Trial Outcomes & Findings for Comparison of NN1250 Plus Insulin Aspart With Insulin Detemir Plus Insulin Aspart in Type 1 Diabetes (NCT NCT01074268)

NCT ID: NCT01074268

Last Updated: 2017-03-06

Results Overview

Change from baseline in HbA1c after 26 weeks of treatment

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

456 participants

Primary outcome timeframe

Week 0, Week 26

Results posted on

2017-03-06

Participant Flow

The trial was conducted at 55 sites in 7 countries: Brazil (2), Finland (8), India (10), Italy (6), Japan (15), Macedonia (1) and United Kingdom (13). For the extension trial, one trial site in Italy did not enroll any subject since approval was not obtained before the start of the trial from the IEC.

All subjects who completed the 26-week main trial (NN1250-3585, NCT01074268) and were found to be eligible for the extension trial were offered to participate in the 26-week extension trial (NN1250-3725). The total duration of treatment was 52 weeks (26 weeks + 26 weeks), separated by 1 week of follow-up from the main trial.

Participant milestones

Participant milestones
Measure	IDeg OD Insulin degludec (IDeg) was given subcutaneously (s.c.) once daily (OD) in the evening in combination with insulin aspart (IAsp) as meal-time insulin. IDeg OD was given for 26 weeks in the main period and for another 26 weeks in the extension period.	IDet OD Insulin detemir (IDet) was given subcutaneously (s.c.) once daily (OD) in the evening or twice daily (BID) morning and evening in combination with insulin aspart (IAsp) as meal-time insulin. IDet was given for 26 weeks in the main period and for another 26 weeks in the extension period.
Main: Week 0 to 26 (NN1250-3585) STARTED	303	153
Main: Week 0 to 26 (NN1250-3585) Full Analysis Set	302	153
Main: Week 0 to 26 (NN1250-3585) Exposed	301	152
Main: Week 0 to 26 (NN1250-3585) COMPLETED	283	138
Main: Week 0 to 26 (NN1250-3585) NOT COMPLETED	20	15
Extension: Week 27 to 52 (NN1250-3725) STARTED	248	122
Extension: Week 27 to 52 (NN1250-3725) COMPLETED	242	115
Extension: Week 27 to 52 (NN1250-3725) NOT COMPLETED	6	7

Reasons for withdrawal

Reasons for withdrawal
Measure	IDeg OD Insulin degludec (IDeg) was given subcutaneously (s.c.) once daily (OD) in the evening in combination with insulin aspart (IAsp) as meal-time insulin. IDeg OD was given for 26 weeks in the main period and for another 26 weeks in the extension period.	IDet OD Insulin detemir (IDet) was given subcutaneously (s.c.) once daily (OD) in the evening or twice daily (BID) morning and evening in combination with insulin aspart (IAsp) as meal-time insulin. IDet was given for 26 weeks in the main period and for another 26 weeks in the extension period.
Main: Week 0 to 26 (NN1250-3585) Adverse Event	3	1
Main: Week 0 to 26 (NN1250-3585) Lack of Efficacy	0	2
Main: Week 0 to 26 (NN1250-3585) Protocol Violation	3	4
Main: Week 0 to 26 (NN1250-3585) Withdrawal criteria	6	3
Main: Week 0 to 26 (NN1250-3585) Unclassified	8	5
Extension: Week 27 to 52 (NN1250-3725) Adverse Event	1	1
Extension: Week 27 to 52 (NN1250-3725) Protocol Violation	0	2
Extension: Week 27 to 52 (NN1250-3725) Withdrawal criteria	2	2
Extension: Week 27 to 52 (NN1250-3725) Unclassified	3	2

Baseline Characteristics

Comparison of NN1250 Plus Insulin Aspart With Insulin Detemir Plus Insulin Aspart in Type 1 Diabetes

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	IDeg OD n=302 Participants Insulin degludec (IDeg) was given subcutaneously (s.c.) once daily (OD) in the evening in combination with insulin aspart (IAsp) as meal-time insulin. IDeg OD was given for 26 weeks in the main period and for another 26 weeks in the extension period.	IDet OD n=153 Participants Insulin detemir (IDet) was given subcutaneously (s.c.) once daily (OD) in the evening or twice daily (BID) morning and evening in combination with insulin aspart (IAsp) as meal-time insulin. IDet was given for 26 weeks in the main period and for another 26 weeks in the extension period.	Total n=455 Participants Total of all reporting groups
Age, Continuous	41.1 years STANDARD_DEVIATION 14.9 • n=5 Participants	41.7 years STANDARD_DEVIATION 14.4 • n=7 Participants	41.3 years STANDARD_DEVIATION 14.7 • n=5 Participants
Sex: Female, Male Female	152 Participants n=5 Participants	67 Participants n=7 Participants	219 Participants n=5 Participants
Sex: Female, Male Male	150 Participants n=5 Participants	86 Participants n=7 Participants	236 Participants n=5 Participants
Glycosylated haemoglobin (HbA1c)	8.0 percentage of glycosylated haemoglobin STANDARD_DEVIATION 1.0 • n=5 Participants	8.0 percentage of glycosylated haemoglobin STANDARD_DEVIATION 0.9 • n=7 Participants	8.0 percentage of glycosylated haemoglobin STANDARD_DEVIATION 0.9 • n=5 Participants
Fasting plasma glucose (FPG)	9.9 mmol/L STANDARD_DEVIATION 4.0 • n=5 Participants	9.5 mmol/L STANDARD_DEVIATION 4.0 • n=7 Participants	9.8 mmol/L STANDARD_DEVIATION 4.0 • n=5 Participants

