Trial Outcomes & Findings for A Research Study to Show the Effect of Aprocitentan in the Treatment of Difficult to Control (Resistant) High Blood Pressure (Hypertension) and Find Out More About Its Safety (NCT NCT03541174)

NCT ID: NCT03541174

Last Updated: 2023-03-21

Results Overview

Changes from baseline to Week 4 in mean trough SiSBP were analyzed using a mixed model. Participants had their blood pressure (BP) measured at the study site using the automated oscillometric sphygmomanometer (Microlife WatchBP® Office) which was provided to each site. BP was to be measured at trough (before taking the study treatment and SBAT). The BP assessment, participant preparation (e.g., arm selection, arm position, cuff size) was standardized and followed the American Heart Association guidelines / Canadian Education Program on Hypertension. The participant was resting undisturbed, alone (unattended) in a quiet place for 5 minutes at each visit. BP was measured at each visit with the same device, which recorded five sitting blood pressure readings (one per minute, the first value was excluded from the average). A negative change indicates a decrease in SiSBP from baseline.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 730 participants
• Primary outcome timeframe: Pre-dose Day 1 (Part 1 double-blind randomized baseline) up to Week 4 (End of double-blind randomized part 1)
• Results posted on: 2023-03-21

Participant Flow

The study was done from 18 June 2018 to 25 April 2022.

730 participants are considered to be enrolled in the study and were randomized to study treatment.

Participant milestones

Measure	Aprocitentan 12.5 mg in Part 1 (Double-blind) Participants were randomized and received aprocitentan 12.5 mg, orally, once daily in the morning for 4 weeks.	Aprocitentan 25 mg in Part 1 (Double-blind) Participants were randomized and received aprocitentan 25 mg, orally, once daily in the morning for 4 weeks.	Placebo in Part 1 (Double-blind) Participants were randomized and received placebo (matching aprocitentan), orally, once daily in the morning for 4 weeks.	Aprocitentan 25 mg in Part 2 (Single-blind) Participants that completed the double-blind part received aprocitentan 25 mg, orally, once daily in the morning for 32 weeks.	Aprocitentan 25 mg in Part 3 (Double-blind Withdrawal) After the 32-week single-blind, single-arm aprocitentan 25 mg (Part 2), participants were re-randomized and received aprocitentan 25 mg, orally, once daily in the morning for 12 weeks.	Placebo in Part 3 (Double-blind Withdrawal) After the 32-week single-blind, single-arm aprocitentan 25 mg (Part 2), participants were re-randomized and received placebo (matching aprocitentan), orally, once daily in the morning for 12 weeks.
Part 1 Double-Blind STARTED	243	243	244	0	0	0
Part 1 Double-Blind Safety Set	243	245	242	0	0	0
Part 1 Double-Blind COMPLETED	232	234	238	0	0	0
Part 1 Double-Blind NOT COMPLETED	11	9	6	0	0	0
Part 2 Single-Blind STARTED	0	0	0	704	0	0
Part 2 Single-Blind COMPLETED	0	0	0	613	0	0
Part 2 Single-Blind NOT COMPLETED	0	0	0	91	0	0
Part 3 Double-Blind Withdrawal STARTED	0	0	0	0	307	307
Part 3 Double-Blind Withdrawal Safety Set	0	0	0	0	310	303
Part 3 Double-Blind Withdrawal COMPLETED	0	0	0	0	288	289
Part 3 Double-Blind Withdrawal NOT COMPLETED	0	0	0	0	19	18

Reasons for withdrawal

Measure	Aprocitentan 12.5 mg in Part 1 (Double-blind) Participants were randomized and received aprocitentan 12.5 mg, orally, once daily in the morning for 4 weeks.	Aprocitentan 25 mg in Part 1 (Double-blind) Participants were randomized and received aprocitentan 25 mg, orally, once daily in the morning for 4 weeks.	Placebo in Part 1 (Double-blind) Participants were randomized and received placebo (matching aprocitentan), orally, once daily in the morning for 4 weeks.	Aprocitentan 25 mg in Part 2 (Single-blind) Participants that completed the double-blind part received aprocitentan 25 mg, orally, once daily in the morning for 32 weeks.	Aprocitentan 25 mg in Part 3 (Double-blind Withdrawal) After the 32-week single-blind, single-arm aprocitentan 25 mg (Part 2), participants were re-randomized and received aprocitentan 25 mg, orally, once daily in the morning for 12 weeks.	Placebo in Part 3 (Double-blind Withdrawal) After the 32-week single-blind, single-arm aprocitentan 25 mg (Part 2), participants were re-randomized and received placebo (matching aprocitentan), orally, once daily in the morning for 12 weeks.
Part 1 Double-Blind Adverse Event	6	5	2	0	0	0
Part 1 Double-Blind Withdrawal by Subject	2	2	1	0	0	0
Part 1 Double-Blind Other reasons	3	2	3	0	0	0
Part 2 Single-Blind Adverse Event	0	0	0	25	0	0
Part 2 Single-Blind Lack of Efficacy	0	0	0	1	0	0
Part 2 Single-Blind Withdrawal by Subject	0	0	0	19	0	0
Part 2 Single-Blind Lost to Follow-up	0	0	0	8	0	0
Part 2 Single-Blind Death	0	0	0	5	0	0
Part 2 Single-Blind Pregnancy	0	0	0	1	0	0
Part 2 Single-Blind Other reasons	0	0	0	32	0	0
Part 3 Double-Blind Withdrawal Adverse Event	0	0	0	0	8	7
Part 3 Double-Blind Withdrawal Withdrawal by Subject	0	0	0	0	1	4
Part 3 Double-Blind Withdrawal Lost to Follow-up	0	0	0	0	0	1
Part 3 Double-Blind Withdrawal Other reasons	0	0	0	0	9	6
Part 3 Double-Blind Withdrawal Re-randomized in part 3, however no drug dispensed	0	0	0	0	1	0

