Effect of Selexipag on Daily Life Physical Activity of Pa... | NCT03078907

Status Module

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Selexipag	Experimental	Selexipag is up-titrated from Day 1 to Week 12 to the individualized highest tolerated dose (HTD), which can range from 200 mcg b.i.d. to 1600 mcg b.i.d., in 200 mcg steps starting with 200 mcg b.i.d. Then, the dose is increased in increments of 200 mcg b.i.d., usually at weekly intervals, depending on the dose tolerability. Up-titration is followed by a stable maintenance treatment period at the highest tolerated dose, from Week 13 to Week 24.	Drug: Selexipag
Placebo	Placebo Comparator	Regimen and titration scheme similar to those in the selexipag group	Drug: Placebo

Interventions

Name	Type	Description	Arm Group Labels	Other Names
Selexipag	Drug	Film-coated tablets for oral use; one tablet (200 mcg) to eight tablets (1600 mcg) are administered depending on the individual tolerability.	Selexipag

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Change From Baseline to Week 24 in Actigraphy Assessed Daily Life Physical Activity (DLPA) for Variables Expressed in Minutes	Change from baseline to Week 24 of the DLPA activity parameters for daily time spent in non-sedentary activity (NSA) (as defined by Freedson '98 and Koster '16) and daily time spent in moderate-to-vigorous physical activity (MVPA) as defined by Freedson '98 were reported. These variables were assessed by actigraphy and were expressed in minutes. Freedson 1998 established ranges of activity counts obtained from a hip worn accelerometer corresponding to commonly employed MET categories. Based on this work, threshold between sedentary and NSA was defined. This threshold is often referred to as Freedson's 1998 publication. Koster 2016 defined the threshold between sedentary and NSA based on wrist-worn accelerometers on non-dominant hand, respectively. Positive change from baseline means improvement.	Baseline and Week 24 (data analysis was done during 14-Days each for Baseline and for Week 24 and mean value reported)
Change From Baseline to Week 24 in Actigraphy DLPA for Variables Expressed in Percentage (%)	Change from baseline to Week 24 of the DLPA activity parameters for daily time spent in non-sedentary activity (NSA) (Freedson '98), daily time spent in moderate-to-vigorous physical activity (MVPA) (Freedson '98) and dailytime spent in NSA (Koster '16) were reported. These variables were assessed by actigraphy and were expressed in percentage (%). Freedson 1998 established ranges of activity counts obtained from a hip worn accelerometer corresponding to commonly employed MET categories. Based on this work, threshold between sedentary and NSA was defined. This threshold is often referred to as Freedson's 1998 publication. Koster 2016 defined the threshold between sedentary and NSA based on wrist-worn accelerometers on non-dominant hand, respectively. Positive change from baseline means improvement.	Baseline and Week 24 (data analysis was done during 14-Days each for Baseline and for Week 24 and mean value reported)
Change From Baseline to Week 24 in Actigraphy DLPA for Variables Expressed in Counts Per Minute (Counts/Minute)	Change from baseline to Week 24 of the DLPA activity parameter for total daily activities and NSA (Koster '16) were reported. These variables were assessed by actigraphy and were expressed in counts/minutes. Koster 2016 defined the threshold between sedentary and NSA based on wrist-worn accelerometers on non-dominant hand, respectively. Positive change from baseline means improvement.

Secondary Outcomes

Measure	Description	Time Frame
Change From Baseline to Week 24 in Pulmonary Arterial Hypertension-Symptoms and Impact (PAH-SYMPACT) Score	PAH-SYMPACT has 2 main parts: symptoms (cardiopulmonary and cardiovascular) and impact (physical impacts and cognitive/emotional). The symptom part is a questionnaire completed daily for 7 consecutive days and contains 11 items. The impact part has a 7-day recall period and is completed on 7th day of symptoms questionnaire data collection period. It contains 11 items pertaining to impact of PAH. The average Cardiopulmonary Symptoms and cardiovascular symptoms domain scores are determined based on daily scores of 6 and 5 items, respectively, reported on a 5-point Likert scale with score range from 0=best to 4=worst. The Physical impacts and Cognitive/emotional domain consists of 7 items reported on a 5-point Likert scale (from 0 to 4). The value 0 = "not at all"/"with no difficulty at all" and value 4 = "very much"/"extremely"/ "not able at all". Mean value on each of 7-day period was calculated for each specific domain score and corresponding mean change from baseline was reported.

