cape	South Africa	7925
84	Novo Nordisk Investigational Site	Aberdeen		United Kingdom	AB25 1LD
85	Novo Nordisk Investigational Site	Birmingham		United Kingdom	B9 5SS
86	Novo Nordisk Investigational Site	Bradford		United Kingdom	BD9 6RJ
87	Novo Nordisk Investigational Site	Glasgow		United Kingdom	G21 3UW
88	Novo Nordisk Investigational Site	Guildford		United Kingdom	GU2 7XX
89	Novo Nordisk Investigational Site	Leeds		United Kingdom	LS9 7TF
90	Novo Nordisk Investigational Site	Llantrisant		United Kingdom	CF72 8XR
91	Novo Nordisk Investigational Site	Sheffield		United Kingdom	S5 7AU

Sponsors and Collaborators

• Novo Nordisk A/S

Investigators

• Study Director: Global Clinical Registry (GCR, 1452), Novo Nordisk A/S

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Clinical Trials at Novo Nordisk

Publications

None provided.

• Responsible Party: Novo Nordisk A/S
• ClinicalTrials.gov Identifier: NCT00982228
• Other Study ID Numbers: NN1250-3583; 2008-005774-13; U1111-1111-8789; 2009-015755-24; U1111-1116-1578; NCT01198041
• First Posted: Sep 23, 2009
• Last Update Posted: Apr 6, 2017
• Last Verified: Mar 1, 2017

• Additional relevant MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 1; Insulin; Insulin, Globin Zinc; Insulin Glargine; Insulin Aspart

Study Results

Participant Flow

Recruitment Details	The trial was conducted at 79 sites in 6 countries: France (6), Germany (5), Russia (7), South Africa (3), United Kingdom (U.K.) (6) and United States (U.S.) (52).
Pre-assignment Detail	All subjects who completed the 52-week main trial (NN1250-3583, NCT00982228) and were found to be eligible for the extension trial were offered to participate in the 52-week extension trial (NN1250-3644).

Arm/Group Title	IDeg OD	IGlar OD
Arm/Group Description	Insulin degludec (IDeg) was given subcutaneously (s.c.) once daily (OD) in the evening in combination with insulin aspart (IAsp) as meal time insulin. IDeg was given for 52 weeks in the main period and for an additional 52 weeks in the extension period.	Insulin glargine (IGlar) was given s.c. once daily (OD) according to approved labelling in combination with insulin aspart (IAsp) as meal time insulin. IGlar was given for 52 weeks in the main period and for additional 52 weeks in the extension period.
Period Title: Main: Week 0 to 52 (NN1250-3583)
STARTED	472	157
Full Analysis Set	472	157
Exposed	472	154
COMPLETED	404	137
NOT COMPLETED	68	20
Period Title: Main: Week 0 to 52 (NN1250-3583)
STARTED	351	118
COMPLETED	330	113
NOT COMPLETED	21	5

Baseline Characteristics

Arm/Group Title	IDeg OD	IGlar OD	Total
Arm/Group Description	Insulin degludec (IDeg) was given subcutaneously (s.c.) once daily (OD) in the evening in combination with insulin aspart (IAsp) as meal time insulin. IDeg was given for 52 weeks in the main period and for an additional 52 weeks in the extension period.	Insulin glargine (IGlar) was given s.c. once daily (OD) according to approved labelling in combination with insulin aspart (IAsp) as meal time insulin. IGlar was given for 52 weeks in the main period and for additional 52 weeks in the extension period.	Total of all reporting groups
Overall Participants	472	157	629
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	42.8 (13.7)	43.7 (13.3)	43.0 (13.6)
Sex: Female, Male (Count of Participants)
Female	194 41.1%	67 42.7%	261 41.5%
Male	278 58.9%	90 57.3%	368 58.5%
Glycosylated haemoglobin (HbA1c) (percentage of glycosylated haemoglobin) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [percentage of glycosylated haemoglobin]	7.7 (0.9)	7.7 (1.0)	7.7 (1.0)
Fasting plasma glucose (FPG) (mmol/L) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mmol/L]	9.1 (4.0)	9.7 (4.4)	9.3 (4.1)

Outcome Measures

1. Primary Outcome

Title	Main Trial (Primary Endpoint): Change in Glycosylated Haemoglobin (HbA1c) After 52 Weeks of Treatment
Description	Change from baseline in HbA1c after 52 weeks of treatment
Time Frame	Week 0, Week 52

Outcome Measure Data

Analysis Population Description

The full analysis set (FAS) included all randomised subjects and missing data was imputed using LOCF (last observation carried forward).

