Trial Outcomes & Findings for Riociguat rEplacing PDE-5i Therapy evaLuated Against Continued PDE-5i thErapy (NCT NCT02891850)

NCT ID: NCT02891850

Last Updated: 2021-02-26

Results Overview

The treatment is assessed as efficient (participants with satisfactory clinical response) in case at least 2 out of the following 3 criteria were fulfilled * 6 Minute Walking Distance increase by ≥ 10% or ≥ 30 m from baseline to Week 24 * World Health Organization Functional Class (WHO FC) I or II at Week 24 * N-terminal pro-brain natriuretic peptide (NT-proBNP) reduction ≥ 30% from baseline to Week 24 (NT-proBNP ratio Week 24/baseline ≤ 0.7) and in absence of the defined criteria of clinical worsening

• Recruitment status: COMPLETED
• Study phase: PHASE4
• Target enrollment: 225 participants
• Primary outcome timeframe: At Week 24
• Results posted on: 2021-02-26

Participant Flow

Study was conducted at multiple centers in 21 countries between 11-JAN-2017 (first participant first visit) and 03-MAR-2020 (last participant last visit).

293 participants were screened in this study. Of these, 67 participants did not enter the treatment period (60 screening failures; 2 withdraw during screening; 2 withdraw following physician decision; 3 withdraw due to other reasons). 226 participants were randomized, of which 1 participant withdraw before treated.

Participant milestones

Measure	Riociguat Participants received BAY63-2521 tablets at a dosage of 0.5 mg, 1.0 mg, 1.5 mg, 2.0 mg, and 2.5 mg three times a day (TID) for 24 weeks, started with 1.0 mg TID, followed by a dose adjustment period of 8 weeks, then stayed at the optimal dose period of 16 weeks.	PDE-5i Participants remained on their current pulmonary arterial hypertension (PAH) treatment on tadalafil (20 to 40 mg/day) or sildenafil (at least 60 mg/day) for 24 weeks at the discretion of the investigator.
Overall Study STARTED	111	114
Overall Study COMPLETED	104	107
Overall Study NOT COMPLETED	7	7

Reasons for withdrawal

Measure	Riociguat Participants received BAY63-2521 tablets at a dosage of 0.5 mg, 1.0 mg, 1.5 mg, 2.0 mg, and 2.5 mg three times a day (TID) for 24 weeks, started with 1.0 mg TID, followed by a dose adjustment period of 8 weeks, then stayed at the optimal dose period of 16 weeks.	PDE-5i Participants remained on their current pulmonary arterial hypertension (PAH) treatment on tadalafil (20 to 40 mg/day) or sildenafil (at least 60 mg/day) for 24 weeks at the discretion of the investigator.
Overall Study Adverse Event	3	0
Overall Study Death	0	4
Overall Study Physician Decision	1	0
Overall Study Pregnancy	1	0
Overall Study Withdrawal by Subject	2	3

Baseline Characteristics

Riociguat rEplacing PDE-5i Therapy evaLuated Against Continued PDE-5i thErapy

Baseline characteristics by cohort

Measure	Riociguat n=111 Participants Participants received BAY63-2521 tablets at a dosage of 0.5 mg, 1.0 mg, 1.5 mg, 2.0 mg, and 2.5 mg three times a day (TID) for 24 weeks, started with 1.0 mg TID, followed by a dose adjustment period of 8 weeks, then stayed at the optimal dose period of 16 weeks.	PDE-5i n=114 Participants Participants remained on their current pulmonary arterial hypertension (PAH) treatment on tadalafil (20 to 40 mg/day) or sildenafil (at least 60 mg/day) for 24 weeks at the discretion of the investigator.	Total n=225 Participants Total of all reporting groups
Age, Continuous	49.4 years STANDARD_DEVIATION 16.16 • n=5 Participants	49.2 years STANDARD_DEVIATION 15.64 • n=7 Participants	49.3 years STANDARD_DEVIATION 15.86 • n=5 Participants
Sex: Female, Male Female	82 Participants n=5 Participants	95 Participants n=7 Participants	177 Participants n=5 Participants
Sex: Female, Male Male	29 Participants n=5 Participants	19 Participants n=7 Participants	48 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	32 Participants n=5 Participants	31 Participants n=7 Participants	63 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	75 Participants n=5 Participants	80 Participants n=7 Participants	155 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	4 Participants n=5 Participants	3 Participants n=7 Participants	7 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Asian	17 Participants n=5 Participants	19 Participants n=7 Participants	36 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	4 Participants n=5 Participants	5 Participants n=7 Participants	9 Participants n=5 Participants
Race (NIH/OMB) White	86 Participants n=5 Participants	89 Participants n=7 Participants	175 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	3 Participants n=5 Participants	1 Participants n=7 Participants	4 Participants n=5 Participants