PRIMARY outcome

Timeframe: Week 0, Week 26

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

Change from baseline in HbA1c after 26 weeks of treatment

Outcome measures

Outcome measures
Measure	IDeg OD n=302 Participants Insulin degludec (IDeg) was given subcutaneously (s.c.) once daily (OD) in the evening in combination with insulin aspart (IAsp) as meal-time insulin. IDeg OD was given for 26 weeks in the main period and for another 26 weeks in the extension period.	IDet OD n=153 Participants Insulin detemir (IDet) was given subcutaneously (s.c.) once daily (OD) in the evening or twice daily (BID) morning and evening in combination with insulin aspart (IAsp) as meal-time insulin. IDet was given for 26 weeks in the main period and for another 26 weeks in the extension period.
Main Trial (Primary Endpoint): Change in Glycosylated Haemoglobin (HbA1c) After 26 Weeks of Treatment	-0.73 percentage of glycosylated haemoglobin Standard Deviation 0.88	-0.65 percentage of glycosylated haemoglobin Standard Deviation 0.86

PRIMARY outcome

Timeframe: Week 0 to Week 52 + 7 days follow up

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

Rate of AEs per 100 patient years of exposure. Severity assessed by investigator. Mild: no/transient symptoms, no interference with subject's daily activities. Moderate: marked symptoms, moderate interference with subject's daily activities. Severe: considerable interference with subject's daily activities, unacceptable. Serious AE: AE that at any dose results in any of the following death, a life-threatening experience, in-subject hospitalization/prolongation of existing hospitalisation, persistent/significant disability/incapacity/congenital anomaly/birth defect or important medical issues

Outcome measures

Outcome measures
Measure	IDeg OD n=301 Participants Insulin degludec (IDeg) was given subcutaneously (s.c.) once daily (OD) in the evening in combination with insulin aspart (IAsp) as meal-time insulin. IDeg OD was given for 26 weeks in the main period and for another 26 weeks in the extension period.	IDet OD n=152 Participants Insulin detemir (IDet) was given subcutaneously (s.c.) once daily (OD) in the evening or twice daily (BID) morning and evening in combination with insulin aspart (IAsp) as meal-time insulin. IDet was given for 26 weeks in the main period and for another 26 weeks in the extension period.
Extension Trial (Primary Endpoint): Rate of Treatment Emergent Adverse Events (AEs) Adverse events (AEs)	459 Events/100 years of patient exposure	420 Events/100 years of patient exposure
Extension Trial (Primary Endpoint): Rate of Treatment Emergent Adverse Events (AEs) Serious AE	20 Events/100 years of patient exposure	17 Events/100 years of patient exposure
Extension Trial (Primary Endpoint): Rate of Treatment Emergent Adverse Events (AEs) Severe AE	23 Events/100 years of patient exposure	35 Events/100 years of patient exposure
Extension Trial (Primary Endpoint): Rate of Treatment Emergent Adverse Events (AEs) Moderate AE	48 Events/100 years of patient exposure	45 Events/100 years of patient exposure
Extension Trial (Primary Endpoint): Rate of Treatment Emergent Adverse Events (AEs) Mild AE	388 Events/100 years of patient exposure	341 Events/100 years of patient exposure
Extension Trial (Primary Endpoint): Rate of Treatment Emergent Adverse Events (AEs) Fatal AE	0 Events/100 years of patient exposure	0 Events/100 years of patient exposure

SECONDARY outcome

Timeframe: Week 0, Week 52

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

Change from baseline in HbA1c after 52 weeks of treatment

Outcome measures

Outcome measures
Measure	IDeg OD n=302 Participants Insulin degludec (IDeg) was given subcutaneously (s.c.) once daily (OD) in the evening in combination with insulin aspart (IAsp) as meal-time insulin. IDeg OD was given for 26 weeks in the main period and for another 26 weeks in the extension period.	IDet OD n=153 Participants Insulin detemir (IDet) was given subcutaneously (s.c.) once daily (OD) in the evening or twice daily (BID) morning and evening in combination with insulin aspart (IAsp) as meal-time insulin. IDet was given for 26 weeks in the main period and for another 26 weeks in the extension period.
Extension Trial (Secondary Endpoint): Change in Glycosylated Haemoglobin (HbA1c) After 52 Weeks of Treatment	-0.46 percentage of glycosylated haemoglobin Standard Deviation 0.93	-0.47 percentage of glycosylated haemoglobin Standard Deviation 0.88

SECONDARY outcome

Timeframe: Week 26

Population: The FAS included all randomised subjects and missing data was imputed using LOCF. For 5 subjects, all 9-point SMPG values were missing.