Baseline Characteristics

A Research Study to Show the Effect of Aprocitentan in the Treatment of Difficult to Control (Resistant) High Blood Pressure (Hypertension) and Find Out More About Its Safety

Baseline characteristics by cohort

Measure	Aprocitentan 12.5 mg in Part 1 (Double-blind) n=243 Participants Participants randomized to aprocitentan 12.5 mg, orally, once daily in the morning for 4 weeks.	Aprocitentan 25 mg in Part 1 (Double-blind) n=243 Participants Participants randomized to aprocitentan 25 mg, orally, once daily in the morning for 4 weeks.	Placebo in Part 1 (Double-blind) n=244 Participants Participants randomized to placebo (matching aprocitentan), orally, once daily in the morning for 4 weeks.	Total n=730 Participants Total of all reporting groups
Age, Continuous	61.2 years STANDARD_DEVIATION 10.3 • n=5 Participants	61.7 years STANDARD_DEVIATION 10.4 • n=7 Participants	62.2 years STANDARD_DEVIATION 11.2 • n=5 Participants	61.7 years STANDARD_DEVIATION 10.6 • n=4 Participants
Sex: Female, Male Female	99 Participants n=5 Participants	98 Participants n=7 Participants	99 Participants n=5 Participants	296 Participants n=4 Participants
Sex: Female, Male Male	144 Participants n=5 Participants	145 Participants n=7 Participants	145 Participants n=5 Participants	434 Participants n=4 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	28 Participants n=5 Participants	22 Participants n=7 Participants	23 Participants n=5 Participants	73 Participants n=4 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	213 Participants n=5 Participants	219 Participants n=7 Participants	218 Participants n=5 Participants	650 Participants n=4 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	2 Participants n=5 Participants	2 Participants n=7 Participants	3 Participants n=5 Participants	7 Participants n=4 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Asian	11 Participants n=5 Participants	14 Participants n=7 Participants	13 Participants n=5 Participants	38 Participants n=4 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	1 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants
Race (NIH/OMB) Black or African American	28 Participants n=5 Participants	28 Participants n=7 Participants	26 Participants n=5 Participants	82 Participants n=4 Participants
Race (NIH/OMB) White	203 Participants n=5 Participants	200 Participants n=7 Participants	202 Participants n=5 Participants	605 Participants n=4 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants	4 Participants n=4 Participants
Region of Enrollment Australia	8 participants n=5 Participants	8 participants n=7 Participants	7 participants n=5 Participants	23 participants n=4 Participants
Region of Enrollment Belgium	1 participants n=5 Participants	3 participants n=7 Participants	4 participants n=5 Participants	8 participants n=4 Participants
Region of Enrollment Canada	8 participants n=5 Participants	7 participants n=7 Participants	6 participants n=5 Participants	21 participants n=4 Participants
Region of Enrollment China	6 participants n=5 Participants	11 participants n=7 Participants	10 participants n=5 Participants	27 participants n=4 Participants
Region of Enrollment Czechia	10 participants n=5 Participants	3 participants n=7 Participants	15 participants n=5 Participants	28 participants n=4 Participants
Region of Enrollment Finland	9 participants n=5 Participants	5 participants n=7 Participants	2 participants n=5 Participants	16 participants n=4 Participants
Region of Enrollment France	0 participants n=5 Participants	4 participants n=7 Participants	3 participants n=5 Participants	7 participants n=4 Participants
Region of Enrollment Germany	3 participants n=5 Participants	6 participants n=7 Participants	9 participants n=5 Participants	18 participants n=4 Participants
Region of Enrollment Greece	5 participants n=5 Participants	1 participants n=7 Participants	2 participants n=5 Participants	8 participants n=4 Participants
Region of Enrollment Hungary	1 participants n=5 Participants	4 participants n=7 Participants	1 participants n=5 Participants	6 participants n=4 Participants
Region of Enrollment Israel	5 participants n=5 Participants	2 participants n=7 Participants	3 participants n=5 Participants	10 participants n=4 Participants
Region of Enrollment Italy	3 participants n=5 Participants	2 participants n=7 Participants	0 participants n=5 Participants	5 participants n=4 Participants
Region of Enrollment Lithuania	2 participants n=5 Participants	4 participants n=7 Participants	4 participants n=5 Participants	10 participants n=4 Participants
Region of Enrollment Netherlands	2 participants n=5 Participants	3 participants n=7 Participants	3 participants n=5 Participants	8 participants n=4 Participants
Region of Enrollment Poland	15 participants n=5 Participants	16 participants n=7 Participants	20 participants n=5 Participants	51 participants n=4 Participants
Region of Enrollment Russia	61 participants n=5 Participants	56 participants n=7 Participants	49 participants n=5 Participants	166 participants n=4 Participants
Region of Enrollment Spain	4 participants n=5 Participants	8 participants n=7 Participants	6 participants n=5 Participants	18 participants n=4 Participants
Region of Enrollment Ukraine	30 participants n=5 Participants	26 participants n=7 Participants	30 participants n=5 Participants	86 participants n=4 Participants
Region of Enrollment United Kingdom	2 participants n=5 Participants	0 participants n=7 Participants	1 participants n=5 Participants	3 participants n=4 Participants
Region of Enrollment United States	68 participants n=5 Participants	74 participants n=7 Participants	69 participants n=5 Participants	211 participants n=4 Participants
Body Mass Index at Screening Visit	33.6 kg/m^2 STANDARD_DEVIATION 6.2 • n=5 Participants	34.3 kg/m^2 STANDARD_DEVIATION 6.8 • n=7 Participants	33.3 kg/m^2 STANDARD_DEVIATION 5.6 • n=5 Participants	33.7 kg/m^2 STANDARD_DEVIATION 6.2 • n=4 Participants

PRIMARY outcome

Timeframe: Pre-dose Day 1 (Part 1 double-blind randomized baseline) up to Week 4 (End of double-blind randomized part 1)

Population: The Full Analysis Set (FAS) includes all participants who were randomized and had a baseline sitting systolic blood pressure, measured by automated office blood pressure measurement. Baseline was defined as the last measurement before randomization.

