Trial Outcomes & Findings for Comparison of NN1250 With Insulin Glargine in Type 2 Diabetes (NCT NCT01006291)

NCT ID: NCT01006291

Last Updated: 2017-02-09

Results Overview

Change from baseline in HbA1c after 26 weeks of treatment

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

687 participants

Primary outcome timeframe

Week 0, Week 26

Results posted on

2017-02-09

Participant Flow

The trial was conducted at 69 sites in 14 countries: Hungary (3 sites), Macedonia (1 site), Serbia (3 sites), Finland (7 sites), Norway (6 sites), United Kingdom (6 sites), Argentina (4 sites), Mexico (2 sites), South Africa (3 sites), India (10 sites), Malaysia (5 sites), Taiwan (3 sites), Russian Federation (8 sites) and Israel (8 sites).

Participant milestones

Participant milestones
Measure	IDeg OD FF Insulin degludec (IDeg) was given once daily (OD) subcutaneously (s.c.) with or without pre-trial OADs for 26 weeks with alternating morning and evening dosing according to a fixed flexible (FF) schedule (approximately 8-40 hours intervals between doses).	IDeg OD Insulin degludec (IDeg) was given once daily (OD) subcutaneously (s.c.) at main evening meal with or without pre-trial OADs for 26 weeks.	IGlar OD Insulin glargine (IGlar) was given once daily (OD) subcutaneously (s.c.) according to local labelling with or without pre-trial OADs for 26 weeks.
Overall Study STARTED	229	228	230
Overall Study Exposed	230	226	229
Overall Study COMPLETED	203	204	203
Overall Study NOT COMPLETED	26	24	27

Reasons for withdrawal

Reasons for withdrawal
Measure	IDeg OD FF Insulin degludec (IDeg) was given once daily (OD) subcutaneously (s.c.) with or without pre-trial OADs for 26 weeks with alternating morning and evening dosing according to a fixed flexible (FF) schedule (approximately 8-40 hours intervals between doses).	IDeg OD Insulin degludec (IDeg) was given once daily (OD) subcutaneously (s.c.) at main evening meal with or without pre-trial OADs for 26 weeks.	IGlar OD Insulin glargine (IGlar) was given once daily (OD) subcutaneously (s.c.) according to local labelling with or without pre-trial OADs for 26 weeks.
Overall Study Adverse Event	2	1	2
Overall Study Lack of Efficacy	2	2	1
Overall Study Protocol Violation	3	3	3
Overall Study Withdrawal criteria	5	4	4
Overall Study Other	14	14	17

Baseline Characteristics

Comparison of NN1250 With Insulin Glargine in Type 2 Diabetes

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	IDeg OD FF n=229 Participants Insulin degludec (IDeg) was given once daily (OD) subcutaneously (s.c.) with or without pre-trial OADs for 26 weeks with alternating morning and evening dosing according to a fixed flexible (FF) schedule (approximately 8-40 hours intervals between doses).	IDeg OD n=228 Participants Insulin degludec (IDeg) was given once daily (OD) subcutaneously (s.c.) at main evening meal with or without pre-trial OADs for 26 weeks.	IGlar OD n=230 Participants Insulin glargine (IGlar) was given once daily (OD) subcutaneously (s.c.) according to local labelling with or without pre-trial OADs for 26 weeks.	Total n=687 Participants Total of all reporting groups
Age, Continuous	56.2 years STANDARD_DEVIATION 10.3 • n=5 Participants	56.5 years STANDARD_DEVIATION 9.6 • n=7 Participants	56.7 years STANDARD_DEVIATION 8.8 • n=5 Participants	56.4 years STANDARD_DEVIATION 9.6 • n=4 Participants
Gender Female	94 Participants n=5 Participants	104 Participants n=7 Participants	119 Participants n=5 Participants	317 Participants n=4 Participants
Gender Male	135 Participants n=5 Participants	124 Participants n=7 Participants	111 Participants n=5 Participants	370 Participants n=4 Participants
Glycosylated haemoglobin (HbA1c)	8.5 percentage of glycosylated haemoglobin STANDARD_DEVIATION 1.0 • n=5 Participants	8.4 percentage of glycosylated haemoglobin STANDARD_DEVIATION 0.9 • n=7 Participants	8.4 percentage of glycosylated haemoglobin STANDARD_DEVIATION 0.9 • n=5 Participants	8.4 percentage of glycosylated haemoglobin STANDARD_DEVIATION 0.9 • n=4 Participants
Fasting plasma glucose (FPG)	9.0 mmol/L STANDARD_DEVIATION 2.6 • n=5 Participants	8.8 mmol/L STANDARD_DEVIATION 2.8 • n=7 Participants	9.0 mmol/L STANDARD_DEVIATION 2.8 • n=5 Participants	8.9 mmol/L STANDARD_DEVIATION 2.7 • n=4 Participants

