BEGIN™: A Trial Investigating the Efficacy and Safety of Insulin Degludec in Children and Adolescents With Type 1 Diabetes Mellitus

• Sponsor: Novo Nordisk A/S (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01513473
• Collaborator: (none)
• Enrollment: 350
• Locations: 81
• Arms: 2
• Actual Duration (Months): 18.4
• Patients Per Site: 4.3
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

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

The aim of this trial is to investigate the efficacy and safety of insulin degludec in children and adolescents with type 1 diabetes mellitus.

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

Study Design

• Study Type: Interventional
• Actual Enrollment: 350 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A 26-week, Multinational, Multi-centre, Open-Labelled, Randomised, Parallel, Efficacy and Safety Comparison of Insulin Degludec and Insulin Detemir in Children and Adolescents 1 to Less Than 18 Years With Type 1 Diabetes Mellitus on a Basal-bolus Regimen With Insulin Aspart as Bolus Insulin, Followed by a 26-week Extension Investigating Long Term Safety (BEGIN™: Young 1)
• Actual Study Start Date: Jan 16, 2012
• Actual Primary Completion Date: Jul 30, 2013
• Actual Study Completion Date: Jul 30, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Insulin Degludec + Insulin Aspart	Drug: insulin degludec; Injected subcutaneously (under the skin) once daily. Dose individually adjusted.; Drug: insulin aspart; Injected subcutaneously (under the skin) as mealtime bolus insulin. Dose individually adjusted.
Experimental: Insulin Detemir +Insulin Aspart	Drug: insulin detemir; Injected subcutaneously (under the skin) once or twice daily. Dose individually adjusted.; Drug: insulin aspart; Injected subcutaneously (under the skin) as mealtime bolus insulin. Dose individually adjusted.

Outcome Measures

Primary Outcome Measures

1. Change From Baseline in HbA1c (Glycosylated Haemoglobin) (%) at 26 Weeks (Analysed by Central Laboratory) [Week 0, week 26]

   Change from baseline in HbA1c (%) after 26 weeks of treatment.

Secondary Outcome Measures

1. Change From Baseline in HbA1c (%) at 52 Weeks (Analysed by Central Laboratory) [Week 0, week 52]

   Change from baseline in HbA1c (%) after 52 weeks of treatments.

2. Change From Baseline in Fasting Blood Glucose (FPG) at 26 Weeks (Analysed by Central Laboratory) [Week 0, week 26]

   Change from baseline in FPG after 26 weeks of treatment.

3. Change From Baseline in Fasting Blood Glucose (FPG) at 52 Weeks (Analysed by Central Laboratory) [Week 0, week 52]

   Change from baseline in FPG after 52 weeks of treatment.

4. Number of Treatment Emergent Adverse Events (TEAEs) [After 26 weeks and 52 weeks of treatment]

   TEAE is defined as an event that has onset date on or after the first day of exposure to randomised treatment and no later than 7 days after the last day of randomised treatment.

5. Number of Hypoglycaemic Episodes [After 26 weeks and 52 weeks of treatment]

   Number of hypoglycaemic episodes (severe episodes or episodes with plasma glucose (PG) below or equal to 3.9 mmol/L (70 mg/dL) with or without symptoms of hypoglycaemia) during the trial; nocturnal [11 p.m. - 7 a.m./23:00 - 07:00] and over the entire day (24 hours)

6. Number of Self-measured Hyperglycaemia (Episodes of PG Above 11.1 mmol/L (200 mg/dL)) [After 26 weeks and 52 weeks of treatment]

   Episodes of PG >11.1mmol/L (200mg/dL)

7. Number of Episodes With Self Monitored Blood Ketones Above 1.5 mmol (Capillary Blood Ketone Measurement to be Performed if Self-measured Plasma Glucose (SMPG) Exceeds 14.0 mmol/l (250 mg/dL)) [After 26 weeks and 52 weeks of treatment]

   Blood ketones > 1.5mmol/L (Capillary blood ketone measurement to be performed if SMPG exceeds 14.0mmol/L (250mg/dL) )after 26 and 52 weeks of treatment

8. Steady-state Plasma Concentrations of Insulin Degludec and Insulin Detemir on Three Different Visits (Three Different Weeks) During the First 26 Weeks of Treatment [Between week 1 and week 26]

   Steady state plasma concentrations of insulin degludec and insulin detemir on three different visits (three different weeks) during the trial.