Arm/Group Title	IDeg OD	IGlar OD
Arm/Group Description	Insulin degludec (IDeg) was given subcutaneously (s.c.) once daily (OD) in the evening in combination with insulin aspart (IAsp) as meal time insulin. IDeg was given for 52 weeks in the main period and for an additional 52 weeks in the extension period.	Insulin glargine (IGlar) was given s.c. once daily (OD) according to approved labelling in combination with insulin aspart (IAsp) as meal time insulin. IGlar was given for 52 weeks in the main period and for additional 52 weeks in the extension period.
Measure Participants	472	157
Mean (Standard Deviation) [percentage of glycosylated haemoglobin]	-0.40 (0.73)	-0.39 (0.84)

2. Primary Outcome

Title	Extension Trial (Primary Endpoint): Rate of Treatment Emergent Adverse Events (AEs)
Description	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.
Time Frame	Week 0 to Week 104 + 7 days follow up

Outcome Measure Data

Analysis Population Description

Safety analysis set (SAS) included all subjects who received at least one dose of the investigational product or its comparator in the main trial including subjects carried through to the extension trial.

Arm/Group Title	IDeg OD	IGlar OD
Arm/Group Description	Insulin degludec (IDeg) was given subcutaneously (s.c.) once daily (OD) in the evening in combination with insulin aspart (IAsp) as meal time insulin. IDeg was given for 52 weeks in the main period and for an additional 52 weeks in the extension period.	Insulin glargine (IGlar) was given s.c. once daily (OD) according to approved labelling in combination with insulin aspart (IAsp) as meal time insulin. IGlar was given for 52 weeks in the main period and for additional 52 weeks in the extension period.
Measure Participants	472	154
Adverse events (AE)	383	374
Serious AE	14	17
Severe AE	22	26
Moderate AE	105	106
Mild AE	256	242
Fatal AE	1	1

3. Primary Outcome

Title	Extension Trial (Primary Endpoint): Rate of Confirmed Hypoglycaemic Episodes
Description	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.
Time Frame	Week 0 to Week 104 + 7 days follow up

Outcome Measure Data

Analysis Population Description

The SAS included all subjects who received at least one dose of the investigational product or its comparator in the main trial including subjects carried through to the extension trial.

Arm/Group Title	IDeg OD	IGlar OD
Arm/Group Description	Insulin degludec (IDeg) was given subcutaneously (s.c.) once daily (OD) in the evening in combination with insulin aspart (IAsp) as meal time insulin. IDeg was given for 52 weeks in the main period and for an additional 52 weeks in the extension period.	Insulin glargine (IGlar) was given s.c. once daily (OD) according to approved labelling in combination with insulin aspart (IAsp) as meal time insulin. IGlar was given for 52 weeks in the main period and for additional 52 weeks in the extension period.
Measure Participants	472	154
Number [Episodes/100 years of patient exposure]	3750	3743

4. Secondary Outcome

Title	Extension Trial (Primary Endpoint): Rate of Nocturnal Confirmed Hypoglycaemic Episodes
Description	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.
Time Frame	Week 0 to Week 104 + 7 days follow up

Outcome Measure Data

Analysis Population Description

The SAS included all subjects who received at least one dose of the investigational product or its comparator in the main trial including subjects carried through to the extension trial.