PRIMARY outcome

Timeframe: Week 0, Week 26

Population: The Full analysis set (FAS) included all randomised subjects and missing data is imputed using last observation carried forward (LOCF). In FAS, subjects contributed to the evaluation 'as randomised'.

Change from baseline in HbA1c after 26 weeks of treatment

Outcome measures

Outcome measures
Measure	IDeg OD FF n=229 Participants Insulin degludec (IDeg) was given once daily (OD) subcutaneously (s.c.) with or without pre-trial OADs for 26 weeks with alternating morning and evening dosing according to a fixed flexible (FF) schedule (approximately 8-40 hours intervals between doses).	IDeg OD n=228 Participants Insulin degludec (IDeg) was given once daily (OD) subcutaneously (s.c.) at main evening meal with or without pre-trial OADs for 26 weeks.	IGlar OD n=230 Participants Insulin glargine (IGlar) was given once daily (OD) subcutaneously (s.c.) according to local labelling with or without pre-trial OADs for 26 weeks.
Change in Glycosylated Haemoglobin (HbA1c)	-1.28 percentage of glycosylated haemoglobin Standard Deviation 1.00	-1.07 percentage of glycosylated haemoglobin Standard Deviation 0.99	-1.26 percentage of glycosylated haemoglobin Standard Deviation 1.07

SECONDARY outcome

Timeframe: Week 26

Population: The FAS included all randomised subjects and missing data is imputed using last observation carried forward (LOCF). In FAS, subjects contributed to the evaluation 'as randomised'. For 28 subjects all 9-point SMPG values were missing.

Mean of SMPG after 26 weeks of treatment. Plasma glucose measured: before breakfast, 90 minutes after start of breakfast, before lunch, 90 minutes after start of lunch, before dinner, 90 minutes after start of dinner, before bedtime, at 4 am and before breakfast.

Outcome measures

Outcome measures
Measure	IDeg OD FF n=216 Participants Insulin degludec (IDeg) was given once daily (OD) subcutaneously (s.c.) with or without pre-trial OADs for 26 weeks with alternating morning and evening dosing according to a fixed flexible (FF) schedule (approximately 8-40 hours intervals between doses).	IDeg OD n=220 Participants Insulin degludec (IDeg) was given once daily (OD) subcutaneously (s.c.) at main evening meal with or without pre-trial OADs for 26 weeks.	IGlar OD n=223 Participants Insulin glargine (IGlar) was given once daily (OD) subcutaneously (s.c.) according to local labelling with or without pre-trial OADs for 26 weeks.
Mean of 9-point Self Measured Plasma Glucose Profile (SMPG)	7.9 mmol/L Standard Deviation 1.8	8.0 mmol/L Standard Deviation 2.1	7.8 mmol/L Standard Deviation 1.9

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. In SAS, subjects contributed to the evaluation 'as treated'.230 subjects in the IDeg Flex group, 226 in the IDeg OD group and 229 in the IGlar OD group

Rate of confirmed hypoglycaemic episodes per 100 patient years of exposure (PYE). Confirmed hypoglycaemic episodes consisted of severe hypoglycaemia as well as minor hypoglycaemic episodes. Severe hypoglycaemic episodes are defined as requiring assistance to administer carbohydrate, glucagon, or other resuscitative actions. Minor hypoglycaemic episodes are defined as able to treat her/himself and plasma glucose below 3.1 mmol/L.