PRIMARY outcome

Timeframe: At Week 24

Population: Full Analysis Set (FAS) with evaluable participants

The treatment is assessed as efficient (participants with satisfactory clinical response) in case at least 2 out of the following 3 criteria were fulfilled

• 6 Minute Walking Distance increase by ≥ 10% or ≥ 30 m from baseline to Week 24
• World Health Organization Functional Class (WHO FC) I or II at Week 24
• N-terminal pro-brain natriuretic peptide (NT-proBNP) reduction ≥ 30% from baseline to Week 24 (NT-proBNP ratio Week 24/baseline ≤ 0.7) and in absence of the defined criteria of clinical worsening

Outcome measures

Measure	Riociguat n=111 Participants Participants received BAY63-2521 tablets at a dosage of 0.5 mg, 1.0 mg, 1.5 mg, 2.0 mg, and 2.5 mg three times a day (TID) for 24 weeks, started with 1.0 mg TID, followed by a dose adjustment period of 8 weeks, then stayed at the optimal dose period of 16 weeks.	PDE-5i n=113 Participants Participants remained on their current pulmonary arterial hypertension (PAH) treatment on tadalafil (20 to 40 mg/day) or sildenafil (at least 60 mg/day) for 24 weeks at the discretion of the investigator.
Number of Participants With Satisfactory Clinical Response at Week 24 With satisfactory clinical response	45 Participants	23 Participants
Number of Participants With Satisfactory Clinical Response at Week 24 Without satisfactory clinical response	66 Participants	90 Participants

SECONDARY outcome

Timeframe: From baseline and up to 24 weeks

Population: Full Analysis Set (FAS) with evaluable participants

Six-minute walk distance (6MWD) was conducted to test the physical limitations of the participant by assessing the participant's exercise capacity. The distance walked by the participant in 6 minutes was measured.

Outcome measures

Measure	Riociguat n=111 Participants Participants received BAY63-2521 tablets at a dosage of 0.5 mg, 1.0 mg, 1.5 mg, 2.0 mg, and 2.5 mg three times a day (TID) for 24 weeks, started with 1.0 mg TID, followed by a dose adjustment period of 8 weeks, then stayed at the optimal dose period of 16 weeks.	PDE-5i n=113 Participants Participants remained on their current pulmonary arterial hypertension (PAH) treatment on tadalafil (20 to 40 mg/day) or sildenafil (at least 60 mg/day) for 24 weeks at the discretion of the investigator.
Change in 6 Minute Walking Distance (6MWD) With Last Observation Carried Forward From Baseline to 24 Weeks	36.448 meters (m) Standard Deviation 65.9748	13.884 meters (m) Standard Deviation 67.1552

SECONDARY outcome

Timeframe: From baseline and up to 24 weeks

Population: Full Analysis Set (FAS) with evaluable participants

N-terminal pro-brain natriuretic peptide (NT-proBNP) levels in the blood are used for screening, diagnosis of acute congestive heart failure (CHF) and may be useful to establish prognosis in heart failure.

Outcome measures

Measure	Riociguat n=108 Participants Participants received BAY63-2521 tablets at a dosage of 0.5 mg, 1.0 mg, 1.5 mg, 2.0 mg, and 2.5 mg three times a day (TID) for 24 weeks, started with 1.0 mg TID, followed by a dose adjustment period of 8 weeks, then stayed at the optimal dose period of 16 weeks.	PDE-5i n=113 Participants Participants remained on their current pulmonary arterial hypertension (PAH) treatment on tadalafil (20 to 40 mg/day) or sildenafil (at least 60 mg/day) for 24 weeks at the discretion of the investigator.
Change in N-terminal Pro-Brain Natriuretic Peptide (NT-proBNP) With Last Observation Carried Forward at Week 24	-88.234 picograms per milliliter (pg/mL) Standard Deviation 533.9179	81.414 picograms per milliliter (pg/mL) Standard Deviation 1267.6142

SECONDARY outcome

Timeframe: From baseline and up to 24 weeks

Population: Full Analysis Set (FAS) with evaluable participants

The participant's functional class was determined by using the WHO classification. Possible classes range from I (patients with pulmonary hypertension (PH) but without resulting limitation of physical activity) to IV (patients with PH with inability to carry out any physical activity without symptoms).

