Trial Outcomes & Findings for Selexipag (ACT-293987) in Pulmonary Arterial Hypertension (NCT NCT01106014)

Last Updated: 2025-10-27

Results Overview

Time from randomization to the first occurrence of a morbidity event or death (all causes) was analyzed with the Kaplan-Meier method (event-free KM estimates at different time points). Morbidity event was defined as any of the following events confirmed by the Critical Event committee: * Hospitalization for worsening of pulmonary arterial hypertension (PAH), * Worsening of PAH resulting in need for lung transplantation or balloon atrial septostomy, * Initiation of parenteral prostanoid therapy or chronic oxygen therapy due to worsening of PAH, * Disease progression which was defined by a decrease in 6-minute walk distance from baseline (\>=15%, confirmed by a 2nd test on a different day) combined with worsening of WHO FC for patients belonging to WHO FC II/III at baseline, or combined with the need for additional PAH-specific therapy for patients belonging to WHO FC III/IV at baseline. Note: The number of patients at risk decreased over time but this cannot be captured below

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

1156 participants

Primary outcome timeframe

Up to 7 days after end of double-blind treatment (maximum: 4.3 years)

Results posted on

2025-10-27

Participant Flow

A total of 1351 patients were screened from 181 sites in 39 countries worldwide. Of these, 1156 were randomized

Screening assessments were performed up to a maximum of 28 days before baseline

Participant milestones

Participant milestones
Measure	SELEXIPAG During the 12-week titration phase, treatment was initiated at 200 μg twice daily (b.i.d.) and up-titrated weekly in 200 μg b.i.d. increments to the maximum tolerated dose (MTD) for each individual patient but not above 1600 μg b.i.d. At Week 12, patients continued the treatment at their individual MTD up to Week 26. Thereafter the dose could be up-titrated at scheduled visits if needed for patients receiving a dose \< 1600 μg b.i.d. The dose could be decreased at any time in case of tolerability issues.	PLACEBO Matching placebo was administered orally following the same administration schedule as described for selexipag
Overall Study STARTED	574	582
Overall Study COMPLETED	289	252
Overall Study NOT COMPLETED	285	330

Reasons for withdrawal

Reasons for withdrawal
Measure	SELEXIPAG During the 12-week titration phase, treatment was initiated at 200 μg twice daily (b.i.d.) and up-titrated weekly in 200 μg b.i.d. increments to the maximum tolerated dose (MTD) for each individual patient but not above 1600 μg b.i.d. At Week 12, patients continued the treatment at their individual MTD up to Week 26. Thereafter the dose could be up-titrated at scheduled visits if needed for patients receiving a dose \< 1600 μg b.i.d. The dose could be decreased at any time in case of tolerability issues.	PLACEBO Matching placebo was administered orally following the same administration schedule as described for selexipag
Overall Study Morbidity or Mortality primary endpoint	155	242
Overall Study Adverse Event	78	42
Overall Study Withdrawal by Subject	43	37
Overall Study Administrative reason	7	6
Overall Study Lost to Follow-up	2	3