9. Insulin Antibodies (Insulin Degludec Specific, Insulin Detemir Specific, Insulin Aspart Specific and Antibodies Cross-reacting to Human Insulin) [After 52 weeks of treatment]

   Antibody measurements : the values presented are week 52 (LOCF). The measurement of insulin antibodies after 26 and 52 weeks of treatment was done to fulfil the requirement of monitoring the long term immunogenicity. The unit of measure is percentage bound/total (%B/T) for these antibodies. The Antibodies cross reacting to Human Insulin is abbreviated as X-reacting AB Hu Insulin below)

Eligibility Criteria

Criteria

• Ages Eligible for Study: 1 Year to 17 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Informed consent, and child assent as age-appropriate, obtained before any trial-related activities (Trial-related activities are any procedure that would not have been performed during normal management of the subject). The parents or legal representative of the child must sign and date the Informed Consent Form according to local requirements. The child, if possible, parents or legal representative of the child must sign and date the Child Assent Form according to local requirements

• Male or female diagnosed with type 1 diabetes mellitus (T1DM) (based on clinical judgement and supported by laboratory analysis as per local guidelines)

• Ongoing daily treatment with insulin (any regimen) for at least 3 months prior to Visit 1 (screening). No OADs (oral anti-diabetic drugs) are allowed

• HbA1c (glycosylated haemoglobin) maximum 11%

Exclusion Criteria:

• Known or suspected hypersensitivity to trial product(s) or related products

• Previous participation in this trial. Participation is defined as randomisation

• Girls who are pregnant, breastfeeding or intend to become pregnant

• Girls who have had menarche and are not using adequate contraceptive measures according to local requirements

• Known hypoglycaemic unawareness or recurrent severe hypoglycaemic events as judged by the Investigator (trial physician)

• More than 1 diabetic ketoacidosis requiring hospitalisation within the last 3 months prior to Visit 1

• Significant concomitant disease, except for conditions associated with type 1 diabetes mellitus, which in the Investigator's opinion could interfere with the trial