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Male or female between 18 and 75 years old inclusive.
Women of childbearing potential must have a negative serum pregnancy test at planned visits and use an acceptable method of birth control from screening up to 30 days after study treatment discontinuation.
Symptomatic pulmonary arterial hypertension (PAH) belonging to one of the following subgroups only:
- Idiopathic
- Heritable
- Drug or toxin induced
- Associated with one of the following: connective tissue disease; HIV infection; corrected simple congenital heart disease.
With the following hemodynamic characteristics assessed by right heart catheterization (RHC) prior to randomization:
- Mean pulmonary artery pressure (mPAP) ≥ 25 mmHg
- Pulmonary vascular resistance (PVR) ≥ 240 dyn•sec/cm5 (or 3 Wood Units)
- Pulmonary artery wedge pressure (PCWP) or left ventricular end-diastolic pressure (LVEDP) ≤ 15 mmHg.
Treatment with an endothelin receptor antagonist (ERA) for at least 90 days and on a stable dose for 30 days prior to randomization.
If an ERA is given in combination with a phosphodiesterase-5 (PDE-5) inhibitor or soluble guanylate cyclase (sGC) stimulator, these treatments must be ongoing for at least 90 days and on a stable dose for 30 days prior to randomization.
WHO functional class (FC) II or III at randomization
6-minute walk distance (6MWD) ≥ 100 m at screening.
Ability to walk without a walking aid.
Valid baseline data for daily life physical activity (DLPA) and PAH-SYMPACT®.

Exclusion Criteria:

Patients on a PAH-specific monotherapy targeting the nitric oxide pathway (i.e. PDE-5 inhibitor or sGC stimulator).
Patients treated with prostacyclin, prostacyclin analog or selexipag within 3 months prior to screening.
Any hospitalization during the last 30 days prior to screening.
Severe coronary heart disease or unstable angina.
Documented severe hepatic impairment or severe renal insufficiency at screening.
Participation in a cardio-pulmonary rehabilitation program based on exercise training within 8 weeks prior to screening
Any factor or condition likely to affect full participation in the study or compliance with the protocol (such as adherence to protocol mandated procedures), as judged by the investigator.

Name	Affiliation	Role
Thomas Pfister	Actelion	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
LA Biomedical Research Institute		Torrance	California	90502	United States
Northside Hospital

PubMed Identifier	Type	Citation	Retractions
40433632	Derived	Rehman RZU, Parisi F, Ashraf N, Chatterjee M, Frantz RP, Hemnes AR, Manyakov NV, Carrasco-Zevallos OM, Yardibi T, Selej M, Mansi T, Dunnmon P, Kaliukhovich DA. Characteristics of Daily Walking Bouts as Valid and Reliable Indicators of Exercise Capacity in Pulmonary Arterial Hypertension: Insights From the Randomized Controlled Study With Selexipag (TRACE). Pulm Circ. 2025 May 26;15(2):e70097. doi: 10.1002/pul2.70097. eCollection 2025 Apr.
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Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Selexipag	Participants received Selexipag which was up-titrated from Day 1 (Week 1) to Week 12 to the individualized highest tolerated dose (HTD) which ranged from 200 microgram (mcg) to 1600 mcg twice daily (BID) orally. The dose was increased in increments of 200 mcg BID, usually at weekly intervals, depending on the dose tolerability. Up-titration was followed by a stable maintenance treatment period at the highest tolerated dose, from Week 13 to Week 24.

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Dec 5, 2018	Feb 4, 2021

Arm/Group Information

ID	Title	Description
BG000	Selexipag	Participants received Selexipag which was up-titrated from Day 1 (Week 1) to Week 12 to the individualized highest tolerated dose (HTD) which ranged from 200 microgram (mcg) to 1600 mcg twice daily (BID) orally. The dose was increased in increments of 200 mcg BID, usually at weekly intervals, depending on the dose tolerability. Up-titration was followed by a stable maintenance treatment period at the highest tolerated dose, from Week 13 to Week 24.
BG001	Placebo	Participants received one to 8 tablets of 200 (mcg) matching placebo, administered up to a maximum dose up-titrated to 1600 mcg orally twice daily. Up-titration was followed by a stable maintenance treatment period at the highest tolerated dose, from Week 13 to Week 24.
BG002	Total	Total of all reporting groups

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Change From Baseline to Week 24 in Actigraphy Assessed Daily Life Physical Activity (DLPA) for Variables Expressed in Minutes

Change from baseline to Week 24 of the DLPA activity parameters for daily time spent in non-sedentary activity (NSA) (as defined by Freedson '98 and Koster '16) and daily time spent in moderate-to-vigorous physical activity (MVPA) as defined by Freedson '98 were reported. These variables were assessed by actigraphy and were expressed in minutes. Freedson 1998 established ranges of activity counts obtained from a hip worn accelerometer corresponding to commonly employed MET categories. Based on this work, threshold between sedentary and NSA was defined. This threshold is often referred to as Freedson's 1998 publication. Koster 2016 defined the threshold between sedentary and NSA based on wrist-worn accelerometers on non-dominant hand, respectively. Positive change from baseline means improvement.