Baseline Characteristics

Selexipag (ACT-293987) in Pulmonary Arterial Hypertension

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Selexipag n=574 Participants During the 12-week titration phase, treatment was initiated at 200 μg twice daily (b.i.d.) and up-titrated weekly in 200 μg b.i.d. increments to the maximum tolerated dose (MTD) for each individual patient but not above 1600 μg b.i.d. At Week 12, patients continued the treatment at their individual MTD up to Week 26. Thereafter the dose could be up-titrated at scheduled visits if needed for patients receiving a dose \< 1600 μg b.i.d. The dose could be decreased at any time in case of tolerability issues.	Placebo n=582 Participants Matching placebo was administered orally following the same administration schedule as described for selexipag	Total n=1156 Participants Total of all reporting groups
Age, Continuous	48.2 Years STANDARD_DEVIATION 15.19 • n=5 Participants	47.9 Years STANDARD_DEVIATION 15.55 • n=7 Participants	48.1 Years STANDARD_DEVIATION 15.37 • n=5 Participants
Sex: Female, Male Female	457 Participants n=5 Participants	466 Participants n=7 Participants	923 Participants n=5 Participants
Sex: Female, Male Male	117 Participants n=5 Participants	116 Participants n=7 Participants	233 Participants n=5 Participants
Race/Ethnicity, Customized Caucasion / White	376 Participants n=5 Participants	375 Participants n=7 Participants	751 Participants n=5 Participants
Race/Ethnicity, Customized Asian	125 Participants n=5 Participants	120 Participants n=7 Participants	245 Participants n=5 Participants
Race/Ethnicity, Customized Hispanic	51 Participants n=5 Participants	63 Participants n=7 Participants	114 Participants n=5 Participants
Race/Ethnicity, Customized Black	13 Participants n=5 Participants	14 Participants n=7 Participants	27 Participants n=5 Participants
Race/Ethnicity, Customized Other	9 Participants n=5 Participants	10 Participants n=7 Participants	19 Participants n=5 Participants
Region of Enrollment Western Europe & Australia	161 Participants n=5 Participants	160 Participants n=7 Participants	321 Participants n=5 Participants
Region of Enrollment Eastern Europe	149 Participants n=5 Participants	155 Participants n=7 Participants	304 Participants n=5 Participants
Region of Enrollment Asia	115 Participants n=5 Participants	113 Participants n=7 Participants	228 Participants n=5 Participants
Region of Enrollment North America	95 Participants n=5 Participants	98 Participants n=7 Participants	193 Participants n=5 Participants
Region of Enrollment Latin America	54 Participants n=5 Participants	56 Participants n=7 Participants	110 Participants n=5 Participants
PAH etiology Idiopathic	312 Participants n=5 Participants	337 Participants n=7 Participants	649 Participants n=5 Participants
PAH etiology Heritable	13 Participants n=5 Participants	13 Participants n=7 Participants	26 Participants n=5 Participants
PAH etiology Associated with connective tissue disease	167 Participants n=5 Participants	167 Participants n=7 Participants	334 Participants n=5 Participants
PAH etiology Assoc. with corrected (>=12Mo) congenital shunts	60 Participants n=5 Participants	50 Participants n=7 Participants	110 Participants n=5 Participants
PAH etiology Associated with drug or toxin exposure	17 Participants n=5 Participants	10 Participants n=7 Participants	27 Participants n=5 Participants
PAH etiology Associated with HIV infection	5 Participants n=5 Participants	5 Participants n=7 Participants	10 Participants n=5 Participants
Modified NYHA/WHO Functional class (FC) FC I	4 Participants n=5 Participants	5 Participants n=7 Participants	9 Participants n=5 Participants
Modified NYHA/WHO Functional class (FC) FC II	274 Participants n=5 Participants	255 Participants n=7 Participants	529 Participants n=5 Participants
Modified NYHA/WHO Functional class (FC) FC III	293 Participants n=5 Participants	314 Participants n=7 Participants	607 Participants n=5 Participants
Modified NYHA/WHO Functional class (FC) FC IV	3 Participants n=5 Participants	8 Participants n=7 Participants	11 Participants n=5 Participants
PAH medications at baseline None	112 Participants n=5 Participants	124 Participants n=7 Participants	236 Participants n=5 Participants
PAH medications at baseline Endothelin Receptor Agonists (ERA)	94 Participants n=5 Participants	76 Participants n=7 Participants	170 Participants n=5 Participants
PAH medications at baseline Phosphodiesterase type 5 inhibitors (PDE5-I)	189 Participants n=5 Participants	185 Participants n=7 Participants	374 Participants n=5 Participants
PAH medications at baseline ERA and PDE5I in combination	179 Participants n=5 Participants	197 Participants n=7 Participants	376 Participants n=5 Participants
Time since PAH diagnosis	0.9 Years n=5 Participants	1.1 Years n=7 Participants	1.0 Years n=5 Participants
6-minute walk distance (6MWD) at baseline	376 Meters n=5 Participants	369 Meters n=7 Participants	372 Meters n=5 Participants

PRIMARY outcome

Timeframe: Up to 7 days after end of double-blind treatment (maximum: 4.3 years)

Population: The primary endpoint was analyzed using the full analysis set, which includes all randomized patients evaluated according to the study drug to which they have been randomized (intention-to treat analysis set).