Outcome measures

Measure	Riociguat n=111 Participants Participants received BAY63-2521 tablets at a dosage of 0.5 mg, 1.0 mg, 1.5 mg, 2.0 mg, and 2.5 mg three times a day (TID) for 24 weeks, started with 1.0 mg TID, followed by a dose adjustment period of 8 weeks, then stayed at the optimal dose period of 16 weeks.	PDE-5i n=113 Participants Participants remained on their current pulmonary arterial hypertension (PAH) treatment on tadalafil (20 to 40 mg/day) or sildenafil (at least 60 mg/day) for 24 weeks at the discretion of the investigator.
Change in World Health Organization Functional Class (WHO FC) With Last Observation Carried Forward From Baseline to Week 24	-0.5 class Standard Deviation 0.58	-0.2 class Standard Deviation 0.62

SECONDARY outcome

Timeframe: Up to 24 weeks

Population: Full Analysis Set (FAS) with evaluable participants

Clinical worsening was defined as death of any cause, hospitalization due to worsening pulmonary arterial hypertension (PAH) (adjudicated) or disease progression (adjudicated).

Outcome measures

Measure	Riociguat n=111 Participants Participants received BAY63-2521 tablets at a dosage of 0.5 mg, 1.0 mg, 1.5 mg, 2.0 mg, and 2.5 mg three times a day (TID) for 24 weeks, started with 1.0 mg TID, followed by a dose adjustment period of 8 weeks, then stayed at the optimal dose period of 16 weeks.	PDE-5i n=113 Participants Participants remained on their current pulmonary arterial hypertension (PAH) treatment on tadalafil (20 to 40 mg/day) or sildenafil (at least 60 mg/day) for 24 weeks at the discretion of the investigator.
Number of Participants With Adjudicated Clinical Worsening at Week 24	1 Participants	10 Participants

Adverse Events

Riociguat

Serious events: 8 serious events

Other events: 77 other events

Deaths: 0 deaths

PDE-5i

Serious events: 19 serious events

Other events: 72 other events

Deaths: 4 deaths

Serious adverse events

Measure	Riociguat n=111 participants at risk Participants received BAY63-2521 tablets at a dosage of 0.5 mg, 1.0 mg, 1.5 mg, 2.0 mg, and 2.5 mg three times a day (TID) for 24 weeks, started with 1.0 mg TID, followed by a dose adjustment period of 8 weeks, then stayed at the optimal dose period of 16 weeks.	PDE-5i n=114 participants at risk Participants remained on their current pulmonary arterial hypertension (PAH) treatment on tadalafil (20 to 40 mg/day) or sildenafil (at least 60 mg/day) for 24 weeks at the discretion of the investigator.
Blood and lymphatic system disorders Iron deficiency anaemia	0.00% 0/111 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.	0.88% 1/114 • Number of events 1 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.
Cardiac disorders Arrhythmia supraventricular	0.00% 0/111 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.	0.88% 1/114 • Number of events 1 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.
Cardiac disorders Atrial fibrillation	0.00% 0/111 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.	0.88% 1/114 • Number of events 2 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.
Cardiac disorders Cardiac failure	0.00% 0/111 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.	0.88% 1/114 • Number of events 1 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.
Cardiac disorders Right ventricular failure	0.90% 1/111 • Number of events 1 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.	0.00% 0/114 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.
Gastrointestinal disorders Gastrointestinal haemorrhage	0.00% 0/111 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.	0.88% 1/114 • Number of events 1 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.
Gastrointestinal disorders Small intestinal obstruction	0.90% 1/111 • Number of events 3 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.	0.00% 0/114 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.
General disorders Chest pain	0.00% 0/111 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.	0.88% 1/114 • Number of events 1 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.
Infections and infestations Gastroenteritis	0.90% 1/111 • Number of events 1 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.	0.00% 0/114 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.
Infections and infestations Pneumonia	0.00% 0/111 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.	1.8% 2/114 • Number of events 2 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.
Infections and infestations Tracheobronchitis	0.90% 1/111 • Number of events 1 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.	0.00% 0/114 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.
Infections and infestations Viral infection	0.00% 0/111 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.	0.88% 1/114 • Number of events 1 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.
Infections and infestations Respiratory tract infection	0.00% 0/111 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.	0.88% 1/114 • Number of events 1 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.
Investigations Pulmonary arterial pressure increased	0.00% 0/111 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.	0.88% 1/114 • Number of events 1 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.
Metabolism and nutrition disorders Dehydration	0.00% 0/111 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.	0.88% 1/114 • Number of events 1 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.
Musculoskeletal and connective tissue disorders Osteonecrosis	0.90% 1/111 • Number of events 1 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.	0.00% 0/114 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.
Nervous system disorders Epilepsy	0.00% 0/111 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.	0.88% 1/114 • Number of events 1 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.
Nervous system disorders Syncope	0.90% 1/111 • Number of events 1 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.	0.88% 1/114 • Number of events 1 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.00% 0/111 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.	0.88% 1/114 • Number of events 1 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.
Respiratory, thoracic and mediastinal disorders Dyspnoea exertional	0.00% 0/111 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.	0.88% 1/114 • Number of events 1 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.
Respiratory, thoracic and mediastinal disorders Epistaxis	0.90% 1/111 • Number of events 1 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.	0.00% 0/114 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.
Respiratory, thoracic and mediastinal disorders Pulmonary hypertension	0.00% 0/111 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.	1.8% 2/114 • Number of events 2 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.
Respiratory, thoracic and mediastinal disorders Pulmonary arterial hypertension	0.00% 0/111 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.	1.8% 2/114 • Number of events 3 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.
Surgical and medical procedures Drug therapy enhancement	0.00% 0/111 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.	0.88% 1/114 • Number of events 1 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.
Vascular disorders Hypotension	1.8% 2/111 • Number of events 3 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.	0.00% 0/114 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.