Mean of 9-point self-measured plasma glucose profile (SMPG) after week 26. Plasma glucose was measured before breakfast, 90 minutes after the start of breakfast, before lunch, 90 minutes after the start of lunch, before main evening meal, 90 minutes after the start of main evening meal, before bedtime, at 04:00 AM and before breakfast on the following day.

Outcome measures

Outcome measures
Measure	IDeg OD n=299 Participants Insulin degludec (IDeg) was given subcutaneously (s.c.) once daily (OD) in the evening in combination with insulin aspart (IAsp) as meal-time insulin. IDeg OD was given for 26 weeks in the main period and for another 26 weeks in the extension period.	IDet OD n=151 Participants Insulin detemir (IDet) was given subcutaneously (s.c.) once daily (OD) in the evening or twice daily (BID) morning and evening in combination with insulin aspart (IAsp) as meal-time insulin. IDet was given for 26 weeks in the main period and for another 26 weeks in the extension period.
Main Trial (Secondary Endpoint): Mean of 9-point Self Measured Plasma Glucose Profile (SMPG) at Week 26	7.9 mmol/L Standard Deviation 2.1	7.8 mmol/L Standard Deviation 1.9

SECONDARY outcome

Timeframe: Week 52

Population: The FAS included all randomised subjects in the main trial including subjects carried through to the extension trial and missing data was imputed using LOCF. For 4 subjects all 9-point SMPG values were missing.

Mean of 9-point self-measured plasma glucose profile (SMPG) at week 52. Plasma glucose was measured before breakfast, 90 minutes after the start of breakfast, before lunch, 90 minutes after the start of lunch, before main evening meal, 90 minutes after the start of main evening meal, before bedtime, at 04:00 AM and before breakfast on the following day.

Outcome measures

Outcome measures
Measure	IDeg OD n=301 Participants Insulin degludec (IDeg) was given subcutaneously (s.c.) once daily (OD) in the evening in combination with insulin aspart (IAsp) as meal-time insulin. IDeg OD was given for 26 weeks in the main period and for another 26 weeks in the extension period.	IDet OD n=150 Participants Insulin detemir (IDet) was given subcutaneously (s.c.) once daily (OD) in the evening or twice daily (BID) morning and evening in combination with insulin aspart (IAsp) as meal-time insulin. IDet was given for 26 weeks in the main period and for another 26 weeks in the extension period.
Extension Trial (Secondary Endpoint): Mean of 9-point Self Measured Plasma Glucose Profile (SMPG) at Week 52	7.8 mmol/L Standard Deviation 1.9	7.8 mmol/L Standard Deviation 2.0

SECONDARY outcome

Timeframe: Week 0, Week 26

Population: The FAS included all randomised subjects and missing data was imputed using LOCF. For 6 subjects change in FPG values were missing.

Change from baseline in FPG after 26 weeks of treatment

Outcome measures

Outcome measures
Measure	IDeg OD n=301 Participants Insulin degludec (IDeg) was given subcutaneously (s.c.) once daily (OD) in the evening in combination with insulin aspart (IAsp) as meal-time insulin. IDeg OD was given for 26 weeks in the main period and for another 26 weeks in the extension period.	IDet OD n=148 Participants Insulin detemir (IDet) was given subcutaneously (s.c.) once daily (OD) in the evening or twice daily (BID) morning and evening in combination with insulin aspart (IAsp) as meal-time insulin. IDet was given for 26 weeks in the main period and for another 26 weeks in the extension period.
Main Trial (Secondary Endpoint): Change in Fasting Plasma Glucose (FPG) After 26 Weeks of Treatment	-2.60 mmol/L Standard Deviation 4.87	-0.62 mmol/L Standard Deviation 4.49

SECONDARY outcome

Timeframe: Week 0, Week 52

Population: The FAS included all randomised subjects in the main trial including subjects carried through to the extension trial and missing data was imputed using LOCF. For 6 subjects change in FPG values were missing.

Change from baseline in FPG after 52 weeks of treatment

Outcome measures

Outcome measures
Measure	IDeg OD n=301 Participants Insulin degludec (IDeg) was given subcutaneously (s.c.) once daily (OD) in the evening in combination with insulin aspart (IAsp) as meal-time insulin. IDeg OD was given for 26 weeks in the main period and for another 26 weeks in the extension period.	IDet OD n=148 Participants Insulin detemir (IDet) was given subcutaneously (s.c.) once daily (OD) in the evening or twice daily (BID) morning and evening in combination with insulin aspart (IAsp) as meal-time insulin. IDet was given for 26 weeks in the main period and for another 26 weeks in the extension period.
Extension Trial (Secondary Endpoint): Change in Fasting Plasma Glucose (FPG) After 52 Weeks of Treatment	-2.19 mmol/L Standard Deviation 4.99	-0.82 mmol/L Standard Deviation 4.79

SECONDARY outcome

Timeframe: Week 0 to Week 26 + 7 days follow up

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

Rate of confirmed hypoglycaemic episodes per 100 patient years of exposure (PYE). Confirmed hypoglycaemic episodes consisted of severe hypoglycaemia as well as minor hypoglycaemic episodes. Severe hypoglycaemic episodes: episodes requiring active assistance of another person to administer carbohydrate, glucagon, or other resuscitative actions. Minor hypoglycaemic episodes: episodes where the subject was able to treat her/himself and plasma glucose below 3.1 mmol/L, with or without symptoms.