Outcome measures

Outcome measures
Measure	IDeg OD FF n=230 Participants Insulin degludec (IDeg) was given once daily (OD) subcutaneously (s.c.) with or without pre-trial OADs for 26 weeks with alternating morning and evening dosing according to a fixed flexible (FF) schedule (approximately 8-40 hours intervals between doses).	IDeg OD n=226 Participants Insulin degludec (IDeg) was given once daily (OD) subcutaneously (s.c.) at main evening meal with or without pre-trial OADs for 26 weeks.	IGlar OD n=229 Participants Insulin glargine (IGlar) was given once daily (OD) subcutaneously (s.c.) according to local labelling with or without pre-trial OADs for 26 weeks.
Rate of Confirmed Hypoglycaemic Episodes	364 Episodes/100 years of patient exposure	363 Episodes/100 years of patient exposure	348 Episodes/100 years of patient exposure

SECONDARY outcome

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

Rate of nocturnal confirmed hypoglycaemic episodes per 100 patient years of exposure (PYE). Confirmed hypoglycaemic episodes consisted of severe hypoglycaemia as well as minor hypoglycaemic episodes. Severe hypoglycaemic episodes are defined as requiring assistance to administer carbohydrate, glucagon, or other resuscitative actions. Minor hypoglycaemic episodes are defined as able to treat her/himself and plasma glucose below 3.1 mmol/L. Nocturnal hypoglycaemic episodes are defined as occurring between 00:01 and 05:59 a.m.

Outcome measures

Outcome measures
Measure	IDeg OD FF n=230 Participants Insulin degludec (IDeg) was given once daily (OD) subcutaneously (s.c.) with or without pre-trial OADs for 26 weeks with alternating morning and evening dosing according to a fixed flexible (FF) schedule (approximately 8-40 hours intervals between doses).	IDeg OD n=226 Participants Insulin degludec (IDeg) was given once daily (OD) subcutaneously (s.c.) at main evening meal with or without pre-trial OADs for 26 weeks.	IGlar OD n=229 Participants Insulin glargine (IGlar) was given once daily (OD) subcutaneously (s.c.) according to local labelling with or without pre-trial OADs for 26 weeks.
Rate of Nocturnal Confirmed Hypoglycaemic Episodes	63 Episodes/100 years of patient exposure	56 Episodes/100 years of patient exposure	75 Episodes/100 years of patient exposure