Other adverse events

Measure	Riociguat n=111 participants at risk Participants received BAY63-2521 tablets at a dosage of 0.5 mg, 1.0 mg, 1.5 mg, 2.0 mg, and 2.5 mg three times a day (TID) for 24 weeks, started with 1.0 mg TID, followed by a dose adjustment period of 8 weeks, then stayed at the optimal dose period of 16 weeks.	PDE-5i n=114 participants at risk Participants remained on their current pulmonary arterial hypertension (PAH) treatment on tadalafil (20 to 40 mg/day) or sildenafil (at least 60 mg/day) for 24 weeks at the discretion of the investigator.
Surgical and medical procedures Tooth extraction	0.00% 0/111 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.	0.88% 1/114 • Number of events 1 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.
Vascular disorders Circulatory collapse	0.00% 0/111 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.	0.88% 1/114 • Number of events 1 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.
Vascular disorders Flushing	0.90% 1/111 • Number of events 1 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.	0.88% 1/114 • Number of events 1 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.
Vascular disorders Hypertension	0.00% 0/111 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.	0.88% 1/114 • Number of events 1 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.
Vascular disorders Hypotension	11.7% 13/111 • Number of events 19 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.	5.3% 6/114 • Number of events 11 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.
Vascular disorders Orthostatic hypotension	0.00% 0/111 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.	0.88% 1/114 • Number of events 1 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.
Vascular disorders Jugular vein distension	0.00% 0/111 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.	0.88% 1/114 • Number of events 1 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.
Infections and infestations Influenza	0.90% 1/111 • Number of events 1 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.	1.8% 2/114 • Number of events 2 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.
Infections and infestations Laryngitis	0.00% 0/111 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.	1.8% 2/114 • Number of events 2 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.
Infections and infestations Lower respiratory tract infection	0.00% 0/111 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.	0.88% 1/114 • Number of events 1 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.
Infections and infestations Nasopharyngitis	7.2% 8/111 • Number of events 8 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.	4.4% 5/114 • Number of events 5 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.
Infections and infestations Otitis media	0.00% 0/111 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.	0.88% 1/114 • Number of events 1 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.
Infections and infestations Pneumonia	1.8% 2/111 • Number of events 2 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.	0.88% 1/114 • Number of events 1 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.
Infections and infestations Rhinitis	0.00% 0/111 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.	3.5% 4/114 • Number of events 4 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.
Infections and infestations Sinusitis	1.8% 2/111 • Number of events 2 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.	5.3% 6/114 • Number of events 8 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.
Infections and infestations Tonsillitis	0.00% 0/111 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.	0.88% 1/114 • Number of events 1 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.
Infections and infestations Upper respiratory tract infection	3.6% 4/111 • Number of events 4 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.	6.1% 7/114 • Number of events 8 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.
Blood and lymphatic system disorders Anaemia	0.00% 0/111 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.	0.88% 1/114 • Number of events 1 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.
Blood and lymphatic system disorders Anaemia megaloblastic	0.00% 0/111 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.	0.88% 1/114 • Number of events 1 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.
Blood and lymphatic system disorders Iron deficiency anaemia	1.8% 2/111 • Number of events 2 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.	0.00% 0/114 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.
Blood and lymphatic system disorders Leukopenia	0.00% 0/111 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.	1.8% 2/114 • Number of events 2 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.
Blood and lymphatic system disorders Lymphopenia	0.00% 0/111 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.	0.88% 1/114 • Number of events 1 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.
Blood and lymphatic system disorders Neutropenia	0.00% 0/111 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.	0.88% 1/114 • Number of events 1 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.
Cardiac disorders Arrhythmia	0.00% 0/111 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.	0.88% 1/114 • Number of events 1 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.
Cardiac disorders Atrial fibrillation	0.00% 0/111 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.	0.88% 1/114 • Number of events 1 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.
Cardiac disorders Cardiac failure chronic	0.90% 1/111 • Number of events 1 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.	0.00% 0/114 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.
Cardiac disorders Palpitations	2.7% 3/111 • Number of events 4 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.	3.5% 4/114 • Number of events 4 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.
Cardiac disorders Sinus tachycardia	0.90% 1/111 • Number of events 1 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.	0.00% 0/114 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.
Cardiac disorders Tachycardia	0.90% 1/111 • Number of events 1 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.	0.00% 0/114 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.
Cardiac disorders Ventricular extrasystoles	0.00% 0/111 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.	1.8% 2/114 • Number of events 2 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.
Ear and labyrinth disorders Vertigo	1.8% 2/111 • Number of events 3 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.	0.00% 0/114 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.