Outcome measures

Outcome measures
Measure	IDeg OD n=301 Participants Insulin degludec (IDeg) was given subcutaneously (s.c.) once daily (OD) in the evening in combination with insulin aspart (IAsp) as meal-time insulin. IDeg OD was given for 26 weeks in the main period and for another 26 weeks in the extension period.	IDet OD n=152 Participants Insulin detemir (IDet) was given subcutaneously (s.c.) once daily (OD) in the evening or twice daily (BID) morning and evening in combination with insulin aspart (IAsp) as meal-time insulin. IDet was given for 26 weeks in the main period and for another 26 weeks in the extension period.
Main Trial (Secondary Endpoint): Rate of Confirmed Hypoglycaemic Episodes	4583 Episodes/100 years of patient exposure	4569 Episodes/100 years of patient exposure

SECONDARY outcome

Timeframe: Week 0 to Week 26 + 7 days follow up

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

Rate of confirmed hypoglycaemic episodes per 100 patient years of exposure (PYE). Confirmed hypoglycaemic episodes consisted of severe hypoglycaemia as well as minor hypoglycaemic episodes. Severe hypoglycaemic episodes: episodes requiring active assistance of another person to administer carbohydrate, glucagon, or other resuscitative actions. Minor hypoglycaemic episodes: episodes where subject was able to treat her/himself and plasma glucose below 3.1 mmol/L, with or without symptoms. Nocturnal hypoglycaemic episodes are defined as occuring between 00:01 and 05:59 a.m.

Outcome measures

Outcome measures
Measure	IDeg OD n=301 Participants Insulin degludec (IDeg) was given subcutaneously (s.c.) once daily (OD) in the evening in combination with insulin aspart (IAsp) as meal-time insulin. IDeg OD was given for 26 weeks in the main period and for another 26 weeks in the extension period.	IDet OD n=152 Participants Insulin detemir (IDet) was given subcutaneously (s.c.) once daily (OD) in the evening or twice daily (BID) morning and evening in combination with insulin aspart (IAsp) as meal-time insulin. IDet was given for 26 weeks in the main period and for another 26 weeks in the extension period.
Main Trial (Secondary Endpoint): Rate of Nocturnal Confirmed Hypoglycaemic Episodes	414 Episodes/100 years of patient exposure	593 Episodes/100 years of patient exposure

SECONDARY outcome

Timeframe: Week 0 to Week 52 + 7 days follow up

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

Outcome measures

Outcome measures
Measure	IDeg OD n=301 Participants Insulin degludec (IDeg) was given subcutaneously (s.c.) once daily (OD) in the evening in combination with insulin aspart (IAsp) as meal-time insulin. IDeg OD was given for 26 weeks in the main period and for another 26 weeks in the extension period.	IDet OD n=152 Participants Insulin detemir (IDet) was given subcutaneously (s.c.) once daily (OD) in the evening or twice daily (BID) morning and evening in combination with insulin aspart (IAsp) as meal-time insulin. IDet was given for 26 weeks in the main period and for another 26 weeks in the extension period.
Extension Trial (Secondary Endpoint): Rate of Confirmed Hypoglycaemic Episodes	3778 Episodes/100 years of patient exposure	3926 Episodes/100 years of patient exposure

SECONDARY outcome

Timeframe: Week 0 to Week 52 + 7 days follow up

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

Rate of confirmed hypoglycaemic episodes per 100 patient years of exposure (PYE). Confirmed hypoglycaemic episodes consisted of severe hypoglycaemia as well as minor hypoglycaemic episodes. Severe hypoglycaemic episodes: episodes requiring active assistance of another person to administer carbohydrate, glucagon, or other resuscitative actions. Minor hypoglycaemic episodes: episodes where subject was able to treat her/himself and plasma glucose below 3.1 mmol/L, with or without symptoms. Nocturnal hypoglycaemic episodes are defined as occuring between 00:01 and 05:59 a.m.

