BOOST™: Comparison of NN5401 Plus Insulin Aspart With Insulin Detemir Plus Insulin Aspart in Type 1 Diabetes

• Sponsor: Novo Nordisk A/S (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00978627
• Collaborator: (none)
• Enrollment: 548
• Locations: 81
• Arms: 2
• Duration (Months): 9
• Patients Per Site: 6.8
• Patients Per Site Per Month: 0.8

Study Details

Study Description

Brief Summary

This trial is conducted in Europe, Oceania, and the United States of America (USA).

The aim of this clinical trial is to compare NN5401 (insulin degludec/insulin aspart (IDegAsp)) with insulin detemir (IDet) plus insulin aspart in patients with type 1 diabetes (main period) followed by the extension period comparing the long-term safety of NN5401 plus insulin aspart with insulin detemir plus insulin aspart.

The main period is registered internally at Novo Nordisk as NN5401-3594 while the extension period is registered as NN5401-3645.

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

Study Design

• Study Type: Interventional
• Actual Enrollment: 548 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: NN5401-3594: A 26-week, Open-labelled, Two-arm, Parallel, Randomised Trial Comparing Efficacy and Safety of NN5401 Once Daily Plus Insulin Aspart vs. Basal-bolus Treatment With Insulin Detemir Plus Insulin Aspart in Subjects With Type 1 Diabetes / NN5401-3645: An Extension Trial Comparing Safety and Efficacy of NN5401 Plus Meal-time Insulin Aspart for the Remaining Meals With Insulin Detemir Plus Meal-time Insulin Aspart in Type 1 Diabetes (BOOST™: T1)
• Study Start Date: Aug 1, 2009
• Actual Primary Completion Date: May 1, 2010
• Actual Study Completion Date: May 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Experimental: IDegAsp OD	Drug: insulin degludec/insulin aspart; Injected subcutaneously (under the skin) once daily with a meal. Dose was individually adjusted.; Drug: insulin aspart; Injected subcutaneously (under the skin) at the remaining meals. Dose was individually adjusted.
Active Comparator: IDet	Drug: insulin detemir; Injected subcutaneously (under the skin) once daily or twice daily. Dose was individually adjusted.; Drug: insulin aspart; Injected subcutaneously (under the skin) as meal time insulin. Dose was individually adjusted.

Outcome Measures

Primary Outcome Measures

1. Main Trial (Primary Endpoint): Change in Glycosylated Haemoglobin (HbA1c) After 26 Weeks of Treatment [Week 0, Week 26]

   Change from baseline in HbA1c after 26 weeks of treatment

2. Extension Trial (Primary Endpoint): Rate of Confirmed Hypoglycaemic Episodes [Week 0 to Week 53 + 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 were defined as requiring assistance to administer carbohydrate, glucagon, or other resuscitative actions. Minor hypoglycaemic episodes were defined as able to treat her/himself and plasma glucose below 3.1 mmol /L.

3. Extension Trial (Primary Endpoint): Rate of Nocturnal Confirmed Hypoglycaemic Episodes [Week 0 to Week 53 + 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 were defined as requiring assistance to administer carbohydrate, glucagon, or other resuscitative actions. Minor hypoglycaemic episodes were defined as able to treat her/himself and plasma glucose below 3.1 mmol/L. Nocturnal hypoglycaemic episodes were defined as occurring between 00:01 and 05:59 a.m.

4. Extension Trial (Primary Endpoint): Rate of Treatment Emergent Adverse Events (AEs) [Week 0 to Week 53 + 7 days of 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.

Secondary Outcome Measures

1. Main Trial (Secondary Endpoint): Rate of Confirmed Hypoglycaemic Episodes [Week 0 to Week 26 + 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 were defined as requiring assistance to administer carbohydrate, glucagon, or other resuscitative actions. Minor hypoglycaemic episodes were defined as able to treat her/himself and plasma glucose below 3.1 mmol/L.