Eye disorders Astigmatism	0.90% 1/111 • Number of events 1 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.	0.00% 0/114 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.
Eye disorders Cataract	0.00% 0/111 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.	0.88% 1/114 • Number of events 1 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.
Eye disorders Eye irritation	0.00% 0/111 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.	0.88% 1/114 • Number of events 1 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.
Eye disorders Glaucoma	0.90% 1/111 • Number of events 1 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.	0.00% 0/114 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.
Eye disorders Retinal disorder	0.90% 1/111 • Number of events 1 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.	0.00% 0/114 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.
Eye disorders Ocular discomfort	0.00% 0/111 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.	0.88% 1/114 • Number of events 1 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.
Gastrointestinal disorders Abdominal discomfort	2.7% 3/111 • Number of events 3 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.	0.00% 0/114 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.
Gastrointestinal disorders Abdominal distension	0.00% 0/111 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.	0.88% 1/114 • Number of events 1 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.
Gastrointestinal disorders Abdominal pain	2.7% 3/111 • Number of events 3 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.	0.00% 0/114 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.
Gastrointestinal disorders Abdominal pain lower	0.00% 0/111 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.	0.88% 1/114 • Number of events 1 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.
Gastrointestinal disorders Abdominal pain upper	2.7% 3/111 • Number of events 3 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.	0.88% 1/114 • Number of events 1 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.
Gastrointestinal disorders Constipation	3.6% 4/111 • Number of events 5 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.	0.00% 0/114 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.
Gastrointestinal disorders Diarrhoea	5.4% 6/111 • Number of events 6 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.	2.6% 3/114 • Number of events 3 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.
Gastrointestinal disorders Dyspepsia	9.0% 10/111 • Number of events 10 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.	0.00% 0/114 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.
Gastrointestinal disorders Flatulence	0.90% 1/111 • Number of events 1 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.	0.00% 0/114 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.
Gastrointestinal disorders Gastritis	0.00% 0/111 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.	0.88% 1/114 • Number of events 1 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.
Gastrointestinal disorders Gastrooesophageal reflux disease	7.2% 8/111 • Number of events 10 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.	0.88% 1/114 • Number of events 1 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.
Gastrointestinal disorders Gingival hypertrophy	0.90% 1/111 • Number of events 1 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.	0.00% 0/114 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.
Gastrointestinal disorders Irritable bowel syndrome	0.00% 0/111 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.	0.88% 1/114 • Number of events 1 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.
Gastrointestinal disorders Nausea	4.5% 5/111 • Number of events 6 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.	2.6% 3/114 • Number of events 3 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.
Gastrointestinal disorders Toothache	0.00% 0/111 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.	1.8% 2/114 • Number of events 2 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.
Gastrointestinal disorders Vomiting	2.7% 3/111 • Number of events 3 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.	0.00% 0/114 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.
Gastrointestinal disorders Gastrointestinal hypermotility	0.90% 1/111 • Number of events 1 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.	0.00% 0/114 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.
Gastrointestinal disorders Reflux gastritis	0.90% 1/111 • Number of events 1 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.	0.00% 0/114 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.
General disorders Asthenia	0.00% 0/111 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.	1.8% 2/114 • Number of events 2 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.
General disorders Chest discomfort	0.00% 0/111 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.	0.88% 1/114 • Number of events 1 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.
General disorders Chest pain	4.5% 5/111 • Number of events 8 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.	4.4% 5/114 • Number of events 5 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.
General disorders Drug ineffective	0.00% 0/111 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.	0.88% 1/114 • Number of events 1 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.
General disorders Fatigue	5.4% 6/111 • Number of events 7 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.	1.8% 2/114 • Number of events 2 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.
General disorders Malaise	0.90% 1/111 • Number of events 1 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.	0.00% 0/114 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.
General disorders Oedema	1.8% 2/111 • Number of events 2 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.	1.8% 2/114 • Number of events 2 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.
General disorders Oedema mucosal	0.90% 1/111 • Number of events 1 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.	0.00% 0/114 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.
General disorders Oedema peripheral	2.7% 3/111 • Number of events 4 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.	3.5% 4/114 • Number of events 4 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.
General disorders Pyrexia	0.90% 1/111 • Number of events 1 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.	0.00% 0/114 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.
General disorders Peripheral swelling	0.00% 0/111 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.	0.88% 1/114 • Number of events 1 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.