Outcome measures

Outcome measures
Measure	Selexipag n=574 Participants During the 12-week titration phase, treatment was initiated at 200 μg twice daily (b.i.d.) and up-titrated weekly in 200 μg b.i.d. increments to the maximum tolerated dose (MTD) for each individual patient but not above 1600 μg b.i.d. At Week 12, patients continued the treatment at their individual MTD up to Week 26. Thereafter the dose could be up-titrated at scheduled visits if needed for patients receiving a dose \< 1600 μg b.i.d. The dose could be decreased at any time in case of tolerability issues	Placebo n=582 Participants Matching placebo was administered orally following the same administration schedule as described for selexipag
Time From Randomization to the First Morbidity Event or Death (All Causes) up to 7 Days After the Last Study Drug Intake KM estimate at Month 6	91.2 Percentage of patients free of events Interval 88.5 to 93.4	81.7 Percentage of patients free of events Interval 78.2 to 84.7
Time From Randomization to the First Morbidity Event or Death (All Causes) up to 7 Days After the Last Study Drug Intake KM estimate at Month 12	83.1 Percentage of patients free of events Interval 79.5 to 86.1	70.6 Percentage of patients free of events Interval 66.6 to 74.3
Time From Randomization to the First Morbidity Event or Death (All Causes) up to 7 Days After the Last Study Drug Intake KM estimate at Month 18	75.5 Percentage of patients free of events Interval 71.2 to 79.2	61.3 Percentage of patients free of events Interval 56.8 to 65.5
Time From Randomization to the First Morbidity Event or Death (All Causes) up to 7 Days After the Last Study Drug Intake KM estimate at Month 24	67.9 Percentage of patients free of events Interval 63.0 to 72.4	53.9 Percentage of patients free of events Interval 49.0 to 58.5
Time From Randomization to the First Morbidity Event or Death (All Causes) up to 7 Days After the Last Study Drug Intake KM estimate at Month 30	61.9 Percentage of patients free of events Interval 56.3 to 66.9	49.3 Percentage of patients free of events Interval 44.2 to 54.3
Time From Randomization to the First Morbidity Event or Death (All Causes) up to 7 Days After the Last Study Drug Intake KM estimate at Month 36	58.2 Percentage of patients free of events Interval 51.7 to 64.1	41.7 Percentage of patients free of events Interval 35.2 to 48.0

SECONDARY outcome

Timeframe: Week 26

Population: Full analysis set

The 6-minute walk distance test (6MWD) is a non-encouraged test performed in a 30 m long flat corridor, where the patient is instructed to walk as far as possible, back and forth around two cones, with the permission to slow down, rest, or stop if needed. If the patient was used to taking bronchodilators before a walk, he/she was given them 5 to 30 min before the test. Also if the patient was on chronic oxygen therapy, oxygen was given at their standard rate during the test. Absolute change from baseline to Week 26 in 6MWD was measured at trough, i.e., either on the next day after the last study drug administration or at least 12 hours after study drug administration if on the same day.

Outcome measures

Outcome measures
Measure	Selexipag n=574 Participants During the 12-week titration phase, treatment was initiated at 200 μg twice daily (b.i.d.) and up-titrated weekly in 200 μg b.i.d. increments to the maximum tolerated dose (MTD) for each individual patient but not above 1600 μg b.i.d. At Week 12, patients continued the treatment at their individual MTD up to Week 26. Thereafter the dose could be up-titrated at scheduled visits if needed for patients receiving a dose \< 1600 μg b.i.d. The dose could be decreased at any time in case of tolerability issues	Placebo n=582 Participants Matching placebo was administered orally following the same administration schedule as described for selexipag
Change From Baseline to Week 26 in 6-minute Walk Distance (6MWD) at Trough 6MWD at Week 26- Overall	370 Meters Interval 0.0 to 617.0	346 Meters Interval 0.0 to 650.0
Change From Baseline to Week 26 in 6-minute Walk Distance (6MWD) at Trough 6MWD Change from baseline at Week 26	4 Meters Interval -448.0 to 260.0	-9 Meters Interval -438.0 to 262.0
Change From Baseline to Week 26 in 6-minute Walk Distance (6MWD) at Trough 6MWD at baseline - Overall	376 Meters Interval 90.0 to 482.0	369 Meters Interval 50.0 to 515.0