The Full Analysis Set (FAS) included all participants randomly assigned to a study treatment.

Posted

Mean

Standard Deviation

minutes

Baseline and Week 24 (data analysis was done during 14-Days each for Baseline and for Week 24 and mean value reported)

ID	Title	Description
OG000	Selexipag	Participants received Selexipag which was up-titrated from Day 1 (Week 1) to Week 12 to the individualized highest tolerated dose (HTD) which ranged from 200 microgram (mcg) to 1600 mcg twice daily (BID) orally. The dose was increased in increments of 200 mcg BID, usually at weekly intervals, depending on the dose tolerability. Up-titration was followed by a stable maintenance treatment period at the highest tolerated dose, from Week 13 to Week 24.
OG001	Placebo	Participants received one to 8 tablets of 200 (mcg) matching placebo, administered up to a maximum dose up-titrated to 1600 mcg orally twice daily. Up-titration was followed by a stable maintenance treatment period at the highest tolerated dose, from Week 13 to Week 24.

Units	Counts
Participants	OG00053 OG00155

Title

Denominators

Categories

Daily time spent in NSA (Freedson '98)

Title	Measurements
	OG000-15.2± 79.78 OG001-25.2± 72.47

Daily time spent in MVPA (Freedson '98)

Title	Measurements
	OG000

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001	Daily time spent in non-sedentary activity (minutes), Freedson '98	ANCOVA				Least Square (LS) mean	13.79	Standard Error of the Mean	13.695	2-Sided	95	13.366	40.944					Other
OG000 OG001	Daily time spent in MVPA (minutes), Freedson '98

Primary

Change From Baseline to Week 24 in Actigraphy DLPA for Variables Expressed in Percentage (%)

Change from baseline to Week 24 of the DLPA activity parameters for daily time spent in non-sedentary activity (NSA) (Freedson '98), daily time spent in moderate-to-vigorous physical activity (MVPA) (Freedson '98) and dailytime spent in NSA (Koster '16) were reported. These variables were assessed by actigraphy and were expressed in percentage (%). Freedson 1998 established ranges of activity counts obtained from a hip worn accelerometer corresponding to commonly employed MET categories. Based on this work, threshold between sedentary and NSA was defined. This threshold is often referred to as Freedson's 1998 publication. Koster 2016 defined the threshold between sedentary and NSA based on wrist-worn accelerometers on non-dominant hand, respectively. Positive change from baseline means improvement.

The Full Analysis Set (FAS) included all participants randomly assigned to a study treatment.

Posted

Mean

Standard Deviation

Percentage of daily time spent

Baseline and Week 24 (data analysis was done during 14-Days each for Baseline and for Week 24 and mean value reported)

ID	Title	Description
OG000	Selexipag	Participants received Selexipag which was up-titrated from Day 1 (Week 1) to Week 12 to the individualized highest tolerated dose (HTD) which ranged from 200 microgram (mcg) to 1600 mcg twice daily (BID) orally. The dose was increased in increments of 200 mcg BID, usually at weekly intervals, depending on the dose tolerability. Up-titration was followed by a stable maintenance treatment period at the highest tolerated dose, from Week 13 to Week 24.

Primary

Change From Baseline to Week 24 in Actigraphy DLPA for Variables Expressed in Counts Per Minute (Counts/Minute)

Change from baseline to Week 24 of the DLPA activity parameter for total daily activities and NSA (Koster '16) were reported. These variables were assessed by actigraphy and were expressed in counts/minutes. Koster 2016 defined the threshold between sedentary and NSA based on wrist-worn accelerometers on non-dominant hand, respectively. Positive change from baseline means improvement.

The Full Analysis Set (FAS) included all participants randomly assigned to a study treatment.

Posted

Mean

Standard Deviation

counts/minute

Baseline and Week 24 (data analysis was done during 14-Days each for Baseline and for Week 24 and mean value reported)

ID	Title	Description
OG000	Selexipag	Participants received Selexipag which was up-titrated from Day 1 (Week 1) to Week 12 to the individualized highest tolerated dose (HTD) which ranged from 200 microgram (mcg) to 1600 mcg twice daily (BID) orally. The dose was increased in increments of 200 mcg BID, usually at weekly intervals, depending on the dose tolerability. Up-titration was followed by a stable maintenance treatment period at the highest tolerated dose, from Week 13 to Week 24.
OG001	Placebo	Participants received one to 8 tablets of 200 (mcg) matching placebo, administered up to a maximum dose up-titrated to 1600 mcg orally twice daily. Up-titration was followed by a stable maintenance treatment period at the highest tolerated dose, from Week 13 to Week 24.

