Trial Outcomes & Findings for Clinical Study of Pulsed, Inhaled Nitric Oxide Versus Placebo in Symptomatic Subjects With PAH (NCT NCT02725372)

NCT ID: NCT02725372

Last Updated: 2023-02-21

Results Overview

The 6-minute walk distance test (6MWD) is a non-encouraged test performed in a 30 m long flat corridor, where the patient is instructed to walk as far as possible, back and forth around two cones, with the permission to slow down, rest, or stop if needed. All patients were required to complete two walks while on chronic oxygen therapy given at a standard rate during the test and throughout the study while using the investigational product (INOpulse device with nitric oxide or matching placebo). The average of two walks at Week 2 visit (2 weeks after Run-In) was used as the Baseline 6MWD.

• Recruitment status: TERMINATED
• Study phase: PHASE3
• Target enrollment: 207 participants
• Primary outcome timeframe: Change in 6MWD from Week 2 (2 weeks after randomization and run-in period) to Week 18 (end of blinded treatment period)
• Results posted on: 2023-02-21

Participant Flow

50 participants did not meet the inclusion and/or exclusion criteria and were not randomized

Participant milestones

Measure	Inhaled Nitric Oxide Randomized to Inhaled Nitric Oxide at dose of 15mcg/Kg IBW/hr for Run In Period of first 2 weeks (Week 0 and 1). Followed by Inhaled Nitric Oxide at dose of 75 mcg/kg IBW/hr for 16 weeks (Week 2 to Week 18)	Placebo Randomized to Placebo at dose of 15mcg/Kg IBW/hr for Run In Period of first 2 weeks (Week 0 and 1). Followed by Placebo at dose of 75 mcg/kg IBW/hr for additional 16 weeks (Week 2 to Week 16)
Part 1: Blinded Tx (2 Week Run In) STARTED	78	79
Part 1: Blinded Tx (2 Week Run In) Participants That Actually Received Treatment	74	78
Part 1: Blinded Tx (2 Week Run In) COMPLETED	52	59
Part 1: Blinded Tx (2 Week Run In) NOT COMPLETED	26	20
Part 1: Blinded Tx (16 Weeks) STARTED	52	58
Part 1: Blinded Tx (16 Weeks) COMPLETED	40	42
Part 1: Blinded Tx (16 Weeks) NOT COMPLETED	12	16
Part 2: Open Label Extension Period STARTED	40	42
Part 2: Open Label Extension Period COMPLETED	40	42
Part 2: Open Label Extension Period NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Clinical Study of Pulsed, Inhaled Nitric Oxide Versus Placebo in Symptomatic Subjects With PAH

Baseline characteristics by cohort

Measure	Inhaled Nitric Oxide n=52 Participants Includes all randomized subjects that completed 2 week run in period and opted to continue with 16 week treatment period. Treated with Inhaled Nitric Oxide at dose of 75 mcg/Kg IBW/hr	Placebo n=58 Participants Includes all randomized subjects that completed 2 week run in period and opted to continue with 16 week treatment period. Treated with Placebo at dose of 75 mcg/Kg IBW/hr	Total n=110 Participants Total of all reporting groups
Age, Continuous	65 Years n=5 Participants	63 Years n=7 Participants	64 Years n=5 Participants
Sex: Female, Male Female	40 Participants n=5 Participants	36 Participants n=7 Participants	76 Participants n=5 Participants
Sex: Female, Male Male	12 Participants n=5 Participants	22 Participants n=7 Participants	34 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants n=5 Participants	2 Participants n=7 Participants	3 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	51 Participants n=5 Participants	56 Participants n=7 Participants	107 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	1 Participants n=7 Participants	1 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	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) White	52 Participants n=5 Participants	55 Participants n=7 Participants	107 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	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
6 Minute Walk Distance (6MWD)	286 meters n=5 Participants	323 meters n=7 Participants	312 meters n=5 Participants
Oxygen Use (Hours/Day) at Baseline <8 hours per day	46 Participants n=5 Participants	49 Participants n=7 Participants	95 Participants n=5 Participants
Oxygen Use (Hours/Day) at Baseline >8 hours per day	6 Participants n=5 Participants	9 Participants n=7 Participants	15 Participants n=5 Participants
Cardiac Index	2.05 L/minute/m^2 n=5 Participants	2.30 L/minute/m^2 n=7 Participants	2.18 L/minute/m^2 n=5 Participants
Pulmonary Vascular Resistance (PVR) via RHC	726 dynes.second/cm^5 n=5 Participants	940 dynes.second/cm^5 n=7 Participants	839 dynes.second/cm^5 n=5 Participants

