A Trial Investigating the Efficacy and Safety of Insulin Degludec/Insulin Aspart Once Daily Plus Insulin Aspart for the Remaining Meals Versus Insulin Detemir Once or Twice Daily Plus Meal Time Insulin Aspart in Children and Adolescents With Type 1 Diabetes Mellitus

• Sponsor: Novo Nordisk A/S (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01835431
• Collaborator: (none)
• Enrollment: 362
• Locations: 73
• Arms: 2
• Actual Duration (Months): 12.7
• Patients Per Site: 5
• Patients Per Site Per Month: 0.4

Study Details

Study Description

Brief Summary

This trial is conducted in Asia, Europe and North and South America. The aim of the trial is to investigate the efficacy and safety of insulin degludec/insulin aspart once daily plus insulin aspart for the remaining meals in children and adolescents with type 1 diabetes mellitus.

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

Study Design

• Study Type: Interventional
• Actual Enrollment: 362 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Trial Investigating the Efficacy and Safety of Insulin Degludec/Insulin Aspart Once Daily Plus Insulin Aspart for the Remaining Meals Versus Insulin Detemir Once or Twice Daily Plus Meal Time Insulin Aspart in Children and Adolescents With Type 1 Diabetes Mellitus
• Actual Study Start Date: Oct 17, 2013
• Actual Primary Completion Date: Nov 7, 2014
• Actual Study Completion Date: Nov 7, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Insulin degludec/insulin aspart	Drug: insulin degludec/insulin aspart; Administered subcutaneously (s.c., under the skin) once daily with a main meal. Dose individually adjusted.; Drug: insulin aspart; Administered s.c. with the remaining meals. Dose individually adjusted.
Active Comparator: Insulin detemir	Drug: insulin detemir; Administered s.c. once or twice daily. Dose individually adjusted. Subjects will continue with their pre-trial dosing scheme (once (OD) or twice daily (BID)) and will be allowed to switch from OD to BID dosing.; Drug: insulin aspart; Administered s.c. at meal-times. Dose individually adjusted.

Outcome Measures

Primary Outcome Measures

1. Change From Baseline in HbA1c (Glycosylated Haemoglobin) (%) [Week 0 to week 16]

   Percentage point change in glycosylated haemoglobin A1c (HbA1c) from baseline (week 0) to 16 Weeks. Change from baseline summary statistics at week 16 contains only those who had both baseline and week 16 assesment.

Secondary Outcome Measures

1. Change From Baseline in Fasting Plasma Glucose [week 0, week 16]

   Change from baseline in FPG after 16 weeks of treatment. Change from baseline summary statistics at week 16 contains only those who had both baseline and week 16 assesment.

2. Incidence of Treatment Emergent Adverse Events (TEAEs) [After 16 weeks of treatment]

   A Treatment Emergent Adverse Event (TEAE) was defined as an event with onset date on or after the first day of exposure to randomised treatment and no later than 7 days after the last day on randomised treatment.

3. Number of Treatment Emergent Confirmed Hypoglycaemic Episodes (Plasma Glucose (PG) Below 3.1mmol/L (56mg/dL) or Severe Hypoglycaemia) [After 16 weeks of treatment]

   Treatment emergent hypoglycaemic episodes (PG < 3.1 mmol/L (56 mg/dL) or severe hypoglycaemia). Confirmed hypoglycaemic episodes were defined as episodes that were either: Severe (i.e. the child is having altered mental status and cannot assist in their care, is semiconscious or unconscious or in coma with or without convulsions and may require parenteral therapy (glucagon or i.v. glucose), or An episode biochemically confirmed by PG value of <3.1 mmol/L (56 mg/dL), with or without symptoms consistent with hypoglycaemia.

4. Number of Treatment Emergent Nocturnal Confirmed Hypoglycaemic Episodes [After 16 weeks of treatment]

   The confirmed hypoglycaemic episodes occurring between 23:00 and 07:00 were considered for this endpoint

5. Number of Hyperglycaemic Episodes (PG Above 14.0 mmol/L (250 mg/dL) Where Subject Looks/Feels Ill [After 16 weeks of treatment]

   The episode of hyperglycaemia was noted when the glucose measurement was 14.0mmol/L or above and the subject looked /felt ill.