Primary

Change From Baseline to Week 24 in Actigraphy DLPA for Variables Expressed in Counts

Change from baseline to Week 24 of the DLPA activity parameters for volume of non-sedentary activity (Koster '16)were reported. These variables were assessed by actigraphy and were expressed in counts. Koster 2016 defined the threshold between sedentary and NSA based on wrist-worn accelerometers on non-dominant hand, respectively. Positive change from baseline means improvement.

The Full Analysis Set (FAS) included all participants randomly assigned to a study treatment.

Posted

Mean

Standard Deviation

counts

Baseline and Week 24 (data analysis was done during 14-Days each for Baseline and for Week 24 and mean value reported)

ID	Title	Description
OG000	Selexipag	Participants received Selexipag which was up-titrated from Day 1 (Week 1) to Week 12 to the individualized highest tolerated dose (HTD) which ranged from 200 microgram (mcg) to 1600 mcg twice daily (BID) orally. The dose was increased in increments of 200 mcg BID, usually at weekly intervals, depending on the dose tolerability. Up-titration was followed by a stable maintenance treatment period at the highest tolerated dose, from Week 13 to Week 24.
OG001	Placebo	Participants received one to 8 tablets of 200 (mcg) matching placebo, administered up to a maximum dose up-titrated to 1600 mcg orally twice daily. Up-titration was followed by a stable maintenance treatment period at the highest tolerated dose, from Week 13 to Week 24.

Primary

Change From Baseline to Week 24 in Actigraphy DLPA for Variable Expressed in Step Counts

Change from baseline to Week 24 of the DLPA activity parameters for number of steps during awake time were reported. These variables were assessed by actigraphy and were expressed in step counts. Positive change from baseline means improvement.

The Full Analysis Set (FAS) included all participants randomly assigned to a study treatment.

Posted

Mean

Standard Deviation

step counts

Baseline and Week 24 (data analysis was done during 14-Days each for Baseline and for Week 24 and mean value reported)

ID	Title	Description
OG000	Selexipag	Participants received Selexipag which was up-titrated from Day 1 (Week 1) to Week 12 to the individualized highest tolerated dose (HTD) which ranged from 200 microgram (mcg) to 1600 mcg twice daily (BID) orally. The dose was increased in increments of 200 mcg BID, usually at weekly intervals, depending on the dose tolerability. Up-titration was followed by a stable maintenance treatment period at the highest tolerated dose, from Week 13 to Week 24.
OG001	Placebo	Participants received one to 8 tablets of 200 (mcg) matching placebo, administered up to a maximum dose up-titrated to 1600 mcg orally twice daily. Up-titration was followed by a stable maintenance treatment period at the highest tolerated dose, from Week 13 to Week 24.

Primary

Change From Baseline to Week 24 in Actigraphy DLPA for Variables Expressed in Step Counts/Minute

The Full Analysis Set (FAS) included all participants randomly assigned to a study treatment.

Posted

Mean

Standard Deviation

step counts/minute

Baseline and Week 24 (data analysis was done during 14-Days each for Baseline and for Week 24 and mean value reported)

ID	Title	Description
OG000	Selexipag	Participants received Selexipag which was up-titrated from Day 1 (Week 1) to Week 12 to the individualized highest tolerated dose (HTD) which ranged from 200 microgram (mcg) to 1600 mcg twice daily (BID) orally. The dose was increased in increments of 200 mcg BID, usually at weekly intervals, depending on the dose tolerability. Up-titration was followed by a stable maintenance treatment period at the highest tolerated dose, from Week 13 to Week 24.
OG001	Placebo	Participants received one to 8 tablets of 200 (mcg) matching placebo, administered up to a maximum dose up-titrated to 1600 mcg orally twice daily. Up-titration was followed by a stable maintenance treatment period at the highest tolerated dose, from Week 13 to Week 24.

Primary

Change From Baseline to Week 24 in Total Sleep Time (TST)

TST (in minutes) was assessed by actigraphy.

The FAS included all participants randomly assigned to a study treatment. Data was not reported because the sleep episodes were not identified due to unexpected inaccuracy in automated sleep detection algorithm which resulted in missing/unreliable sleep data which would mislead the design of future trials and the interpretation of sleep results.