SECONDARY outcome

Timeframe: Week 26

Population: Full analysis set. Patients with WHO FC IV at baseline were excluded from this analysis as they could not shift to a worse category

Outcome measures

Outcome measures
Measure	Selexipag n=571 Participants During the 12-week titration phase, treatment was initiated at 200 μg twice daily (b.i.d.) and up-titrated weekly in 200 μg b.i.d. increments to the maximum tolerated dose (MTD) for each individual patient but not above 1600 μg b.i.d. At Week 12, patients continued the treatment at their individual MTD up to Week 26. Thereafter the dose could be up-titrated at scheduled visits if needed for patients receiving a dose \< 1600 μg b.i.d. The dose could be decreased at any time in case of tolerability issues	Placebo n=574 Participants Matching placebo was administered orally following the same administration schedule as described for selexipag
Absence of Worsening From Baseline to Week 26 in Modified NYHA/WHO Functional Class (WHO FC)	77.8 Percentage of patients	74.9 Percentage of patients

Adverse Events

Selexipag

Serious events: 252 serious events

Other events: 544 other events

Deaths: 0 deaths

Placebo

Serious events: 272 serious events

Other events: 486 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Clinical trial disclosure desk

Actelion Pharmaceuticals Ltd

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: LTE60

Measure	Selexipag n=575 participants at risk This group includes patients who received at least one dose of selexipag. One subject who was randomized to placebo received a single dose of 8 tablets of selexipag due to an error in the dispensation of the medication bottle. Therefore, this patient was assigned to the selexipag group in the safety analysis set.	Placebo n=577 participants at risk This group includes patients who received at least one dose of placebo. Four patients who were randomized to placebo never received the drugs and another patient received selexipag by mistake (see Selexipag group for more details). Therefore, these patients were excluded from the placebo group in the safety analysis set.
Gastrointestinal disorders ABDOMINAL PAIN	7.7% 44/575 • Number of events 54 • From baseline up to up to 7 days after end of treatment (EOT) Median duration of exposure to study drug was 70.7 weeks (range: 0.3-216.7 weeks) in the selexipag group and 63.7 weeks (range: 0.7-192.0 weeks) in the placebo group	5.0% 29/577 • Number of events 37 • From baseline up to up to 7 days after end of treatment (EOT) Median duration of exposure to study drug was 70.7 weeks (range: 0.3-216.7 weeks) in the selexipag group and 63.7 weeks (range: 0.7-192.0 weeks) in the placebo group
Gastrointestinal disorders ABDOMINAL PAIN UPPER	5.9% 34/575 • Number of events 39 • From baseline up to up to 7 days after end of treatment (EOT) Median duration of exposure to study drug was 70.7 weeks (range: 0.3-216.7 weeks) in the selexipag group and 63.7 weeks (range: 0.7-192.0 weeks) in the placebo group	5.5% 32/577 • Number of events 38 • From baseline up to up to 7 days after end of treatment (EOT) Median duration of exposure to study drug was 70.7 weeks (range: 0.3-216.7 weeks) in the selexipag group and 63.7 weeks (range: 0.7-192.0 weeks) in the placebo group
Blood and lymphatic system disorders ANAEMIA	7.5% 43/575 • Number of events 53 • From baseline up to up to 7 days after end of treatment (EOT) Median duration of exposure to study drug was 70.7 weeks (range: 0.3-216.7 weeks) in the selexipag group and 63.7 weeks (range: 0.7-192.0 weeks) in the placebo group	4.9% 28/577 • Number of events 37 • From baseline up to up to 7 days after end of treatment (EOT) Median duration of exposure to study drug was 70.7 weeks (range: 0.3-216.7 weeks) in the selexipag group and 63.7 weeks (range: 0.7-192.0 weeks) in the placebo group