6. Number of Hyperglycaemic Episodes (PG Above 14.0 mmol/L (250 mg/dL) Where Subject Looks/Feels Ill With Ketosis (Blood Ketones Above 1.5 mmol/L) [After 16 weeks of treatment]

   The episode of hyperglycaemia was noted when the glucose measurement was 14.0mmol/L or above and the subject looked /felt ill. The ketone meaurement involved an additional finger prick and ketosis was considered present if blood ketones were higher than 1.5mmol/L

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 obtained before any trial related activities. Trial related activities are any procedures that are carried out as part of the trial, including activities to determine suitability for the trial - Subjects diagnosed with type 1 diabetes mellitus - HbA1c below or equal to 11.0% Exclusion Criteria: - Known hypoglycaemic unawareness or recurrent severe hypoglycaemic events as judged by the investigator - More than 1 episode of diabetic ketoacidosis requiring hospitalisation within the last 3 months prior to Visit 1 (Screening) - Any chronic disorder or significant concomitant disease, which in the investigator's opinion might jeopardise the subject's safety or compliance with the protocol

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Novo Nordisk Investigational Site	Phoenix	Arizona	United States	85053
2	Novo Nordisk Investigational Site	Tucson	Arizona	United States	85724
3	Novo Nordisk Investigational Site	Sacramento	California	United States	95816
4	Novo Nordisk Investigational Site	Aurora	Colorado	United States	80045
5	Novo Nordisk Investigational Site	Jacksonville	Florida	United States	32207
6	Novo Nordisk Investigational Site	Maitland	Florida	United States	32751
7	Novo Nordisk Investigational Site	Melbourne	Florida	United States	32901
8	Novo Nordisk Investigational Site	Tallahassee	Florida	United States	32308
9	Novo Nordisk Investigational Site	Tampa	Florida	United States	33612
10	Novo Nordisk Investigational Site	Atlanta	Georgia	United States	30322
11	Novo Nordisk Investigational Site	Atlanta	Georgia	United States	30339
12	Novo Nordisk Investigational Site	Idaho Falls	Idaho	United States	83404-7596
13	Novo Nordisk Investigational Site	Springfield	Illinois	United States	62703
14	Novo Nordisk Investigational Site	Indianapolis	Indiana	United States	46202
15	Novo Nordisk Investigational Site	Iowa City	Iowa	United States	52242
16	Novo Nordisk Investigational Site	Lexington	Kentucky	United States	40503
17	Novo Nordisk Investigational Site	Baltimore	Maryland	United States	21229
18	Novo Nordisk Investigational Site	Worcester	Massachusetts	United States	01655
19	Novo Nordisk Investigational Site	Kansas City	Missouri	United States	64111
20	Novo Nordisk Investigational Site	Buffalo	New York	United States	14203
21	Novo Nordisk Investigational Site	Tulsa	Oklahoma	United States	74135
22	Novo Nordisk Investigational Site	Philadelphia	Pennsylvania	United States	19104
23	Novo Nordisk Investigational Site	Philadelphia	Pennsylvania	United States	19107
24	Novo Nordisk Investigational Site	Dallas	Texas	United States	75231
25	Novo Nordisk Investigational Site	Brussels		Belgium	1090
26	Novo Nordisk Investigational Site	Brussels		Belgium	1200
27	Novo Nordisk Investigational Site	Leuven		Belgium	3000
28	Novo Nordisk Investigational Site	Curitiba	Parana	Brazil	80810-040
29	Novo Nordisk Investigational Site	Porto Alegre	Rio Grande Do Sul	Brazil	91350-250
30	Novo Nordisk Investigational Site	São Paulo	Sao Paulo	Brazil	01228-200
31	Novo Nordisk Investigational Site	Vancouver	British Columbia	Canada	V6H 3V4
32	Novo Nordisk Investigational Site	London	Ontario	Canada	N6A 5W9
33	Novo Nordisk Investigational Site	Mississauga	Ontario	Canada	L5B 1B8
34	Novo Nordisk Investigational Site	Montreal	Quebec	Canada	H3T 1C5
35	Novo Nordisk Investigational Site	Montreal	Quebec	Canada	HIT 2M4
36	Novo Nordisk Investigational Site	Zagreb		Croatia	10 000
37	Novo Nordisk Investigational Site	Zagreb		Croatia	10000
38	Novo Nordisk Investigational Site	Olomouc		Czechia	779 00
39	Novo Nordisk Investigational Site	Pardubice		Czechia	53203
40	Novo Nordisk Investigational Site	Prague 5		Czechia	15018
41	Novo Nordisk Investigational Site	Hyderabad	Andhra Pradesh	India	500034
42	Novo Nordisk Investigational Site	Bangalore	Karnataka	India	560034
43	Novo Nordisk Investigational Site	Mumbai	Maharashtra	India	400008
44	Novo Nordisk Investigational Site	Mumbai	Maharashtra	India	400012
45	Novo Nordisk Investigational Site	New Dehli	New Delhi	India	110029
46	Novo Nordisk Investigational Site	Chennai	Tamil Nadu	India	600086
47	Novo Nordisk Investigational Site	Beer Sheva		Israel	84101
48	Novo Nordisk Investigational Site	Haifa		Israel	31096
49	Novo Nordisk Investigational Site	Petah Tikva		Israel	49202
50	Novo Nordisk Investigational Site	Tel Aviv		Israel
51	Novo Nordisk Investigational Site	Tel Hashomer		Israel	52621
52	Novo Nordisk Investigational Site	Zerifin		Israel	70300
53	Novo Nordisk Investigational Site	Skopje		North Macedonia	1000
54	Novo Nordisk Investigational Site	Gdansk		Poland	80-952
55	Novo Nordisk Investigational Site	Warszawa		Poland	04-730
56	Novo Nordisk Investigational Site	Warszawa		Poland	04-736
57	Novo Nordisk Investigational Site	Moscow		Russian Federation	125373
58	Novo Nordisk Investigational Site	Novosibirsk		Russian Federation	630048
59	Novo Nordisk Investigational Site	Saint-Petersburg		Russian Federation	191144
60	Novo Nordisk Investigational Site	Tomsk		Russian Federation	634050
61	Novo Nordisk Investigational Site	Ufa		Russian Federation	450106
62	Novo Nordisk Investigational Site	Belgrade		Serbia	11070
63	Novo Nordisk Investigational Site	Nis		Serbia	18 000
64	Novo Nordisk Investigational Site	Novi Sad		Serbia	21000
65	Novo Nordisk Investigational Site	Ljubljana		Slovenia	1525
66	Novo Nordisk Investigational Site	Johannesburg	Gauteng	South Africa	2193
67	Novo Nordisk Investigational Site	Pretoria	Gauteng	South Africa	0181
68	Novo Nordisk Investigational Site	Mayville	KwaZulu-Natal	South Africa	4058
69	Novo Nordisk Investigational Site	Barcelona		Spain	08035
70	Novo Nordisk Investigational Site	Esplugues Llobregat(Barcelona)		Spain	08950
71	Novo Nordisk Investigational Site	Leganés		Spain	28911
72	Novo Nordisk Investigational Site	Madrid		Spain	28034
73	Novo Nordisk Investigational Site	Madrid		Spain	28046