Posted

Baseline and Week 24 (data analysis was done during 14-Days each for Baseline and for Week 24 and mean value reported)

ID	Title	Description
OG000	Selexipag	Participants received Selexipag which was up-titrated from Day 1 (Week 1) to Week 12 to the individualized highest tolerated dose (HTD) which ranged from 200 microgram (mcg) to 1600 mcg twice daily (BID) orally. The dose was increased in increments of 200 mcg BID, usually at weekly intervals, depending on the dose tolerability. Up-titration was followed by a stable maintenance treatment period at the highest tolerated dose, from Week 13 to Week 24.
OG001	Placebo	Participants received one to 8 tablets of 200 (mcg) matching placebo, administered up to a maximum dose up-titrated to 1600 mcg orally twice daily. Up-titration was followed by a stable maintenance treatment period at the highest tolerated dose, from Week 13 to Week 24.

Primary

Change From Baseline to Week 24 in Wake After Sleep Onset (WASO)

WASO (in minutes) was assessed by actigraphy.

Posted

Baseline and Week 24 (data collection was done during 14-Days each for Baseline and for Week 24)

ID	Title	Description
OG000	Selexipag	Participants received Selexipag which was up-titrated from Day 1 (Week 1) to Week 12 to the individualized highest tolerated dose (HTD) which ranged from 200 microgram (mcg) to 1600 mcg twice daily (BID) orally. The dose was increased in increments of 200 mcg BID, usually at weekly intervals, depending on the dose tolerability. Up-titration was followed by a stable maintenance treatment period at the highest tolerated dose, from Week 13 to Week 24.
OG001	Placebo	Participants received one to 8 tablets of 200 (mcg) matching placebo, administered up to a maximum dose up-titrated to 1600 mcg orally twice daily. Up-titration was followed by a stable maintenance treatment period at the highest tolerated dose, from Week 13 to Week 24.

Primary

Change From Baseline to Week 24 in Number of Awakenings

Number of awakenings was assessed by actigraphy.

Posted

Baseline and Week 24 (data collection was done during 14-Days each for Baseline and for Week 24)

ID	Title	Description
OG000	Selexipag	Participants received Selexipag which was up-titrated from Day 1 (Week 1) to Week 12 to the individualized highest tolerated dose (HTD) which ranged from 200 microgram (mcg) to 1600 mcg twice daily (BID) orally. The dose was increased in increments of 200 mcg BID, usually at weekly intervals, depending on the dose tolerability. Up-titration was followed by a stable maintenance treatment period at the highest tolerated dose, from Week 13 to Week 24.
OG001	Placebo	Participants received one to 8 tablets of 200 (mcg) matching placebo, administered up to a maximum dose up-titrated to 1600 mcg orally twice daily. Up-titration was followed by a stable maintenance treatment period at the highest tolerated dose, from Week 13 to Week 24.

Primary

Change From Baseline to Week 24 in Sleep Efficiency (SE)

SE (in percentage) was assessed by actigraphy. Sleep efficiency was defined as the TST divided by the time in bed (minutes) multiplied by 100. TST was the duration in minutes including REM sleep plus NREM sleep during the time spent in bed.

Posted

Baseline and Week 24 (data collection was done during 14-Days each for Baseline and for Week 24)

ID	Title	Description
OG000	Selexipag	Participants received Selexipag which was up-titrated from Day 1 (Week 1) to Week 12 to the individualized highest tolerated dose (HTD) which ranged from 200 microgram (mcg) to 1600 mcg twice daily (BID) orally. The dose was increased in increments of 200 mcg BID, usually at weekly intervals, depending on the dose tolerability. Up-titration was followed by a stable maintenance treatment period at the highest tolerated dose, from Week 13 to Week 24.
OG001	Placebo	Participants received one to 8 tablets of 200 (mcg) matching placebo, administered up to a maximum dose up-titrated to 1600 mcg orally twice daily. Up-titration was followed by a stable maintenance treatment period at the highest tolerated dose, from Week 13 to Week 24.

Secondary

Change From Baseline to Week 24 in Pulmonary Arterial Hypertension-Symptoms and Impact (PAH-SYMPACT) Score

PAH-SYMPACT has 2 main parts: symptoms (cardiopulmonary and cardiovascular) and impact (physical impacts and cognitive/emotional). The symptom part is a questionnaire completed daily for 7 consecutive days and contains 11 items. The impact part has a 7-day recall period and is completed on 7th day of symptoms questionnaire data collection period. It contains 11 items pertaining to impact of PAH. The average Cardiopulmonary Symptoms and cardiovascular symptoms domain scores are determined based on daily scores of 6 and 5 items, respectively, reported on a 5-point Likert scale with score range from 0=best to 4=worst. The Physical impacts and Cognitive/emotional domain consists of 7 items reported on a 5-point Likert scale (from 0 to 4). The value 0 = "not at all"/"with no difficulty at all" and value 4 = "very much"/"extremely"/ "not able at all". Mean value on each of 7-day period was calculated for each specific domain score and corresponding mean change from baseline was reported.