PRIMARY outcome

Timeframe: Change in 6MWD from Week 2 (2 weeks after randomization and run-in period) to Week 18 (end of blinded treatment period)

Population: 6MWD Change from Week 2 (2 weeks after randomization and run-in period) to Week 18 (end of blinded treatment period) (Week 18). MMRM model includes Baseline 6MWD as covariate, Treatment Group, Visit, Prostanoids usage status and Treatment by Visit Interaction as fixed effects. No imputation performed for primary analysis. ITT analysis set only includes study participants that completed 16 weeks of Part 1 blinded treatment.

The 6-minute walk distance test (6MWD) is a non-encouraged test performed in a 30 m long flat corridor, where the patient is instructed to walk as far as possible, back and forth around two cones, with the permission to slow down, rest, or stop if needed. All patients were required to complete two walks while on chronic oxygen therapy given at a standard rate during the test and throughout the study while using the investigational product (INOpulse device with nitric oxide or matching placebo). The average of two walks at Week 2 visit (2 weeks after Run-In) was used as the Baseline 6MWD.

Outcome measures

Measure	Inhaled Nitric Oxide 75mcg/KgIBW/Hr n=52 Participants Part 1: Blinded Treatment - 75 mcg/Kg IBW/hr for 16 weeks (included only participants who were compliant in the first 2 weeks)	Placebo n=58 Participants Part 1 Blinded Treatment - Placebo dose setting 75 mcg/kg IBW/hr for 16 weeks (included only participants who were compliant in the first 2 weeks)
Change in 6-minute Walk Distance (6MWD) From Baseline (Randomization) to End of Treatment Period (Week 18)	4.88 meters Standard Error 6.90	2.89 meters Standard Error 10.13

SECONDARY outcome

Timeframe: From Randomization to Week 18 (End of blinded treatment period)

Population: ITT analysis population

Clinical worsening was assessed continuously from Randomization to Week 18 (End of blinded treatment period). Clinical worsening events were defined as death (all causes), atrial septostomy, hospitalization due to worsening of pulmonary arterial hypertension (PAH), initiation of new pulmonary arterial hypertension treatment including endothelin receptor antagonists [ERAs], phosphodiesterase type-5 [PDE-5] inhibitors or prostanoids, an increase in existing treatment of ERA or PDE-5, increase in the dose or frequency of an inhaled prostanoids, or an increase in the dose of an intravenous or subcutaneous prostanoids by >10%, a decrease of >15% from baseline or >30% compared with the last study related measurement in 6MWD or worsening of WHO Functional Class (e.g., from Class II to Class III or IV, OR Class III to Class IV). All worsening events were entered by the study sites into the eCRF.

Outcome measures

Measure	Inhaled Nitric Oxide 75mcg/KgIBW/Hr n=52 Participants Part 1: Blinded Treatment - 75 mcg/Kg IBW/hr for 16 weeks (included only participants who were compliant in the first 2 weeks)	Placebo n=58 Participants Part 1 Blinded Treatment - Placebo dose setting 75 mcg/kg IBW/hr for 16 weeks (included only participants who were compliant in the first 2 weeks)
Time (in Days) to First Clinical Worsening Event (TTCW)	22 Days Standard Deviation 42.3	19 Days Standard Deviation 32.8

SECONDARY outcome

Timeframe: From Randomization to Week 18 (End of blinded treatment period)

Population: ITT analysis population

WHO FC (where Class I is defined as "No limitations in daily physical activities. No symptoms of dyspnea and with routine exertion" and Class IV is defined as "Inability to perform even minimal activities. Signs and symptoms of right heart failure may be present. Dyspnea present at rest") for PAH was taken at randomization (Week 0) for all participants and was assessed after blinded treatment (Week 18). The number of participants that had an improvement (lower functional class) as compared to baseline were measured.