Changes from baseline to Week 4 in mean trough SiSBP were analyzed using a mixed model. Participants had their blood pressure (BP) measured at the study site using the automated oscillometric sphygmomanometer (Microlife WatchBP® Office) which was provided to each site. BP was to be measured at trough (before taking the study treatment and SBAT). The BP assessment, participant preparation (e.g., arm selection, arm position, cuff size) was standardized and followed the American Heart Association guidelines / Canadian Education Program on Hypertension. The participant was resting undisturbed, alone (unattended) in a quiet place for 5 minutes at each visit. BP was measured at each visit with the same device, which recorded five sitting blood pressure readings (one per minute, the first value was excluded from the average). A negative change indicates a decrease in SiSBP from baseline.

Outcome measures

Measure	Aprocitentan 12.5 mg in Part 1 (Double-blind) n=243 Participants Participants randomized to aprocitentan 12.5 mg, orally, once daily in the morning for 4 weeks.	Aprocitentan 25 mg in Part 1 (Double-blind) n=243 Participants Participants randomized to aprocitentan 25 mg, orally, once daily in the morning for 4 weeks.	Placebo in Part 1 (Double-blind) n=244 Participants Participants randomized to placebo (matching aprocitentan), orally, once daily in the morning for 4 weeks.
Change From Baseline to Week 4 of Double-blind Treatment in Mean Trough Sitting Systolic Blood Pressure (SiSBP) Measured by Automated Office Blood Pressure Measurement	-15.26 mmHg Interval -17.36 to -13.17	-15.20 mmHg Interval -17.27 to -13.13	-11.47 mmHg Interval -13.57 to -9.38

SECONDARY outcome

Timeframe: Pre-dose Week 36 (Part 3 double-blind-withdrawal baseline) up to Week 40

Population: The modified FAS (mFAS) includes all participants from the FAS who were re-randomized in the double-blind-withdrawal part (DB-WD) of the study and who have a DB-WD baseline sitting systolic blood pressure, measured by automatic office blood pressure measurement device at trough. Baseline was defined as the last measurement before re-randomization.

Changes from double-blind withdrawal baseline (Week 36) to Week 40 in mean trough SiSBP were analyzed using a mixed model. Participants had their blood pressure (BP) measured at the study site using the automated oscillometric sphygmomanometer (Microlife WatchBP® Office) which was provided to each site. BP was to be measured at trough (before taking the study treatment and SBAT). The BP assessment, participant preparation (e.g., arm selection, arm position, cuff size) was standardized and followed the American Heart Association guidelines / Canadian Education Program on Hypertension. The participant was resting undisturbed, alone (unattended) in a quiet place for 5 minutes at each visit. BP was measured at each visit with the same device, which recorded five sitting blood pressure readings (one per minute, the first value was excluded from the average). A negative change indicates a decrease in SiSBP from baseline.

Outcome measures

Measure	Aprocitentan 12.5 mg in Part 1 (Double-blind) n=307 Participants Participants randomized to aprocitentan 12.5 mg, orally, once daily in the morning for 4 weeks.	Aprocitentan 25 mg in Part 1 (Double-blind) n=307 Participants Participants randomized to aprocitentan 25 mg, orally, once daily in the morning for 4 weeks.	Placebo in Part 1 (Double-blind) Participants randomized to placebo (matching aprocitentan), orally, once daily in the morning for 4 weeks.
Change From Double-blind Withdrawal Baseline (Week 36) to Week 40 in Mean Trough Sitting Systolic Blood Pressure (SiSBP) Measured by Unattended Automated Office Blood Pressure Measurement	-1.47 mmHg Interval -2.97 to 0.04	4.36 mmHg Interval 2.87 to 5.85	—

SECONDARY outcome

Timeframe: Pre-dose Day 1 (Part 1 double-blind randomized baseline) up to Week 4 (End of double-blind randomized part 1)

Population: The Full Analysis Set (FAS) includes all participants who were randomized and had a baseline sitting systolic blood pressure, measured by automated office blood pressure measurement. Baseline was defined as the last measurement before randomization.

Changes from baseline to Week 4 in mean trough SiDBP were analyzed using a mixed model. Participants had their blood pressure (BP) measured at the study site using the automated oscillometric sphygmomanometer (Microlife WatchBP® Office) which was provided to each site. BP was to be measured at trough (before taking the study treatment and SBAT). The BP assessment, participant preparation (e.g., arm selection, arm position, cuff size) was standardized and followed the American Heart Association guidelines / Canadian Education Program on Hypertension. BP was measured at each visit with the same device, which recorded five sitting blood pressure readings (one per minute, the first value was excluded from the average). The participant was resting undisturbed, alone (unattended) in a quiet place for 5 minutes at each visit. A negative change indicates a decrease in SiDBP from baseline.