The FAS included all participants randomly assigned to a study treatment. Here, 'N' (Number of participants analyzed) included all participants evaluated for this outcome measure. Here, 'n' (number analyzed) signifies the number of participants evaluable for a specified category.

Posted

Mean

Standard Deviation

units on a scale

Baseline and Week 24

ID	Title	Description
OG000	Selexipag	Participants received Selexipag which was up-titrated from Day 1 (Week 1) to Week 12 to the individualized highest tolerated dose (HTD) which ranged from 200 microgram (mcg) to 1600 mcg twice daily (BID) orally. The dose was increased in increments of 200 mcg BID, usually at weekly intervals, depending on the dose tolerability. Up-titration was followed by a stable maintenance treatment period at the highest tolerated dose, from Week 13 to Week 24.

Secondary

Number of Participants With Change From Baseline to Week 24 in World Health Organization Functional Class (WHO FC)

The WHO FC of pulmonary hypertension is a physical activity rating scale as follows: Class I (No limitation of physical activity); Class II (Slight limitation of physical activity); Class III (Marked limitation of physical activity); and Class IV (Inability to carry out any physical activity without symptoms). The change from baseline in WHO FC was classified into "Improved", "No change" and "Worsened" compared to baseline. Deterioration, No Change, and Improvement are based on shift of risk category (I, II, III, IV) from baseline in WHO Functional Class.

The FAS included all participants randomly assigned to a study treatment. Here 'N' (number of participants analyzed) included all participants who were with assessments at both baseline and post-baseline time point.

Posted

Count of Participants

Participants

Baseline and Week 24

ID	Title	Description
OG000	Selexipag	Participants received Selexipag which was up-titrated from Day 1 (Week 1) to Week 12 to the individualized highest tolerated dose (HTD) which ranged from 200 microgram (mcg) to 1600 mcg twice daily (BID) orally. The dose was increased in increments of 200 mcg BID, usually at weekly intervals, depending on the dose tolerability. Up-titration was followed by a stable maintenance treatment period at the highest tolerated dose, from Week 13 to Week 24.
OG001	Placebo

Secondary

Change From Baseline to Week 24 in 6-Minute Walk Distance (6MWD)

The 6MWD was the total distance walked during 6 minutes. Mean change from baseline (distance walked at Week 24 minus distance walked at baseline) was reported.

The FAS included all participants randomly assigned to a study treatment. Here, N (Number of participants analyzed) signifies number of participants evaluable for this endpoint.

Posted

Mean

Standard Deviation

meters

Baseline and Week 24

ID	Title	Description
OG000	Selexipag	Participants received Selexipag which was up-titrated from Day 1 (Week 1) to Week 12 to the individualized highest tolerated dose (HTD) which ranged from 200 microgram (mcg) to 1600 mcg twice daily (BID) orally. The dose was increased in increments of 200 mcg BID, usually at weekly intervals, depending on the dose tolerability. Up-titration was followed by a stable maintenance treatment period at the highest tolerated dose, from Week 13 to Week 24.
OG001	Placebo	Participants received one to 8 tablets of 200 (mcg) matching placebo, administered up to a maximum dose up-titrated to 1600 mcg orally twice daily. Up-titration was followed by a stable maintenance treatment period at the highest tolerated dose, from Week 13 to Week 24.

Secondary

Change From Baseline to Week 24 in Borg Dyspnea Score

The Borg dyspneas score was a self-rating scale to evaluate the severity of dyspnea (from 0 "no shortness of breath at all" to 10 "very, very severe / maximal") shortness of breath. It was completed immediately after the 6-minute walk test at Week 24 and at baseline. Mean change from baseline in scoring was reported.

The FAS included all participants randomly assigned to a study treatment. Here, N (Number of Participants Analyzed) signifies number of participants evaluable for this outcome measure.

Posted

Mean

Standard Deviation

units on a scale

Baseline and Week 24

ID	Title	Description
OG000	Selexipag	Participants received Selexipag which was up-titrated from Day 1 (Week 1) to Week 12 to the individualized highest tolerated dose (HTD) which ranged from 200 microgram (mcg) to 1600 mcg twice daily (BID) orally. The dose was increased in increments of 200 mcg BID, usually at weekly intervals, depending on the dose tolerability. Up-titration was followed by a stable maintenance treatment period at the highest tolerated dose, from Week 13 to Week 24.
OG001	Placebo	Participants received one to 8 tablets of 200 (mcg) matching placebo, administered up to a maximum dose up-titrated to 1600 mcg orally twice daily. Up-titration was followed by a stable maintenance treatment period at the highest tolerated dose, from Week 13 to Week 24.