2. Main Trial (Secondary Endpoint): Mean of 9-point Self Measured Plasma Glucose Profile (SMPG) at Week 26 [Week 26]

   Overall mean of 9-point SMPG at 26 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.

3. Extension Trial (Secondary Endpoint): Change in Glycosylated Haemoglobin (HbA1c) After 52 Weeks of Treatment [Week 0, Week 53]

   Change from baseline in HbA1c after 52 weeks of treatment

4. Main Trial (Secondary Endpoint): Rate of Nocturnal Confirmed Hypoglycaemic Episodes [Week 0 to Week 26 + 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 were defined as requiring assistance to administer carbohydrate, glucagon, or other resuscitative actions. Minor hypoglycaemic episodes were defined as able to treat her/himself and plasma glucose below 3.1 mmol/L. Nocturnal hypoglycaemic episodes were defined as occurring between 00:01 and 05:59 a.m.

5. Extension Trial (Secondary Endpoint): Change in Fasting Plasma Glucose (FPG) After 52 Weeks of Treatment [Week 0, Week 53]

   Change from baseline in FPG after 52 weeks of treatment.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• FOR THE MAIN TRIAL, NN5401-3594:

• Type 1 diabetes mellitus for at least 12 months

• Ongoing daily treatment with insulin (in a basal bolus regimen, premix insulin regimen, self mix regimen) for at least 12 months

• HbA1c 7.0-10.0% (both inclusive)

• BMI (Body Mass Index) below or equal to 35.0 kg/m^2

• FOR THE EXTENSION TRIAL, NN5401-3645:

• The subject must have completed the six-month treatment period in trial NN5401-3594

Exclusion Criteria:

• FOR THE MAIN TRIAL, NN5401-3594:

• Treatment with other insulin regimens than insulin in a basal bolus regimen/premix insulin regimen/self mix regimen within 3 months

• Cardiovascular disease within the last 6 months

• Uncontrolled treated/untreated severe hypertension

• Pregnancy, breast-feeding, the intention of becoming pregnant or not using adequate contraceptive measures according to local requirements

• Cancer and medical history of cancer

• FOR THE EXTENSION TRIAL, NN5401-3645:

• Anticipated significant lifestyle changes during the trial

• Pregnancy, breast-feeding, the intention of becoming pregnant or not using adequate contraceptive measures