Outcome measures

Outcome measures
Measure	IDeg OD n=301 Participants Insulin degludec (IDeg) was given subcutaneously (s.c.) once daily (OD) in the evening in combination with insulin aspart (IAsp) as meal-time insulin. IDeg OD was given for 26 weeks in the main period and for another 26 weeks in the extension period.	IDet OD n=152 Participants Insulin detemir (IDet) was given subcutaneously (s.c.) once daily (OD) in the evening or twice daily (BID) morning and evening in combination with insulin aspart (IAsp) as meal-time insulin. IDet was given for 26 weeks in the main period and for another 26 weeks in the extension period.
Extension Trial (Secondary Endpoint): Rate of Nocturnal Confirmed Hypoglycaemic Episodes	338 Episodes/100 years of patient exposure	481 Episodes/100 years of patient exposure

Adverse Events

IDeg OD

Serious events: 36 serious events

Other events: 185 other events

Deaths: 0 deaths

IDet OD

Serious events: 11 serious events

Other events: 89 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	IDeg OD n=301 participants at risk Insulin degludec (IDeg) was given subcutaneously (s.c.) once daily (OD) in the evening in combination with insulin aspart (IAsp) as meal-time insulin. IDeg OD was given for 26 weeks in the main period and for another 26 weeks in the extension period.	IDet OD n=152 participants at risk Insulin detemir (IDet) was given subcutaneously (s.c.) once daily (OD) in the evening or twice daily (BID) morning and evening in combination with insulin aspart (IAsp) as meal-time insulin. IDet was given for 26 weeks in the main period and for another 26 weeks in the extension period.
Infections and infestations Nasopharyngitis	31.2% 94/301 • Number of events 162 • The adverse events were collected in a timeframe of 52 weeks + 7 days follow up The SAS included all subjects who received at least one dose of the investigational product or its comparator.	32.2% 49/152 • Number of events 79 • The adverse events were collected in a timeframe of 52 weeks + 7 days follow up The SAS included all subjects who received at least one dose of the investigational product or its comparator.
Infections and infestations Upper respiratory tract infection	11.3% 34/301 • Number of events 61 • The adverse events were collected in a timeframe of 52 weeks + 7 days follow up The SAS included all subjects who received at least one dose of the investigational product or its comparator.	11.2% 17/152 • Number of events 28 • The adverse events were collected in a timeframe of 52 weeks + 7 days follow up The SAS included all subjects who received at least one dose of the investigational product or its comparator.
Metabolism and nutrition disorders Hypoglycaemia	5.0% 15/301 • Number of events 25 • The adverse events were collected in a timeframe of 52 weeks + 7 days follow up The SAS included all subjects who received at least one dose of the investigational product or its comparator.	7.2% 11/152 • Number of events 13 • The adverse events were collected in a timeframe of 52 weeks + 7 days follow up The SAS included all subjects who received at least one dose of the investigational product or its comparator.
Nervous system disorders Headache	14.0% 42/301 • Number of events 84 • The adverse events were collected in a timeframe of 52 weeks + 7 days follow up The SAS included all subjects who received at least one dose of the investigational product or its comparator.	7.9% 12/152 • Number of events 25 • The adverse events were collected in a timeframe of 52 weeks + 7 days follow up The SAS included all subjects who received at least one dose of the investigational product or its comparator.
Respiratory, thoracic and mediastinal disorders Cough	7.0% 21/301 • Number of events 23 • The adverse events were collected in a timeframe of 52 weeks + 7 days follow up The SAS included all subjects who received at least one dose of the investigational product or its comparator.	5.3% 8/152 • Number of events 12 • The adverse events were collected in a timeframe of 52 weeks + 7 days follow up The SAS included all subjects who received at least one dose of the investigational product or its comparator.
Eye disorders Diabetic retinopathy	6.6% 20/301 • Number of events 22 • The adverse events were collected in a timeframe of 52 weeks + 7 days follow up The SAS included all subjects who received at least one dose of the investigational product or its comparator.	4.6% 7/152 • Number of events 7 • The adverse events were collected in a timeframe of 52 weeks + 7 days follow up The SAS included all subjects who received at least one dose of the investigational product or its comparator.
Gastrointestinal disorders Diarrhoea	6.6% 20/301 • Number of events 25 • The adverse events were collected in a timeframe of 52 weeks + 7 days follow up The SAS included all subjects who received at least one dose of the investigational product or its comparator.	5.9% 9/152 • Number of events 10 • The adverse events were collected in a timeframe of 52 weeks + 7 days follow up The SAS included all subjects who received at least one dose of the investigational product or its comparator.
General disorders Pyrexia	5.3% 16/301 • Number of events 24 • The adverse events were collected in a timeframe of 52 weeks + 7 days follow up The SAS included all subjects who received at least one dose of the investigational product or its comparator.	5.9% 9/152 • Number of events 10 • The adverse events were collected in a timeframe of 52 weeks + 7 days follow up The SAS included all subjects who received at least one dose of the investigational product or its comparator.
Infections and infestations Gastroenteritis	7.3% 22/301 • Number of events 23 • The adverse events were collected in a timeframe of 52 weeks + 7 days follow up The SAS included all subjects who received at least one dose of the investigational product or its comparator.	6.6% 10/152 • Number of events 11 • The adverse events were collected in a timeframe of 52 weeks + 7 days follow up The SAS included all subjects who received at least one dose of the investigational product or its comparator.
Infections and infestations Influenza	4.7% 14/301 • Number of events 14 • The adverse events were collected in a timeframe of 52 weeks + 7 days follow up The SAS included all subjects who received at least one dose of the investigational product or its comparator.	5.9% 9/152 • Number of events 10 • The adverse events were collected in a timeframe of 52 weeks + 7 days follow up The SAS included all subjects who received at least one dose of the investigational product or its comparator.
Musculoskeletal and connective tissue disorders Back pain	7.0% 21/301 • Number of events 24 • The adverse events were collected in a timeframe of 52 weeks + 7 days follow up The SAS included all subjects who received at least one dose of the investigational product or its comparator.	3.3% 5/152 • Number of events 5 • The adverse events were collected in a timeframe of 52 weeks + 7 days follow up The SAS included all subjects who received at least one dose of the investigational product or its comparator.