Secondary

Change From Baseline to Week 24 in N-Terminal Pro B-type Natriuretic Peptide (NT-proBNP)

Change from baseline to Week 24 in NT-pro BNP levels was reported. The negative change from baseline means improvement.

The FAS included all participants randomly assigned to a study treatment. Here, N (Number of Participants Analyzed) signifies number of participants evaluable for this endpoint.

Posted

Mean

Standard Deviation

nanogram per liter (ng/L)

Baseline and Week 24

ID	Title	Description
OG000	Selexipag	Participants received Selexipag which was up-titrated from Day 1 (Week 1) to Week 12 to the individualized highest tolerated dose (HTD) which ranged from 200 microgram (mcg) to 1600 mcg twice daily (BID) orally. The dose was increased in increments of 200 mcg BID, usually at weekly intervals, depending on the dose tolerability. Up-titration was followed by a stable maintenance treatment period at the highest tolerated dose, from Week 13 to Week 24.
OG001	Placebo	Participants received one to 8 tablets of 200 (mcg) matching placebo, administered up to a maximum dose up-titrated to 1600 mcg orally twice daily. Up-titration was followed by a stable maintenance treatment period at the highest tolerated dose, from Week 13 to Week 24.

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Selexipag	Participants received Selexipag which was up-titrated from Day 1 (Week 1) to Week 12 to the individualized highest tolerated dose (HTD) which ranged from 200 microgram (mcg) to 1600 mcg twice daily (BID) orally. The dose was increased in increments of 200 mcg BID, usually at weekly intervals, depending on the dose tolerability. Up-titration was followed by a stable maintenance treatment period at the highest tolerated dose, from Week 13 to Week 24.	0	53	3	53	52	53
EG001	Placebo	Participants received one to 8 tablets of 200 (mcg) matching placebo, administered up to a maximum dose up-titrated to 1600 mcg orally twice daily. Up-titration was followed by a stable maintenance treatment period at the highest tolerated dose, from Week 13 to Week 24.	0	55	6	55	52	55