Arm/Group Title	IDeg OD	IGlar OD
Arm/Group Description	Insulin degludec (IDeg) was given subcutaneously (s.c.) once daily (OD) in the evening in combination with insulin aspart (IAsp) as meal time insulin. IDeg was given for 52 weeks in the main period and for an additional 52 weeks in the extension period.	Insulin glargine (IGlar) was given s.c. once daily (OD) according to approved labelling in combination with insulin aspart (IAsp) as meal time insulin. IGlar was given for 52 weeks in the main period and for additional 52 weeks in the extension period.
Measure Participants	472	154
Number [Episodes/100 years of patient exposure]	390	532

5. Primary Outcome

Title	Extension Trial (Primary Endpoint): Cross-reacting Antibodies to Human Insulin
Description	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.
Time Frame	Week 0, Week 106

Outcome Measure Data

Analysis Population Description

The SAS included all subjects who received at least one dose of the investigational product or its comparator in the main trial including subjects carried through to the extension trial.

Arm/Group Title	IDeg OD	IGlar OD
Arm/Group Description	Insulin degludec (IDeg) was given subcutaneously (s.c.) once daily (OD) in the evening in combination with insulin aspart (IAsp) as meal time insulin. IDeg was given for 52 weeks in the main period and for an additional 52 weeks in the extension period.	Insulin glargine (IGlar) was given s.c. once daily (OD) according to approved labelling in combination with insulin aspart (IAsp) as meal time insulin. IGlar was given for 52 weeks in the main period and for additional 52 weeks in the extension period.
Measure Participants	335	111
Mean (Standard Deviation) [%B/T]	11.3 (15.6)	11.0 (16.0)

6. Secondary Outcome

Title	Extension Trial (Secondary Endpoint): Change in Glycosylated Haemoglobin (HbA1c) After 104 Weeks of Treatment
Description	Change from baseline in HbA1c after 104 weeks of treatment
Time Frame	Week 0, Week 104

Outcome Measure Data

Analysis Population Description

The FAS included all randomised subjects in the main trial including subjects carried through to the extension trial and missing data was imputed using LOCF.

Arm/Group Title	IDeg OD	IGlar OD
Arm/Group Description	Insulin degludec (IDeg) was given subcutaneously (s.c.) once daily (OD) in the evening in combination with insulin aspart (IAsp) as meal time insulin. IDeg was given for 52 weeks in the main period and for an additional 52 weeks in the extension period.	Insulin glargine (IGlar) was given s.c. once daily (OD) according to approved labelling in combination with insulin aspart (IAsp) as meal time insulin. IGlar was given for 52 weeks in the main period and for additional 52 weeks in the extension period.
Measure Participants	472	157
Mean (Standard Deviation) [percentage of glycosylated haemoglobin]	-0.27 (0.75)	-0.24 (0.86)

7. Secondary Outcome

Title	Extension Trial (Secondary Endpoint): Mean of 9-point Self Measured Plasma Glucose Profile (SMPG) at Week 104 of Treatment
Description	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.
Time Frame	Treatment week 104

Outcome Measure Data

Analysis Population Description

The FAS included all randomised subjects in the main trial including subjects carried through to the extension trial and missing data was imputed using LOCF. For 12 subjects all 9-point SMPG values were missing.

Arm/Group Title	IDeg OD	IGlar OD
Arm/Group Description	Insulin degludec (IDeg) was given subcutaneously (s.c.) once daily (OD) in the evening in combination with insulin aspart (IAsp) as meal time insulin. IDeg was given for 52 weeks in the main period and for an additional 52 weeks in the extension period.	Insulin glargine (IGlar) was given s.c. once daily (OD) according to approved labelling in combination with insulin aspart (IAsp) as meal time insulin. IGlar was given for 52 weeks in the main period and for additional 52 weeks in the extension period.
Measure Participants	463	154
Mean (Standard Deviation) [mmol/L]	8.0 (2.2)	8.1 (2.2)

8. Secondary Outcome

Title	Main Trial (Secondary Endpoint): Rate of Confirmed Hypoglycaemic Episodes
Description	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.
Time Frame	Week 0 to Week 52 + 7 days follow up

Outcome Measure Data

Analysis Population Description

The SAS included all subjects who received at least one dose of the investigational product or its comparator.

