Trial Outcomes & Findings for Comparison of Two Insulin Degludec Formulations in Subjects With Type 2 Diabetes Mellitus (NCT NCT01364428)

NCT ID: NCT01364428

Last Updated: 2017-03-06

Results Overview

Change from baseline in HbA1c after 22 weeks of treatment

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

373 participants

Primary outcome timeframe

Week 0, Week 22

Results posted on

2017-03-06

Participant Flow

The trial was conducted at 44 sites within United States of America.

Subjects who were treated with basal insulin in combination with unchanged dosing of oral antidiabetic drug treatment (e.g. metformin, pioglitazone or DPP-IV inhibitor) in any approved dose or combination at unchanged dosing for at least 12 weeks prior to randomisation in a 1:1 manner to IDeg 200 U/mL or IDeg.

Participant milestones

Participant milestones
Measure	IDeg 200 U/mL Insulin degludec 200 U/mL (IDeg 200 U/mL) in a 3 mL prefilled pen PDS290 was given subcutaneously once daily in combination with pre-trial oral antidiabetic drug treatment(metformin, insulin secretagogue \[sulfonylurea or glinide\], alpha-glucosidase inhibitor, pioglitazone or DPP-IV inhibitor). IDeg 200 U/mL was administered at any time of the day but preferably at the same time each day.	IDeg Insulin degludec 100 U/mL (IDeg) in a 3 mL prefilled pen PDS290 was given subcutaneously once daily in combination with pre-trial oral antidiabetic drug treatment (metformin, insulin secretagogue \[sulfonylurea or glinide\], alpha-glucosidase inhibitor, pioglitazone or DPP-IV inhibitor). IDeg was administered at any time of the day but preferably at the same time each day.
Overall Study STARTED	186	187
Overall Study Exposed	184	187
Overall Study COMPLETED	166	172
Overall Study NOT COMPLETED	20	15

Reasons for withdrawal

Reasons for withdrawal
Measure	IDeg 200 U/mL Insulin degludec 200 U/mL (IDeg 200 U/mL) in a 3 mL prefilled pen PDS290 was given subcutaneously once daily in combination with pre-trial oral antidiabetic drug treatment(metformin, insulin secretagogue \[sulfonylurea or glinide\], alpha-glucosidase inhibitor, pioglitazone or DPP-IV inhibitor). IDeg 200 U/mL was administered at any time of the day but preferably at the same time each day.	IDeg Insulin degludec 100 U/mL (IDeg) in a 3 mL prefilled pen PDS290 was given subcutaneously once daily in combination with pre-trial oral antidiabetic drug treatment (metformin, insulin secretagogue \[sulfonylurea or glinide\], alpha-glucosidase inhibitor, pioglitazone or DPP-IV inhibitor). IDeg was administered at any time of the day but preferably at the same time each day.
Overall Study Adverse Event	1	2
Overall Study Protocol Violation	2	0
Overall Study Withdrawal Criteria	14	10
Overall Study Other	3	3

Baseline Characteristics

Comparison of Two Insulin Degludec Formulations in Subjects With Type 2 Diabetes Mellitus

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	IDeg 200 U/mL n=186 Participants Insulin degludec 200 U/mL (IDeg 200 U/mL) in a 3 mL prefilled pen PDS290 was given subcutaneously once daily in combination with pre-trial oral antidiabetic drug treatment(metformin, insulin secretagogue \[sulfonylurea or glinide\], alpha-glucosidase inhibitor, pioglitazone or DPP-IV inhibitor). IDeg 200 U/mL was administered at any time of the day but preferably at the same time each day.	IDeg n=187 Participants Insulin degludec 100 U/mL (IDeg) in a 3 mL prefilled pen PDS290 was given subcutaneously once daily in combination with pre-trial oral antidiabetic drug treatment (metformin, insulin secretagogue \[sulfonylurea or glinide\], alpha-glucosidase inhibitor, pioglitazone or DPP-IV inhibitor). IDeg was administered at any time of the day but preferably at the same time each day.	Total n=373 Participants Total of all reporting groups
Glycosylated haemoglobin (HbA1c)	8.1 percentage of glycosylated haemoglobin STANDARD_DEVIATION 0.9 • n=5 Participants	8.2 percentage of glycosylated haemoglobin STANDARD_DEVIATION 0.9 • n=7 Participants	8.2 percentage of glycosylated haemoglobin STANDARD_DEVIATION 0.9 • n=5 Participants
Fasting plasma glucose (FPG)	8.3 mmol/L STANDARD_DEVIATION 3.0 • n=5 Participants	8.3 mmol/L STANDARD_DEVIATION 3.4 • n=7 Participants	8.3 mmol/L STANDARD_DEVIATION 3.2 • n=5 Participants
Sex: Female, Male Female	98 Participants n=5 Participants	70 Participants n=7 Participants	168 Participants n=5 Participants
Sex: Female, Male Male	88 Participants n=5 Participants	117 Participants n=7 Participants	205 Participants n=5 Participants
Age, Continuous	59.3 years STANDARD_DEVIATION 10.0 • n=5 Participants	60.3 years STANDARD_DEVIATION 10.2 • n=7 Participants	59.8 years STANDARD_DEVIATION 10.1 • n=5 Participants