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Novo Nordisk Investigational Site	La Mesa	California	United States	91942
2	Novo Nordisk Investigational Site	Lancaster	California	United States	93534
3	Novo Nordisk Investigational Site	Mission Hills	California	United States	91345
4	Novo Nordisk Investigational Site	North Hollywood	California	United States	91606
5	Novo Nordisk Investigational Site	Salinas	California	United States	93901
6	Novo Nordisk Investigational Site	Valencia	California	United States	91355
7	Novo Nordisk Investigational Site	Aurora	Colorado	United States	80045
8	Novo Nordisk Investigational Site	Miami	Florida	United States	33156
9	Novo Nordisk Investigational Site	Miami	Florida	United States	33169
10	Novo Nordisk Investigational Site	Atlanta	Georgia	United States	30318
11	Novo Nordisk Investigational Site	Lawrenceville	Georgia	United States	30046
12	Novo Nordisk Investigational Site	Roswell	Georgia	United States	30076
13	Novo Nordisk Investigational Site	Honolulu	Hawaii	United States	96814
14	Novo Nordisk Investigational Site	Chicago	Illinois	United States	60607
15	Novo Nordisk Investigational Site	Shawnee Mission	Kansas	United States	66204
16	Novo Nordisk Investigational Site	Lexington	Kentucky	United States	40503
17	Novo Nordisk Investigational Site	Eagan	Minnesota	United States	55123
18	Novo Nordisk Investigational Site	Minneapolis	Minnesota	United States	55416
19	Novo Nordisk Investigational Site	St. Peters	Missouri	United States	63376
20	Novo Nordisk Investigational Site	Butte	Montana	United States	59701
21	Novo Nordisk Investigational Site	Omaha	Nebraska	United States	68131
22	Novo Nordisk Investigational Site	Henderson	Nevada	United States	89052-2649
23	Novo Nordisk Investigational Site	Albany	New York	United States	12206
24	Novo Nordisk Investigational Site	Northport	New York	United States	11768
25	Novo Nordisk Investigational Site	Morehead City	North Carolina	United States	28557
26	Novo Nordisk Investigational Site	Greer	South Carolina	United States	29651
27	Novo Nordisk Investigational Site	Dallas	Texas	United States	75390-9302
28	Novo Nordisk Investigational Site	San Antonio	Texas	United States	78215
29	Novo Nordisk Investigational Site	San Antonio	Texas	United States	78240
30	Novo Nordisk Investigational Site	Seattle	Washington	United States	98105
31	Novo Nordisk Investigational Site	Broadmeadow	New South Wales	Australia	2292
32	Novo Nordisk Investigational Site	Camperdown	New South Wales	Australia	2050
33	Novo Nordisk Investigational Site	Coffs Harbour	New South Wales	Australia	2450
34	Novo Nordisk Investigational Site	Keswick	South Australia	Australia	5035
35	Novo Nordisk Investigational Site	Box Hill	Victoria	Australia	3128
36	Novo Nordisk Investigational Site	Fitzroy		Australia	3065
37	Novo Nordisk Investigational Site	Geelong		Australia	3220
38	Novo Nordisk Investigational Site	Aalborg		Denmark	9100
39	Novo Nordisk Investigational Site	Gentofte		Denmark	2820
40	Novo Nordisk Investigational Site	Århus C		Denmark	8000
41	Novo Nordisk Investigational Site	Auxerre		France	89000
42	Novo Nordisk Investigational Site	Narbonne		France	11108
43	Novo Nordisk Investigational Site	Nimes		France	30006
44	Novo Nordisk Investigational Site	Pointe à Pitre		France	97159
45	Novo Nordisk Investigational Site	Petah Tikva		Israel	49202
46	Novo Nordisk Investigational Site	Rishon Le Zion		Israel	75650
47	Novo Nordisk Investigational Site	Tel Hashomer		Israel	52621
48	Novo Nordisk Investigational Site	Lodz		Poland	91-738
49	Novo Nordisk Investigational Site	Lodz		Poland	93-338
50	Novo Nordisk Investigational Site	Sopot		Poland	81-756
51	Novo Nordisk Investigational Site	Szczecin		Poland	70-376
52	Novo Nordisk Investigational Site	Warszawa		Poland	02-507
53	Novo Nordisk Investigational Site	Warszawa		Poland	02-692
54	Novo Nordisk Investigational Site	Bayamon		Puerto Rico	00961
55	Novo Nordisk Investigational Site	Cluj Napoca	Cluj	Romania	400006
56	Novo Nordisk Investigational Site	Brasov		Romania	500365
57	Novo Nordisk Investigational Site	Bucharest		Romania	020042
58	Novo Nordisk Investigational Site	Bucharest		Romania	020475
59	Novo Nordisk Investigational Site	Buzau		Romania	120203
60	Novo Nordisk Investigational Site	Iasi		Romania	700547
61	Novo Nordisk Investigational Site	Oradea		Romania	410169
62	Novo Nordisk Investigational Site	Sibiu		Romania	550245
63	Novo Nordisk Investigational Site	Kemerovo		Russian Federation	650066
64	Novo Nordisk Investigational Site	Kursk		Russian Federation	305035
65	Novo Nordisk Investigational Site	Moscow		Russian Federation	117036
66	Novo Nordisk Investigational Site	Moscow		Russian Federation	125367
67	Novo Nordisk Investigational Site	Penza		Russian Federation	440026
68	Novo Nordisk Investigational Site	Saint-Petersburg		Russian Federation	195257
69	Novo Nordisk Investigational Site	Samara		Russian Federation	443067
70	Novo Nordisk Investigational Site	Saratov		Russian Federation	410053
71	Novo Nordisk Investigational Site	Saratov		Russian Federation	410710
72	Novo Nordisk Investigational Site	Smolensk		Russian Federation	214019
73	Novo Nordisk Investigational Site	Volgograd		Russian Federation	400138
74	Novo Nordisk Investigational Site	Bristol		United Kingdom	BS10 5NB
75	Novo Nordisk Investigational Site	Dundee		United Kingdom	DD1 9SY
76	Novo Nordisk Investigational Site	Edinburgh		United Kingdom	EH16 4SA
77	Novo Nordisk Investigational Site	Leicester		United Kingdom	LE1 5WW
78	Novo Nordisk Investigational Site	Liverpool		United Kingdom	L7 8XP
79	Novo Nordisk Investigational Site	Oxford		United Kingdom	OX3 7LE
80	Novo Nordisk Investigational Site	Salford		United Kingdom	M6 8HD
81	Novo Nordisk Investigational Site	Wirral, Merseyside		United Kingdom	CH63 4JY