Adverse Events

IDeg OD FF

Serious events: 6 serious events

Other events: 58 other events

Deaths: 0 deaths

IDeg OD

Serious events: 8 serious events

Other events: 57 other events

Deaths: 0 deaths

IGlar OD

Serious events: 4 serious events

Other events: 53 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	IDeg OD FF n=230 participants at risk Insulin degludec (IDeg) was given once daily (OD) subcutaneously (s.c.) with or without pre-trial OADs for 26 weeks with alternating morning and evening dosing according to a fixed flexible (FF) schedule (approximately 8-40 hours intervals between doses).	IDeg OD n=226 participants at risk Insulin degludec (IDeg) was given once daily (OD) subcutaneously (s.c.) at main evening meal with or without pre-trial OADs for 26 weeks.	IGlar OD n=229 participants at risk Insulin glargine (IGlar) was given once daily (OD) subcutaneously (s.c.) according to local labelling with or without pre-trial OADs for 26 weeks.
Gastrointestinal disorders Diarrhoea	4.3% 10/230 • Number of events 12 • The adverse events were collected in a time frame of 26 weeks + 7 days follow up Safety analysis set includes all subjects who received at least one dose of the investigational product or its comparator.	6.2% 14/226 • Number of events 17 • The adverse events were collected in a time frame of 26 weeks + 7 days follow up Safety analysis set includes all subjects who received at least one dose of the investigational product or its comparator.	4.4% 10/229 • Number of events 11 • The adverse events were collected in a time frame of 26 weeks + 7 days follow up Safety analysis set includes all subjects who received at least one dose of the investigational product or its comparator.
Infections and infestations Nasopharyngitis	10.0% 23/230 • Number of events 28 • The adverse events were collected in a time frame of 26 weeks + 7 days follow up Safety analysis set includes all subjects who received at least one dose of the investigational product or its comparator.	8.8% 20/226 • Number of events 28 • The adverse events were collected in a time frame of 26 weeks + 7 days follow up Safety analysis set includes all subjects who received at least one dose of the investigational product or its comparator.	7.9% 18/229 • Number of events 21 • The adverse events were collected in a time frame of 26 weeks + 7 days follow up Safety analysis set includes all subjects who received at least one dose of the investigational product or its comparator.
Infections and infestations Upper respiratory tract infection	8.7% 20/230 • Number of events 21 • The adverse events were collected in a time frame of 26 weeks + 7 days follow up Safety analysis set includes all subjects who received at least one dose of the investigational product or its comparator.	4.9% 11/226 • Number of events 14 • The adverse events were collected in a time frame of 26 weeks + 7 days follow up Safety analysis set includes all subjects who received at least one dose of the investigational product or its comparator.	8.7% 20/229 • Number of events 27 • The adverse events were collected in a time frame of 26 weeks + 7 days follow up Safety analysis set includes all subjects who received at least one dose of the investigational product or its comparator.
Musculoskeletal and connective tissue disorders Back pain	5.2% 12/230 • Number of events 13 • The adverse events were collected in a time frame of 26 weeks + 7 days follow up Safety analysis set includes all subjects who received at least one dose of the investigational product or its comparator.	4.0% 9/226 • Number of events 9 • The adverse events were collected in a time frame of 26 weeks + 7 days follow up Safety analysis set includes all subjects who received at least one dose of the investigational product or its comparator.	2.6% 6/229 • Number of events 9 • The adverse events were collected in a time frame of 26 weeks + 7 days follow up Safety analysis set includes all subjects who received at least one dose of the investigational product or its comparator.
Nervous system disorders Dizziness	1.3% 3/230 • Number of events 3 • The adverse events were collected in a time frame of 26 weeks + 7 days follow up Safety analysis set includes all subjects who received at least one dose of the investigational product or its comparator.	1.3% 3/226 • Number of events 3 • The adverse events were collected in a time frame of 26 weeks + 7 days follow up Safety analysis set includes all subjects who received at least one dose of the investigational product or its comparator.	5.2% 12/229 • Number of events 13 • The adverse events were collected in a time frame of 26 weeks + 7 days follow up Safety analysis set includes all subjects who received at least one dose of the investigational product or its comparator.
Nervous system disorders Headache	7.0% 16/230 • Number of events 25 • The adverse events were collected in a time frame of 26 weeks + 7 days follow up Safety analysis set includes all subjects who received at least one dose of the investigational product or its comparator.	7.1% 16/226 • Number of events 18 • The adverse events were collected in a time frame of 26 weeks + 7 days follow up Safety analysis set includes all subjects who received at least one dose of the investigational product or its comparator.	3.9% 9/229 • Number of events 12 • The adverse events were collected in a time frame of 26 weeks + 7 days follow up Safety analysis set includes 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 FF n=230 participants at risk Insulin degludec (IDeg) was given once daily (OD) subcutaneously (s.c.) with or without pre-trial OADs for 26 weeks with alternating morning and evening dosing according to a fixed flexible (FF) schedule (approximately 8-40 hours intervals between doses).	IDeg OD n=226 participants at risk Insulin degludec (IDeg) was given once daily (OD) subcutaneously (s.c.) at main evening meal with or without pre-trial OADs for 26 weeks.	IGlar OD n=229 participants at risk Insulin glargine (IGlar) was given once daily (OD) subcutaneously (s.c.) according to local labelling with or without pre-trial OADs for 26 weeks.