PRIMARY outcome

Timeframe: Week 0, Week 22

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 22 weeks of treatment

Outcome measures

Outcome measures
Measure	IDeg 200 U/mL n=186 Participants Insulin degludec 200 U/mL (IDeg 200 U/mL) in a 3 mL prefilled pen PDS290 was given subcutaneously once daily in combination with pre-trial oral antidiabetic drug treatment(metformin, insulin secretagogue \[sulfonylurea or glinide\], alpha-glucosidase inhibitor, pioglitazone or DPP-IV inhibitor). IDeg 200 U/mL was administered at any time of the day but preferably at the same time each day.	IDeg n=187 Participants Insulin degludec 100 U/mL (IDeg) in a 3 mL prefilled pen PDS290 was given subcutaneously once daily in combination with pre-trial oral antidiabetic drug treatment (metformin, insulin secretagogue \[sulfonylurea or glinide\], alpha-glucosidase inhibitor, pioglitazone or DPP-IV inhibitor). IDeg was administered at any time of the day but preferably at the same time each day.
Change in Glycosylated Haemoglobin (HbA1c)	-0.79 percentage of glycosylated haemoglobin Standard Deviation 0.89	-0.70 percentage of glycosylated haemoglobin Standard Deviation 0.90

SECONDARY outcome

Timeframe: Week 0, Week 22

Population: The full analysis set (FAS) included all randomised subjects and missing data was imputed using last observation carried forward (LOCF). For 5 subjects baseline values were missing.

Change from baseline in FPG after 22 weeks of treatment.

Outcome measures

Outcome measures
Measure	IDeg 200 U/mL n=182 Participants Insulin degludec 200 U/mL (IDeg 200 U/mL) in a 3 mL prefilled pen PDS290 was given subcutaneously once daily in combination with pre-trial oral antidiabetic drug treatment(metformin, insulin secretagogue \[sulfonylurea or glinide\], alpha-glucosidase inhibitor, pioglitazone or DPP-IV inhibitor). IDeg 200 U/mL was administered at any time of the day but preferably at the same time each day.	IDeg n=186 Participants Insulin degludec 100 U/mL (IDeg) in a 3 mL prefilled pen PDS290 was given subcutaneously once daily in combination with pre-trial oral antidiabetic drug treatment (metformin, insulin secretagogue \[sulfonylurea or glinide\], alpha-glucosidase inhibitor, pioglitazone or DPP-IV inhibitor). IDeg was administered at any time of the day but preferably at the same time each day.
Change in Fasting Plasma Glucose (FPG)	-2.26 mmol/L Standard Deviation 3.07	-2.40 mmol/L Standard Deviation 3.42