• The receipt of any investigational drug within 1 month prior to Visit 1

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Novo Nordisk Investigational Site	Little Rock	Arkansas	United States	72202
2	Novo Nordisk Investigational Site	Orange	California	United States	92868
3	Novo Nordisk Investigational Site	San Diego	California	United States	92123
4	Novo Nordisk Investigational Site	Aurora	Colorado	United States	80045
5	Novo Nordisk Investigational Site	New Haven	Connecticut	United States	06511
6	Novo Nordisk Investigational Site	Gainesville	Florida	United States	32608
7	Novo Nordisk Investigational Site	Jacksonville	Florida	United States	32207
8	Novo Nordisk Investigational Site	Maitland	Florida	United States	32751
9	Novo Nordisk Investigational Site	Melbourne	Florida	United States	32901
10	Novo Nordisk Investigational Site	Tallahassee	Florida	United States	32308
11	Novo Nordisk Investigational Site	Atlanta	Georgia	United States	30322
12	Novo Nordisk Investigational Site	Atlanta	Georgia	United States	30339
13	Novo Nordisk Investigational Site	Lexington	Kentucky	United States	40503
14	Novo Nordisk Investigational Site	Louisville	Kentucky	United States	40202
15	Novo Nordisk Investigational Site	Baltimore	Maryland	United States	21201
16	Novo Nordisk Investigational Site	Baltimore	Maryland	United States	21229
17	Novo Nordisk Investigational Site	Boston	Massachusetts	United States	02215
18	Novo Nordisk Investigational Site	Worcester	Massachusetts	United States	01655
19	Novo Nordisk Investigational Site	Buffalo	New York	United States	14203
20	Novo Nordisk Investigational Site	Akron	Ohio	United States	44308
21	Novo Nordisk Investigational Site	Cincinnati	Ohio	United States	45229
22	Novo Nordisk Investigational Site	Hershey	Pennsylvania	United States	17033
23	Novo Nordisk Investigational Site	Philadelphia	Pennsylvania	United States	19104
24	Novo Nordisk Investigational Site	Pittsburgh	Pennsylvania	United States	15224
25	Novo Nordisk Investigational Site	Dallas	Texas	United States	75235
26	Novo Nordisk Investigational Site	San Antonio	Texas	United States	78207
27	Novo Nordisk Investigational Site	Norfolk	Virginia	United States	23507
28	Novo Nordisk Investigational Site	Richmond	Virginia	United States	23235
29	Novo Nordisk Investigational Site	Sofia		Bulgaria	1606
30	Novo Nordisk Investigational Site	Varna		Bulgaria	9010
31	Novo Nordisk Investigational Site	Espoo		Finland	02740
32	Novo Nordisk Investigational Site	Kuopio		Finland	70210
33	Novo Nordisk Investigational Site	Mikkeli		Finland	50100
34	Novo Nordisk Investigational Site	OYS		Finland	90029
35	Novo Nordisk Investigational Site	Pori		Finland	28500
36	Novo Nordisk Investigational Site	BRON cedex		France	69677
37	Novo Nordisk Investigational Site	Paris		France	75015
38	Novo Nordisk Investigational Site	Rennes		France	35056
39	Novo Nordisk Investigational Site	Toulouse		France	31059
40	Novo Nordisk Investigational Site	Berlin		Germany	13353
41	Novo Nordisk Investigational Site	Hannover		Germany	30173
42	Novo Nordisk Investigational Site	Ludwigshafen		Germany	67059
43	Novo Nordisk Investigational Site	Münster		Germany	48155
44	Novo Nordisk Investigational Site	Chieti		Italy	66100
45	Novo Nordisk Investigational Site	Genova		Italy	16147
46	Novo Nordisk Investigational Site	Roma		Italy	00165
47	Novo Nordisk Investigational Site	Chuo-shi, Yamanashi		Japan	409 3898
48	Novo Nordisk Investigational Site	Fukushima		Japan	963-8851
49	Novo Nordisk Investigational Site	Iruma-gun, Saitama		Japan	350 0495
50	Novo Nordisk Investigational Site	Kobe-shi, Hyogo		Japan	657-0846
51	Novo Nordisk Investigational Site	Kochi-shi, Kochi		Japan	780 0952
52	Novo Nordisk Investigational Site	Kumamoto-shi, Kumamoto		Japan	860 8556
53	Novo Nordisk Investigational Site	Maebashi-shi, Gunma		Japan	371-8511
54	Novo Nordisk Investigational Site	Musashino-shi, Tokyo		Japan	180 0023
55	Novo Nordisk Investigational Site	Niigata-shi, Niigata		Japan	951 8520
56	Novo Nordisk Investigational Site	Osaka-shi, Osaka		Japan	545 8586
57	Novo Nordisk Investigational Site	Sendai-shi, Miyagi		Japan	980 8574
58	Novo Nordisk Investigational Site	Tokyo		Japan	157 8535
59	Novo Nordisk Investigational Site	Tokyo		Japan	162 8666
60	Novo Nordisk Investigational Site	Toyonaka-city, Osaka		Japan	560 0004
61	Novo Nordisk Investigational Site	Tsu-shi, Mie		Japan	514 0125
62	Novo Nordisk Investigational Site	Almere		Netherlands	1315 RA
63	Novo Nordisk Investigational Site	Amersfoort		Netherlands	3816 CP
64	Novo Nordisk Investigational Site	Eindhoven		Netherlands	5623 EJ
65	Novo Nordisk Investigational Site	Nijmegen		Netherlands	6532 CL
66	Novo Nordisk Investigational Site	Rotterdam		Netherlands	3011 TA
67	Novo Nordisk Investigational Site	Skopje		North Macedonia	1000
68	Novo Nordisk Investigational Site	Moscow		Russian Federation	117036
69	Novo Nordisk Investigational Site	Moscow		Russian Federation	119049
70	Novo Nordisk Investigational Site	Moscow		Russian Federation	125373
71	Novo Nordisk Investigational Site	Novosibirsk		Russian Federation	630048
72	Novo Nordisk Investigational Site	Saint-Petersburg		Russian Federation	191144
73	Novo Nordisk Investigational Site	Saratov		Russian Federation	410028
74	Novo Nordisk Investigational Site	Saratov		Russian Federation	410054
75	Novo Nordisk Investigational Site	Johannesburg	Gauteng	South Africa	2193
76	Novo Nordisk Investigational Site	Cape Town	Western Cape	South Africa	7925
77	Novo Nordisk Investigational Site	Aberdeen		United Kingdom	AB25 2ZG
78	Novo Nordisk Investigational Site	Birmingham		United Kingdom	B4 6NH
79	Novo Nordisk Investigational Site	Manchester		United Kingdom	M13 9WL
80	Novo Nordisk Investigational Site	Norwich		United Kingdom	NR4 7UY
81	Novo Nordisk Investigational Site	Sheffield		United Kingdom	S102TH

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

• Thalange N, Deeb L, Klingensmith G, Franco DR, Bardtrum L, Tutkunkardas D, Danne T. The rate of hyperglycemia and ketosis with insulin degludec-based treatment compared with insulin detemir in pediatric patients with type 1 diabetes: An analysis of data from two randomized trials. Pediatr Diabetes. 2019 May;20(3):314-320. doi: 10.1111/pedi.12821. Epub 2019 Feb 10.