Musculoskeletal and connective tissue disorders ARTHRALGIA	10.8% 62/575 • Number of events 82 • From baseline up to up to 7 days after end of treatment (EOT) Median duration of exposure to study drug was 70.7 weeks (range: 0.3-216.7 weeks) in the selexipag group and 63.7 weeks (range: 0.7-192.0 weeks) in the placebo group	7.6% 44/577 • Number of events 57 • From baseline up to up to 7 days after end of treatment (EOT) Median duration of exposure to study drug was 70.7 weeks (range: 0.3-216.7 weeks) in the selexipag group and 63.7 weeks (range: 0.7-192.0 weeks) in the placebo group
General disorders ASTHENIA	5.0% 29/575 • Number of events 33 • From baseline up to up to 7 days after end of treatment (EOT) Median duration of exposure to study drug was 70.7 weeks (range: 0.3-216.7 weeks) in the selexipag group and 63.7 weeks (range: 0.7-192.0 weeks) in the placebo group	4.2% 24/577 • Number of events 27 • From baseline up to up to 7 days after end of treatment (EOT) Median duration of exposure to study drug was 70.7 weeks (range: 0.3-216.7 weeks) in the selexipag group and 63.7 weeks (range: 0.7-192.0 weeks) in the placebo group
Musculoskeletal and connective tissue disorders BACK PAIN	5.9% 34/575 • Number of events 36 • From baseline up to up to 7 days after end of treatment (EOT) Median duration of exposure to study drug was 70.7 weeks (range: 0.3-216.7 weeks) in the selexipag group and 63.7 weeks (range: 0.7-192.0 weeks) in the placebo group	6.1% 35/577 • Number of events 38 • From baseline up to up to 7 days after end of treatment (EOT) Median duration of exposure to study drug was 70.7 weeks (range: 0.3-216.7 weeks) in the selexipag group and 63.7 weeks (range: 0.7-192.0 weeks) in the placebo group
Infections and infestations BRONCHITIS	7.3% 42/575 • Number of events 46 • From baseline up to up to 7 days after end of treatment (EOT) Median duration of exposure to study drug was 70.7 weeks (range: 0.3-216.7 weeks) in the selexipag group and 63.7 weeks (range: 0.7-192.0 weeks) in the placebo group	7.1% 41/577 • Number of events 49 • From baseline up to up to 7 days after end of treatment (EOT) Median duration of exposure to study drug was 70.7 weeks (range: 0.3-216.7 weeks) in the selexipag group and 63.7 weeks (range: 0.7-192.0 weeks) in the placebo group
General disorders CHEST PAIN	5.9% 34/575 • Number of events 37 • From baseline up to up to 7 days after end of treatment (EOT) Median duration of exposure to study drug was 70.7 weeks (range: 0.3-216.7 weeks) in the selexipag group and 63.7 weeks (range: 0.7-192.0 weeks) in the placebo group	6.8% 39/577 • Number of events 54 • From baseline up to up to 7 days after end of treatment (EOT) Median duration of exposure to study drug was 70.7 weeks (range: 0.3-216.7 weeks) in the selexipag group and 63.7 weeks (range: 0.7-192.0 weeks) in the placebo group
Respiratory, thoracic and mediastinal disorders COUGH	9.7% 56/575 • Number of events 67 • From baseline up to up to 7 days after end of treatment (EOT) Median duration of exposure to study drug was 70.7 weeks (range: 0.3-216.7 weeks) in the selexipag group and 63.7 weeks (range: 0.7-192.0 weeks) in the placebo group	11.6% 67/577 • Number of events 87 • From baseline up to up to 7 days after end of treatment (EOT) Median duration of exposure to study drug was 70.7 weeks (range: 0.3-216.7 weeks) in the selexipag group and 63.7 weeks (range: 0.7-192.0 weeks) in the placebo group