SECONDARY outcome

Timeframe: Week 0 to Week 22 + 7 days follow up

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

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

Outcome measures

Outcome measures
Measure	IDeg 200 U/mL n=184 Participants Insulin degludec 200 U/mL (IDeg 200 U/mL) in a 3 mL prefilled pen PDS290 was given subcutaneously once daily in combination with pre-trial oral antidiabetic drug treatment(metformin, insulin secretagogue \[sulfonylurea or glinide\], alpha-glucosidase inhibitor, pioglitazone or DPP-IV inhibitor). IDeg 200 U/mL was administered at any time of the day but preferably at the same time each day.	IDeg n=187 Participants Insulin degludec 100 U/mL (IDeg) in a 3 mL prefilled pen PDS290 was given subcutaneously once daily in combination with pre-trial oral antidiabetic drug treatment (metformin, insulin secretagogue \[sulfonylurea or glinide\], alpha-glucosidase inhibitor, pioglitazone or DPP-IV inhibitor). IDeg was administered at any time of the day but preferably at the same time each day.
Rate of Treatment Emergent Adverse Events (AEs) Adverse events (AEs)	416 Events/100 years of patient exposure	300 Events/100 years of patient exposure
Rate of Treatment Emergent Adverse Events (AEs) Serious AEs	20 Events/100 years of patient exposure	16 Events/100 years of patient exposure
Rate of Treatment Emergent Adverse Events (AEs) Severe AEs	27 Events/100 years of patient exposure	21 Events/100 years of patient exposure
Rate of Treatment Emergent Adverse Events (AEs) Moderate AEs	130 Events/100 years of patient exposure	107 Events/100 years of patient exposure
Rate of Treatment Emergent Adverse Events (AEs) Mild AEs	259 Events/100 years of patient exposure	172 Events/100 years of patient exposure
Rate of Treatment Emergent Adverse Events (AEs) Fatal AEs	0 Events/100 years of patient exposure	0 Events/100 years of patient exposure

SECONDARY outcome

Timeframe: Week 0 to Week 22 + 7 days follow up

Population: The safety analysis set 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 were defined as requiring assistance to administer carbohydrate, glucagon, or other resuscitative actions. Minor hypoglycaemic episodes were defined as able to treat her/himself and plasma glucose below 3.1 mmol/L.

Outcome measures

Outcome measures
Measure	IDeg 200 U/mL n=184 Participants Insulin degludec 200 U/mL (IDeg 200 U/mL) in a 3 mL prefilled pen PDS290 was given subcutaneously once daily in combination with pre-trial oral antidiabetic drug treatment(metformin, insulin secretagogue \[sulfonylurea or glinide\], alpha-glucosidase inhibitor, pioglitazone or DPP-IV inhibitor). IDeg 200 U/mL was administered at any time of the day but preferably at the same time each day.	IDeg n=187 Participants Insulin degludec 100 U/mL (IDeg) in a 3 mL prefilled pen PDS290 was given subcutaneously once daily in combination with pre-trial oral antidiabetic drug treatment (metformin, insulin secretagogue \[sulfonylurea or glinide\], alpha-glucosidase inhibitor, pioglitazone or DPP-IV inhibitor). IDeg was administered at any time of the day but preferably at the same time each day.
Rate of Confirmed Hypoglycaemic Episodes	517 Episodes/100 years of patient exposure	566 Episodes/100 years of patient exposure

SECONDARY outcome

Timeframe: Week 0 to Week 22 + 7 days follow up

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

Outcome measures

Outcome measures
Measure	IDeg 200 U/mL n=184 Participants Insulin degludec 200 U/mL (IDeg 200 U/mL) in a 3 mL prefilled pen PDS290 was given subcutaneously once daily in combination with pre-trial oral antidiabetic drug treatment(metformin, insulin secretagogue \[sulfonylurea or glinide\], alpha-glucosidase inhibitor, pioglitazone or DPP-IV inhibitor). IDeg 200 U/mL was administered at any time of the day but preferably at the same time each day.	IDeg n=187 Participants Insulin degludec 100 U/mL (IDeg) in a 3 mL prefilled pen PDS290 was given subcutaneously once daily in combination with pre-trial oral antidiabetic drug treatment (metformin, insulin secretagogue \[sulfonylurea or glinide\], alpha-glucosidase inhibitor, pioglitazone or DPP-IV inhibitor). IDeg was administered at any time of the day but preferably at the same time each day.
Rate of Nocturnal Confirmed Hypoglycaemic Episodes	127 Episodes/100 years of patient exposure	170 Episodes/100 years of patient exposure