Outcome measures

Measure	Aprocitentan 12.5 mg in Part 1 (Double-blind) n=243 Participants Participants randomized to aprocitentan 12.5 mg, orally, once daily in the morning for 4 weeks.	Aprocitentan 25 mg in Part 1 (Double-blind) n=243 Participants Participants randomized to aprocitentan 25 mg, orally, once daily in the morning for 4 weeks.	Placebo in Part 1 (Double-blind) n=244 Participants Participants randomized to placebo (matching aprocitentan), orally, once daily in the morning for 4 weeks.
Change From Baseline to Week 4 of Double-blind Treatment in Mean Trough Sitting Diastolic Blood Pressure (SiDBP) Measured by Unattended Automated Office Blood Pressure Measurement	-10.43 mmHg Interval -11.58 to -9.27	-10.95 mmHg Interval -12.09 to -9.82	-6.48 mmHg Interval -7.63 to -5.33

SECONDARY outcome

Timeframe: Pre-dose Day 1 (Part 1 double-blind randomized baseline) and Week 4 (End of double-blind randomized part 1)

Population: The ambulatory blood pressure monitoring full analysis set (aFAS) includes all participants from the FAS who have a baseline 24-hour mean systolic and diastolic blood pressure measured by ambulatory blood pressure monitoring with a total duration of at least 21 hours and at least 70% valid readings.

ABPM devices were provided to each site by the central blood pressure laboratory. On the first day after all visit assessments were performed, the ABPM device (Mobil-O-Graph NG) was fitted to the participant. The following day (i.e., second day), the participant came back to site to have the ABPM device removed. ABPM data collected over the 24-hours was electronically transferred to the central BP laboratory. Systolic blood pressure and diastolic blood pressure were measured at predetermined times every 20 minutes from 06:00 to 21:59, and every 30 minutes from 22:00 to 05:59. For each participant and at each visit (baseline and Week 4) the 24-hour mean SBP (or DBP) was calculated from the area under the SBP (or DBP) time curve and divided by the time span. A negative change indicates a decrease in 24-hour mean systolic / diastolic blood pressure from baseline.

Outcome measures

Measure	Aprocitentan 12.5 mg in Part 1 (Double-blind) n=206 Participants Participants randomized to aprocitentan 12.5 mg, orally, once daily in the morning for 4 weeks.	Aprocitentan 25 mg in Part 1 (Double-blind) n=207 Participants Participants randomized to aprocitentan 25 mg, orally, once daily in the morning for 4 weeks.	Placebo in Part 1 (Double-blind) n=220 Participants Participants randomized to placebo (matching aprocitentan), orally, once daily in the morning for 4 weeks.
Changes From Baseline to Week 4 of Double-blind Treatment in 24-hour Mean Systolic (SBP) and Diastolic Blood Pressure (DBP) Measured by Ambulatory Blood Pressure Monitoring 24-hour mean systolic blood pressure	-6.73 mmHg Interval -8.2 to -5.26	-8.44 mmHg Interval -9.88 to -7.0	-2.55 mmHg Interval -4.0 to -1.1
Changes From Baseline to Week 4 of Double-blind Treatment in 24-hour Mean Systolic (SBP) and Diastolic Blood Pressure (DBP) Measured by Ambulatory Blood Pressure Monitoring 24-hour mean diastolic blood pressure	-6.25 mmHg Interval -7.2 to -5.29	-7.74 mmHg Interval -8.67 to -6.8	-1.92 mmHg Interval -2.87 to -0.98

SECONDARY outcome

Timeframe: Pre-dose Week 36 (Part 3 double-blind-withdrawal baseline) up to Week 40

Population: The modified FAS (mFAS) includes all participants in the FAS who were re-randomized in the double-blind-withdraw part of the study and who had a week 36 sitting systolic blood pressure, measured by automated office blood pressure measurement. Baseline was defined as the last measurement before re-randomization into part 3 of the double-blind withdrawal part of the study.

Changes from double-blind withdrawal (Week 36) to Week 40 in mean trough SiDBP were analyzed using a mixed model. Participants had their blood pressure (BP) measured at the study site using the automated oscillometric sphygmomanometer (Microlife WatchBP® Office) which was provided to each site. BP was to be measured at trough (before taking the study treatment and SBAT). The BP assessment, participant preparation (e.g., arm selection, arm position, cuff size) was standardized and followed the American Heart Association guidelines / Canadian Education Program on Hypertension. The participant was resting undisturbed, alone (unattended) in a quiet place for 5 minutes at each visit. BP was measured at each visit with the same device, which recorded five sitting blood pressure readings (one per minute, the first value was excluded from the average). A negative change indicates a decrease in SiDBP from baseline.

Outcome measures

Measure	Aprocitentan 12.5 mg in Part 1 (Double-blind) n=307 Participants Participants randomized to aprocitentan 12.5 mg, orally, once daily in the morning for 4 weeks.	Aprocitentan 25 mg in Part 1 (Double-blind) n=307 Participants Participants randomized to aprocitentan 25 mg, orally, once daily in the morning for 4 weeks.	Placebo in Part 1 (Double-blind) Participants randomized to placebo (matching aprocitentan), orally, once daily in the morning for 4 weeks.
Change From Double-blind Withdrawal Baseline (Week 36) to Week 40 of Double-blind-withdrawal (DB-WD) Treatment in Trough Sitting Diastolic Blood Pressure (SiDBP) Measured by Unattended Automated Office Blood Pressure	-0.52 mmHg Interval -1.54 to 0.5	4.67 mmHg Interval 3.66 to 5.68	—

SECONDARY outcome

Timeframe: From Week 36 (Part 3 double-blind-withdrawal baseline) and Week 40

Population: The modified ambulatory blood pressure monitoring full analysis set (maFAS) includes all participants from the modified Full Analysis Set (mFAS) who had a double-blind withdrawal (DB-WD) baseline 24-hour mean systolic and diastolic blood pressure, measured by ambulatory blood Pressure monitoring (ABPM) with a total duration of at least 21 hours and at least 70% valid readings.