Blood and lymphatic system disorders Anaemia	0.00% 0/230 • The adverse events were collected in a time frame of 26 weeks + 7 days follow up Safety analysis set includes all subjects who received at least one dose of the investigational product or its comparator.	0.44% 1/226 • Number of events 1 • The adverse events were collected in a time frame of 26 weeks + 7 days follow up Safety analysis set includes all subjects who received at least one dose of the investigational product or its comparator.	0.00% 0/229 • The adverse events were collected in a time frame of 26 weeks + 7 days follow up Safety analysis set includes all subjects who received at least one dose of the investigational product or its comparator.
Cardiac disorders Acute coronary syndrome	0.00% 0/230 • The adverse events were collected in a time frame of 26 weeks + 7 days follow up Safety analysis set includes all subjects who received at least one dose of the investigational product or its comparator.	0.00% 0/226 • The adverse events were collected in a time frame of 26 weeks + 7 days follow up Safety analysis set includes all subjects who received at least one dose of the investigational product or its comparator.	0.44% 1/229 • Number of events 1 • The adverse events were collected in a time frame of 26 weeks + 7 days follow up Safety analysis set includes all subjects who received at least one dose of the investigational product or its comparator.
Cardiac disorders Coronary artery disease	0.00% 0/230 • The adverse events were collected in a time frame of 26 weeks + 7 days follow up Safety analysis set includes all subjects who received at least one dose of the investigational product or its comparator.	0.00% 0/226 • The adverse events were collected in a time frame of 26 weeks + 7 days follow up Safety analysis set includes all subjects who received at least one dose of the investigational product or its comparator.	0.44% 1/229 • Number of events 1 • The adverse events were collected in a time frame of 26 weeks + 7 days follow up Safety analysis set includes all subjects who received at least one dose of the investigational product or its comparator.
Cardiac disorders Myocardial infarction	0.00% 0/230 • The adverse events were collected in a time frame of 26 weeks + 7 days follow up Safety analysis set includes all subjects who received at least one dose of the investigational product or its comparator.	0.44% 1/226 • Number of events 1 • The adverse events were collected in a time frame of 26 weeks + 7 days follow up Safety analysis set includes all subjects who received at least one dose of the investigational product or its comparator.	0.00% 0/229 • The adverse events were collected in a time frame of 26 weeks + 7 days follow up Safety analysis set includes all subjects who received at least one dose of the investigational product or its comparator.
General disorders Chest pain	0.43% 1/230 • Number of events 1 • The adverse events were collected in a time frame of 26 weeks + 7 days follow up Safety analysis set includes all subjects who received at least one dose of the investigational product or its comparator.	0.00% 0/226 • The adverse events were collected in a time frame of 26 weeks + 7 days follow up Safety analysis set includes all subjects who received at least one dose of the investigational product or its comparator.	0.00% 0/229 • The adverse events were collected in a time frame of 26 weeks + 7 days follow up Safety analysis set includes all subjects who received at least one dose of the investigational product or its comparator.
General disorders Death	0.00% 0/230 • The adverse events were collected in a time frame of 26 weeks + 7 days follow up Safety analysis set includes all subjects who received at least one dose of the investigational product or its comparator.	0.00% 0/226 • The adverse events were collected in a time frame of 26 weeks + 7 days follow up Safety analysis set includes all subjects who received at least one dose of the investigational product or its comparator.	0.44% 1/229 • Number of events 1 • The adverse events were collected in a time frame of 26 weeks + 7 days follow up Safety analysis set includes all subjects who received at least one dose of the investigational product or its comparator.
Infections and infestations Appendicitis	0.00% 0/230 • The adverse events were collected in a time frame of 26 weeks + 7 days follow up Safety analysis set includes all subjects who received at least one dose of the investigational product or its comparator.	0.44% 1/226 • Number of events 1 • The adverse events were collected in a time frame of 26 weeks + 7 days follow up Safety analysis set includes all subjects who received at least one dose of the investigational product or its comparator.	0.00% 0/229 • The adverse events were collected in a time frame of 26 weeks + 7 days follow up Safety analysis set includes all subjects who received at least one dose of the investigational product or its comparator.