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: NCT01835431
• Other Study ID Numbers: NN5401-3816; 2012-003566-41; U1111-1133-0958; PIP no. be confirmed
• First Posted: Apr 19, 2013
• Last Update Posted: Jun 11, 2019
• Last Verified: Jun 1, 2019

• 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 63 sites in 14 countries as follows: Belgium: 3 sites; Brazil: 1 sites; Canada: 3 sites; Czech Republic 3 sites; Croatia: 2 sites; Israel: 6 sites; Macedonia: 2 sites; Poland: 3 sites; Russia: 5 sites; Serbia: 4 sites; Slovenia: 1 sites; South Africa: 2 sites; Spain: 5 sites; and United States: 23 sites.

Arm/Group Title	IDegAsp OD	IDet OD/BID
Arm/Group Description	Insulin degludec/insulin aspart (IDegAsp) once daily (OD) 2-4U was administered subcutaneously in the thigh, upper arm (deltoid area) or abdomen with the main meal and IAsp was given with the remaining meals 1-3 times daily for 16 weeks.	Insulin detemir (IDet) OD/BID (once daily /twice daily) 2-4U was administered subcutaneously in the thigh, upper arm (deltoid area) or abdomen with the main meal and IAsp was given with the remaining meals 2-4 times daily for 16 weeks
Period Title: Overall Study
STARTED	182	180
Exposed	181	179
COMPLETED	174	168
NOT COMPLETED	8	12