Arm/Group Title	IDeg OD	IGlar OD
Arm/Group Description	Insulin degludec (IDeg) was given subcutaneously (s.c.) once daily (OD) in the evening in combination with insulin aspart (IAsp) as meal time insulin. IDeg was given for 52 weeks in the main period and for an additional 52 weeks in the extension period.	Insulin glargine (IGlar) was given s.c. once daily (OD) according to approved labelling in combination with insulin aspart (IAsp) as meal time insulin. IGlar was given for 52 weeks in the main period and for additional 52 weeks in the extension period.
Measure Participants	472	154
Number [Episodes/100 years of patient exposure]	4254	4018

9. Secondary Outcome

Title	Main Trial (Secondary Endpoint): Rate of Nocturnal Confirmed Hypoglycaemic Episodes
Description	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.
Time Frame	Week 0 to Week 52 + 7 days follow up

Outcome Measure Data

Analysis Population Description

The SAS included all subjects who received at least one dose of the investigational product or its comparator.

Arm/Group Title	IDeg OD	IGlar OD
Arm/Group Description	Insulin degludec (IDeg) was given subcutaneously (s.c.) once daily (OD) in the evening in combination with insulin aspart (IAsp) as meal time insulin. IDeg was given for 52 weeks in the main period and for an additional 52 weeks in the extension period.	Insulin glargine (IGlar) was given s.c. once daily (OD) according to approved labelling in combination with insulin aspart (IAsp) as meal time insulin. IGlar was given for 52 weeks in the main period and for additional 52 weeks in the extension period.
Measure Participants	472	154
Number [Episodes/100 years of patient exposure]	441	586

10. Secondary Outcome

Title	Main Trial (Secondary Endpoint): Mean of 9-point Self Measured Plasma Glucose Profile (SMPG) at Week 52
Description	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.
Time Frame	Week 52

Outcome Measure Data

Analysis Population Description

The FAS included all randomised subjects and missing data was imputed using LOCF. For 7 subjects all 9-point SMPG values were missing.

Arm/Group Title	IDeg OD	IGlar OD
Arm/Group Description	Insulin degludec (IDeg) was given subcutaneously (s.c.) once daily (OD) in the evening in combination with insulin aspart (IAsp) as meal time insulin. IDeg was given for 52 weeks in the main period and for an additional 52 weeks in the extension period.	Insulin glargine (IGlar) was given s.c. once daily (OD) according to approved labelling in combination with insulin aspart (IAsp) as meal time insulin. IGlar was given for 52 weeks in the main period and for additional 52 weeks in the extension period.
Measure Participants	467	155
Mean (Standard Deviation) [mmol/L]	8.1 (2.3)	8.3 (2.4)