Adverse Events

IDeg 200 U/mL

Serious events: 9 serious events

Other events: 45 other events

Deaths: 0 deaths

IDeg

Serious events: 11 serious events

Other events: 26 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	IDeg 200 U/mL n=184 participants at risk Insulin degludec 200 U/mL (IDeg 200 U/mL) in a 3 mL prefilled pen PDS290 was given subcutaneously once daily in combination with pre-trial oral antidiabetic drug treatment(metformin, insulin secretagogue \[sulfonylurea or glinide\], alpha-glucosidase inhibitor, pioglitazone or DPP-IV inhibitor). IDeg 200 U/mL was administered at any time of the day but preferably at the same time each day.	IDeg n=187 participants at risk Insulin degludec 100 U/mL (IDeg) in a 3 mL prefilled pen PDS290 was given subcutaneously once daily in combination with pre-trial oral antidiabetic drug treatment (metformin, insulin secretagogue \[sulfonylurea or glinide\], alpha-glucosidase inhibitor, pioglitazone or DPP-IV inhibitor). IDeg was administered at any time of the day but preferably at the same time each day.
Gastrointestinal disorders Diarrhoea	9.2% 17/184 • Number of events 20 • The adverse events were collected in a time frame of 22 weeks + 7 days follow up. The safety analysis set included all subjects who received at least one dose of the investigational product or its comparator.	2.1% 4/187 • Number of events 4 • The adverse events were collected in a time frame of 22 weeks + 7 days follow up. The safety analysis set included all subjects who received at least one dose of the investigational product or its comparator.
Infections and infestations Nasopharyngitis	9.8% 18/184 • Number of events 19 • The adverse events were collected in a time frame of 22 weeks + 7 days follow up. The safety analysis set included all subjects who received at least one dose of the investigational product or its comparator.	6.4% 12/187 • Number of events 14 • The adverse events were collected in a time frame of 22 weeks + 7 days follow up. The safety analysis set included all subjects who received at least one dose of the investigational product or its comparator.
Infections and infestations Upper respiratory tract infection	8.2% 15/184 • Number of events 17 • The adverse events were collected in a time frame of 22 weeks + 7 days follow up. The safety analysis set included all subjects who received at least one dose of the investigational product or its comparator.	5.3% 10/187 • Number of events 10 • The adverse events were collected in a time frame of 22 weeks + 7 days follow up. The safety analysis set 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 200 U/mL n=184 participants at risk Insulin degludec 200 U/mL (IDeg 200 U/mL) in a 3 mL prefilled pen PDS290 was given subcutaneously once daily in combination with pre-trial oral antidiabetic drug treatment(metformin, insulin secretagogue \[sulfonylurea or glinide\], alpha-glucosidase inhibitor, pioglitazone or DPP-IV inhibitor). IDeg 200 U/mL was administered at any time of the day but preferably at the same time each day.	IDeg n=187 participants at risk Insulin degludec 100 U/mL (IDeg) in a 3 mL prefilled pen PDS290 was given subcutaneously once daily in combination with pre-trial oral antidiabetic drug treatment (metformin, insulin secretagogue \[sulfonylurea or glinide\], alpha-glucosidase inhibitor, pioglitazone or DPP-IV inhibitor). IDeg was administered at any time of the day but preferably at the same time each day.
Cardiac disorders Coronary artery disease	1.1% 2/184 • Number of events 2 • The adverse events were collected in a time frame of 22 weeks + 7 days follow up. The safety analysis set included all subjects who received at least one dose of the investigational product or its comparator.	0.00% 0/187 • The adverse events were collected in a time frame of 22 weeks + 7 days follow up. The safety analysis set included all subjects who received at least one dose of the investigational product or its comparator.
Gastrointestinal disorders Diverticulum intestinal haemorrhagic	0.54% 1/184 • Number of events 1 • The adverse events were collected in a time frame of 22 weeks + 7 days follow up. The safety analysis set included all subjects who received at least one dose of the investigational product or its comparator.	0.00% 0/187 • The adverse events were collected in a time frame of 22 weeks + 7 days follow up. The safety analysis set included all subjects who received at least one dose of the investigational product or its comparator.
Gastrointestinal disorders Pancreatitis	0.54% 1/184 • Number of events 1 • The adverse events were collected in a time frame of 22 weeks + 7 days follow up. The safety analysis set included all subjects who received at least one dose of the investigational product or its comparator.	0.53% 1/187 • Number of events 1 • The adverse events were collected in a time frame of 22 weeks + 7 days follow up. The safety analysis set included all subjects who received at least one dose of the investigational product or its comparator.