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

• Hirsch IB, Franek E, Mersebach H, Bardtrum L, Hermansen K. Safety and efficacy of insulin degludec/insulin aspart with bolus mealtime insulin aspart compared with standard basal-bolus treatment in people with Type 1 diabetes: 1-year results from a randomized clinical trial (BOOST(®) T1). Diabet Med. 2017 Feb;34(2):167-173. doi: 10.1111/dme.13068. Epub 2016 Feb 19.

• Responsible Party: Novo Nordisk A/S
• ClinicalTrials.gov Identifier: NCT00978627
• Other Study ID Numbers: NN5401-3594; 2008-005769-71; U1111-1111-8943; 2009-013412-13; U1111-1113-2475; NCT01087606
• First Posted: Sep 17, 2009
• Last Update Posted: Mar 20, 2017
• Last Verified: Feb 1, 2017

• Additional relevant MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 1; Insulin; Insulin, Globin Zinc; Insulin Aspart; Insulin, Long-Acting; Insulin degludec, insulin aspart drug combination; Insulin Detemir

Study Results

Participant Flow

Recruitment Details	The trial was conducted at 79 sites in 9 countries: Denmark (3 sites), Poland (6 sites), Romania (8 sites), France (3 sites), United Kingdom (8 sites), Russian Federation (11 sites), Israel (4 sites), Australia (7 sites), and United States (29 sites). Some sites did not enrol subjects in the extension period.
Pre-assignment Detail	The total duration of treatment was up to 52 weeks (26 weeks [main trial: NN5401-3594, NCT00978627] + 26 weeks [extension trial: NN5401-3645]), separated by 1 week of wash-out period; during which subjects were treated with Neutral Protamine Hagedorn (NPH) insulin twice daily (BID) in combination with insulin aspart.

Arm/Group Title	IDegAsp OD	IDet
Arm/Group Description	Insulin degludec/insulin aspart (IDegAsp) was given subcutaneously (s.c.) once daily (OD) with a main meal in combination with mealtime insulin aspart (IAsp) for the remaining meals. The regimen was given for 26 weeks in the main period and for an additional 26 weeks in the extension period.	Insulin detemir (Idet) was given subcutaneously (s.c) once daily (OD) in the evening or twice daily (BID) in combination with mealtime insulin aspart (Iasp). The regimen was given for 26 weeks in the main period and for an additional 26 weeks in the extension period.
Period Title: Main: Week 0 to 26 (NN5401-3594)
STARTED	366	182
Exposed	362	180
COMPLETED	320	156
NOT COMPLETED	46	26
Period Title: Main: Week 0 to 26 (NN5401-3594)
STARTED	254	122
COMPLETED	233	113
NOT COMPLETED	21	9