Metabolism and nutrition disorders DECREASED APPETITE	5.9% 34/575 • Number of events 38 • From baseline up to up to 7 days after end of treatment (EOT) Median duration of exposure to study drug was 70.7 weeks (range: 0.3-216.7 weeks) in the selexipag group and 63.7 weeks (range: 0.7-192.0 weeks) in the placebo group	3.3% 19/577 • Number of events 23 • From baseline up to up to 7 days after end of treatment (EOT) Median duration of exposure to study drug was 70.7 weeks (range: 0.3-216.7 weeks) in the selexipag group and 63.7 weeks (range: 0.7-192.0 weeks) in the placebo group
Gastrointestinal disorders DIARRHOEA	42.1% 242/575 • Number of events 375 • From baseline up to up to 7 days after end of treatment (EOT) Median duration of exposure to study drug was 70.7 weeks (range: 0.3-216.7 weeks) in the selexipag group and 63.7 weeks (range: 0.7-192.0 weeks) in the placebo group	18.9% 109/577 • Number of events 137 • From baseline up to up to 7 days after end of treatment (EOT) Median duration of exposure to study drug was 70.7 weeks (range: 0.3-216.7 weeks) in the selexipag group and 63.7 weeks (range: 0.7-192.0 weeks) in the placebo group
Nervous system disorders DIZZINESS	14.8% 85/575 • Number of events 111 • From baseline up to up to 7 days after end of treatment (EOT) Median duration of exposure to study drug was 70.7 weeks (range: 0.3-216.7 weeks) in the selexipag group and 63.7 weeks (range: 0.7-192.0 weeks) in the placebo group	14.7% 85/577 • Number of events 106 • From baseline up to up to 7 days after end of treatment (EOT) Median duration of exposure to study drug was 70.7 weeks (range: 0.3-216.7 weeks) in the selexipag group and 63.7 weeks (range: 0.7-192.0 weeks) in the placebo group
Respiratory, thoracic and mediastinal disorders DYSPNOEA	13.7% 79/575 • Number of events 100 • From baseline up to up to 7 days after end of treatment (EOT) Median duration of exposure to study drug was 70.7 weeks (range: 0.3-216.7 weeks) in the selexipag group and 63.7 weeks (range: 0.7-192.0 weeks) in the placebo group	19.1% 110/577 • Number of events 143 • From baseline up to up to 7 days after end of treatment (EOT) Median duration of exposure to study drug was 70.7 weeks (range: 0.3-216.7 weeks) in the selexipag group and 63.7 weeks (range: 0.7-192.0 weeks) in the placebo group
General disorders FATIGUE	8.0% 46/575 • Number of events 54 • From baseline up to up to 7 days after end of treatment (EOT) Median duration of exposure to study drug was 70.7 weeks (range: 0.3-216.7 weeks) in the selexipag group and 63.7 weeks (range: 0.7-192.0 weeks) in the placebo group	10.1% 58/577 • Number of events 72 • From baseline up to up to 7 days after end of treatment (EOT) Median duration of exposure to study drug was 70.7 weeks (range: 0.3-216.7 weeks) in the selexipag group and 63.7 weeks (range: 0.7-192.0 weeks) in the placebo group
Vascular disorders FLUSHING	12.0% 69/575 • Number of events 80 • From baseline up to up to 7 days after end of treatment (EOT) Median duration of exposure to study drug was 70.7 weeks (range: 0.3-216.7 weeks) in the selexipag group and 63.7 weeks (range: 0.7-192.0 weeks) in the placebo group	5.0% 29/577 • Number of events 31 • From baseline up to up to 7 days after end of treatment (EOT) Median duration of exposure to study drug was 70.7 weeks (range: 0.3-216.7 weeks) in the selexipag group and 63.7 weeks (range: 0.7-192.0 weeks) in the placebo group