Additional Information

Public Access to Clinical Trials

Novo Nordisk A/S

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee 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.
Publication restrictions are in place

Restriction type: OTHER

Measure	IDeg OD n=301 participants at risk Insulin degludec (IDeg) was given subcutaneously (s.c.) once daily (OD) in the evening in combination with insulin aspart (IAsp) as meal-time insulin. IDeg OD was given for 26 weeks in the main period and for another 26 weeks in the extension period.	IDet OD n=152 participants at risk Insulin detemir (IDet) was given subcutaneously (s.c.) once daily (OD) in the evening or twice daily (BID) morning and evening in combination with insulin aspart (IAsp) as meal-time insulin. IDet was given for 26 weeks in the main period and for another 26 weeks in the extension period.
Endocrine disorders Hyperthyroidism	0.33% 1/301 • Number of events 1 • The adverse events were collected in a timeframe of 52 weeks + 7 days follow up The SAS included all subjects who received at least one dose of the investigational product or its comparator.	0.66% 1/152 • Number of events 1 • The adverse events were collected in a timeframe of 52 weeks + 7 days follow up The SAS included all subjects who received at least one dose of the investigational product or its comparator.
Gastrointestinal disorders Abdominal pain upper	0.33% 1/301 • Number of events 1 • The adverse events were collected in a timeframe of 52 weeks + 7 days follow up The SAS included all subjects who received at least one dose of the investigational product or its comparator.	0.00% 0/152 • The adverse events were collected in a timeframe of 52 weeks + 7 days follow up The SAS included all subjects who received at least one dose of the investigational product or its comparator.
Infections and infestations Abscess oral	0.33% 1/301 • Number of events 1 • The adverse events were collected in a timeframe of 52 weeks + 7 days follow up The SAS included all subjects who received at least one dose of the investigational product or its comparator.	0.00% 0/152 • The adverse events were collected in a timeframe of 52 weeks + 7 days follow up The SAS included all subjects who received at least one dose of the investigational product or its comparator.
Infections and infestations Cellulitis	0.33% 1/301 • Number of events 1 • The adverse events were collected in a timeframe of 52 weeks + 7 days follow up The SAS included all subjects who received at least one dose of the investigational product or its comparator.	0.00% 0/152 • The adverse events were collected in a timeframe of 52 weeks + 7 days follow up The SAS included all subjects who received at least one dose of the investigational product or its comparator.
Infections and infestations Pyelonephritis	0.33% 1/301 • Number of events 1 • The adverse events were collected in a timeframe of 52 weeks + 7 days follow up The SAS included all subjects who received at least one dose of the investigational product or its comparator.	0.00% 0/152 • The adverse events were collected in a timeframe of 52 weeks + 7 days follow up The SAS included all subjects who received at least one dose of the investigational product or its comparator.
Injury, poisoning and procedural complications Fractured ischium	0.33% 1/301 • Number of events 1 • The adverse events were collected in a timeframe of 52 weeks + 7 days follow up The SAS included all subjects who received at least one dose of the investigational product or its comparator.	0.00% 0/152 • The adverse events were collected in a timeframe of 52 weeks + 7 days follow up The SAS included all subjects who received at least one dose of the investigational product or its comparator.
Injury, poisoning and procedural complications Heat stroke	0.33% 1/301 • Number of events 1 • The adverse events were collected in a timeframe of 52 weeks + 7 days follow up The SAS included all subjects who received at least one dose of the investigational product or its comparator.	0.00% 0/152 • The adverse events were collected in a timeframe of 52 weeks + 7 days follow up The SAS included all subjects who received at least one dose of the investigational product or its comparator.
Injury, poisoning and procedural complications Rib fracture	0.33% 1/301 • Number of events 1 • The adverse events were collected in a timeframe of 52 weeks + 7 days follow up The SAS included all subjects who received at least one dose of the investigational product or its comparator.	0.00% 0/152 • The adverse events were collected in a timeframe of 52 weeks + 7 days follow up The SAS included all subjects who received at least one dose of the investigational product or its comparator.
Injury, poisoning and procedural complications Subdural haematoma	0.33% 1/301 • Number of events 1 • The adverse events were collected in a timeframe of 52 weeks + 7 days follow up The SAS included all subjects who received at least one dose of the investigational product or its comparator.	0.00% 0/152 • The adverse events were collected in a timeframe of 52 weeks + 7 days follow up The SAS included all subjects who received at least one dose of the investigational product or its comparator.
Injury, poisoning and procedural complications Wrong drug administered	0.33% 1/301 • Number of events 1 • The adverse events were collected in a timeframe of 52 weeks + 7 days follow up The SAS included all subjects who received at least one dose of the investigational product or its comparator.	0.00% 0/152 • The adverse events were collected in a timeframe of 52 weeks + 7 days follow up The SAS included all subjects who received at least one dose of the investigational product or its comparator.