• Responsible Party: Novo Nordisk A/S
• ClinicalTrials.gov Identifier: NCT01513473
• Other Study ID Numbers: NN1250-3561; 2011-003148-39; P/44/2010; U1111-1122-4758
• First Posted: Jan 20, 2012
• Last Update Posted: Jun 13, 2019
• Last Verified: Jun 1, 2019

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

Study Results

Participant Flow

Recruitment Details	The trial was conducted at 72 sites in 12 countries as follows: Bulgaria (2), Finland (5), France (4), Germany (3), Italy (2), Japan (15), Netherlands (5), Republic of Macedonia (2), Russian Federation (6), South Africa (2), United Kingdom (4), United States (22)

Arm/Group Title	IDeg + IAsp	IDet + IAsp
Arm/Group Description	Subjects from 1 to 18 years of age were randomised into treatment arms, IDeg OD as basal insulin and IAsp as mealtime bolus insulin for a period of 26 weeks followed by extension trial for a period of 26 weeks. IDeg was given once a day at approximately the same time of the day. Basal and bolus insulin titration was done according to the lowest pre-breakfast SMPG value measured on the three days prior to the visit/ phone contact for IDeg.	Subjects from 1 to 18 years of age were randomised into treatment arms, IDet OD as basal insulin and IAsp as mealtime bolus insulin for a period of 26 weeks followed by extension trial for a period of 26 weeks. IDet was given once a day at approximately the same time of the day. Basal and bolus insulin titration was done according to the lowest pre-breakfast SMPG value measured on the three days prior to the visit/ phone contact for IDet.
Period Title: Main Trial (26 Weeks)
STARTED	174	176
Exposed	174	175
COMPLETED	170	165
NOT COMPLETED	4	11
Period Title: Main Trial (26 Weeks)
STARTED	152	128
COMPLETED	151	122
NOT COMPLETED	1	6

Baseline Characteristics

Arm/Group Title	IDeg + IAsp	IDet + IAsp	Total
Arm/Group Description	Subjects from 1 to 18 years of age were randomised into treatment arms, IDeg OD as basal insulin and IAsp as mealtime bolus insulin for a period of 26 weeks followed by extension trial for a period of 26 weeks. IDeg was given once a day at approximately the same time of the day. Basal and bolus insulin titration was done according to the lowest pre-breakfast SMPG value measured on the three days prior to the visit/ phone contact for IDeg.	Subjects from 1 to 18 years of age were randomised into treatment arms, IDet OD as basal insulin and IAsp as mealtime bolus insulin for a period of 26 weeks followed by extension trial for a period of 26 weeks. IDet was given once a day at approximately the same time of the day. Basal and bolus insulin titration was done according to the lowest pre-breakfast SMPG value measured on the three days prior to the visit/ phone contact for IDet.	Total of all reporting groups
Overall Participants	174	176	350
Age (Count of Participants)
<=18 years	174 100%	176 100%	350 100%
Between 18 and 65 years	0 0%	0 0%	0 0%
>=65 years	0 0%	0 0%	0 0%
Sex: Female, Male (Count of Participants)
Female	78 44.8%	78 44.3%	156 44.6%
Male	96 55.2%	98 55.7%	194 55.4%

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in HbA1c (Glycosylated Haemoglobin) (%) at 26 Weeks (Analysed by Central Laboratory)
Description	Change from baseline in HbA1c (%) after 26 weeks of treatment.
Time Frame	Week 0, week 26

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS) Included all randomised subjects. LOCF values are presented for this endpoint.

Arm/Group Title	IDeg + IAsp	IDet + IAsp
Arm/Group Description	Subjects from 1 to 18 years of age were randomised into treatment arms, IDeg OD as basal insulin and IAsp as mealtime bolus insulin for a period of 26 weeks followed by extension trial for a period of 26 weeks. IDeg was given once a day at approximately the same time of the day. Basal and bolus insulin titration was done according to the lowest pre-breakfast SMPG value measured on the three days prior to the visit/ phone contact for IDeg.	Subjects from 1 to 18 years of age were randomised into treatment arms, IDet OD as basal insulin and IAsp as mealtime bolus insulin for a period of 26 weeks followed by extension trial for a period of 26 weeks. IDet was given once a day at approximately the same time of the day. Basal and bolus insulin titration was done according to the lowest pre-breakfast SMPG value measured on the three days prior to the visit/ phone contact for IDet.
Measure Participants	174	176
Mean (Standard Deviation) [percentage of glycosylated haemoglobin]	-0.20 (0.95)	-0.31 (0.89)

2. Secondary Outcome

Title	Change From Baseline in HbA1c (%) at 52 Weeks (Analysed by Central Laboratory)
Description	Change from baseline in HbA1c (%) after 52 weeks of treatments.
Time Frame	Week 0, week 52

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS) Included all randomised subjects. LOCF values are presented for this endpoint.