General disorders Chest pain	0.54% 1/184 • Number of events 1 • The adverse events were collected in a time frame of 22 weeks + 7 days follow up. The safety analysis set included all subjects who received at least one dose of the investigational product or its comparator.	0.00% 0/187 • The adverse events were collected in a time frame of 22 weeks + 7 days follow up. The safety analysis set included all subjects who received at least one dose of the investigational product or its comparator.
Hepatobiliary disorders Cholecystitis	0.54% 1/184 • Number of events 1 • The adverse events were collected in a time frame of 22 weeks + 7 days follow up. The safety analysis set included all subjects who received at least one dose of the investigational product or its comparator.	0.00% 0/187 • The adverse events were collected in a time frame of 22 weeks + 7 days follow up. The safety analysis set included all subjects who received at least one dose of the investigational product or its comparator.
Hepatobiliary disorders Cholelithiasis	0.54% 1/184 • Number of events 1 • The adverse events were collected in a time frame of 22 weeks + 7 days follow up. The safety analysis set included all subjects who received at least one dose of the investigational product or its comparator.	0.53% 1/187 • Number of events 1 • The adverse events were collected in a time frame of 22 weeks + 7 days follow up. The safety analysis set included all subjects who received at least one dose of the investigational product or its comparator.
Infections and infestations Diverticulitis	0.00% 0/184 • The adverse events were collected in a time frame of 22 weeks + 7 days follow up. The safety analysis set included all subjects who received at least one dose of the investigational product or its comparator.	0.53% 1/187 • Number of events 1 • The adverse events were collected in a time frame of 22 weeks + 7 days follow up. The safety analysis set included all subjects who received at least one dose of the investigational product or its comparator.
Infections and infestations Osteomyelitis	0.54% 1/184 • Number of events 1 • The adverse events were collected in a time frame of 22 weeks + 7 days follow up. The safety analysis set included all subjects who received at least one dose of the investigational product or its comparator.	0.00% 0/187 • The adverse events were collected in a time frame of 22 weeks + 7 days follow up. The safety analysis set included all subjects who received at least one dose of the investigational product or its comparator.
Infections and infestations Viral infection	0.54% 1/184 • Number of events 1 • The adverse events were collected in a time frame of 22 weeks + 7 days follow up. The safety analysis set included all subjects who received at least one dose of the investigational product or its comparator.	0.00% 0/187 • The adverse events were collected in a time frame of 22 weeks + 7 days follow up. The safety analysis set included all subjects who received at least one dose of the investigational product or its comparator.
Injury, poisoning and procedural complications Heat stroke	0.00% 0/184 • The adverse events were collected in a time frame of 22 weeks + 7 days follow up. The safety analysis set included all subjects who received at least one dose of the investigational product or its comparator.	0.53% 1/187 • Number of events 1 • The adverse events were collected in a time frame of 22 weeks + 7 days follow up. The safety analysis set included all subjects who received at least one dose of the investigational product or its comparator.
Injury, poisoning and procedural complications Hip fracture	0.54% 1/184 • Number of events 1 • The adverse events were collected in a time frame of 22 weeks + 7 days follow up. The safety analysis set included all subjects who received at least one dose of the investigational product or its comparator.	0.00% 0/187 • The adverse events were collected in a time frame of 22 weeks + 7 days follow up. The safety analysis set included all subjects who received at least one dose of the investigational product or its comparator.
Metabolism and nutrition disorders Hypoglycaemia	0.00% 0/184 • The adverse events were collected in a time frame of 22 weeks + 7 days follow up. The safety analysis set included all subjects who received at least one dose of the investigational product or its comparator.	0.53% 1/187 • Number of events 1 • The adverse events were collected in a time frame of 22 weeks + 7 days follow up. The safety analysis set included all subjects who received at least one dose of the investigational product or its comparator.