Adverse Events

Time Frame	The adverse events were collected in a time frame of 104 weeks + 1 week after last dose in main trial + 1 more week after last dose in extension trial.
Adverse Event Reporting Description	The SAS included all subjects who received at least one dose of the investigational product or its comparator.
Arm/Group Title	IDeg OD		IGlar OD
Arm/Group Description	Insulin degludec (IDeg) was given subcutaneously (s.c.) once daily (OD) in the evening in combination with insulin aspart (IAsp) as meal time insulin. IDeg was given for 52 weeks in the main period and for an additional 52 weeks in the extension period.		Insulin glargine (IGlar) was given s.c. once daily (OD) according to approved labelling in combination with insulin aspart (IAsp) as meal time insulin. IGlar was given for 52 weeks in the main period and for additional 52 weeks in the extension period.
All Cause Mortality
	IDeg OD		IGlar OD
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	IDeg OD		IGlar OD
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	71/472 (15%)		29/154 (18.8%)
Cardiac disorders
Acute myocardial infarction	1/472 (0.2%)	1	0/154 (0%)	0
Myocardial infarction	2/472 (0.4%)	2	1/154 (0.6%)	1
Bundle branch block left	0/472 (0%)	0	1/154 (0.6%)	1
Coronary artery disease	2/472 (0.4%)	2	0/154 (0%)	0
Pericarditis	1/472 (0.2%)	1	0/154 (0%)	0
Ventricular arrhythmia	0/472 (0%)	0	1/154 (0.6%)	1
Ventricular Tachycardia	1/472 (0.2%)	1	0/154 (0%)	0
Ear and labyrinth disorders
Tympanic membrane perforation	1/472 (0.2%)	1	0/154 (0%)	0
Gastrointestinal disorders
Colitis	1/472 (0.2%)	1	0/154 (0%)	0
Diabetic gastroparesis	0/472 (0%)	0	1/154 (0.6%)	1
Gastritis	0/472 (0%)	0	1/154 (0.6%)	1
Inguinal hernia	1/472 (0.2%)	1	0/154 (0%)	0
Melaena	1/472 (0.2%)	1	0/154 (0%)	0
Salivary gland calculus	1/472 (0.2%)	1	0/154 (0%)	0
Gastric ulcer	1/472 (0.2%)	1	0/154 (0%)	0
Pancreatic pseudocyst	1/472 (0.2%)	1	0/154 (0%)	0
Pancreatitis acute	1/472 (0.2%)	1	0/154 (0%)	0
Vomiting	1/472 (0.2%)	1	0/154 (0%)	0
General disorders
Sudden death	1/472 (0.2%)	1	1/154 (0.6%)	1
Hepatobiliary disorders
Cholelithiasis	1/472 (0.2%)	1	0/154 (0%)	0
Immune system disorders
Allergy to animal	1/472 (0.2%)	1	0/154 (0%)	0
Infections and infestations
Cellulitis	1/472 (0.2%)	1	0/154 (0%)	0
Cholecystitis infective	0/472 (0%)	0	1/154 (0.6%)	1
Gastroenteritis	0/472 (0%)	0	1/154 (0.6%)	1
Pneumonia	1/472 (0.2%)	1	1/154 (0.6%)	1
Pulmonary tuberculoma	0/472 (0%)	0	1/154 (0.6%)	1
Pulmonary tuberculosis	0/472 (0%)	0	1/154 (0.6%)	1
Appendicitis	1/472 (0.2%)	1	1/154 (0.6%)	1
Upper respiratory tract infection	1/472 (0.2%)	1	0/154 (0%)	0
Injury, poisoning and procedural complications
Forearm fracture	1/472 (0.2%)	1	0/154 (0%)	0
Incorrect dose administered	2/472 (0.4%)	2	0/154 (0%)	0
Joint injury	1/472 (0.2%)	1	0/154 (0%)	0
Pneumothorax traumatic	0/472 (0%)	0	1/154 (0.6%)	1
Road traffic accident	0/472 (0%)	0	1/154 (0.6%)	1
Accidental Overdose	1/472 (0.2%)	1	0/154 (0%)	0
Cervical vertebral fracture	1/472 (0.2%)	1	0/154 (0%)	0
Hip fracture	1/472 (0.2%)	1	0/154 (0%)	0
Injury	0/472 (0%)	0	1/154 (0.6%)	1
Tendon Rupture	0/472 (0%)	0	1/154 (0.6%)	1
Metabolism and nutrition disorders
Diabetic ketoacidosis	2/472 (0.4%)	2	3/154 (1.9%)	3
Hypoglycaemia	27/472 (5.7%)	38	7/154 (4.5%)	10
Hypoglycaemic seizure	3/472 (0.6%)	3	2/154 (1.3%)	2