ABPM devices were provided to each site by the central blood pressure laboratory. On the first day after all visit assessments were performed, the ABPM device (Mobil-O-Graph NG) was fitted to the participant. The following day (i.e., second day), the participant came back to site to have the ABPM device removed. ABPM data collected over the 24-hours was electronically transferred to the central BP laboratory. Systolic blood pressure and diastolic blood pressure were measured at predetermined times every 20 minutes from 06:00 to 21:59, and every 30 minutes from 22:00 to 05:59. For each participant and at each visit (the double-blind withdrawal baseline [Week 36] and the week 40) the 24-hour mean SBP (or DBP) was calculated from the area under the SBP (or DBP) time curve. A negative change indicates a decrease in 24-hour mean systolic / diastolic blood pressure from baseline.

Outcome measures

Measure	Aprocitentan 12.5 mg in Part 1 (Double-blind) n=237 Participants Participants randomized to aprocitentan 12.5 mg, orally, once daily in the morning for 4 weeks.	Aprocitentan 25 mg in Part 1 (Double-blind) n=241 Participants Participants randomized to aprocitentan 25 mg, orally, once daily in the morning for 4 weeks.	Placebo in Part 1 (Double-blind) Participants randomized to placebo (matching aprocitentan), orally, once daily in the morning for 4 weeks.
Changes From Double-blind Withdrawal Baseline (Week 36) to Week 40 of Double-blind-withdrawal (DB-WD) Treatment in 24-hour Mean Systolic (SBP) and Diastolic Blood Pressure (DBP) Measured by Ambulatory Blood Pressure Monitoring 24-hour mean systolic blood pressure	-0.07 mmHg Interval -1.46 to 1.32	6.46 mmHg Interval 5.06 to 7.85	—
Changes From Double-blind Withdrawal Baseline (Week 36) to Week 40 of Double-blind-withdrawal (DB-WD) Treatment in 24-hour Mean Systolic (SBP) and Diastolic Blood Pressure (DBP) Measured by Ambulatory Blood Pressure Monitoring 24-hour mean diastolic blood pressure	-0.47 mmHg Interval -1.34 to 0.4	6.28 mmHg Interval 5.4 to 7.15	—

Adverse Events

Aprocitentan 12.5 mg in Part 1 (Double-blind)

Serious events: 8 serious events

Other events: 16 other events

Deaths: 1 deaths

Aprocitentan 25 mg in Part 1 (Double-blind)

Serious events: 8 serious events

Other events: 34 other events

Deaths: 0 deaths

Placebo in Part 1 (Double-blind)

Serious events: 3 serious events

Other events: 5 other events

Deaths: 0 deaths

Aprocitentan 25 mg in Part 2 (Single-blind)

Serious events: 82 serious events

Other events: 95 other events

Deaths: 9 deaths

Aprocitentan 25 mg in Part 3 (Double-blind Withdrawal)

Serious events: 18 serious events

Other events: 6 other events

Deaths: 1 deaths

Placebo in Part 3 (Double-blind Withdrawal)