Outcome measures

Measure	Inhaled Nitric Oxide 75mcg/KgIBW/Hr n=52 Participants Part 1: Blinded Treatment - 75 mcg/Kg IBW/hr for 16 weeks (included only participants who were compliant in the first 2 weeks)	Placebo n=58 Participants Part 1 Blinded Treatment - Placebo dose setting 75 mcg/kg IBW/hr for 16 weeks (included only participants who were compliant in the first 2 weeks)
Number of Participants With an Improvement in World Health Organization Functional Class (WHO FC) Baseline (Randomization) to End of Treatment Period (Week 18)	2 Participants	1 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: From Screening (28 days prior to baseline/randomization) to end of Blinded Treatment Period (Week 18)

Population: ITT analysis population who had NT Pro BNP levels at Screening and at the end of blinded treatment period (Week 18)

Plasma NT-proBNP concentration is a useful biomarker for the severity of PAH as it is associated with changes in right heart morphology and function. NT-proBNP sample collection occurred at Screening visit (prior to starting study drug at Randomization) and after 16 weeks of blinded treatment therapy (Week 18). The change in NT-proBNP between Screening (28 days prior to baseline/randomization) and the end of blinded treatment period (Week 18) is reported.

Outcome measures

Measure	Inhaled Nitric Oxide 75mcg/KgIBW/Hr n=34 Participants Part 1: Blinded Treatment - 75 mcg/Kg IBW/hr for 16 weeks (included only participants who were compliant in the first 2 weeks)	Placebo n=30 Participants Part 1 Blinded Treatment - Placebo dose setting 75 mcg/kg IBW/hr for 16 weeks (included only participants who were compliant in the first 2 weeks)
Change in Plasma N-Terminal Pro-brain Natriuretic Peptide (NT-proBNP) From Screening to End of Treatment Period (Week 18)	117.8 pg/mL Standard Error 22.8	207.9 pg/mL Standard Error 24.8

OTHER_PRE_SPECIFIED outcome

Timeframe: From Randomization to Week 18 (End of blinded treatment period)

Population: ITT analysis population

The Borg dyspneas score is a self-rating scale to evaluate the severity of dyspnea (from 0 "no shortness of breath at all" to 10 "very, very severe / maximal") shortness of breath, where high score on the scale signifies a worse score. The self assessment was collected from each participant immediately after each 6-minute walk test throughout the blinded treatment period. The change in Borg dyspnea Score at the end of the blinded treatment period (Week 18) compared to baseline (randomization) (Week 0) is reported.

Outcome measures

Measure	Inhaled Nitric Oxide 75mcg/KgIBW/Hr n=52 Participants Part 1: Blinded Treatment - 75 mcg/Kg IBW/hr for 16 weeks (included only participants who were compliant in the first 2 weeks)	Placebo n=58 Participants Part 1 Blinded Treatment - Placebo dose setting 75 mcg/kg IBW/hr for 16 weeks (included only participants who were compliant in the first 2 weeks)
Change in Borg Dyspnea Scale Immediately Following 6-minute Walk Test (6MWT) From Baseline (Randomization) to End of Treatment Period (Week 18)	-0.47 Scores on a Scale Standard Error 0.23	-0.23 Scores on a Scale Standard Error 0.23

OTHER_PRE_SPECIFIED outcome

Timeframe: From Randomization to Week 18 (End of blinded treatment period)

Population: ITT analysis population

Unsatisfactory Clinical Response was defined as the number of participants with WHO Functional Class III (defined as moderate dyspnea with routine activities and activities of daily living. No symptoms at rest.) or Class IV (defined as inability to perform even minimal activities. Signs and symptoms of right heart failure may be present. Dyspnea present at rest) with no improvement in 6-minute walk distance (6MWD) from baseline to end of blinded treatment period (Week 18).