Metabolism and nutrition disorders Hyponatraemia	0.54% 1/184 • Number of events 1 • The adverse events were collected in a time frame of 22 weeks + 7 days follow up. The safety analysis set included all subjects who received at least one dose of the investigational product or its comparator.	0.53% 1/187 • Number of events 1 • The adverse events were collected in a time frame of 22 weeks + 7 days follow up. The safety analysis set included all subjects who received at least one dose of the investigational product or its comparator.
Musculoskeletal and connective tissue disorders Arthralgia	0.54% 1/184 • Number of events 1 • The adverse events were collected in a time frame of 22 weeks + 7 days follow up. The safety analysis set included all subjects who received at least one dose of the investigational product or its comparator.	0.00% 0/187 • The adverse events were collected in a time frame of 22 weeks + 7 days follow up. The safety analysis set included all subjects who received at least one dose of the investigational product or its comparator.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Ovarian epithelial cancer	0.00% 0/184 • The adverse events were collected in a time frame of 22 weeks + 7 days follow up. The safety analysis set included all subjects who received at least one dose of the investigational product or its comparator.	0.53% 1/187 • Number of events 1 • The adverse events were collected in a time frame of 22 weeks + 7 days follow up. The safety analysis set included all subjects who received at least one dose of the investigational product or its comparator.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Prostate cancer	0.00% 0/184 • The adverse events were collected in a time frame of 22 weeks + 7 days follow up. The safety analysis set included all subjects who received at least one dose of the investigational product or its comparator.	0.53% 1/187 • Number of events 1 • The adverse events were collected in a time frame of 22 weeks + 7 days follow up. The safety analysis set included all subjects who received at least one dose of the investigational product or its comparator.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Tongue neoplasm malignant	0.00% 0/184 • The adverse events were collected in a time frame of 22 weeks + 7 days follow up. The safety analysis set included all subjects who received at least one dose of the investigational product or its comparator.	0.53% 1/187 • Number of events 1 • The adverse events were collected in a time frame of 22 weeks + 7 days follow up. The safety analysis set included all subjects who received at least one dose of the investigational product or its comparator.
Psychiatric disorders Alcohol abuse	0.54% 1/184 • Number of events 1 • The adverse events were collected in a time frame of 22 weeks + 7 days follow up. The safety analysis set included all subjects who received at least one dose of the investigational product or its comparator.	0.00% 0/187 • The adverse events were collected in a time frame of 22 weeks + 7 days follow up. The safety analysis set included all subjects who received at least one dose of the investigational product or its comparator.
Psychiatric disorders Anxiety	0.00% 0/184 • The adverse events were collected in a time frame of 22 weeks + 7 days follow up. The safety analysis set included all subjects who received at least one dose of the investigational product or its comparator.	0.53% 1/187 • Number of events 1 • The adverse events were collected in a time frame of 22 weeks + 7 days follow up. The safety analysis set included all subjects who received at least one dose of the investigational product or its comparator.
Psychiatric disorders Drug abuse	0.54% 1/184 • Number of events 1 • The adverse events were collected in a time frame of 22 weeks + 7 days follow up. The safety analysis set included all subjects who received at least one dose of the investigational product or its comparator.	0.00% 0/187 • The adverse events were collected in a time frame of 22 weeks + 7 days follow up. The safety analysis set included all subjects who received at least one dose of the investigational product or its comparator.
Psychiatric disorders Suicidal ideation	0.00% 0/184 • The adverse events were collected in a time frame of 22 weeks + 7 days follow up. The safety analysis set included all subjects who received at least one dose of the investigational product or its comparator.	1.1% 2/187 • Number of events 2 • The adverse events were collected in a time frame of 22 weeks + 7 days follow up. The safety analysis set included all subjects who received at least one dose of the investigational product or its comparator.
Respiratory, thoracic and mediastinal disorders Cough	0.54% 1/184 • Number of events 1 • The adverse events were collected in a time frame of 22 weeks + 7 days follow up. The safety analysis set included all subjects who received at least one dose of the investigational product or its comparator.	0.00% 0/187 • The adverse events were collected in a time frame of 22 weeks + 7 days follow up. The safety analysis set included all subjects who received at least one dose of the investigational product or its comparator.