Baseline Characteristics

Arm/Group Title	IDegAsp OD	IDet OD/BID	Total
Arm/Group Description	Insulin degludec/insulin aspart (IDegAsp) once daily (OD) 2-4U was administered subcutaneously in the thigh, upper arm (deltoid area) or abdomen with the main meal and IAsp was given with the remaining meals 1-3 times daily for 16 weeks.	Insulin detemir (IDet) OD/BID (once daily /twice daily) 2-4U was administered subcutaneously in the thigh, upper arm (deltoid area) or abdomen with the main meal and IAsp was given with the remaining meals 2-4 times daily for 16 weeks	Total of all reporting groups
Overall Participants	182	180	362
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	10.5 (4.3)	10.8 (4.6)	10.6 (4.5)
Sex: Female, Male (Count of Participants)
Female	93 51.1%	94 52.2%	187 51.7%
Male	89 48.9%	86 47.8%	175 48.3%
HbA1c (percentage (%)) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [percentage (%)]	8.1 (1.2)	8.1 (1.2)	8.1 (1.2)
Fasting plasma Glucose (FPG) (mmol/L) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mmol/L]	8.6 (4.4)	8.1 (4.2)	8.4 (4.3)

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in HbA1c (Glycosylated Haemoglobin) (%)
Description	Percentage point change in glycosylated haemoglobin A1c (HbA1c) from baseline (week 0) to 16 Weeks. Change from baseline summary statistics at week 16 contains only those who had both baseline and week 16 assesment.
Time Frame	Week 0 to week 16

Outcome Measure Data

Analysis Population Description

The FAS included all randomised subjects. 20 subjects were withdrawn and only 4 subjects though completed the study did not have assesments.

Arm/Group Title	IDegAsp OD	IDet OD/BID
Arm/Group Description	Insulin degludec/insulin aspart (IDegAsp) once daily (OD) 2-4U was administered subcutaneously in the thigh, upper arm (deltoid area) or abdomen with the main meal and IAsp was given with the remaining meals 1-3 times daily for 16 weeks.	Insulin detemir (IDet) OD/BID (once daily /twice daily) 2-4U was administered subcutaneously in the thigh, upper arm (deltoid area) or abdomen with the main meal and IAsp was given with the remaining meals 2-4 times daily for 16 weeks
Measure Participants	173	165
Mean (Standard Deviation) [percentage (%)]	-0.3 (1.0)	-0.3 (0.9)

2. Secondary Outcome

Title	Change From Baseline in Fasting Plasma Glucose
Description	Change from baseline in FPG after 16 weeks of treatment. Change from baseline summary statistics at week 16 contains only those who had both baseline and week 16 assesment.
Time Frame	week 0, week 16

Outcome Measure Data

Analysis Population Description

The FAS included all randomised subjects. 338 subjects had assessment at baseline, 326 had assessment at week 16, 2 subjects were withdrawn before exposure and 22 subjects week 16 assessment was not done.

Arm/Group Title	IDegAsp OD	IDet OD/BID
Arm/Group Description	Insulin degludec/insulin aspart (IDegAsp) once daily (OD) 2-4U was administered subcutaneously in the thigh, upper arm (deltoid area) or abdomen with the main meal and IAsp was given with the remaining meals 1-3 times daily for 16 weeks.	Insulin detemir (IDet) OD/BID (once daily /twice daily) 2-4U was administered subcutaneously in the thigh, upper arm (deltoid area) or abdomen with the main meal and IAsp was given with the remaining meals 2-4 times daily for 16 weeks
Measure Participants	162	148
Mean (Standard Deviation) [mmol/L]	-0.3 (6.4)	-0.1 (4.8)

3. Secondary Outcome

Title	Incidence of Treatment Emergent Adverse Events (TEAEs)
Description	A Treatment Emergent Adverse Event (TEAE) was defined as an event with onset date on or after the first day of exposure to randomised treatment and no later than 7 days after the last day on randomised treatment.
Time Frame	After 16 weeks of treatment

Outcome Measure Data

Analysis Population Description

The Safety analysis set (SAS) included all subjects receiving at least one dose of the trial product or its comparator

Arm/Group Title	IDegAsp OD	IDet OD/BID
Arm/Group Description	Insulin degludec/insulin aspart (IDegAsp) once daily (OD) 2-4U was administered subcutaneously in the thigh, upper arm (deltoid area) or abdomen with the main meal and IAsp was given with the remaining meals 1-3 times daily for 16 weeks.	Insulin detemir (IDet) OD/BID (once daily /twice daily) 2-4U was administered subcutaneously in the thigh, upper arm (deltoid area) or abdomen with the main meal and IAsp was given with the remaining meals 2-4 times daily for 16 weeks
Measure Participants	181	179
Number [number of events]	501	460