Serious events: 9 serious events

Other events: 4 other events

Deaths: 0 deaths

Serious adverse events

Measure	Aprocitentan 12.5 mg in Part 1 (Double-blind) n=243 participants at risk Participants received aprocitentan 12.5 mg, orally, once daily in the morning for 4 weeks.	Aprocitentan 25 mg in Part 1 (Double-blind) n=245 participants at risk Participants received aprocitentan 25 mg, orally, once daily in the morning for 4 weeks.	Placebo in Part 1 (Double-blind) n=242 participants at risk Participants received placebo, orally, once daily in the morning for 4 weeks.	Aprocitentan 25 mg in Part 2 (Single-blind) n=704 participants at risk All participants received aprocitentan 25 mg, orally, once daily in the morning for 32 weeks.	Aprocitentan 25 mg in Part 3 (Double-blind Withdrawal) n=310 participants at risk After 32-weeks in the single-blind, single-arm part, participants received aprocitentan 25 mg, orally, once daily in the morning for 12 weeks.	Placebo in Part 3 (Double-blind Withdrawal) n=303 participants at risk After 32-weeks in the single-blind, single-arm part, participants received placebo (matching aprocitentan), orally, once daily in the morning for 12 weeks.
Blood and lymphatic system disorders Anaemia	0.00% 0/243 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/245 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/242 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.14% 1/704 • Number of events 1 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/310 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/303 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.
Cardiac disorders Acute left ventricular failure	0.00% 0/243 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/245 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/242 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/704 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.32% 1/310 • Number of events 1 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/303 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.
Cardiac disorders Acute myocardial infarction	0.00% 0/243 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/245 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/242 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.28% 2/704 • Number of events 2 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/310 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/303 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.
Cardiac disorders Angina unstable	0.00% 0/243 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/245 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/242 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.71% 5/704 • Number of events 5 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.32% 1/310 • Number of events 1 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/303 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.
Cardiac disorders Atrial fibrillation	0.00% 0/243 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/245 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/242 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.43% 3/704 • Number of events 3 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.97% 3/310 • Number of events 3 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/303 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.
Cardiac disorders Atrioventricular block	0.00% 0/243 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/245 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/242 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.14% 1/704 • Number of events 1 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/310 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/303 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.
Cardiac disorders Atrioventricular block second degree	0.00% 0/243 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/245 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/242 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.14% 1/704 • Number of events 1 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/310 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/303 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.
Cardiac disorders Cardiac failure	0.00% 0/243 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.41% 1/245 • Number of events 1 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/242 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.14% 1/704 • Number of events 1 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/310 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/303 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.
Cardiac disorders Cardiac failure acute	0.00% 0/243 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/245 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/242 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/704 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/310 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.33% 1/303 • Number of events 1 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.
Cardiac disorders Cardiac failure chronic	0.00% 0/243 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.41% 1/245 • Number of events 1 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/242 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.14% 1/704 • Number of events 1 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/310 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/303 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.
Cardiac disorders Cardiac failure congestive	0.00% 0/243 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/245 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/242 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.43% 3/704 • Number of events 3 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/310 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/303 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.
Cardiac disorders Cardiogenic shock	0.00% 0/243 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/245 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/242 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/704 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.32% 1/310 • Number of events 1 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/303 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.
Cardiac disorders Coronary artery disease	0.00% 0/243 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/245 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/242 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.28% 2/704 • Number of events 2 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/310 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/303 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.
Cardiac disorders Coronary artery dissection	0.00% 0/243 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/245 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/242 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/704 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/310 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.33% 1/303 • Number of events 1 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.
Cardiac disorders Left ventricular dysfunction	0.00% 0/243 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/245 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/242 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.14% 1/704 • Number of events 1 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/310 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/303 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.
Cardiac disorders Myocardial infarction	0.41% 1/243 • Number of events 1 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/245 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/242 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.28% 2/704 • Number of events 2 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.32% 1/310 • Number of events 1 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/303 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.
Ear and labyrinth disorders Meniere's disease	0.00% 0/243 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.41% 1/245 • Number of events 1 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/242 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/704 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/310 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/303 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.
Ear and labyrinth disorders Vestibular ataxia	0.00% 0/243 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/245 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/242 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.14% 1/704 • Number of events 1 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/310 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/303 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.
Gastrointestinal disorders Gastrointestinal haemorrhage	0.00% 0/243 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/245 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/242 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.14% 1/704 • Number of events 1 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/310 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/303 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.
Gastrointestinal disorders Pancreatitis chronic	0.00% 0/243 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.41% 1/245 • Number of events 1 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/242 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/704 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.32% 1/310 • Number of events 1 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/303 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.
Gastrointestinal disorders Rectal fissure	0.00% 0/243 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/245 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/242 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.14% 1/704 • Number of events 1 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/310 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/303 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.
Gastrointestinal disorders Umbilical hernia, obstructive	0.00% 0/243 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/245 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/242 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.14% 1/704 • Number of events 1 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/310 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/303 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.
Gastrointestinal disorders Upper gastrointestinal haemorrhage	0.00% 0/243 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/245 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/242 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.14% 1/704 • Number of events 1 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/310 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/303 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.
General disorders Chest pain	0.00% 0/243 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.41% 1/245 • Number of events 1 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/242 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.14% 1/704 • Number of events 1 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/310 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/303 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.
General disorders Death	0.00% 0/243 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/245 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/242 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.14% 1/704 • Number of events 1 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/310 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/303 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.
General disorders Multiple organ dysfunction syndrome	0.00% 0/243 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/245 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/242 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/704 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.32% 1/310 • Number of events 1 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/303 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.
General disorders Oedema peripheral	0.00% 0/243 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.41% 1/245 • Number of events 1 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/242 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/704 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/310 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/303 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.
General disorders Pyrexia	0.00% 0/243 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/245 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/242 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.14% 1/704 • Number of events 1 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/310 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/303 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.
General disorders Sudden cardiac death	0.00% 0/243 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/245 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/242 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.14% 1/704 • Number of events 1 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/310 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/303 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.
Hepatobiliary disorders Cholecystitis acute	0.41% 1/243 • Number of events 1 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/245 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/242 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/704 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/310 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/303 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.
Infections and infestations Abscess jaw	0.00% 0/243 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.41% 1/245 • Number of events 1 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/242 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/704 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/310 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/303 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.
Infections and infestations COVID-19	0.00% 0/243 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/245 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/242 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/704 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.32% 1/310 • Number of events 1 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/303 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.
Infections and infestations COVID-19 pneumonia	0.82% 2/243 • Number of events 2 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/245 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.41% 1/242 • Number of events 1 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	2.0% 14/704 • Number of events 14 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	1.3% 4/310 • Number of events 4 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.66% 2/303 • Number of events 2 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.
Infections and infestations Cellulitis	0.00% 0/243 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.82% 2/245 • Number of events 2 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/242 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/704 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/310 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/303 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.
Infections and infestations Cholecystitis infective	0.00% 0/243 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/245 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/242 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/704 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.32% 1/310 • Number of events 1 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/303 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.
Infections and infestations Diabetic gangrene	0.00% 0/243 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/245 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/242 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.14% 1/704 • Number of events 1 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/310 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/303 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.
Infections and infestations Diverticulitis	0.00% 0/243 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/245 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/242 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.14% 1/704 • Number of events 1 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/310 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/303 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.
Infections and infestations Erysipelas	0.00% 0/243 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/245 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/242 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.14% 1/704 • Number of events 1 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/310 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/303 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.
Infections and infestations Gastroenteritis	0.00% 0/243 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/245 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/242 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.14% 1/704 • Number of events 1 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/310 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/303 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.
Infections and infestations Peritonsillar abscess	0.00% 0/243 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/245 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.41% 1/242 • Number of events 1 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/704 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/310 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/303 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.
Infections and infestations Pneumonia	0.41% 1/243 • Number of events 1 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.41% 1/245 • Number of events 1 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/242 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.28% 2/704 • Number of events 2 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.65% 2/310 • Number of events 2 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/303 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.
Infections and infestations Pneumonia bacterial	0.00% 0/243 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/245 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/242 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.14% 1/704 • Number of events 1 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/310 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/303 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.
Infections and infestations Pyelonephritis acute	0.00% 0/243 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/245 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.41% 1/242 • Number of events 1 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.14% 1/704 • Number of events 1 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/310 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/303 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.
Infections and infestations Sepsis	0.00% 0/243 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/245 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.41% 1/242 • Number of events 1 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/704 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/310 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/303 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.
Infections and infestations Ureteritis	0.00% 0/243 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/245 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/242 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.14% 1/704 • Number of events 1 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/310 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/303 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.
Infections and infestations Urinary tract infection	0.00% 0/243 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/245 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/242 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.14% 1/704 • Number of events 1 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/310 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/303 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.
Infections and infestations Wound infection	0.00% 0/243 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/245 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/242 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.14% 1/704 • Number of events 1 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/310 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/303 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.
Injury, poisoning and procedural complications Chest injury	0.00% 0/243 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/245 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/242 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.14% 1/704 • Number of events 1 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/310 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/303 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.
Injury, poisoning and procedural complications Procedural intestinal perforation	0.00% 0/243 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/245 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/242 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.14% 1/704 • Number of events 1 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/310 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/303 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.
Injury, poisoning and procedural complications Road traffic accident	0.00% 0/243 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/245 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/242 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.14% 1/704 • Number of events 1 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/310 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/303 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.