Arm/Group Title	IDeg + IAsp	IDet + IAsp
Arm/Group Description	Subjects from 1 to 18 years of age were randomised into treatment arms, IDeg OD as basal insulin and IAsp as mealtime bolus insulin for a period of 26 weeks followed by extension trial for a period of 26 weeks. IDeg was given once a day at approximately the same time of the day. Basal and bolus insulin titration was done according to the lowest pre-breakfast SMPG value measured on the three days prior to the visit/ phone contact for IDeg.	Subjects from 1 to 18 years of age were randomised into treatment arms, IDet OD as basal insulin and IAsp as mealtime bolus insulin for a period of 26 weeks followed by extension trial for a period of 26 weeks. IDet was given once a day at approximately the same time of the day. Basal and bolus insulin titration was done according to the lowest pre-breakfast SMPG value measured on the three days prior to the visit/ phone contact for IDet.
Measure Participants	174	176
Mean (Standard Deviation) [percentage of glycosylated haemoglobin]	-0.27 (1.07)	-0.22 (1.03)

3. Secondary Outcome

Title	Change From Baseline in Fasting Blood Glucose (FPG) at 26 Weeks (Analysed by Central Laboratory)
Description	Change from baseline in FPG after 26 weeks of treatment.
Time Frame	Week 0, week 26

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS) Included all randomised subjects. LOCF values are presented for this endpoint. 338 subjects were considered, as 12 excluded from PP analysis set, 1 withdrawn, 11 subjects did not have a valid HbA1c measurements after 12 weeks. FPG samples were missing for 9 subjects.

Arm/Group Title	IDeg + IAsp	IDet + IAsp
Arm/Group Description	Subjects from 1 to 18 years of age were randomised into treatment arms, IDeg OD as basal insulin and IAsp as mealtime bolus insulin for a period of 26 weeks followed by extension trial for a period of 26 weeks. IDeg was given once a day at approximately the same time of the day. Basal and bolus insulin titration was done according to the lowest pre-breakfast SMPG value measured on the three days prior to the visit/ phone contact for IDeg.	Subjects from 1 to 18 years of age were randomised into treatment arms, IDet OD as basal insulin and IAsp as mealtime bolus insulin for a period of 26 weeks followed by extension trial for a period of 26 weeks. IDet was given once a day at approximately the same time of the day. Basal and bolus insulin titration was done according to the lowest pre-breakfast SMPG value measured on the three days prior to the visit/ phone contact for IDet.
Measure Participants	157	160
Mean (Standard Deviation) [mmol/L]	-0.67 (5.99)	0.50 (8.37)

4. Secondary Outcome

Title	Change From Baseline in Fasting Blood Glucose (FPG) at 52 Weeks (Analysed by Central Laboratory)
Description	Change from baseline in FPG after 52 weeks of treatment.
Time Frame	Week 0, week 52

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS) Included all randomised subjects. LOCF values are presented for this endpoint. 338 subjects were considered, as 12 excluded from PP analysis set, 1 withdrawn, 11 subjects did not have a valid HbA1c measurements after 12 weeks.

Arm/Group Title	IDeg + IAsp	IDet + IAsp
Arm/Group Description	Subjects from 1 to 18 years of age were randomised into treatment arms, IDeg OD as basal insulin and IAsp as mealtime bolus insulin for a period of 26 weeks followed by extension trial for a period of 26 weeks. IDeg was given once a day at approximately the same time of the day. Basal and bolus insulin titration was done according to the lowest pre-breakfast SMPG value measured on the three days prior to the visit/ phone contact for IDeg.	Subjects from 1 to 18 years of age were randomised into treatment arms, IDet OD as basal insulin and IAsp as mealtime bolus insulin for a period of 26 weeks followed by extension trial for a period of 26 weeks. IDet was given once a day at approximately the same time of the day. Basal and bolus insulin titration was done according to the lowest pre-breakfast SMPG value measured on the three days prior to the visit/ phone contact for IDet.
Measure Participants	157	160
Mean (Standard Deviation) [mmol/L]	-1.29 (6.53)	1.10 (8.24)

5. Secondary Outcome

Title	Number of Treatment Emergent Adverse Events (TEAEs)
Description	TEAE is defined as an event that has onset date on or after the first day of exposure to randomised treatment and no later than 7 days after the last day of randomised treatment.
Time Frame	After 26 weeks and 52 weeks of treatment

Outcome Measure Data

Analysis Population Description

Safety analysis set included all subjects receiving at least one dose of investigational product.

Arm/Group Title	IDeg + IAsp	IDet + IAsp
Arm/Group Description	Subjects from 1 to 18 years of age were randomised into treatment arms, IDeg OD as basal insulin and IAsp as mealtime bolus insulin for a period of 26 weeks followed by extension trial for a period of 26 weeks. IDeg was given once a day at approximately the same time of the day. Basal and bolus insulin titration was done according to the lowest pre-breakfast SMPG value measured on the three days prior to the visit/ phone contact for IDeg.	Subjects from 1 to 18 years of age were randomised into treatment arms, IDet OD as basal insulin and IAsp as mealtime bolus insulin for a period of 26 weeks followed by extension trial for a period of 26 weeks. IDet was given once a day at approximately the same time of the day. Basal and bolus insulin titration was done according to the lowest pre-breakfast SMPG value measured on the three days prior to the visit/ phone contact for IDet.
Measure Participants	174	175
TEAEs -26 weeks	810	761
TEAEs -52 weeks	1462	1266

6. Secondary Outcome

Title	Number of Hypoglycaemic Episodes
Description	Number of hypoglycaemic episodes (severe episodes or episodes with plasma glucose (PG) below or equal to 3.9 mmol/L (70 mg/dL) with or without symptoms of hypoglycaemia) during the trial; nocturnal [11 p.m. - 7 a.m./23:00 - 07:00] and over the entire day (24 hours)
Time Frame	After 26 weeks and 52 weeks of treatment

Outcome Measure Data

Analysis Population Description

Safety analysis set included all subjects receiving at least one dose of investigational product.