Nervous system disorders HEADACHE	65.0% 374/575 • Number of events 649 • From baseline up to up to 7 days after end of treatment (EOT) Median duration of exposure to study drug was 70.7 weeks (range: 0.3-216.7 weeks) in the selexipag group and 63.7 weeks (range: 0.7-192.0 weeks) in the placebo group	32.8% 189/577 • Number of events 261 • From baseline up to up to 7 days after end of treatment (EOT) Median duration of exposure to study drug was 70.7 weeks (range: 0.3-216.7 weeks) in the selexipag group and 63.7 weeks (range: 0.7-192.0 weeks) in the placebo group
Musculoskeletal and connective tissue disorders MYALGIA	15.7% 90/575 • Number of events 120 • From baseline up to up to 7 days after end of treatment (EOT) Median duration of exposure to study drug was 70.7 weeks (range: 0.3-216.7 weeks) in the selexipag group and 63.7 weeks (range: 0.7-192.0 weeks) in the placebo group	5.9% 34/577 • Number of events 37 • From baseline up to up to 7 days after end of treatment (EOT) Median duration of exposure to study drug was 70.7 weeks (range: 0.3-216.7 weeks) in the selexipag group and 63.7 weeks (range: 0.7-192.0 weeks) in the placebo group
Infections and infestations NASOPHARYNGITIS	13.0% 75/575 • Number of events 105 • From baseline up to up to 7 days after end of treatment (EOT) Median duration of exposure to study drug was 70.7 weeks (range: 0.3-216.7 weeks) in the selexipag group and 63.7 weeks (range: 0.7-192.0 weeks) in the placebo group	10.9% 63/577 • Number of events 95 • From baseline up to up to 7 days after end of treatment (EOT) Median duration of exposure to study drug was 70.7 weeks (range: 0.3-216.7 weeks) in the selexipag group and 63.7 weeks (range: 0.7-192.0 weeks) in the placebo group
Gastrointestinal disorders NAUSEA	33.4% 192/575 • Number of events 265 • From baseline up to up to 7 days after end of treatment (EOT) Median duration of exposure to study drug was 70.7 weeks (range: 0.3-216.7 weeks) in the selexipag group and 63.7 weeks (range: 0.7-192.0 weeks) in the placebo group	18.5% 107/577 • Number of events 136 • From baseline up to up to 7 days after end of treatment (EOT) Median duration of exposure to study drug was 70.7 weeks (range: 0.3-216.7 weeks) in the selexipag group and 63.7 weeks (range: 0.7-192.0 weeks) in the placebo group
General disorders OEDEMA PERIPHERAL	13.4% 77/575 • Number of events 90 • From baseline up to up to 7 days after end of treatment (EOT) Median duration of exposure to study drug was 70.7 weeks (range: 0.3-216.7 weeks) in the selexipag group and 63.7 weeks (range: 0.7-192.0 weeks) in the placebo group	17.3% 100/577 • Number of events 138 • From baseline up to up to 7 days after end of treatment (EOT) Median duration of exposure to study drug was 70.7 weeks (range: 0.3-216.7 weeks) in the selexipag group and 63.7 weeks (range: 0.7-192.0 weeks) in the placebo group
Musculoskeletal and connective tissue disorders PAIN IN EXTREMITY	16.5% 95/575 • Number of events 142 • From baseline up to up to 7 days after end of treatment (EOT) Median duration of exposure to study drug was 70.7 weeks (range: 0.3-216.7 weeks) in the selexipag group and 63.7 weeks (range: 0.7-192.0 weeks) in the placebo group	8.0% 46/577 • Number of events 62 • From baseline up to up to 7 days after end of treatment (EOT) Median duration of exposure to study drug was 70.7 weeks (range: 0.3-216.7 weeks) in the selexipag group and 63.7 weeks (range: 0.7-192.0 weeks) in the placebo group
Musculoskeletal and connective tissue disorders PAIN IN JAW	25.7% 148/575 • Number of events 188 • From baseline up to up to 7 days after end of treatment (EOT) Median duration of exposure to study drug was 70.7 weeks (range: 0.3-216.7 weeks) in the selexipag group and 63.7 weeks (range: 0.7-192.0 weeks) in the placebo group	6.2% 36/577 • Number of events 38 • From baseline up to up to 7 days after end of treatment (EOT) Median duration of exposure to study drug was 70.7 weeks (range: 0.3-216.7 weeks) in the selexipag group and 63.7 weeks (range: 0.7-192.0 weeks) in the placebo group