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Atrial Flutter	Cardiac disorders	MedDRA Version 22.0	Non-systematic Assessment	EG0001 affected53 at risk EG0011 affected55 at risk
Right Ventricular Failure	Cardiac disorders	MedDRA Version 22.0	Non-systematic Assessment	EG0001 affected53 at risk EG0010 affected55 at risk
Vision Blurred	Eye disorders	MedDRA Version 22.0	Non-systematic Assessment	EG0000 affected53 at risk EG0011 affected55 at risk
Glossitis	Gastrointestinal disorders	MedDRA Version 22.0	Non-systematic Assessment	EG0000 affected53 at risk EG0011 affected55 at risk
Pneumonia	Infections and infestations	MedDRA Version 22.0	Non-systematic Assessment	EG0000 affected53 at risk EG0011 affected55 at risk
Migraine	Nervous system disorders	MedDRA Version 22.0	Non-systematic Assessment	EG0001 affected53 at risk EG0010 affected55 at risk
Multiple Sclerosis Relapse	Nervous system disorders	MedDRA Version 22.0	Non-systematic Assessment	EG0000 affected53 at risk EG0011 affected55 at risk
Syncope	Nervous system disorders	MedDRA Version 22.0	Non-systematic Assessment	EG0000 affected53 at risk EG0011 affected55 at risk
Pleural Effusion	Respiratory, thoracic and mediastinal disorders	MedDRA Version 22.0	Non-systematic Assessment	EG0000 affected53 at risk EG0011 affected55 at risk
Thyroid Nodule Removal	Surgical and medical procedures	MedDRA Version 22.0	Non-systematic Assessment	EG0000 affected53 at risk EG0011 affected55 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Palpitations	Cardiac disorders	MedDRA Version 22.0	Non-systematic Assessment	EG0002 affected53 at risk EG0014 affected55 at risk
Abdominal Distension	Gastrointestinal disorders	MedDRA Version 22.0	Non-systematic Assessment	EG0001 affected53 at risk EG0013 affected55 at risk
Abdominal Pain Upper	Gastrointestinal disorders	MedDRA Version 22.0	Non-systematic Assessment	EG0002 affected53 at risk EG0013 affected55 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA Version 22.0	Non-systematic Assessment	EG00028 affected53 at risk EG00123 affected55 at risk
Dyspepsia	Gastrointestinal disorders	MedDRA Version 22.0	Non-systematic Assessment	EG0006 affected53 at risk EG0010 affected55 at risk
Nausea	Gastrointestinal disorders	MedDRA Version 22.0	Non-systematic Assessment	EG00022 affected53 at risk EG00115 affected55 at risk
Vomiting	Gastrointestinal disorders	MedDRA Version 22.0	Non-systematic Assessment	EG00013 affected53 at risk EG0014 affected55 at risk
Fatigue	General disorders	MedDRA Version 22.0	Non-systematic Assessment	EG0005 affected53 at risk EG0014 affected55 at risk
Non-Cardiac Chest Pain	General disorders	MedDRA Version 22.0	Non-systematic Assessment	EG0002 affected53 at risk EG0017 affected55 at risk
Oedema Peripheral	General disorders	MedDRA Version 22.0	Non-systematic Assessment	EG0003 affected53 at risk EG0013 affected55 at risk
Lower Respiratory Tract Infection	Infections and infestations	MedDRA Version 22.0	Non-systematic Assessment	EG0002 affected53 at risk EG0013 affected55 at risk
Nasopharyngitis	Infections and infestations	MedDRA Version 22.0	Non-systematic Assessment	EG0005 affected53 at risk EG00114 affected55 at risk
Respiratory Tract Infection	Infections and infestations	MedDRA Version 22.0	Non-systematic Assessment	EG0001 affected53 at risk EG0013 affected55 at risk
Tonsillitis	Infections and infestations	MedDRA Version 22.0	Non-systematic Assessment	EG0000 affected53 at risk EG0013 affected55 at risk
Upper Respiratory Tract Infection	Infections and infestations	MedDRA Version 22.0	Non-systematic Assessment	EG0006 affected53 at risk EG0016 affected55 at risk
Urinary Tract Infection	Infections and infestations	MedDRA Version 22.0	Non-systematic Assessment	EG0000 affected53 at risk EG0014 affected55 at risk
Decreased Appetite	Metabolism and nutrition disorders	MedDRA Version 22.0	Non-systematic Assessment	EG0004 affected53 at risk EG0011 affected55 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA Version 22.0	Non-systematic Assessment	EG00011 affected53 at risk EG0018 affected55 at risk
Back Pain	Musculoskeletal and connective tissue disorders	MedDRA Version 22.0	Non-systematic Assessment	EG0004 affected53 at risk EG0016 affected55 at risk
Myalgia	Musculoskeletal and connective tissue disorders	MedDRA Version 22.0	Non-systematic Assessment	EG0006 affected53 at risk EG0013 affected55 at risk
Pain in Extremity	Musculoskeletal and connective tissue disorders	MedDRA Version 22.0	Non-systematic Assessment	EG00011 affected53 at risk EG0011 affected55 at risk
Pain in Jaw	Musculoskeletal and connective tissue disorders	MedDRA Version 22.0	Non-systematic Assessment	EG00020 affected53 at risk EG0015 affected55 at risk
Dizziness	Nervous system disorders	MedDRA Version 22.0	Non-systematic Assessment	EG0007 affected53 at risk EG0017 affected55 at risk
Headache	Nervous system disorders	MedDRA Version 22.0	Non-systematic Assessment	EG00041 affected53 at risk EG00126 affected55 at risk
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA Version 22.0	Non-systematic Assessment	EG0003 affected53 at risk EG0013 affected55 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA Version 22.0	Non-systematic Assessment	EG0004 affected53 at risk EG0016 affected55 at risk
Epistaxis	Respiratory, thoracic and mediastinal disorders	MedDRA Version 22.0	Non-systematic Assessment	EG0003 affected53 at risk EG0013 affected55 at risk
Nasal Congestion	Respiratory, thoracic and mediastinal disorders	MedDRA Version 22.0	Non-systematic Assessment	EG0005 affected53 at risk EG0012 affected55 at risk
Oropharyngeal Pain	Respiratory, thoracic and mediastinal disorders	MedDRA Version 22.0	Non-systematic Assessment	EG0002 affected53 at risk EG0014 affected55 at risk
Rash	Skin and subcutaneous tissue disorders	MedDRA Version 22.0	Non-systematic Assessment	EG0002 affected53 at risk EG0013 affected55 at risk
Flushing	Vascular disorders	MedDRA Version 22.0	Non-systematic Assessment	EG0005 affected53 at risk EG0016 affected55 at risk
Hot Flush	Vascular disorders	MedDRA Version 22.0	Non-systematic Assessment	EG0000 affected53 at risk EG0013 affected55 at risk

ID	Term
D006976	Hypertension, Pulmonary
D008171	Lung Diseases
D012140	Respiratory Tract Diseases
D001519	Behavior

ID	Term
D000081029	Pulmonary Arterial Hypertension
D009043	Motor Activity