Hypoglycaemic unconsciousness	15/472 (3.2%)	20	4/154 (2.6%)	4
Musculoskeletal and connective tissue disorders
Arthritis reactive	0/472 (0%)	0	1/154 (0.6%)	1
Bone pain	1/472 (0.2%)	1	0/154 (0%)	0
Musculoskeletal chest pain	1/472 (0.2%)	1	0/154 (0%)	0
Tenosynovitis	1/472 (0.2%)	1	0/154 (0%)	0
Neck pain	0/472 (0%)	0	1/154 (0.6%)	1
Osteonecrosis	0/472 (0%)	0	1/154 (0.6%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Squamous cell carcinoma	1/472 (0.2%)	1	0/154 (0%)	0
Thyroid cancer	0/472 (0%)	0	1/154 (0.6%)	1
Gallbladder cancer metastatic	0/472 (0%)	0	1/154 (0.6%)	1
Glioblastoma	1/472 (0.2%)	1	0/154 (0%)	0
Oesophageal adenocarcinoma	1/472 (0.2%)	1	0/154 (0%)	0
Nervous system disorders
Convulsion	1/472 (0.2%)	1	0/154 (0%)	0
Hypoglycaemic coma	1/472 (0.2%)	1	0/154 (0%)	0
Transient ischaemic attack	1/472 (0.2%)	1	0/154 (0%)	0
Headache	0/472 (0%)	0	1/154 (0.6%)	1
Hypoglycaemic encephalopathy	0/472 (0%)	0	1/154 (0.6%)	1
Syncope	1/472 (0.2%)	1	0/154 (0%)	0
Renal and urinary disorders
Nephrolithiasis	0/472 (0%)	0	1/154 (0.6%)	1
Renal failure acute	0/472 (0%)	0	1/154 (0.6%)	1
Reproductive system and breast disorders
Cervical dysplasia	0/472 (0%)	0	1/154 (0.6%)	1
Respiratory, thoracic and mediastinal disorders
Epistaxis	1/472 (0.2%)	1	0/154 (0%)	0
Skin and subcutaneous tissue disorders
Skin ulcer	1/472 (0.2%)	1	0/154 (0%)	0
Other (Not Including Serious) Adverse Events
	IDeg OD		IGlar OD
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	353/472 (74.8%)		118/154 (76.6%)
Gastrointestinal disorders
Diarrhoea	39/472 (8.3%)	44	9/154 (5.8%)	12
Nausea	40/472 (8.5%)	57	14/154 (9.1%)	18
Vomiting	25/472 (5.3%)	26	11/154 (7.1%)	15
Immune system disorders
Seasonal allergy	10/472 (2.1%)	11	10/154 (6.5%)	10
Infections and infestations
Bronchitis	38/472 (8.1%)	46	11/154 (7.1%)	17
Gastroenteritis	44/472 (9.3%)	49	9/154 (5.8%)	10
Influenza	44/472 (9.3%)	53	17/154 (11%)	19
Nasopharyngitis	160/472 (33.9%)	284	51/154 (33.1%)	105
Sinusitis	58/472 (12.3%)	93	23/154 (14.9%)	31
Upper respiratory tract infection	122/472 (25.8%)	208	31/154 (20.1%)	48
Urinary tract infection	35/472 (7.4%)	40	12/154 (7.8%)	16
Gastrointestinal viral	25/472 (5.3%)	27	6/154 (3.9%)	9
Injury, poisoning and procedural complications
Wrong drug administered	31/472 (6.6%)	35	6/154 (3.9%)	6
Metabolism and nutrition disorders
Hypoglycaemia	44/472 (9.3%)	70	13/154 (8.4%)	18
Musculoskeletal and connective tissue disorders
Back Pain	33/472 (7%)	46	9/154 (5.8%)	15
Nervous system disorders
Headache	84/472 (17.8%)	162	22/154 (14.3%)	39
Respiratory, thoracic and mediastinal disorders
Cough	33/472 (7%)	37	17/154 (11%)	19
Oropharyngeal pain	34/472 (7.2%)	46	14/154 (9.1%)	19
Nasal congestion	17/472 (3.6%)	18	11/154 (7.1%)	13
Sinus congestion	22/472 (4.7%)	25	9/154 (5.8%)	12

Limitations/Caveats

[Not Specified]

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Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

Novo Nordisk maintains the right to be informed of any Investigator plans for publication and to review any scientific paper, presentation, communication or other information concerning the investigation described in this protocol. Any such communication must be submitted in writing to the Novo Nordisk trial manager prior to submission for comments. Comments will be given within four weeks from receipt of the planned communication.