Outcome measures

Measure	Inhaled Nitric Oxide 75mcg/KgIBW/Hr n=52 Participants Part 1: Blinded Treatment - 75 mcg/Kg IBW/hr for 16 weeks (included only participants who were compliant in the first 2 weeks)	Placebo n=58 Participants Part 1 Blinded Treatment - Placebo dose setting 75 mcg/kg IBW/hr for 16 weeks (included only participants who were compliant in the first 2 weeks)
Number of Participants With an Unsatisfactory Clinical Response From Baseline (Randomization) to End of Treatment Period (Week 18)	32 Participants	35 Participants

Adverse Events

Part 1:Blinded Tx (2 Week Run In & 16 Weeks) Inhaled Nitric Oxide and Part 2 - Inhaled Nitric Oxide

Serious events: 13 serious events

Other events: 22 other events

Deaths: 2 deaths

Part 1:Blinded Tx (2 Week Run In & 16 Weeks) Placebo and Part 2 - Placebo

Serious events: 10 serious events

Other events: 25 other events

Deaths: 3 deaths

Serious adverse events

Measure	Part 1:Blinded Tx (2 Week Run In & 16 Weeks) Inhaled Nitric Oxide and Part 2 - Inhaled Nitric Oxide n=74 participants at risk Part 1 Randomized to Inhaled Nitric Oxide that was actually treated at dose of 15mcg/Kg IBW/hr for Run In Period of first 2 weeks (Week 0 and 1). Followed by Inhaled Nitric Oxide at dose of 75 mcg/kg IBW/hr for 16 weeks (Week 2 to Week 18) Part 2 Following by open label treatment with Inhaled Nitric Oxide	Part 1:Blinded Tx (2 Week Run In & 16 Weeks) Placebo and Part 2 - Placebo n=78 participants at risk Randomized to Placebo that was actually treated at at dose of 15mcg/Kg IBW/hr for Run In Period of first 2 weeks (Week 0 and 1). Followed by placebo at dose of 75 mcg/kg IBW/hr for 16 weeks (Week 2 to Week 18) Part 2 Following by open label treatment with Inhaled Nitric Oxide
Blood and lymphatic system disorders Anaemia	1.4% 1/74 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.	0.00% 0/78 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.
Cardiac disorders Atrial fibrillation	1.4% 1/74 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.	0.00% 0/78 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.
Cardiac disorders Cardiac disorder	1.4% 1/74 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.	0.00% 0/78 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.
Cardiac disorders Cardiac failure	1.4% 1/74 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.	0.00% 0/78 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.
Cardiac disorders Cardiac failure chronic	0.00% 0/74 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.	1.3% 1/78 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.
Cardiac disorders Presyncope	1.4% 1/74 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.	0.00% 0/78 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.
Cardiac disorders Supraventricular tachycardia	1.4% 1/74 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.	0.00% 0/78 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.
Congenital, familial and genetic disorders Atrial septal defect	1.4% 1/74 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.	0.00% 0/78 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.
Gastrointestinal disorders Diarrhoea	1.4% 1/74 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.	0.00% 0/78 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.
Gastrointestinal disorders Gastritis	1.4% 1/74 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.	0.00% 0/78 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.
Gastrointestinal disorders Gastroenteritis viral	0.00% 0/74 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.	1.3% 1/78 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.
Gastrointestinal disorders Gastrointestinal haemorrhage	1.4% 1/74 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.	0.00% 0/78 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.
Gastrointestinal disorders Vomiting	1.4% 1/74 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.	0.00% 0/78 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.
General disorders General physical health deterioration	0.00% 0/74 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.	1.3% 1/78 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.
Infections and infestations Pneumonia	1.4% 1/74 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.	1.3% 1/78 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.
Infections and infestations Respiratory tract infection	0.00% 0/74 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.	2.6% 2/78 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.
Infections and infestations Clostridium difficile infection	1.4% 1/74 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.	0.00% 0/78 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.
Infections and infestations Device related infection	1.4% 1/74 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.	0.00% 0/78 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.
Infections and infestations Influenza	1.4% 1/74 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.	0.00% 0/78 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.
Infections and infestations Upper respiratory tract infection	0.00% 0/74 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.	1.3% 1/78 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.
Metabolism and nutrition disorders Dehydration	0.00% 0/74 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.	1.3% 1/78 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.
Metabolism and nutrition disorders Hypokalaemia	1.4% 1/74 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.	0.00% 0/78 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.
Musculoskeletal and connective tissue disorders Tibia fracture	0.00% 0/74 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.	1.3% 1/78 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.00% 0/74 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.	2.6% 2/78 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.
Respiratory, thoracic and mediastinal disorders Pneumonia	1.4% 1/74 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.	1.3% 1/78 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.
Respiratory, thoracic and mediastinal disorders Pulmonary arterial hypertension	1.4% 1/74 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.	1.3% 1/78 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.
Respiratory, thoracic and mediastinal disorders Pulmonary hypertension	1.4% 1/74 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.	0.00% 0/78 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.
Respiratory, thoracic and mediastinal disorders Respiratory failure	1.4% 1/74 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.	0.00% 0/78 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.
Surgical and medical procedures Lung transplant	1.4% 1/74 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.	0.00% 0/78 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.
Vascular disorders Pulmonary embolism	1.4% 1/74 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.	0.00% 0/78 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.