Arm/Group Title	IDeg + IAsp	IDet + IAsp
Arm/Group Description	Subjects from 1 to 18 years of age were randomised into treatment arms, IDeg OD as basal insulin and IAsp as mealtime bolus insulin for a period of 26 weeks followed by extension trial for a period of 26 weeks. IDeg was given once a day at approximately the same time of the day. Basal and bolus insulin titration was done according to the lowest pre-breakfast SMPG value measured on the three days prior to the visit/ phone contact for IDeg.	Subjects from 1 to 18 years of age were randomised into treatment arms, IDet OD as basal insulin and IAsp as mealtime bolus insulin for a period of 26 weeks followed by extension trial for a period of 26 weeks. IDet was given once a day at approximately the same time of the day. Basal and bolus insulin titration was done according to the lowest pre-breakfast SMPG value measured on the three days prior to the visit/ phone contact for IDet.
Measure Participants	174	175
26 weeks (entire day)	11712	10991
26 weeks (nocturnal)	1261	1458
52 weeks (entire day)	21560	18373
52 weeks (nocturnal)	2336	2586

7. Secondary Outcome

Title	Number of Self-measured Hyperglycaemia (Episodes of PG Above 11.1 mmol/L (200 mg/dL))
Description	Episodes of PG >11.1mmol/L (200mg/dL)
Time Frame	After 26 weeks and 52 weeks of treatment

Outcome Measure Data

Analysis Population Description

Safety analysis set included all subjects receiving at least one dose of investigational product.

Arm/Group Title	IDeg + IAsp	IDet + IAsp
Arm/Group Description	Subjects from 1 to 18 years of age were randomised into treatment arms, IDeg OD as basal insulin and IAsp as mealtime bolus insulin for a period of 26 weeks followed by extension trial for a period of 26 weeks. IDeg was given once a day at approximately the same time of the day. Basal and bolus insulin titration was done according to the lowest pre-breakfast SMPG value measured on the three days prior to the visit/ phone contact for IDeg.	Subjects from 1 to 18 years of age were randomised into treatment arms, IDet OD as basal insulin and IAsp as mealtime bolus insulin for a period of 26 weeks followed by extension trial for a period of 26 weeks. IDet was given once a day at approximately the same time of the day. Basal and bolus insulin titration was done according to the lowest pre-breakfast SMPG value measured on the three days prior to the visit/ phone contact for IDet.
Measure Participants	174	175
26 weeks	31264	31173
52 weeks	58679	52831

8. Secondary Outcome

Title	Number of Episodes With Self Monitored Blood Ketones Above 1.5 mmol (Capillary Blood Ketone Measurement to be Performed if Self-measured Plasma Glucose (SMPG) Exceeds 14.0 mmol/l (250 mg/dL))
Description	Blood ketones > 1.5mmol/L (Capillary blood ketone measurement to be performed if SMPG exceeds 14.0mmol/L (250mg/dL) )after 26 and 52 weeks of treatment
Time Frame	After 26 weeks and 52 weeks of treatment

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS) Included all randomised subjects

Arm/Group Title	IDeg + IAsp	IDet + IAsp
Arm/Group Description	Subjects from 1 to 18 years of age were randomised into treatment arms, IDeg OD as basal insulin and IAsp as mealtime bolus insulin for a period of 26 weeks followed by extension trial for a period of 26 weeks. IDeg was given once a day at approximately the same time of the day. Basal and bolus insulin titration was done according to the lowest pre-breakfast SMPG value measured on the three days prior to the visit/ phone contact for IDeg.	Subjects from 1 to 18 years of age were randomised into treatment arms, IDet OD as basal insulin and IAsp as mealtime bolus insulin for a period of 26 weeks followed by extension trial for a period of 26 weeks. IDet was given once a day at approximately the same time of the day. Basal and bolus insulin titration was done according to the lowest pre-breakfast SMPG value measured on the three days prior to the visit/ phone contact for IDet.
Measure Participants	174	175
26 weeks	44	86
52 weeks	109	161

9. Secondary Outcome

Title	Steady-state Plasma Concentrations of Insulin Degludec and Insulin Detemir on Three Different Visits (Three Different Weeks) During the First 26 Weeks of Treatment
Description	Steady state plasma concentrations of insulin degludec and insulin detemir on three different visits (three different weeks) during the trial.
Time Frame	Between week 1 and week 26

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS) Included all randomised subjects. 1 subject was excluded from the analysis in the IDet arm as he was withdrawn before exposure to trial drug.