Infections and infestations Subcutaneous abscess	0.00% 0/230 • The adverse events were collected in a time frame of 26 weeks + 7 days follow up Safety analysis set includes all subjects who received at least one dose of the investigational product or its comparator.	0.44% 1/226 • Number of events 1 • The adverse events were collected in a time frame of 26 weeks + 7 days follow up Safety analysis set includes all subjects who received at least one dose of the investigational product or its comparator.	0.00% 0/229 • The adverse events were collected in a time frame of 26 weeks + 7 days follow up Safety analysis set includes all subjects who received at least one dose of the investigational product or its comparator.
Infections and infestations Urinary tract infection	0.87% 2/230 • Number of events 2 • The adverse events were collected in a time frame of 26 weeks + 7 days follow up Safety analysis set includes all subjects who received at least one dose of the investigational product or its comparator.	0.00% 0/226 • The adverse events were collected in a time frame of 26 weeks + 7 days follow up Safety analysis set includes all subjects who received at least one dose of the investigational product or its comparator.	0.00% 0/229 • The adverse events were collected in a time frame of 26 weeks + 7 days follow up Safety analysis set includes all subjects who received at least one dose of the investigational product or its comparator.
Metabolism and nutrition disorders Hypoglycaemia	0.00% 0/230 • The adverse events were collected in a time frame of 26 weeks + 7 days follow up Safety analysis set includes all subjects who received at least one dose of the investigational product or its comparator.	0.44% 1/226 • Number of events 1 • The adverse events were collected in a time frame of 26 weeks + 7 days follow up Safety analysis set includes all subjects who received at least one dose of the investigational product or its comparator.	0.00% 0/229 • The adverse events were collected in a time frame of 26 weeks + 7 days follow up Safety analysis set includes all subjects who received at least one dose of the investigational product or its comparator.
Metabolism and nutrition disorders Hypoglycaemic unconsciousness	0.00% 0/230 • The adverse events were collected in a time frame of 26 weeks + 7 days follow up Safety analysis set includes all subjects who received at least one dose of the investigational product or its comparator.	0.44% 1/226 • Number of events 1 • The adverse events were collected in a time frame of 26 weeks + 7 days follow up Safety analysis set includes all subjects who received at least one dose of the investigational product or its comparator.	0.00% 0/229 • The adverse events were collected in a time frame of 26 weeks + 7 days follow up Safety analysis set includes all subjects who received at least one dose of the investigational product or its comparator.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Colon cancer	0.00% 0/230 • The adverse events were collected in a time frame of 26 weeks + 7 days follow up Safety analysis set includes all subjects who received at least one dose of the investigational product or its comparator.	0.44% 1/226 • Number of events 1 • The adverse events were collected in a time frame of 26 weeks + 7 days follow up Safety analysis set includes all subjects who received at least one dose of the investigational product or its comparator.	0.00% 0/229 • The adverse events were collected in a time frame of 26 weeks + 7 days follow up Safety analysis set includes all subjects who received at least one dose of the investigational product or its comparator.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Myelodysplastic syndrome	0.00% 0/230 • The adverse events were collected in a time frame of 26 weeks + 7 days follow up Safety analysis set includes all subjects who received at least one dose of the investigational product or its comparator.	0.44% 1/226 • Number of events 1 • The adverse events were collected in a time frame of 26 weeks + 7 days follow up Safety analysis set includes all subjects who received at least one dose of the investigational product or its comparator.	0.00% 0/229 • The adverse events were collected in a time frame of 26 weeks + 7 days follow up Safety analysis set includes all subjects who received at least one dose of the investigational product or its comparator.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Oral neoplasm benign	0.00% 0/230 • The adverse events were collected in a time frame of 26 weeks + 7 days follow up Safety analysis set includes all subjects who received at least one dose of the investigational product or its comparator.	0.44% 1/226 • Number of events 1 • The adverse events were collected in a time frame of 26 weeks + 7 days follow up Safety analysis set includes all subjects who received at least one dose of the investigational product or its comparator.	0.00% 0/229 • The adverse events were collected in a time frame of 26 weeks + 7 days follow up Safety analysis set includes all subjects who received at least one dose of the investigational product or its comparator.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Pituitary tumour benign	0.00% 0/230 • The adverse events were collected in a time frame of 26 weeks + 7 days follow up Safety analysis set includes all subjects who received at least one dose of the investigational product or its comparator.	0.00% 0/226 • The adverse events were collected in a time frame of 26 weeks + 7 days follow up Safety analysis set includes all subjects who received at least one dose of the investigational product or its comparator.	0.44% 1/229 • Number of events 1 • The adverse events were collected in a time frame of 26 weeks + 7 days follow up Safety analysis set includes all subjects who received at least one dose of the investigational product or its comparator.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Renal cancer	0.43% 1/230 • Number of events 1 • The adverse events were collected in a time frame of 26 weeks + 7 days follow up Safety analysis set includes all subjects who received at least one dose of the investigational product or its comparator.	0.00% 0/226 • The adverse events were collected in a time frame of 26 weeks + 7 days follow up Safety analysis set includes all subjects who received at least one dose of the investigational product or its comparator.	0.00% 0/229 • The adverse events were collected in a time frame of 26 weeks + 7 days follow up Safety analysis set includes all subjects who received at least one dose of the investigational product or its comparator.