Injury, poisoning and procedural complications Subdural haemorrhage	0.00% 0/243 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/245 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/242 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.14% 1/704 • Number of events 1 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/310 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/303 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.
Injury, poisoning and procedural complications Tibia fracture	0.00% 0/243 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/245 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/242 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.14% 1/704 • Number of events 1 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/310 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/303 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.
Injury, poisoning and procedural complications Traumatic intracranial haemorrhage	0.00% 0/243 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/245 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/242 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.14% 1/704 • Number of events 1 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/310 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/303 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.
Investigations Blood creatinine increased	0.00% 0/243 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/245 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/242 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.14% 1/704 • Number of events 1 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/310 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/303 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.
Investigations Blood pressure increased	0.00% 0/243 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.41% 1/245 • Number of events 1 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/242 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/704 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/310 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/303 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.
Metabolism and nutrition disorders Hyperkalaemia	0.00% 0/243 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/245 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/242 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.28% 2/704 • Number of events 2 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/310 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/303 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.
Metabolism and nutrition disorders Hypoglycaemia	0.00% 0/243 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/245 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/242 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.14% 1/704 • Number of events 1 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/310 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/303 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.
Musculoskeletal and connective tissue disorders Musculoskeletal chest pain	0.00% 0/243 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/245 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/242 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.14% 1/704 • Number of events 1 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/310 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/303 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.
Musculoskeletal and connective tissue disorders Osteoarthritis	0.00% 0/243 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/245 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/242 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.14% 1/704 • Number of events 1 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/310 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/303 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.
Musculoskeletal and connective tissue disorders Osteochondrosis	0.00% 0/243 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/245 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/242 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.14% 1/704 • Number of events 1 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/310 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/303 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.
Musculoskeletal and connective tissue disorders Rotator cuff syndrome	0.00% 0/243 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/245 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/242 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.14% 1/704 • Number of events 1 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/310 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/303 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Adenocarcinoma of colon	0.00% 0/243 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/245 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/242 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.14% 1/704 • Number of events 1 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/310 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/303 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Invasive breast carcinoma	0.00% 0/243 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/245 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/242 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.14% 1/704 • Number of events 1 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/310 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/303 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lung neoplasm malignant	0.00% 0/243 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/245 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/242 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.14% 1/704 • Number of events 1 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/310 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/303 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Mantle cell lymphoma	0.00% 0/243 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/245 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/242 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.14% 1/704 • Number of events 1 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/310 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/303 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastatic neoplasm	0.00% 0/243 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/245 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/242 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.14% 1/704 • Number of events 1 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/310 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/303 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Renal cancer	0.00% 0/243 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/245 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/242 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/704 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/310 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.33% 1/303 • Number of events 1 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Renal cell carcinoma	0.00% 0/243 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/245 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/242 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.14% 1/704 • Number of events 1 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/310 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/303 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.
Nervous system disorders Brain oedema	0.00% 0/243 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/245 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/242 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.14% 1/704 • Number of events 1 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/310 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/303 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.
Nervous system disorders Cerebral infarction	0.41% 1/243 • Number of events 1 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/245 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/242 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/704 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/310 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/303 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.
Nervous system disorders Cerebrovascular accident	0.00% 0/243 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.41% 1/245 • Number of events 1 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/242 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.28% 2/704 • Number of events 2 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/310 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/303 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.
Nervous system disorders Facial paresis	0.00% 0/243 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/245 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/242 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/704 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.32% 1/310 • Number of events 1 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/303 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.
Nervous system disorders Haemorrhage intracranial	0.00% 0/243 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/245 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/242 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/704 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/310 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.33% 1/303 • Number of events 1 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.
Nervous system disorders Ischaemic stroke	0.41% 1/243 • Number of events 1 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/245 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.41% 1/242 • Number of events 1 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/704 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/310 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.33% 1/303 • Number of events 1 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.
Nervous system disorders Seizure	0.00% 0/243 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/245 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/242 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.14% 1/704 • Number of events 1 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/310 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/303 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.
Nervous system disorders Syncope	0.00% 0/243 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/245 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/242 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.28% 2/704 • Number of events 2 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/310 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/303 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.
Nervous system disorders Transient ischaemic attack	0.00% 0/243 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/245 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/242 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.14% 1/704 • Number of events 1 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.32% 1/310 • Number of events 1 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/303 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.
Renal and urinary disorders Acute kidney injury	0.00% 0/243 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/245 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/242 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.14% 1/704 • Number of events 1 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/310 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/303 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.
Renal and urinary disorders Calculus urinary	0.00% 0/243 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/245 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/242 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.28% 2/704 • Number of events 2 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/310 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/303 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.
Renal and urinary disorders Nephropathy toxic	0.00% 0/243 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/245 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/242 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.14% 1/704 • Number of events 1 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/310 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/303 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.
Renal and urinary disorders Ureteric stenosis	0.00% 0/243 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/245 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/242 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.14% 1/704 • Number of events 2 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/310 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/303 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.
Reproductive system and breast disorders Endometrial hyperplasia	0.00% 0/243 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/245 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/242 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/704 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/310 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.33% 1/303 • Number of events 1 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.
Reproductive system and breast disorders Uterine polyp	0.00% 0/243 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/245 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/242 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.14% 1/704 • Number of events 1 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/310 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/303 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.
Respiratory, thoracic and mediastinal disorders Asthma	0.00% 0/243 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/245 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/242 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.14% 1/704 • Number of events 1 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/310 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/303 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.00% 0/243 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/245 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/242 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.14% 1/704 • Number of events 1 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.32% 1/310 • Number of events 1 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/303 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	0.41% 1/243 • Number of events 1 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/245 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/242 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/704 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/310 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/303 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.
Respiratory, thoracic and mediastinal disorders Pulmonary oedema	0.00% 0/243 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.41% 1/245 • Number of events 1 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/242 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.14% 1/704 • Number of events 1 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/310 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/303 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.
Respiratory, thoracic and mediastinal disorders Respiratory failure	0.00% 0/243 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/245 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/242 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.14% 1/704 • Number of events 1 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/310 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/303 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.
Skin and subcutaneous tissue disorders Angioedema	0.00% 0/243 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/245 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/242 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/704 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/310 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.33% 1/303 • Number of events 1 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.
Skin and subcutaneous tissue disorders Dermatitis allergic	0.00% 0/243 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/245 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/242 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.14% 1/704 • Number of events 1 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/310 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/303 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.
Skin and subcutaneous tissue disorders Skin ulcer	0.00% 0/243 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/245 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/242 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/704 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.32% 1/310 • Number of events 1 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/303 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.
Surgical and medical procedures Coronary artery bypass	0.00% 0/243 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/245 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/242 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.14% 1/704 • Number of events 1 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/310 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/303 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.
Surgical and medical procedures Hip arthroplasty	0.41% 1/243 • Number of events 1 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/245 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/242 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/704 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/310 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/303 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.
Surgical and medical procedures Peripheral artery bypass	0.00% 0/243 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/245 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/242 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.14% 1/704 • Number of events 1 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/310 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/303 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.
Surgical and medical procedures Toe amputation	0.00% 0/243 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/245 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/242 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.14% 1/704 • Number of events 1 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/310 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/303 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.
Vascular disorders Aortic stenosis	0.00% 0/243 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/245 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/242 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/704 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.32% 1/310 • Number of events 1 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/303 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.
Vascular disorders Deep vein thrombosis	0.41% 1/243 • Number of events 1 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/245 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/242 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.14% 1/704 • Number of events 1 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/310 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/303 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.
Vascular disorders Distributive shock	0.00% 0/243 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/245 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/242 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.14% 1/704 • Number of events 1 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/310 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/303 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.
Vascular disorders Hypertension	0.00% 0/243 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/245 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/242 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/704 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.32% 1/310 • Number of events 1 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/303 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.
Vascular disorders Hypertensive crisis	0.00% 0/243 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/245 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/242 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.14% 1/704 • Number of events 1 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/310 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/303 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.
Vascular disorders Hypertensive urgency	0.00% 0/243 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/245 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/242 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.14% 1/704 • Number of events 1 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/310 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/303 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.
Vascular disorders Hypotension	0.00% 0/243 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/245 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/242 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.14% 1/704 • Number of events 1 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/310 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/303 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.
Vascular disorders Intermittent claudication	0.00% 0/243 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/245 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/242 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.14% 1/704 • Number of events 1 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/310 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/303 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.
Vascular disorders Peripheral artery stenosis	0.00% 0/243 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/245 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/242 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.14% 1/704 • Number of events 1 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/310 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	0.00% 0/303 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.