Hepatobiliary disorders Hepatomegaly	0.00% 0/111 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.	0.88% 1/114 • Number of events 1 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.
Immune system disorders Drug hypersensitivity	0.00% 0/111 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.	0.88% 1/114 • Number of events 1 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.
Immune system disorders Hypersensitivity	0.00% 0/111 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.	0.88% 1/114 • Number of events 1 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.
Infections and infestations Acute sinusitis	0.00% 0/111 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.	0.88% 1/114 • Number of events 1 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.
Infections and infestations Body tinea	0.90% 1/111 • Number of events 1 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.	0.00% 0/114 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.
Infections and infestations Bronchitis	0.90% 1/111 • Number of events 1 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.	1.8% 2/114 • Number of events 2 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.
Infections and infestations Conjunctivitis	0.00% 0/111 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.	0.88% 1/114 • Number of events 1 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.
Infections and infestations Diverticulitis	0.00% 0/111 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.	0.88% 1/114 • Number of events 1 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.
Infections and infestations Enterobiasis	0.90% 1/111 • Number of events 1 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.	0.00% 0/114 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.
Infections and infestations Eye infection	0.00% 0/111 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.	0.88% 1/114 • Number of events 1 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.
Infections and infestations Fungal infection	0.90% 1/111 • Number of events 1 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.	0.00% 0/114 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.
Infections and infestations Gastroenteritis	0.90% 1/111 • Number of events 1 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.	0.00% 0/114 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.
Infections and infestations Hepatitis E	0.90% 1/111 • Number of events 1 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.	0.00% 0/114 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.
Infections and infestations Herpes zoster	0.90% 1/111 • Number of events 1 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.	0.00% 0/114 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.
Infections and infestations Urinary tract infection	1.8% 2/111 • Number of events 2 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.	2.6% 3/114 • Number of events 3 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.
Infections and infestations Viral infection	0.90% 1/111 • Number of events 1 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.	0.00% 0/114 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.
Infections and infestations Pharyngotonsillitis	0.90% 1/111 • Number of events 1 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.	0.00% 0/114 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.
Infections and infestations Febrile infection	0.00% 0/111 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.	0.88% 1/114 • Number of events 1 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.
Infections and infestations Bronchitis viral	0.00% 0/111 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.	0.88% 1/114 • Number of events 1 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.
Infections and infestations Mycobacterial infection	0.00% 0/111 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.	0.88% 1/114 • Number of events 1 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.
Infections and infestations Respiratory tract infection	0.90% 1/111 • Number of events 2 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.	0.00% 0/114 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.
Injury, poisoning and procedural complications Ligament sprain	0.90% 1/111 • Number of events 1 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.	0.00% 0/114 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.
Injury, poisoning and procedural complications Muscle strain	0.00% 0/111 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.	0.88% 1/114 • Number of events 1 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.
Injury, poisoning and procedural complications Limb injury	0.90% 1/111 • Number of events 1 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.	0.00% 0/114 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.
Injury, poisoning and procedural complications Bone contusion	0.90% 1/111 • Number of events 1 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.	0.88% 1/114 • Number of events 1 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.
Investigations Blood pressure decreased	0.90% 1/111 • Number of events 1 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.	0.00% 0/114 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.
Investigations Blood pressure systolic increased	0.00% 0/111 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.	0.88% 1/114 • Number of events 1 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.
Investigations Catheterisation cardiac	0.90% 1/111 • Number of events 1 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.	0.00% 0/114 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.
Investigations Haemoglobin decreased	0.00% 0/111 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.	0.88% 1/114 • Number of events 1 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.
Investigations Prothrombin time prolonged	0.00% 0/111 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.	0.88% 1/114 • Number of events 1 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.
Investigations Hepatic enzyme increased	0.90% 1/111 • Number of events 1 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.	0.00% 0/114 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.
Investigations N-terminal prohormone brain natriuretic peptide increased	0.00% 0/111 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.	0.88% 1/114 • Number of events 1 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.
Metabolism and nutrition disorders Dehydration	0.00% 0/111 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.	0.88% 1/114 • Number of events 1 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.