Investigations Exocrine pancreatic function test abn	0.33% 1/301 • Number of events 1 • The adverse events were collected in a timeframe of 52 weeks + 7 days follow up The SAS included all subjects who received at least one dose of the investigational product or its comparator.	0.00% 0/152 • The adverse events were collected in a timeframe of 52 weeks + 7 days follow up The SAS included all subjects who received at least one dose of the investigational product or its comparator.
Metabolism and nutrition disorders Dehydration	0.00% 0/301 • The adverse events were collected in a timeframe of 52 weeks + 7 days follow up The SAS included all subjects who received at least one dose of the investigational product or its comparator.	0.66% 1/152 • Number of events 1 • The adverse events were collected in a timeframe of 52 weeks + 7 days follow up The SAS included all subjects who received at least one dose of the investigational product or its comparator.
Metabolism and nutrition disorders Diabetic ketoacidosis	0.66% 2/301 • Number of events 2 • The adverse events were collected in a timeframe of 52 weeks + 7 days follow up The SAS included all subjects who received at least one dose of the investigational product or its comparator.	0.66% 1/152 • Number of events 1 • The adverse events were collected in a timeframe of 52 weeks + 7 days follow up The SAS included all subjects who received at least one dose of the investigational product or its comparator.
Metabolism and nutrition disorders Hyperglycaemia	0.00% 0/301 • The adverse events were collected in a timeframe of 52 weeks + 7 days follow up The SAS included all subjects who received at least one dose of the investigational product or its comparator.	0.66% 1/152 • Number of events 1 • The adverse events were collected in a timeframe of 52 weeks + 7 days follow up The SAS included all subjects who received at least one dose of the investigational product or its comparator.
Metabolism and nutrition disorders Hypoglycaemia	4.0% 12/301 • Number of events 16 • The adverse events were collected in a timeframe of 52 weeks + 7 days follow up The SAS included all subjects who received at least one dose of the investigational product or its comparator.	3.3% 5/152 • Number of events 8 • The adverse events were collected in a timeframe of 52 weeks + 7 days follow up The SAS included all subjects who received at least one dose of the investigational product or its comparator.
Metabolism and nutrition disorders Hypoglycaemic unconsciousness	3.0% 9/301 • Number of events 9 • The adverse events were collected in a timeframe of 52 weeks + 7 days follow up The SAS included all subjects who received at least one dose of the investigational product or its comparator.	3.3% 5/152 • Number of events 6 • The adverse events were collected in a timeframe of 52 weeks + 7 days follow up The SAS included all subjects who received at least one dose of the investigational product or its comparator.
Metabolism and nutrition disorders Ketosis	0.33% 1/301 • Number of events 1 • The adverse events were collected in a timeframe of 52 weeks + 7 days follow up The SAS included all subjects who received at least one dose of the investigational product or its comparator.	0.00% 0/152 • The adverse events were collected in a timeframe of 52 weeks + 7 days follow up The SAS included all subjects who received at least one dose of the investigational product or its comparator.
Musculoskeletal and connective tissue disorders Lumbar spinal stenosis	0.33% 1/301 • Number of events 1 • The adverse events were collected in a timeframe of 52 weeks + 7 days follow up The SAS included all subjects who received at least one dose of the investigational product or its comparator.	0.00% 0/152 • The adverse events were collected in a timeframe of 52 weeks + 7 days follow up The SAS included all subjects who received at least one dose of the investigational product or its comparator.
Nervous system disorders Grand mal convulsion	0.33% 1/301 • Number of events 1 • The adverse events were collected in a timeframe of 52 weeks + 7 days follow up The SAS included all subjects who received at least one dose of the investigational product or its comparator.	0.00% 0/152 • The adverse events were collected in a timeframe of 52 weeks + 7 days follow up The SAS included all subjects who received at least one dose of the investigational product or its comparator.
Nervous system disorders Hypoglycaemic coma	1.3% 4/301 • Number of events 4 • The adverse events were collected in a timeframe of 52 weeks + 7 days follow up The SAS included all subjects who received at least one dose of the investigational product or its comparator.	0.66% 1/152 • Number of events 1 • The adverse events were collected in a timeframe of 52 weeks + 7 days follow up The SAS included all subjects who received at least one dose of the investigational product or its comparator.
Nervous system disorders Petit mal epilepsy	0.00% 0/301 • The adverse events were collected in a timeframe of 52 weeks + 7 days follow up The SAS included all subjects who received at least one dose of the investigational product or its comparator.	0.66% 1/152 • Number of events 1 • The adverse events were collected in a timeframe of 52 weeks + 7 days follow up The SAS included all subjects who received at least one dose of the investigational product or its comparator.