Baseline Characteristics

Arm/Group Title	IDegAsp OD	IDet	Total
Arm/Group Description	Insulin degludec/insulin aspart (IDegAsp) was given subcutaneously (s.c.) once daily (OD) with a main meal in combination with mealtime insulin aspart (IAsp) for the remaining meals. The regimen was given for 26 weeks in the main period and for an additional 26 weeks in the extension period.	Insulin detemir (Idet) was given subcutaneously (s.c) once daily (OD) in the evening or twice daily (BID) in combination with mealtime insulin aspart (Iasp). The regimen was given for 26 weeks in the main period and for an additional 26 weeks in the extension period.	Total of all reporting groups
Overall Participants	366	182	548
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	40.7 (12.8)	42.6 (13.8)	41.3 (13.2)
Sex: Female, Male (Count of Participants)
Female	176 48.1%	100 54.9%	276 50.4%
Male	190 51.9%	82 45.1%	272 49.6%
Glycosylated haemoglobin (HbA1c) (percentage of glycosylated haemoglobin) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [percentage of glycosylated haemoglobin]	8.3 (0.8)	8.3 (0.7)	8.3 (0.8)
Fasting plasma glucose (FPG) (mmol/L) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mmol/L]	10.3 (4.7)	11.0 (4.8)	10.5 (4.8)

Outcome Measures

1. Primary Outcome

Title	Main Trial (Primary Endpoint): Change in Glycosylated Haemoglobin (HbA1c) After 26 Weeks of Treatment
Description	Change from baseline in HbA1c after 26 weeks of treatment
Time Frame	Week 0, Week 26

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	IDegAsp OD	IDet
Arm/Group Description	Insulin degludec/insulin aspart (IDegAsp) was given subcutaneously (s.c.) once daily (OD) with a main meal in combination with mealtime insulin aspart (IAsp) for the remaining meals. The regimen was given for 26 weeks in the main period and for an additional 26 weeks in the extension period.	Insulin detemir (Idet) was given subcutaneously (s.c) once daily (OD) in the evening or twice daily (BID) in combination with mealtime insulin aspart (Iasp). The regimen was given for 26 weeks in the main period and for an additional 26 weeks in the extension period.
Measure Participants	366	182
Mean (Standard Deviation) [percentage of glycosylated haemoglobin]	-0.73 (0.83)	-0.68 (0.77)

2. 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 were defined as requiring assistance to administer carbohydrate, glucagon, or other resuscitative actions. Minor hypoglycaemic episodes were defined as able to treat her/himself and plasma glucose below 3.1 mmol/L.
Time Frame	Week 0 to Week 26 + 7 days follow up

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	IDegAsp OD	IDet
Arm/Group Description	Insulin degludec/insulin aspart (IDegAsp) was given subcutaneously (s.c.) once daily (OD) with a main meal in combination with mealtime insulin aspart (IAsp) for the remaining meals. The regimen was given for 26 weeks in the main period and for an additional 26 weeks in the extension period.	Insulin detemir (Idet) was given subcutaneously (s.c) once daily (OD) in the evening or twice daily (BID) in combination with mealtime insulin aspart (Iasp). The regimen was given for 26 weeks in the main period and for an additional 26 weeks in the extension period.
Measure Participants	362	180
Number [Episodes/100 years of patient exposure]	3917	4434

3. Secondary Outcome

Title	Main Trial (Secondary Endpoint): Mean of 9-point Self Measured Plasma Glucose Profile (SMPG) at Week 26
Description	Overall mean of 9-point SMPG at 26 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 26

Outcome Measure Data

Analysis Population Description

The full analysis set (FAS) included all randomised subjects and missing data were imputed using last observation carried forward (LOCF). For 22 subjects all 9-point SMPG values were missing.