Metabolism and nutrition disorders Fluid retention	0.90% 1/111 • Number of events 1 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.	0.00% 0/114 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.
Metabolism and nutrition disorders Gout	0.00% 0/111 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.	0.88% 1/114 • Number of events 1 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.
Metabolism and nutrition disorders Hyperuricaemia	0.00% 0/111 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.	0.88% 1/114 • Number of events 1 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.
Metabolism and nutrition disorders Hypokalaemia	0.00% 0/111 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.	3.5% 4/114 • Number of events 4 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.
Metabolism and nutrition disorders Iron deficiency	1.8% 2/111 • Number of events 2 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.	3.5% 4/114 • Number of events 4 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.
Metabolism and nutrition disorders Decreased appetite	0.90% 1/111 • Number of events 1 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.	0.00% 0/114 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.
Metabolism and nutrition disorders Type 2 diabetes mellitus	0.00% 0/111 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.	0.88% 1/114 • Number of events 1 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.
Musculoskeletal and connective tissue disorders Arthralgia	0.90% 1/111 • Number of events 1 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.	2.6% 3/114 • Number of events 3 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.
Musculoskeletal and connective tissue disorders Arthritis	0.00% 0/111 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.	0.88% 1/114 • Number of events 1 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.
Musculoskeletal and connective tissue disorders Back pain	0.90% 1/111 • Number of events 1 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.	5.3% 6/114 • Number of events 6 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.
Musculoskeletal and connective tissue disorders Muscle spasms	1.8% 2/111 • Number of events 2 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.	0.88% 1/114 • Number of events 1 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.
Musculoskeletal and connective tissue disorders Musculoskeletal pain	0.00% 0/111 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.	0.88% 1/114 • Number of events 1 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.
Musculoskeletal and connective tissue disorders Myalgia	0.90% 1/111 • Number of events 1 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.	0.88% 1/114 • Number of events 1 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.
Musculoskeletal and connective tissue disorders Neck pain	1.8% 2/111 • Number of events 2 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.	0.88% 1/114 • Number of events 1 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.
Musculoskeletal and connective tissue disorders Pain in extremity	0.00% 0/111 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.	0.88% 1/114 • Number of events 2 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.
Musculoskeletal and connective tissue disorders Pain in jaw	0.90% 1/111 • Number of events 1 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.	0.00% 0/114 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.
Musculoskeletal and connective tissue disorders Spinal osteoarthritis	0.00% 0/111 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.	0.88% 1/114 • Number of events 1 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.
Musculoskeletal and connective tissue disorders Systemic lupus erythematosus	0.90% 1/111 • Number of events 1 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.	0.00% 0/114 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.
Musculoskeletal and connective tissue disorders Intervertebral disc protrusion	0.00% 0/111 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.	0.88% 1/114 • Number of events 1 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.
Nervous system disorders Diabetic neuropathy	0.90% 1/111 • Number of events 1 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.	0.00% 0/114 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.
Nervous system disorders Dizziness	4.5% 5/111 • Number of events 5 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.	1.8% 2/114 • Number of events 2 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.
Nervous system disorders Headache	12.6% 14/111 • Number of events 16 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.	7.0% 8/114 • Number of events 8 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.
Nervous system disorders Hypoaesthesia	0.90% 1/111 • Number of events 1 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.	0.00% 0/114 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.
Nervous system disorders Migraine	0.90% 1/111 • Number of events 1 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.	0.00% 0/114 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.
Nervous system disorders Presyncope	0.90% 1/111 • Number of events 1 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.	1.8% 2/114 • Number of events 2 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.
Nervous system disorders Syncope	0.00% 0/111 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.	1.8% 2/114 • Number of events 2 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.
Psychiatric disorders Anxiety	0.00% 0/111 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.	0.88% 1/114 • Number of events 3 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.
Psychiatric disorders Depression	1.8% 2/111 • Number of events 2 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.	0.00% 0/114 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.
Psychiatric disorders Insomnia	0.00% 0/111 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.	2.6% 3/114 • Number of events 3 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.
Psychiatric disorders Sleep disorder	0.00% 0/111 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.	0.88% 1/114 • Number of events 1 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.
Psychiatric disorders Stress	0.90% 1/111 • Number of events 1 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.	0.00% 0/114 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.
Renal and urinary disorders Polyuria	0.00% 0/111 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.	0.88% 1/114 • Number of events 1 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.
Renal and urinary disorders Urinary incontinence	0.00% 0/111 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.	0.88% 1/114 • Number of events 1 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.
