Primary endpoint was endurance time during constant work rate ergometry to symptom limitation at 75% of maximal work capacity after 6 weeks of treatment. Mixed effects model on log10 transformation data. Adjusted means are back transformed to report as geometric means. Standard errors (SEs) are calculated using the delta method.

Full analysis set (FAS). FAS is defined as all patients that were randomised, received treatment and had baseline data and any evaluable post-dose data for the primary endpoint.

Isotime is defined as the endurance time of the constant work rate exercise test of shortest duration from Baseline visit, and Week 6 of each of the three treatment periods.

Full analysis set (FAS). FAS is defined as all patients that were randomised, received treatment and had baseline data and any evaluable post-dose data for the primary endpoint. Only patients who have baseline and at least one post-baseline measurement available were included in the analysis.

Isotime is defined as the endurance time of the constant work rate exercise test of shortest duration from Baseline visit, and Week 6 of each of the three treatment periods.

Borg scale rates discomfort with breathing at rest, during exercise and at end-exercise on a scale from 0=Nothing at all to 10=Maximal discomfort.

Full analysis set (FAS). FAS is defined as all patients that were randomised, received treatment and had baseline data and any evaluable post-dose data for the primary endpoint.

Full analysis set (FAS). FAS is defined as all patients that were randomised, received treatment and had baseline data and any evaluable post-dose data for the primary endpoint. Only patients who have baseline and at least one post-baseline measurement available were included in the analysis.

Full analysis set (FAS). FAS is defined as all patients that were randomised, received treatment and had baseline data and any evaluable post-dose data for the primary endpoint. Only patients who have baseline and at least one post-baseline measurement available were included in the analysis.

Borg scale rates discomfort with breathing at rest, during exercise and at end-exercise on a scale from 0=Nothing at all to 10=Maximal discomfort.

Full analysis set (FAS). FAS is defined as all patients that were randomised, received treatment and had baseline data and any evaluable post-dose data for the primary endpoint. Only patients who have baseline and at least one post-baseline measurement available were included in the analysis.

Borg scale rates discomfort with breathing at rest, during exercise and at end-exercise on a scale from 0=Nothing at all to 10=Maximal discomfort.

Full analysis set (FAS). FAS is defined as all patients that were randomised, received treatment and had baseline data and any evaluable post-dose data for the primary endpoint.

Full analysis set (FAS). FAS is defined as all patients that were randomised, received treatment and had baseline data and any evaluable post-dose data for the primary endpoint. Only patients who have baseline and at least one post-baseline measurement available were included in the analysis.

Full analysis set (FAS). FAS is defined as all patients that were randomised, received treatment and had baseline data and any evaluable post-dose data for the primary endpoint. Only patients who have baseline and at least one post-baseline measurement available were included in the analysis.

Measured using body plethysmography

Full analysis set (FAS). FAS is defined as all patients that were randomised, received treatment and had baseline data and any evaluable post-dose data for the primary endpoint. Only patients who have baseline and at least one post-baseline measurement available were included in the analysis.

Measured using body plethysmography

Full analysis set (FAS). FAS is defined as all patients that were randomised, received treatment and had baseline data and any evaluable post-dose data for the primary endpoint. Only patients who have baseline and at least one post-baseline measurement available were included in the analysis.

Measured using body plethysmography

Full analysis set (FAS). FAS is defined as all patients that were randomised, received treatment and had baseline data and any evaluable post-dose data for the primary endpoint. Only patients who have baseline and at least one post-baseline measurement available were included in the analysis.

Full analysis set (FAS). FAS is defined as all patients that were randomised, received treatment and had baseline data and any evaluable post-dose data for the primary endpoint. Only patients who have baseline and at least one post-baseline measurement available were included in the analysis.

Full analysis set (FAS). FAS is defined as all patients that were randomised, received treatment and had baseline data and any evaluable post-dose data for the primary endpoint. Only patients who have baseline and at least one post-baseline measurement available were included in the analysis.

Full analysis set (FAS). FAS is defined as all patients that were randomised, received treatment and had baseline data and any evaluable post-dose data for the primary endpoint. Only patients who have baseline and at least one post-baseline measurement available were included in the analysis.

Full analysis set (FAS). FAS is defined as all patients that were randomised, received treatment and had baseline data and any evaluable post-dose data for the primary endpoint. Only patients who have baseline and at least one post-baseline measurement available were included in the analysis.

Full analysis set (FAS). FAS is defined as all patients that were randomised, received treatment and had baseline data and any evaluable post-dose data for the primary endpoint. Only patients who have baseline and at least one post-baseline measurement available were included in the analysis.

Full analysis set (FAS). FAS is defined as all patients that were randomised, received treatment and had baseline data and any evaluable post-dose data for the primary endpoint. Only patients who have baseline and at least one post-baseline measurement available were included in the analysis.

Full analysis set (FAS). FAS is defined as all patients that were randomised, received treatment and had baseline data and any evaluable post-dose data for the primary endpoint. Only patients who have baseline and at least one post-baseline measurement available were included in the analysis.

Change from Baseline to Day 43 in Blood Pressure with spirometry. Baseline is defined as mean of pre-treatment values at a given time point.

Treated set. Statistics only include patients with both a baseline and a post dose value.

Change from Baseline to Day 43 in Pulse rate with spirometry. Baseline is defined as mean of pre-treatment values at a given time point.

Treated set. Statistics only include patients with both a baseline and a post dose value.

Number of Patients with notable changes in heart rate (HR). Notable HR increase defined as >=25% increase and on-treatment HR > 100 bpm; Notable HR decrease defined as >=25% decrease and on-treatment HR < 50 bpm.

Treated set.

Number of Patients with notable increase in PR intervals. Notable PR interval increase defined as >=25% increase and on-treatment PR interval > 200 ms.

Treated set.

Number of Patients with notable increase in QRS intervals. Notable QRS interval increase defined as >=10% increase and on-treatment QRS interval > 110 ms.

Treated set.