Arm/Group Title	IDeg + IAsp	IDet + IAsp
Arm/Group Description	Subjects from 1 to 18 years of age were randomised into treatment arms, IDeg OD as basal insulin and IAsp as mealtime bolus insulin for a period of 26 weeks followed by extension trial for a period of 26 weeks. IDeg was given once a day at approximately the same time of the day. Basal and bolus insulin titration was done according to the lowest pre-breakfast SMPG value measured on the three days prior to the visit/ phone contact for IDeg.	Subjects from 1 to 18 years of age were randomised into treatment arms, IDet OD as basal insulin and IAsp as mealtime bolus insulin for a period of 26 weeks followed by extension trial for a period of 26 weeks. IDet was given once a day at approximately the same time of the day. Basal and bolus insulin titration was done according to the lowest pre-breakfast SMPG value measured on the three days prior to the visit/ phone contact for IDet.
Measure Participants	174	175
week 2	4540.4 (3999.0)	3972.2 (6721.8)
week 12	4148.1 (3726.9)	5430.1 (9067.7)
week 26	4105.6 (3456.5)	6377.0 (10930.6)

10. Secondary Outcome

Title	Insulin Antibodies (Insulin Degludec Specific, Insulin Detemir Specific, Insulin Aspart Specific and Antibodies Cross-reacting to Human Insulin)
Description	Antibody measurements : the values presented are week 52 (LOCF). The measurement of insulin antibodies after 26 and 52 weeks of treatment was done to fulfil the requirement of monitoring the long term immunogenicity. The unit of measure is percentage bound/total (%B/T) for these antibodies. The Antibodies cross reacting to Human Insulin is abbreviated as X-reacting AB Hu Insulin below)
Time Frame	After 52 weeks of treatment

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS) Included all randomised subjects. LOCF values are presented for this endpoint.

Arm/Group Title	IDeg + IAsp	IDet + IAsp
Arm/Group Description	Subjects from 1 to 18 years of age were randomised into treatment arms, IDeg OD as basal insulin and IAsp as mealtime bolus insulin for a period of 26 weeks followed by extension trial for a period of 26 weeks. IDeg was given once a day at approximately the same time of the day. Basal and bolus insulin titration was done according to the lowest pre-breakfast SMPG value measured on the three days prior to the visit/ phone contact for IDeg.	Subjects from 1 to 18 years of age were randomised into treatment arms, IDet OD as basal insulin and IAsp as mealtime bolus insulin for a period of 26 weeks followed by extension trial for a period of 26 weeks. IDet was given once a day at approximately the same time of the day. Basal and bolus insulin titration was done according to the lowest pre-breakfast SMPG value measured on the three days prior to the visit/ phone contact for IDet.
Measure Participants	174	175
Insulin aspart specific antibodies	1.1 (2.6)	1.5 (2.3)
Insulin Detemir specific antibodies	NA (NA)	6.1 (6.5)
Insulin Degludec specific antibodies	0 (0.3)	NA (NA)
X-reacting AB Hu Insulin	17.2 (7.7)	26.0 (19.3)