Other adverse events

Measure	Aprocitentan 12.5 mg in Part 1 (Double-blind) n=243 participants at risk Participants received aprocitentan 12.5 mg, orally, once daily in the morning for 4 weeks.	Aprocitentan 25 mg in Part 1 (Double-blind) n=245 participants at risk Participants received aprocitentan 25 mg, orally, once daily in the morning for 4 weeks.	Placebo in Part 1 (Double-blind) n=242 participants at risk Participants received placebo, orally, once daily in the morning for 4 weeks.	Aprocitentan 25 mg in Part 2 (Single-blind) n=704 participants at risk All participants received aprocitentan 25 mg, orally, once daily in the morning for 32 weeks.	Aprocitentan 25 mg in Part 3 (Double-blind Withdrawal) n=310 participants at risk After 32-weeks in the single-blind, single-arm part, participants received aprocitentan 25 mg, orally, once daily in the morning for 12 weeks.	Placebo in Part 3 (Double-blind Withdrawal) n=303 participants at risk After 32-weeks in the single-blind, single-arm part, participants received placebo (matching aprocitentan), orally, once daily in the morning for 12 weeks.
General disorders Oedema peripheral	6.6% 16/243 • Number of events 16 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	13.9% 34/245 • Number of events 34 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	2.1% 5/242 • Number of events 5 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	13.5% 95/704 • Number of events 102 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	1.9% 6/310 • Number of events 7 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.	1.3% 4/303 • Number of events 4 • Adverse events (AEs) were considered treatment-emergent, if the onset date is between the first intake of treatment up to 30 days after the stop of study treatment. Study treatment was for up to 48 weeks. In Part 1 double-blind (DB) treatment was for 4 weeks. Part 2 single-blind (SB) study treatment was for 32 weeks. In Part 3 double-blind withdrawal (DB-WD) study treatment was for 12 weeks. Only participants entering the randomized treatment period were considered enrolled for the study and are included in AE analysis. The Run-in period was designed to exclude potential placebo responders and is not part of statistical analysis of this study.

Additional Information

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