4. Secondary Outcome

Title	Number of Treatment Emergent Confirmed Hypoglycaemic Episodes (Plasma Glucose (PG) Below 3.1mmol/L (56mg/dL) or Severe Hypoglycaemia)
Description	Treatment emergent hypoglycaemic episodes (PG < 3.1 mmol/L (56 mg/dL) or severe hypoglycaemia). Confirmed hypoglycaemic episodes were defined as episodes that were either: Severe (i.e. the child is having altered mental status and cannot assist in their care, is semiconscious or unconscious or in coma with or without convulsions and may require parenteral therapy (glucagon or i.v. glucose), or An episode biochemically confirmed by PG value of <3.1 mmol/L (56 mg/dL), with or without symptoms consistent with hypoglycaemia.
Time Frame	After 16 weeks of treatment

Outcome Measure Data

Analysis Population Description

The SAS included all subjects receiving at least one dose of the trial product or its comparator

Arm/Group Title	IDegAsp OD	IDet OD/BID
Arm/Group Description	Insulin degludec/insulin aspart (IDegAsp) once daily (OD) 2-4U was administered subcutaneously in the thigh, upper arm (deltoid area) or abdomen with the main meal and IAsp was given with the remaining meals 1-3 times daily for 16 weeks.	Insulin detemir (IDet) OD/BID (once daily /twice daily) 2-4U was administered subcutaneously in the thigh, upper arm (deltoid area) or abdomen with the main meal and IAsp was given with the remaining meals 2-4 times daily for 16 weeks
Measure Participants	181	179
Number [episodes]	2532	2672

5. Secondary Outcome

Title	Number of Treatment Emergent Nocturnal Confirmed Hypoglycaemic Episodes
Description	The confirmed hypoglycaemic episodes occurring between 23:00 and 07:00 were considered for this endpoint
Time Frame	After 16 weeks of treatment

Outcome Measure Data

Analysis Population Description

The SAS included all subjects receiving at least one dose of the trial product or its comparator

Arm/Group Title	IDegAsp OD	IDet OD/BID
Arm/Group Description	Insulin degludec/insulin aspart (IDegAsp) once daily (OD) 2-4U was administered subcutaneously in the thigh, upper arm (deltoid area) or abdomen with the main meal and IAsp was given with the remaining meals 1-3 times daily for 16 weeks.	Insulin detemir (IDet) OD/BID (once daily /twice daily) 2-4U was administered subcutaneously in the thigh, upper arm (deltoid area) or abdomen with the main meal and IAsp was given with the remaining meals 2-4 times daily for 16 weeks
Measure Participants	181	179
Number [episodes]	316	291

6. Secondary Outcome

Title	Number of Hyperglycaemic Episodes (PG Above 14.0 mmol/L (250 mg/dL) Where Subject Looks/Feels Ill
Description	The episode of hyperglycaemia was noted when the glucose measurement was 14.0mmol/L or above and the subject looked /felt ill.
Time Frame	After 16 weeks of treatment

Outcome Measure Data

Analysis Population Description

The SAS included all subjects receiving at least one dose of the trial product or its comparator

Arm/Group Title	IDegAsp OD	IDet OD/BID
Arm/Group Description	Insulin degludec/insulin aspart (IDegAsp) once daily (OD) 2-4U was administered subcutaneously in the thigh, upper arm (deltoid area) or abdomen with the main meal and IAsp was given with the remaining meals 1-3 times daily for 16 weeks.	Insulin detemir (IDet) OD/BID (once daily /twice daily) 2-4U was administered subcutaneously in the thigh, upper arm (deltoid area) or abdomen with the main meal and IAsp was given with the remaining meals 2-4 times daily for 16 weeks
Measure Participants	181	179
Number [episodes]	599	449

7. Secondary Outcome

Title	Number of Hyperglycaemic Episodes (PG Above 14.0 mmol/L (250 mg/dL) Where Subject Looks/Feels Ill With Ketosis (Blood Ketones Above 1.5 mmol/L)
Description	The episode of hyperglycaemia was noted when the glucose measurement was 14.0mmol/L or above and the subject looked /felt ill. The ketone meaurement involved an additional finger prick and ketosis was considered present if blood ketones were higher than 1.5mmol/L
Time Frame	After 16 weeks of treatment