Adverse Events

Time Frame	Treatment emergent events (after first trial product administration and no later than 7 days after last trial product administration)
Adverse Event Reporting Description	Safety analysis set included all subjects receiving at least one dose of investigational product.
Arm/Group Title	IDeg + IAsp		IDet + IAsp
Arm/Group Description	Subjects from 1 to 18 years of age were randomised into treatment arms, IDeg OD as basal insulin and IAsp as mealtime bolus insulin for a period of 26 weeks followed by extension trial for a period of 26 weeks. IDeg was given once a day at approximately the same time of the day. Basal and bolus insulin titration was done according to the lowest pre-breakfast SMPG value measured on the three days prior to the visit/ phone contact for IDeg.		Subjects from 1 to 18 years of age were randomised into treatment arms, IDet OD as basal insulin and IAsp as mealtime bolus insulin for a period of 26 weeks followed by extension trial for a period of 26 weeks. IDet was given once a day at approximately the same time of the day. Basal and bolus insulin titration was done according to the lowest pre-breakfast SMPG value measured on the three days prior to the visit/ phone contact for IDet.
All Cause Mortality
	IDeg + IAsp		IDet + IAsp
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	IDeg + IAsp		IDet + IAsp
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	18/174 (10.3%)		16/175 (9.1%)
Gastrointestinal disorders
Faecaloma	1/174 (0.6%)	1	0/175 (0%)	0
Vomiting	0/174 (0%)	0	1/175 (0.6%)	1
Infections and infestations
Appendicitis	1/174 (0.6%)	1	2/175 (1.1%)	2
Bronchitis	1/174 (0.6%)	1	0/175 (0%)	0
Gastroenteritis	1/174 (0.6%)	1	2/175 (1.1%)	2
Gastroenteritis viral	0/174 (0%)	0	2/175 (1.1%)	2
Pharyngitis	0/174 (0%)	0	1/175 (0.6%)	1
Respiratory tract infection viral	1/174 (0.6%)	1	0/175 (0%)	0
Urinary tract infection	1/174 (0.6%)	1	0/175 (0%)	0
Injury, poisoning and procedural complications
Accidental overdose	1/174 (0.6%)	1	0/175 (0%)	0
Toxicity to various agents	1/174 (0.6%)	1	0/175 (0%)	0
Wrong drug administered	1/174 (0.6%)	1	0/175 (0%)	0
Investigations
Blood ketone body increased	1/174 (0.6%)	2	2/175 (1.1%)	4
Body temperature increased	1/174 (0.6%)	1	0/175 (0%)	0
Metabolism and nutrition disorders
Dehydration	0/174 (0%)	0	1/175 (0.6%)	1
Diabetic ketoacidosis	1/174 (0.6%)	1	0/175 (0%)	0
Hypoglycaemia	5/174 (2.9%)	7	2/175 (1.1%)	2
Ketosis	1/174 (0.6%)	1	1/175 (0.6%)	1
Nervous system disorders
Convulsion	1/174 (0.6%)	1	0/175 (0%)	0
Headache	1/174 (0.6%)	1	0/175 (0%)	0
Hypoglycaemic seizure	1/174 (0.6%)	1	3/175 (1.7%)	4
Hypoglycaemic unconsciousness	1/174 (0.6%)	1	1/175 (0.6%)	1
Loss of consciousness	0/174 (0%)	0	1/175 (0.6%)	1
Psychiatric disorders
Anxiety disorder	0/174 (0%)	0	1/175 (0.6%)	1
Respiratory, thoracic and mediastinal disorders
Cough	0/174 (0%)	0	1/175 (0.6%)	1
Other (Not Including Serious) Adverse Events
	IDeg + IAsp		IDet + IAsp
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	146/174 (83.9%)		143/175 (81.7%)
Ear and labyrinth disorders
Ear pain	10/174 (5.7%)	12	5/175 (2.9%)	5
Gastrointestinal disorders
Abdominal pain	12/174 (6.9%)	16	8/175 (4.6%)	12
Abdominal pain upper	28/174 (16.1%)	42	17/175 (9.7%)	30
Diarrhoea	22/174 (12.6%)	26	17/175 (9.7%)	25
Nausea	13/174 (7.5%)	18	9/175 (5.1%)	12
Vomiting	26/174 (14.9%)	38	22/175 (12.6%)	35
General disorders
Pyrexia	30/174 (17.2%)	59	28/175 (16%)	45
Infections and infestations
Bronchitis	9/174 (5.2%)	10	8/175 (4.6%)	11
Ear infection	9/174 (5.2%)	11	11/175 (6.3%)	11
Gastroenteritis	15/174 (8.6%)	19	22/175 (12.6%)	25
Gastroenteritis viral	10/174 (5.7%)	15	8/175 (4.6%)	13
Influenza	16/174 (9.2%)	19	18/175 (10.3%)	21
Nasopharyngitis	72/174 (41.4%)	177	67/175 (38.3%)	141
Pharyngitis	6/174 (3.4%)	7	9/175 (5.1%)	13
Rhinitis	12/174 (6.9%)	19	14/175 (8%)	23
Sinusitis	9/174 (5.2%)	13	6/175 (3.4%)	6
Upper respiratory tract infection	34/174 (19.5%)	56	24/175 (13.7%)	58
Viral infection	6/174 (3.4%)	8	10/175 (5.7%)	18
Investigations
Blood ketone body increased	31/174 (17.8%)	78	46/175 (26.3%)	131
Metabolism and nutrition disorders
Hypoglycaemia	26/174 (14.9%)	62	17/175 (9.7%)	31
Musculoskeletal and connective tissue disorders
Pain in extremity	11/174 (6.3%)	16	5/175 (2.9%)	5
Nervous system disorders
Headache	46/174 (26.4%)	106	51/175 (29.1%)	121
Respiratory, thoracic and mediastinal disorders
Cough	31/174 (17.8%)	52	28/175 (16%)	41
Nasal congestion	13/174 (7.5%)	17	7/175 (4%)	13
Oropharyngeal pain	29/174 (16.7%)	45	34/175 (19.4%)	50

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

Novo Nordisk maintains the right to be informed of plans by any investigator to publish 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 Novo Nordisk before submission for comments. Comments will be given within four weeks from receipt of the planned communication.