Arm/Group Title	IDegAsp OD	IDet
Arm/Group Description	Insulin degludec/insulin aspart (IDegAsp) was given subcutaneously (s.c.) once daily (OD) with a main meal in combination with mealtime insulin aspart (IAsp) for the remaining meals. The regimen was given for 26 weeks in the main period and for an additional 26 weeks in the extension period.	Insulin detemir (Idet) was given subcutaneously (s.c) once daily (OD) in the evening or twice daily (BID) in combination with mealtime insulin aspart (Iasp). The regimen was given for 26 weeks in the main period and for an additional 26 weeks in the extension period.
Measure Participants	349	177
Mean (Standard Deviation) [mmol/L]	8.0 (2.2)	8.4 (2.5)

4. Secondary Outcome

Title	Extension Trial (Secondary 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 53

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	IDegAsp OD	IDet
Arm/Group Description	Insulin degludec/insulin aspart (IDegAsp) was given subcutaneously (s.c.) once daily (OD) with a main meal in combination with mealtime insulin aspart (IAsp) for the remaining meals. The regimen was given for 26 weeks in the main period and for an additional 26 weeks in the extension period.	Insulin detemir (Idet) was given subcutaneously (s.c) once daily (OD) in the evening or twice daily (BID) in combination with mealtime insulin aspart (Iasp). The regimen was given for 26 weeks in the main period and for an additional 26 weeks in the extension period.
Measure Participants	366	182
Mean (Standard Deviation) [percentage of glycosylated haemoglobin]	-0.65 (0.81)	-0.56 (0.80)

5. 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 were defined as requiring assistance to administer carbohydrate, glucagon, or other resuscitative actions. Minor hypoglycaemic episodes were defined as able to treat her/himself and plasma glucose below 3.1 mmol /L.
Time Frame	Week 0 to Week 53 + 7 days follow up

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	IDegAsp OD	IDet
Arm/Group Description	Insulin degludec/insulin aspart (IDegAsp) was given subcutaneously (s.c.) once daily (OD) with a main meal in combination with mealtime insulin aspart (IAsp) for the remaining meals. The regimen was given for 26 weeks in the main period and for an additional 26 weeks in the extension period.	Insulin detemir (Idet) was given subcutaneously (s.c) once daily (OD) in the evening or twice daily (BID) in combination with mealtime insulin aspart (Iasp). The regimen was given for 26 weeks in the main period and for an additional 26 weeks in the extension period.
Measure Participants	362	180
Number [Episodes/100 years of patient exposure]	3183	3673

6. Primary 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 were defined as requiring assistance to administer carbohydrate, glucagon, or other resuscitative actions. Minor hypoglycaemic episodes were defined as able to treat her/himself and plasma glucose below 3.1 mmol/L. Nocturnal hypoglycaemic episodes were defined as occurring between 00:01 and 05:59 a.m.
Time Frame	Week 0 to Week 53 + 7 days follow up

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	IDegAsp OD	IDet
Arm/Group Description	Insulin degludec/insulin aspart (IDegAsp) was given subcutaneously (s.c.) once daily (OD) with a main meal in combination with mealtime insulin aspart (IAsp) for the remaining meals. The regimen was given for 26 weeks in the main period and for an additional 26 weeks in the extension period.	Insulin detemir (Idet) was given subcutaneously (s.c) once daily (OD) in the evening or twice daily (BID) in combination with mealtime insulin aspart (Iasp). The regimen was given for 26 weeks in the main period and for an additional 26 weeks in the extension period.
Measure Participants	362	180
Number [Episodes/100 years of patient exposure]	309	541

7. 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 were defined as requiring assistance to administer carbohydrate, glucagon, or other resuscitative actions. Minor hypoglycaemic episodes were defined as able to treat her/himself and plasma glucose below 3.1 mmol/L. Nocturnal hypoglycaemic episodes were defined as occurring between 00:01 and 05:59 a.m.
Time Frame	Week 0 to Week 26 + 7 days follow up

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	IDegAsp OD	IDet
Arm/Group Description	Insulin degludec/insulin aspart (IDegAsp) was given subcutaneously (s.c.) once daily (OD) with a main meal in combination with mealtime insulin aspart (IAsp) for the remaining meals. The regimen was given for 26 weeks in the main period and for an additional 26 weeks in the extension period.	Insulin detemir (Idet) was given subcutaneously (s.c) once daily (OD) in the evening or twice daily (BID) in combination with mealtime insulin aspart (Iasp). The regimen was given for 26 weeks in the main period and for an additional 26 weeks in the extension period.
Measure Participants	362	180
Number [Episodes/100 years of patient exposure]	371	572