Skin and subcutaneous tissue disorders Swelling face	0.33% 1/301 • Number of events 1 • The adverse events were collected in a timeframe of 52 weeks + 7 days follow up The SAS included all subjects who received at least one dose of the investigational product or its comparator.	0.00% 0/152 • The adverse events were collected in a timeframe of 52 weeks + 7 days follow up The SAS included all subjects who received at least one dose of the investigational product or its comparator.
Infections and infestations Gastroenteritis	0.00% 0/301 • The adverse events were collected in a timeframe of 52 weeks + 7 days follow up The SAS included all subjects who received at least one dose of the investigational product or its comparator.	1.3% 2/152 • Number of events 2 • The adverse events were collected in a timeframe of 52 weeks + 7 days follow up The SAS included all subjects who received at least one dose of the investigational product or its comparator.
Injury, poisoning and procedural complications Contusion	0.33% 1/301 • Number of events 1 • The adverse events were collected in a timeframe of 52 weeks + 7 days follow up The SAS included all subjects who received at least one dose of the investigational product or its comparator.	0.00% 0/152 • The adverse events were collected in a timeframe of 52 weeks + 7 days follow up The SAS included all subjects who received at least one dose of the investigational product or its comparator.
Injury, poisoning and procedural complications Fall	0.33% 1/301 • Number of events 1 • The adverse events were collected in a timeframe of 52 weeks + 7 days follow up The SAS included all subjects who received at least one dose of the investigational product or its comparator.	0.00% 0/152 • The adverse events were collected in a timeframe of 52 weeks + 7 days follow up The SAS included all subjects who received at least one dose of the investigational product or its comparator.
Injury, poisoning and procedural complications Medication error	0.33% 1/301 • Number of events 1 • The adverse events were collected in a timeframe of 52 weeks + 7 days follow up The SAS included all subjects who received at least one dose of the investigational product or its comparator.	0.00% 0/152 • The adverse events were collected in a timeframe of 52 weeks + 7 days follow up The SAS included all subjects who received at least one dose of the investigational product or its comparator.
Injury, poisoning and procedural complications Radius fracture	0.33% 1/301 • Number of events 1 • The adverse events were collected in a timeframe of 52 weeks + 7 days follow up The SAS included all subjects who received at least one dose of the investigational product or its comparator.	0.00% 0/152 • The adverse events were collected in a timeframe of 52 weeks + 7 days follow up The SAS included all subjects who received at least one dose of the investigational product or its comparator.
Metabolism and nutrition disorders Hypoglycaemia unawareness	0.00% 0/301 • The adverse events were collected in a timeframe of 52 weeks + 7 days follow up The SAS included all subjects who received at least one dose of the investigational product or its comparator.	0.66% 1/152 • Number of events 1 • The adverse events were collected in a timeframe of 52 weeks + 7 days follow up The SAS included all subjects who received at least one dose of the investigational product or its comparator.
Musculoskeletal and connective tissue disorders Back pain	0.33% 1/301 • Number of events 1 • The adverse events were collected in a timeframe of 52 weeks + 7 days follow up The SAS included all subjects who received at least one dose of the investigational product or its comparator.	0.00% 0/152 • The adverse events were collected in a timeframe of 52 weeks + 7 days follow up The SAS included all subjects who received at least one dose of the investigational product or its comparator.
Musculoskeletal and connective tissue disorders Muscle spasms	0.33% 1/301 • Number of events 1 • The adverse events were collected in a timeframe of 52 weeks + 7 days follow up The SAS included all subjects who received at least one dose of the investigational product or its comparator.	0.00% 0/152 • The adverse events were collected in a timeframe of 52 weeks + 7 days follow up The SAS included all subjects who received at least one dose of the investigational product or its comparator.
Nervous system disorders Cerebral infarction	0.33% 1/301 • Number of events 1 • The adverse events were collected in a timeframe of 52 weeks + 7 days follow up The SAS included all subjects who received at least one dose of the investigational product or its comparator.	0.00% 0/152 • The adverse events were collected in a timeframe of 52 weeks + 7 days follow up The SAS included all subjects who received at least one dose of the investigational product or its comparator.
Respiratory, thoracic and mediastinal disorders Asthma	0.33% 1/301 • Number of events 1 • The adverse events were collected in a timeframe of 52 weeks + 7 days follow up The SAS included all subjects who received at least one dose of the investigational product or its comparator.	0.00% 0/152 • The adverse events were collected in a timeframe of 52 weeks + 7 days follow up The SAS included all subjects who received at least one dose of the investigational product or its comparator.