Other adverse events

Measure	Part 1:Blinded Tx (2 Week Run In & 16 Weeks) Inhaled Nitric Oxide and Part 2 - Inhaled Nitric Oxide n=74 participants at risk Part 1 Randomized to Inhaled Nitric Oxide that was actually treated at dose of 15mcg/Kg IBW/hr for Run In Period of first 2 weeks (Week 0 and 1). Followed by Inhaled Nitric Oxide at dose of 75 mcg/kg IBW/hr for 16 weeks (Week 2 to Week 18) Part 2 Following by open label treatment with Inhaled Nitric Oxide	Part 1:Blinded Tx (2 Week Run In & 16 Weeks) Placebo and Part 2 - Placebo n=78 participants at risk Randomized to Placebo that was actually treated at at dose of 15mcg/Kg IBW/hr for Run In Period of first 2 weeks (Week 0 and 1). Followed by placebo at dose of 75 mcg/kg IBW/hr for 16 weeks (Week 2 to Week 18) Part 2 Following by open label treatment with Inhaled Nitric Oxide
Blood and lymphatic system disorders Anaemia	1.4% 1/74 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.	0.00% 0/78 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.
Blood and lymphatic system disorders Lymphadenopathy	1.4% 1/74 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.	0.00% 0/78 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.
Blood and lymphatic system disorders Polycythaemia	1.4% 1/74 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.	0.00% 0/78 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.
Cardiac disorders Right ventricular failure	4.1% 3/74 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.	5.1% 4/78 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.
Cardiac disorders Cardiac failure	0.00% 0/74 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.	2.6% 2/78 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.
Cardiac disorders Oedema peripheral	2.7% 2/74 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.	1.3% 1/78 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.
Cardiac disorders Presyncope	0.00% 0/74 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.	1.3% 1/78 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.
Cardiac disorders Acute coronary syndrome	0.00% 0/74 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.	1.3% 1/78 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.
Cardiac disorders Acute right ventricular failure	0.00% 0/74 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.	1.3% 1/78 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.
Cardiac disorders Angina pectoris	0.00% 0/74 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.	1.3% 1/78 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.
Cardiac disorders Chest pain	1.4% 1/74 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.	0.00% 0/78 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.
Cardiac disorders Fluid overload	1.4% 1/74 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.	0.00% 0/78 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.
Cardiac disorders Palpitations	1.4% 1/74 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.	0.00% 0/78 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.
Cardiac disorders Sinoatrial block	1.4% 1/74 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.	0.00% 0/78 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.
Cardiac disorders Tachycardia	0.00% 0/74 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.	1.3% 1/78 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.
Ear and labyrinth disorders Hypoacusis	1.4% 1/74 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.	0.00% 0/78 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.
Ear and labyrinth disorders Vertigo	0.00% 0/74 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.	1.3% 1/78 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.
Ear and labyrinth disorders Vertigo positional	1.4% 1/74 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.	0.00% 0/78 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.
Eye disorders Cataract	1.4% 1/74 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.	0.00% 0/78 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.
Eye disorders Diabetic retinopathy	0.00% 0/74 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.	1.3% 1/78 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.
Eye disorders Dry eye	1.4% 1/74 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.	0.00% 0/78 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.
Eye disorders Eye infection	0.00% 0/74 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.	1.3% 1/78 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.
Eye disorders Periorbital oedema	0.00% 0/74 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.	1.3% 1/78 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.
Gastrointestinal disorders Diarrhoea	4.1% 3/74 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.	1.3% 1/78 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.
Gastrointestinal disorders Vomiting	1.4% 1/74 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.	1.3% 1/78 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.
Gastrointestinal disorders Gastritis	1.4% 1/74 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.	0.00% 0/78 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.
Gastrointestinal disorders Nausea	1.4% 1/74 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.	1.3% 1/78 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.
Gastrointestinal disorders Abdominal pain upper	0.00% 0/74 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.	1.3% 1/78 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.
Gastrointestinal disorders Dysphagia	0.00% 0/74 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.	1.3% 1/78 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.
Gastrointestinal disorders Gastrointestinal disorder	1.4% 1/74 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.	0.00% 0/78 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.
General disorders Fatigue	4.1% 3/74 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.	1.3% 1/78 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.
General disorders Asthenia	1.4% 1/74 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.	1.3% 1/78 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.