8. Secondary Outcome

Title	Extension Trial (Secondary Endpoint): Change in Fasting Plasma Glucose (FPG) After 52 Weeks of Treatment
Description	Change from baseline in FPG after 52 weeks of treatment.
Time Frame	Week 0, Week 53

Outcome Measure Data

Analysis Population Description

The full analysis set (FAS) included all randomised subjects and missing data were imputed using last observation carried forward (LOCF). For 2 subjects, FPG values were missing.

Arm/Group Title	IDegAsp OD	IDet
Arm/Group Description	Insulin degludec/insulin aspart (IDegAsp) was given subcutaneously (s.c.) once daily (OD) with a main meal in combination with mealtime insulin aspart (IAsp) for the remaining meals. The regimen was given for 26 weeks in the main period and for an additional 26 weeks in the extension period.	Insulin detemir (Idet) was given subcutaneously (s.c) once daily (OD) in the evening or twice daily (BID) in combination with mealtime insulin aspart (Iasp). The regimen was given for 26 weeks in the main period and for an additional 26 weeks in the extension period.
Measure Participants	365	181
Mean (Standard Deviation) [mmol/L]	-1.83 (5.69)	-2.40 (5.86)

9. 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 53 + 7 days of follow up

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	IDegAsp OD	IDet
Arm/Group Description	Insulin degludec/insulin aspart (IDegAsp) was given subcutaneously (s.c.) once daily (OD) with a main meal in combination with mealtime insulin aspart (IAsp) for the remaining meals. The regimen was given for 26 weeks in the main period and for an additional 26 weeks in the extension period.	Insulin detemir (Idet) was given subcutaneously (s.c) once daily (OD) in the evening or twice daily (BID) in combination with mealtime insulin aspart (Iasp). The regimen was given for 26 weeks in the main period and for an additional 26 weeks in the extension period.
Measure Participants	362	180
Adverse event (AE)	408	442
Serious AE	24	19
Severe AE	33	48
Moderate AE	93	83
Mild AE	282	311
Fatal AE	0	0