Nervous system disorders Carotid artery stenosis	0.43% 1/230 • Number of events 1 • The adverse events were collected in a time frame of 26 weeks + 7 days follow up Safety analysis set includes all subjects who received at least one dose of the investigational product or its comparator.	0.00% 0/226 • The adverse events were collected in a time frame of 26 weeks + 7 days follow up Safety analysis set includes all subjects who received at least one dose of the investigational product or its comparator.	0.00% 0/229 • The adverse events were collected in a time frame of 26 weeks + 7 days follow up Safety analysis set includes all subjects who received at least one dose of the investigational product or its comparator.
Nervous system disorders Cerebrovascular accident	0.43% 1/230 • Number of events 1 • The adverse events were collected in a time frame of 26 weeks + 7 days follow up Safety analysis set includes all subjects who received at least one dose of the investigational product or its comparator.	0.00% 0/226 • The adverse events were collected in a time frame of 26 weeks + 7 days follow up Safety analysis set includes all subjects who received at least one dose of the investigational product or its comparator.	0.00% 0/229 • The adverse events were collected in a time frame of 26 weeks + 7 days follow up Safety analysis set includes all subjects who received at least one dose of the investigational product or its comparator.
Reproductive system and breast disorders Adenomyosis	0.00% 0/230 • The adverse events were collected in a time frame of 26 weeks + 7 days follow up Safety analysis set includes all subjects who received at least one dose of the investigational product or its comparator.	0.44% 1/226 • Number of events 1 • The adverse events were collected in a time frame of 26 weeks + 7 days follow up Safety analysis set includes all subjects who received at least one dose of the investigational product or its comparator.	0.00% 0/229 • The adverse events were collected in a time frame of 26 weeks + 7 days follow up Safety analysis set includes all subjects who received at least one dose of the investigational product or its comparator.
Reproductive system and breast disorders Ovarian cyst	0.00% 0/230 • The adverse events were collected in a time frame of 26 weeks + 7 days follow up Safety analysis set includes all subjects who received at least one dose of the investigational product or its comparator.	0.44% 1/226 • Number of events 1 • The adverse events were collected in a time frame of 26 weeks + 7 days follow up Safety analysis set includes all subjects who received at least one dose of the investigational product or its comparator.	0.00% 0/229 • The adverse events were collected in a time frame of 26 weeks + 7 days follow up Safety analysis set includes all subjects who received at least one dose of the investigational product or its comparator.
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.43% 1/230 • Number of events 1 • The adverse events were collected in a time frame of 26 weeks + 7 days follow up Safety analysis set includes all subjects who received at least one dose of the investigational product or its comparator.	0.00% 0/226 • The adverse events were collected in a time frame of 26 weeks + 7 days follow up Safety analysis set includes all subjects who received at least one dose of the investigational product or its comparator.	0.00% 0/229 • The adverse events were collected in a time frame of 26 weeks + 7 days follow up Safety analysis set includes all subjects who received at least one dose of the investigational product or its comparator.
Skin and subcutaneous tissue disorders Angioedema	0.43% 1/230 • Number of events 1 • The adverse events were collected in a time frame of 26 weeks + 7 days follow up Safety analysis set includes all subjects who received at least one dose of the investigational product or its comparator.	0.00% 0/226 • The adverse events were collected in a time frame of 26 weeks + 7 days follow up Safety analysis set includes all subjects who received at least one dose of the investigational product or its comparator.	0.00% 0/229 • The adverse events were collected in a time frame of 26 weeks + 7 days follow up Safety analysis set includes all subjects who received at least one dose of the investigational product or its comparator.
Surgical and medical procedures Transurethral prostatectomy	0.43% 1/230 • Number of events 1 • The adverse events were collected in a time frame of 26 weeks + 7 days follow up Safety analysis set includes all subjects who received at least one dose of the investigational product or its comparator.	0.00% 0/226 • The adverse events were collected in a time frame of 26 weeks + 7 days follow up Safety analysis set includes all subjects who received at least one dose of the investigational product or its comparator.	0.00% 0/229 • The adverse events were collected in a time frame of 26 weeks + 7 days follow up Safety analysis set includes all subjects who received at least one dose of the investigational product or its comparator.