General disorders Oedema peripheral	1.4% 1/74 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.	1.3% 1/78 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.
General disorders Secretion discharge	2.7% 2/74 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.	0.00% 0/78 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.
General disorders Chest pain	0.00% 0/74 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.	1.3% 1/78 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.
General disorders Drug ineffective	0.00% 0/74 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.	1.3% 1/78 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.
General disorders General physical health deterioration	0.00% 0/74 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.	1.3% 1/78 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.
General disorders Influenza like illness	1.4% 1/74 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.	0.00% 0/78 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.
General disorders Oedema	1.4% 1/74 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.	0.00% 0/78 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.
General disorders Pain	1.4% 1/74 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.	0.00% 0/78 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.
General disorders Pyrexia	0.00% 0/74 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.	1.3% 1/78 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.
Hepatobiliary disorders Cholestasis	1.4% 1/74 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.	0.00% 0/78 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.
Hepatobiliary disorders Hepatitis toxic	1.4% 1/74 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.	0.00% 0/78 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.
Immune system disorders Hypersensitivity	1.4% 1/74 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.	0.00% 0/78 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.
Infections and infestations Upper respiratory tract infection	4.1% 3/74 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.	6.4% 5/78 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.
Infections and infestations Influenza	0.00% 0/74 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.	2.6% 2/78 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.
Infections and infestations Respiratory tract infection	0.00% 0/74 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.	2.6% 2/78 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.
Infections and infestations Sinusitis	2.7% 2/74 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.	1.3% 1/78 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.
Infections and infestations Urinary tract infection	2.7% 2/74 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.	1.3% 1/78 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.
Infections and infestations Cellulitis	2.7% 2/74 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.	0.00% 0/78 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.
Infections and infestations Clostridium difficile colitis	2.7% 2/74 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.	0.00% 0/78 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.
Infections and infestations Conjunctivitis	1.4% 1/74 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.	1.3% 1/78 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.
Infections and infestations Pharyngitis	1.4% 1/74 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.	1.3% 1/78 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.
Infections and infestations Viral upper respiratory tract infection	1.4% 1/74 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.	1.3% 1/78 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.
Infections and infestations Bronchitis	1.4% 1/74 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.	0.00% 0/78 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.
Infections and infestations Ear infection	0.00% 0/74 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.	1.3% 1/78 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.
Infections and infestations Erysipelas	0.00% 0/74 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.	1.3% 1/78 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.
Infections and infestations Eye infection	0.00% 0/74 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.	1.3% 1/78 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.
Infections and infestations Laryngitis	1.4% 1/74 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.	0.00% 0/78 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.
Infections and infestations Lower respiratory tract infection	0.00% 0/74 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.	1.3% 1/78 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.
Infections and infestations Oral candidiasis	1.4% 1/74 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.	0.00% 0/78 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.
Infections and infestations Rhinitis	1.4% 1/74 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.	0.00% 0/78 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.
Infections and infestations Sinusitis bacterial	1.4% 1/74 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.	0.00% 0/78 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.
Infections and infestations Urinary tract infection bacterial	1.4% 1/74 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.	0.00% 0/78 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.
Injury, poisoning and procedural complications Fall	0.00% 0/74 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.	1.3% 1/78 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.
Investigations Blood creatinine increased	0.00% 0/74 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.	2.6% 2/78 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.
Investigations Aspartate aminotransferase increased	0.00% 0/74 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.	1.3% 1/78 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.