Outcome Measure Data

Analysis Population Description

The SAS included all subjects receiving at least one dose of the trial product or its comparator

Arm/Group Title	IDegAsp OD	IDet OD/BID
Arm/Group Description	Insulin degludec/insulin aspart (IDegAsp) once daily (OD) 2-4U was administered subcutaneously in the thigh, upper arm (deltoid area) or abdomen with the main meal and IAsp was given with the remaining meals 1-3 times daily for 16 weeks.	Insulin detemir (IDet) OD/BID (once daily /twice daily) 2-4U was administered subcutaneously in the thigh, upper arm (deltoid area) or abdomen with the main meal and IAsp was given with the remaining meals 2-4 times daily for 16 weeks
Measure Participants	181	179
Number [episodes]	6	12

Adverse Events

Time Frame	Onset date on or after the first day of esxposure to randomised treatment and no later than 7 days after the last day on randomised treatment
Adverse Event Reporting Description	The SAS included all subjects receiving at least one dose of the trial product or its comparator
Arm/Group Title	IDegAsp OD		IDet OD/BID
Arm/Group Description	Insulin degludec/insulin aspart (IDegAsp) once daily (OD) 2-4U was administered subcutaneously in the thigh, upper arm (deltoid area) or abdomen with the main meal and IAsp was given with the remaining meals 1-3 times daily for 16 weeks.		Insulin detemir (IDet) OD/BID (once daily /twice daily) 2-4U was administered subcutaneously in the thigh, upper arm (deltoid area) or abdomen with the main meal and IAsp was given with the remaining meals 2-4 times daily for 16 weeks
All Cause Mortality
	IDegAsp OD		IDet OD/BID
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	IDegAsp OD		IDet OD/BID
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	11/181 (6.1%)		7/179 (3.9%)
Congenital, familial and genetic disorders
Developmental glaucoma	1/181 (0.6%)	1	0/179 (0%)	0
Gastrointestinal disorders
Constipation	1/181 (0.6%)	1	0/179 (0%)	0
Gastritis	1/181 (0.6%)	1	0/179 (0%)	0
Infections and infestations
Laryngitis	0/181 (0%)	0	1/179 (0.6%)	1
Viral infection	1/181 (0.6%)	1	1/179 (0.6%)	1
Injury, poisoning and procedural complications
Fall	0/181 (0%)	0	1/179 (0.6%)	1
Fibula Fracture	1/181 (0.6%)	1	0/179 (0%)	0
Tibia Fracture	1/181 (0.6%)	1	0/179 (0%)	0
Metabolism and nutrition disorders
Diabetic Ketoacidosis	1/181 (0.6%)	1	1/179 (0.6%)	1
Hyperglycaemia	0/181 (0%)	0	1/179 (0.6%)	1
Hypoglycaemia	5/181 (2.8%)	5	1/179 (0.6%)	1
Musculoskeletal and connective tissue disorders
Compartment syndrome	1/181 (0.6%)	1	0/179 (0%)	0
Nervous system disorders
Hypoglycaemic seizure	1/181 (0.6%)	1	0/179 (0%)	0
Loss of consciousness	0/181 (0%)	0	1/179 (0.6%)	1
Other (Not Including Serious) Adverse Events
	IDegAsp OD		IDet OD/BID
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	96/181 (53%)		97/179 (54.2%)
Gastrointestinal disorders
Abdominal pain	10/181 (5.5%)	13	7/179 (3.9%)	13
Abdominal pain upper	14/181 (7.7%)	22	17/179 (9.5%)	26
Vomiting	22/181 (12.2%)	25	12/179 (6.7%)	13
General disorders
Pyrexia	17/181 (9.4%)	26	10/179 (5.6%)	15
Infections and infestations
Influenza	9/181 (5%)	10	10/179 (5.6%)	12
Nasopharyngitis	36/181 (19.9%)	43	32/179 (17.9%)	42
Pharyngitis	3/181 (1.7%)	3	10/179 (5.6%)	13
Upper respiratory tract infection	11/181 (6.1%)	12	17/179 (9.5%)	18
Nervous system disorders
Headache	23/181 (12.7%)	47	32/179 (17.9%)	64
Respiratory, thoracic and mediastinal disorders
cough	13/181 (7.2%)	16	9/179 (5%)	9
Oropharyngeal pain	9/181 (5%)	13	13/179 (7.3%)	14

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