Reproductive system and breast disorders Dysmenorrhoea	0.00% 0/111 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.	0.88% 1/114 • Number of events 1 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.
Reproductive system and breast disorders Menometrorrhagia	0.00% 0/111 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.	0.88% 1/114 • Number of events 1 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.
Reproductive system and breast disorders Adnexa uteri cyst	0.00% 0/111 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.	0.88% 1/114 • Number of events 1 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.
Respiratory, thoracic and mediastinal disorders Asthma	0.00% 0/111 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.	0.88% 1/114 • Number of events 1 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.
Respiratory, thoracic and mediastinal disorders Cough	0.00% 0/111 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.	6.1% 7/114 • Number of events 7 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.
Respiratory, thoracic and mediastinal disorders Dry throat	0.90% 1/111 • Number of events 1 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.	0.00% 0/114 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.
Respiratory, thoracic and mediastinal disorders Dyspnoea	2.7% 3/111 • Number of events 4 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.	4.4% 5/114 • Number of events 6 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.
Respiratory, thoracic and mediastinal disorders Dyspnoea exertional	1.8% 2/111 • Number of events 3 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.	0.00% 0/114 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.
Respiratory, thoracic and mediastinal disorders Epistaxis	2.7% 3/111 • Number of events 3 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.	2.6% 3/114 • Number of events 4 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.
Respiratory, thoracic and mediastinal disorders Hypoxia	0.90% 1/111 • Number of events 1 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.	0.00% 0/114 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.
Respiratory, thoracic and mediastinal disorders Lung disorder	0.00% 0/111 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.	0.88% 1/114 • Number of events 1 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.
Respiratory, thoracic and mediastinal disorders Nasal congestion	0.90% 1/111 • Number of events 1 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.	0.88% 1/114 • Number of events 1 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.
Respiratory, thoracic and mediastinal disorders Nasal polyps	0.90% 1/111 • Number of events 1 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.	0.00% 0/114 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.
Respiratory, thoracic and mediastinal disorders Productive cough	0.00% 0/111 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.	0.88% 1/114 • Number of events 1 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	0.00% 0/111 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.	0.88% 1/114 • Number of events 1 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.
Respiratory, thoracic and mediastinal disorders Pulmonary hypertension	0.00% 0/111 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.	0.88% 1/114 • Number of events 1 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.
Respiratory, thoracic and mediastinal disorders Pulmonary oedema	0.90% 1/111 • Number of events 1 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.	0.00% 0/114 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.
Respiratory, thoracic and mediastinal disorders Rhinitis allergic	1.8% 2/111 • Number of events 2 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.	0.00% 0/114 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.
Respiratory, thoracic and mediastinal disorders Rhinorrhoea	0.90% 1/111 • Number of events 1 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.	0.00% 0/114 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.
Respiratory, thoracic and mediastinal disorders Sleep apnoea syndrome	0.90% 1/111 • Number of events 1 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.	0.00% 0/114 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.
Respiratory, thoracic and mediastinal disorders Throat irritation	0.00% 0/111 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.	0.88% 1/114 • Number of events 1 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.
Respiratory, thoracic and mediastinal disorders Paranasal sinus hypersecretion	0.90% 1/111 • Number of events 1 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.	0.00% 0/114 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.
Respiratory, thoracic and mediastinal disorders Pulmonary arterial hypertension	0.00% 0/111 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.	0.88% 1/114 • Number of events 1 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.
Respiratory, thoracic and mediastinal disorders Bronchial hyperreactivity	0.00% 0/111 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.	0.88% 1/114 • Number of events 1 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	0.00% 0/111 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.	1.8% 2/114 • Number of events 2 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.
Skin and subcutaneous tissue disorders Acne	0.00% 0/111 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.	0.88% 1/114 • Number of events 1 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.
Skin and subcutaneous tissue disorders Erythema	0.90% 1/111 • Number of events 1 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.	0.00% 0/114 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.
Skin and subcutaneous tissue disorders Hyperhidrosis	0.90% 1/111 • Number of events 1 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.	0.88% 1/114 • Number of events 1 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.
Skin and subcutaneous tissue disorders Pruritus	0.00% 0/111 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.	0.88% 1/114 • Number of events 1 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.
Skin and subcutaneous tissue disorders Rash	0.00% 0/111 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.	0.88% 1/114 • Number of events 1 • The adverse events were considered to be treatment emergent if they had started or worsened after the first treatment administration and up to 2 days after end of treatment. Since maximum study duration was 24 weeks, this could be up to 24 weeks + 2 days.

Additional Information

Therapeutic Area Head

Bayer

Phone: (+) 1-888-8422937

Email: clinical-trials-contact@bayer.com

Results disclosure agreements

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

Restriction type: LTE60