Investigations Blood bilirubin increased	0.00% 0/74 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.	1.3% 1/78 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.
Investigations Blood glucose increased	0.00% 0/74 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.	1.3% 1/78 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.
Investigations Blood thyroid stimulating hormone increased	1.4% 1/74 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.	0.00% 0/78 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.
Investigations Gamma-glutamyltransferase increased	0.00% 0/74 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.	1.3% 1/78 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.
Investigations International normalised ratio increased	0.00% 0/74 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.	1.3% 1/78 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.
Investigations Monocyte count increased	0.00% 0/74 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.	1.3% 1/78 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.
Investigations N-terminal prohormone brain natriuretic peptide increased	0.00% 0/74 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.	1.3% 1/78 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.
Investigations Platelet count decreased	0.00% 0/74 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.	1.3% 1/78 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.
Investigations Pulmonary function test decreased	0.00% 0/74 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.	1.3% 1/78 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.
Investigations Right ventricular ejection fraction decreased	1.4% 1/74 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.	0.00% 0/78 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.
Investigations Serum ferritin decreased	1.4% 1/74 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.	0.00% 0/78 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.
Investigations Weight increased	0.00% 0/74 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.	1.3% 1/78 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.
Metabolism and nutrition disorders Dehydration	1.4% 1/74 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.	0.00% 0/78 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.
Metabolism and nutrition disorders Hypokalaemia	0.00% 0/74 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.	1.3% 1/78 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.
Metabolism and nutrition disorders Decreased appetite	0.00% 0/74 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.	1.3% 1/78 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.
Metabolism and nutrition disorders Diabetes mellitus	1.4% 1/74 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.	0.00% 0/78 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.
Metabolism and nutrition disorders Fluid overload	1.4% 1/74 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.	0.00% 0/78 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.
Metabolism and nutrition disorders Food intolerance	0.00% 0/74 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.	1.3% 1/78 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.
Metabolism and nutrition disorders Hyperuricaemia	1.4% 1/74 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.	0.00% 0/78 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.
Metabolism and nutrition disorders Hypoglycaemia	0.00% 0/74 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.	1.3% 1/78 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.
Musculoskeletal and connective tissue disorders Arthralgia	1.4% 1/74 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.	2.6% 2/78 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.
Musculoskeletal and connective tissue disorders Back pain	0.00% 0/74 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.	1.3% 1/78 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.
Musculoskeletal and connective tissue disorders Pain in extremity	1.4% 1/74 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.	1.3% 1/78 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.
Musculoskeletal and connective tissue disorders Muscle spasms	1.4% 1/74 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.	0.00% 0/78 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.
Musculoskeletal and connective tissue disorders Myalgia	0.00% 0/74 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.	1.3% 1/78 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.
Musculoskeletal and connective tissue disorders Osteoarthritis	0.00% 0/74 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.	1.3% 1/78 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.
Musculoskeletal and connective tissue disorders Scleroderma	1.4% 1/74 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.	0.00% 0/78 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.
Musculoskeletal and connective tissue disorders Wrist fracture	1.4% 1/74 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.	0.00% 0/78 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.
Nervous system disorders Headache	4.1% 3/74 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.	2.6% 2/78 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.
Nervous system disorders Dizziness	2.7% 2/74 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.	0.00% 0/78 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.
Nervous system disorders Amnesia	1.4% 1/74 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.	0.00% 0/78 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.
Nervous system disorders Neuropathy peripheral	0.00% 0/74 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.	1.3% 1/78 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.
Nervous system disorders Paraesthesia	0.00% 0/74 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.	1.3% 1/78 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.
Nervous system disorders Syncope	0.00% 0/74 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.	1.3% 1/78 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.
Product Issues Device failure	1.4% 1/74 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.	0.00% 0/78 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.