Cardiac disorders PALPITATIONS	5.6% 32/575 • Number of events 40 • From baseline up to up to 7 days after end of treatment (EOT) Median duration of exposure to study drug was 70.7 weeks (range: 0.3-216.7 weeks) in the selexipag group and 63.7 weeks (range: 0.7-192.0 weeks) in the placebo group	5.4% 31/577 • Number of events 41 • From baseline up to up to 7 days after end of treatment (EOT) Median duration of exposure to study drug was 70.7 weeks (range: 0.3-216.7 weeks) in the selexipag group and 63.7 weeks (range: 0.7-192.0 weeks) in the placebo group
Respiratory, thoracic and mediastinal disorders PULMONARY ARTERIAL HYPERTENSION	8.0% 46/575 • Number of events 64 • From baseline up to up to 7 days after end of treatment (EOT) Median duration of exposure to study drug was 70.7 weeks (range: 0.3-216.7 weeks) in the selexipag group and 63.7 weeks (range: 0.7-192.0 weeks) in the placebo group	14.6% 84/577 • Number of events 141 • From baseline up to up to 7 days after end of treatment (EOT) Median duration of exposure to study drug was 70.7 weeks (range: 0.3-216.7 weeks) in the selexipag group and 63.7 weeks (range: 0.7-192.0 weeks) in the placebo group
Nervous system disorders SYNCOPE	5.2% 30/575 • Number of events 35 • From baseline up to up to 7 days after end of treatment (EOT) Median duration of exposure to study drug was 70.7 weeks (range: 0.3-216.7 weeks) in the selexipag group and 63.7 weeks (range: 0.7-192.0 weeks) in the placebo group	5.9% 34/577 • Number of events 42 • From baseline up to up to 7 days after end of treatment (EOT) Median duration of exposure to study drug was 70.7 weeks (range: 0.3-216.7 weeks) in the selexipag group and 63.7 weeks (range: 0.7-192.0 weeks) in the placebo group
Infections and infestations UPPER RESPIRATORY TRACT INFECTION	12.5% 72/575 • Number of events 100 • From baseline up to up to 7 days after end of treatment (EOT) Median duration of exposure to study drug was 70.7 weeks (range: 0.3-216.7 weeks) in the selexipag group and 63.7 weeks (range: 0.7-192.0 weeks) in the placebo group	13.7% 79/577 • Number of events 119 • From baseline up to up to 7 days after end of treatment (EOT) Median duration of exposure to study drug was 70.7 weeks (range: 0.3-216.7 weeks) in the selexipag group and 63.7 weeks (range: 0.7-192.0 weeks) in the placebo group
Infections and infestations URINARY TRACT INFECTION	4.2% 24/575 • Number of events 30 • From baseline up to up to 7 days after end of treatment (EOT) Median duration of exposure to study drug was 70.7 weeks (range: 0.3-216.7 weeks) in the selexipag group and 63.7 weeks (range: 0.7-192.0 weeks) in the placebo group	5.2% 30/577 • Number of events 34 • From baseline up to up to 7 days after end of treatment (EOT) Median duration of exposure to study drug was 70.7 weeks (range: 0.3-216.7 weeks) in the selexipag group and 63.7 weeks (range: 0.7-192.0 weeks) in the placebo group
Gastrointestinal disorders VOMITING	17.9% 103/575 • Number of events 143 • From baseline up to up to 7 days after end of treatment (EOT) Median duration of exposure to study drug was 70.7 weeks (range: 0.3-216.7 weeks) in the selexipag group and 63.7 weeks (range: 0.7-192.0 weeks) in the placebo group	8.3% 48/577 • Number of events 53 • From baseline up to up to 7 days after end of treatment (EOT) Median duration of exposure to study drug was 70.7 weeks (range: 0.3-216.7 weeks) in the selexipag group and 63.7 weeks (range: 0.7-192.0 weeks) in the placebo group