Adverse Events

Time Frame	Week 0 to Week 53 + 7 days of follow up.
Adverse Event Reporting Description	The safety analysis set included all subjects who received at least one dose of the investigational product or its comparator.
Arm/Group Title	IDegAsp OD		IDet
Arm/Group Description	Insulin degludec/insulin aspart (IDegAsp) was given subcutaneously (s.c.) once daily (OD) with a main meal in combination with mealtime insulin aspart (IAsp) for the remaining meals. The regimen was given for 26 weeks in the main period and for an additional 26 weeks in the extension period.		Insulin detemir (Idet) was given subcutaneously (s.c) once daily (OD) in the evening or twice daily (BID) in combination with mealtime insulin aspart (Iasp). The regimen was given for 26 weeks in the main period and for an additional 26 weeks in the extension period.
All Cause Mortality
	IDegAsp OD		IDet
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	IDegAsp OD		IDet
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	46/362 (12.7%)		20/180 (11.1%)
Cardiac disorders
Angina pectoris	1/362 (0.3%)	1	0/180 (0%)	0
Pericardial effusion	1/362 (0.3%)	1	0/180 (0%)	0
Tachyarrhythmia	0/362 (0%)	0	1/180 (0.6%)	1
Eye disorders
Eye haemorrhage	1/362 (0.3%)	1	0/180 (0%)	0
Gastrointestinal disorders
Abdominal pain	1/362 (0.3%)	1	0/180 (0%)	0
Food poisoning	1/362 (0.3%)	1	0/180 (0%)	0
Gastric polyps	1/362 (0.3%)	1	0/180 (0%)	0
Hiatus hernia	2/362 (0.6%)	2	0/180 (0%)	0
Pancreatitis acute	0/362 (0%)	0	1/180 (0.6%)	1
Small intestinal obstruction	0/362 (0%)	0	1/180 (0.6%)	1
Immune system disorders
Hypersensitivity	1/362 (0.3%)	1	0/180 (0%)	0
Infections and infestations
Abscess limb	1/362 (0.3%)	1	0/180 (0%)	0
Gastroenteritis	1/362 (0.3%)	1	0/180 (0%)	0
Meningitis	1/362 (0.3%)	1	0/180 (0%)	0
Pulmonary tuberculosis	1/362 (0.3%)	1	0/180 (0%)	0
Wound infection	1/362 (0.3%)	1	0/180 (0%)	0
Injury, poisoning and procedural complications
Ankle fracture	1/362 (0.3%)	1	1/180 (0.6%)	1
Intentional overdose	1/362 (0.3%)	2	0/180 (0%)	0
Wrong drug administered	2/362 (0.6%)	2	0/180 (0%)	0
Metabolism and nutrition disorders
Diabetic ketoacidosis	1/362 (0.3%)	2	3/180 (1.7%)	3
Hypoglycaemia	15/362 (4.1%)	25	9/180 (5%)	9
Hypoglycaemic seizure	2/362 (0.6%)	3	1/180 (0.6%)	1
Hypoglycaemic unconsciousness	7/362 (1.9%)	7	4/180 (2.2%)	4
Musculoskeletal and connective tissue disorders
Arthralgia	2/362 (0.6%)	2	0/180 (0%)	0
Intervertebral disc degeneration	0/362 (0%)	0	1/180 (0.6%)	1
Intervertebral disc disorder	1/362 (0.3%)	1	0/180 (0%)	0
Intervertebral disc protrusion	1/362 (0.3%)	1	0/180 (0%)	0
Osteoarthritis	1/362 (0.3%)	1	1/180 (0.6%)	1
Rotator cuff syndrome	1/362 (0.3%)	1	0/180 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Bladder cancer	0/362 (0%)	0	1/180 (0.6%)	1
Squamous cell carcinoma of skin	0/362 (0%)	0	1/180 (0.6%)	1
Uterine leiomyoma	0/362 (0%)	0	1/180 (0.6%)	1
Nervous system disorders
Hypoglycaemic coma	1/362 (0.3%)	2	0/180 (0%)	0
Migraine	1/362 (0.3%)	1	0/180 (0%)	0
Psychiatric disorders
Depression	2/362 (0.6%)	2	0/180 (0%)	0
Suicidal ideation	1/362 (0.3%)	1	1/180 (0.6%)	1
Suicide attempt	1/362 (0.3%)	2	0/180 (0%)	0
Reproductive system and breast disorders
Benign prostatic hyperplasia	1/362 (0.3%)	1	0/180 (0%)	0
Respiratory, thoracic and mediastinal disorders
Dyspnoea	0/362 (0%)	0	1/180 (0.6%)	1
Social circumstances
Victim of crime	1/362 (0.3%)	1	0/180 (0%)	0
Other (Not Including Serious) Adverse Events
	IDegAsp OD		IDet
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	166/362 (45.9%)		90/180 (50%)
Gastrointestinal disorders
Diarrhoea	13/362 (3.6%)	14	12/180 (6.7%)	12
Nausea	14/362 (3.9%)	24	9/180 (5%)	10
General disorders
Injection site reaction	5/362 (1.4%)	8	9/180 (5%)	36
Infections and infestations
Gastroenteritis	14/362 (3.9%)	15	9/180 (5%)	10
Influenza	25/362 (6.9%)	25	9/180 (5%)	12
Nasopharyngitis	89/362 (24.6%)	139	38/180 (21.1%)	62
Upper respiratory tract infection	33/362 (9.1%)	48	20/180 (11.1%)	30
Metabolism and nutrition disorders
Hypoglycaemia	29/362 (8%)	40	24/180 (13.3%)	50
Nervous system disorders
Headache	35/362 (9.7%)	102	16/180 (8.9%)	22

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.