Psychiatric disorders Anxiety	1.4% 1/74 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.	1.3% 1/78 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.
Psychiatric disorders Depression	0.00% 0/74 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.	1.3% 1/78 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.
Psychiatric disorders Insomnia	1.4% 1/74 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.	0.00% 0/78 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.
Psychiatric disorders Sleep disorder	0.00% 0/74 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.	1.3% 1/78 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.
Renal and urinary disorders Acute kidney injury	0.00% 0/74 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.	1.3% 1/78 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.
Renal and urinary disorders Chronic kidney disease	1.4% 1/74 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.	0.00% 0/78 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.
Respiratory, thoracic and mediastinal disorders Dyspnoea	6.8% 5/74 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.	6.4% 5/78 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.
Respiratory, thoracic and mediastinal disorders Epistaxis	6.8% 5/74 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.	7.7% 6/78 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.
Respiratory, thoracic and mediastinal disorders Cough	2.7% 2/74 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.	6.4% 5/78 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.
Respiratory, thoracic and mediastinal disorders Pulmonary arterial hypertension	0.00% 0/74 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.	1.3% 1/78 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.
Respiratory, thoracic and mediastinal disorders Bronchitis	1.4% 1/74 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.	1.3% 1/78 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.
Respiratory, thoracic and mediastinal disorders Hypoxia	2.7% 2/74 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.	0.00% 0/78 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.
Respiratory, thoracic and mediastinal disorders Nasal congestion	1.4% 1/74 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.	1.3% 1/78 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.
Respiratory, thoracic and mediastinal disorders Respiratory failure	0.00% 0/74 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.	1.3% 1/78 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.
Respiratory, thoracic and mediastinal disorders Chest discomfort	0.00% 0/74 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.	1.3% 1/78 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.
Respiratory, thoracic and mediastinal disorders Hyperventilation	1.4% 1/74 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.	0.00% 0/78 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.
Respiratory, thoracic and mediastinal disorders Nasal discomfort	1.4% 1/74 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.	0.00% 0/78 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.
Respiratory, thoracic and mediastinal disorders Rhinorrhoea	0.00% 0/74 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.	1.3% 1/78 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.
Respiratory, thoracic and mediastinal disorders Sleep apnoea syndrome	0.00% 0/74 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.	1.3% 1/78 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.
Respiratory, thoracic and mediastinal disorders Sneezing	0.00% 0/74 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.	1.3% 1/78 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.
Skin and subcutaneous tissue disorders Eczema	2.7% 2/74 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.	0.00% 0/78 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.
Skin and subcutaneous tissue disorders Pruritus	2.7% 2/74 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.	0.00% 0/78 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.
Skin and subcutaneous tissue disorders Rash	1.4% 1/74 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.	0.00% 0/78 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.
Skin and subcutaneous tissue disorders Rosacea	1.4% 1/74 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.	0.00% 0/78 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.
Skin and subcutaneous tissue disorders Scab	1.4% 1/74 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.	0.00% 0/78 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.
Surgical and medical procedures Cataract operation	0.00% 0/74 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.	1.3% 1/78 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.
Vascular disorders Hypotension	4.1% 3/74 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.	1.3% 1/78 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.
Vascular disorders Ecchymosis	1.4% 1/74 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.	0.00% 0/78 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.
Vascular disorders Haematoma	0.00% 0/74 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.	1.3% 1/78 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.
Vascular disorders Haemodynamic instability	0.00% 0/74 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.	1.3% 1/78 • Adverse events data collected from all participants that were enrolled in the study and who actually received study treatment in Part 1 (up to 18 weeks) and in Part 2 (up to 30 weeks). Note that adverse events are presented together for Parts 1 (Run-in, Treatment) and 2 (Open label). Adverse events were not monitored/assessed separately for the Run-in (2 week), Blinded Treatment (16 week) period (Part 1) and Open Label (Part 2) periods. The Number of Participants At-Risk includes participants from both Parts 1 and 2.

Additional Information

Bobae Kim

Bellerophon Therapeutics Inc

Phone: (917) 675-2254

Email: bobae.kim@bellerophon.com

Results disclosure agreements

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