Trial Outcomes & Findings for Effect of Selexipag on Daily Life Physical Activity of Patients With Pulmonary Arterial Hypertension. (NCT NCT03078907)
NCT ID: NCT03078907
Last Updated: 2025-03-30
Results Overview
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.
COMPLETED
PHASE4
108 participants
Baseline and Week 24 (data analysis was done during 14-Days each for Baseline and for Week 24 and mean value reported)
2025-03-30
Participant Flow
Participant milestones
| Measure |
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.
|
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.
|
|---|---|---|
|
Overall Study
STARTED
|
53
|
55
|
|
Overall Study
COMPLETED
|
50
|
54
|
|
Overall Study
NOT COMPLETED
|
3
|
1
|
Reasons for withdrawal
| Measure |
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.
|
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.
|
|---|---|---|
|
Overall Study
Adverse Event
|
2
|
0
|
|
Overall Study
Other
|
1
|
0
|
|
Overall Study
Protocol Violation
|
0
|
1
|
Baseline Characteristics
Effect of Selexipag on Daily Life Physical Activity of Patients With Pulmonary Arterial Hypertension.
Baseline characteristics by cohort
| Measure |
Selexipag
n=53 Participants
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.
|
Placebo
n=55 Participants
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.
|
Total
n=108 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
49 years
STANDARD_DEVIATION 14.75 • n=93 Participants
|
49.8 years
STANDARD_DEVIATION 13.63 • n=4 Participants
|
49.4 years
STANDARD_DEVIATION 14.13 • n=27 Participants
|
|
Sex: Female, Male
Female
|
35 Participants
n=93 Participants
|
42 Participants
n=4 Participants
|
77 Participants
n=27 Participants
|
|
Sex: Female, Male
Male
|
18 Participants
n=93 Participants
|
13 Participants
n=4 Participants
|
31 Participants
n=27 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
|
Race (NIH/OMB)
Asian
|
4 Participants
n=93 Participants
|
3 Participants
n=4 Participants
|
7 Participants
n=27 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
|
Race (NIH/OMB)
Black or African American
|
2 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
2 Participants
n=27 Participants
|
|
Race (NIH/OMB)
White
|
44 Participants
n=93 Participants
|
52 Participants
n=4 Participants
|
96 Participants
n=27 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
3 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
3 Participants
n=27 Participants
|
|
Region of Enrollment
AUSTRIA
|
0 participants
n=93 Participants
|
1 participants
n=4 Participants
|
1 participants
n=27 Participants
|
|
Region of Enrollment
FRANCE
|
2 participants
n=93 Participants
|
0 participants
n=4 Participants
|
2 participants
n=27 Participants
|
|
Region of Enrollment
GERMANY
|
6 participants
n=93 Participants
|
5 participants
n=4 Participants
|
11 participants
n=27 Participants
|
|
Region of Enrollment
IRELAND
|
1 participants
n=93 Participants
|
1 participants
n=4 Participants
|
2 participants
n=27 Participants
|
|
Region of Enrollment
NORWAY
|
0 participants
n=93 Participants
|
1 participants
n=4 Participants
|
1 participants
n=27 Participants
|
|
Region of Enrollment
PORTUGAL
|
3 participants
n=93 Participants
|
3 participants
n=4 Participants
|
6 participants
n=27 Participants
|
|
Region of Enrollment
SWEDEN
|
4 participants
n=93 Participants
|
0 participants
n=4 Participants
|
4 participants
n=27 Participants
|
|
Region of Enrollment
SWITZERLAND
|
0 participants
n=93 Participants
|
1 participants
n=4 Participants
|
1 participants
n=27 Participants
|
|
Region of Enrollment
UNITED KINGDOM
|
31 participants
n=93 Participants
|
35 participants
n=4 Participants
|
66 participants
n=27 Participants
|
|
Region of Enrollment
UNITED STATES
|
6 participants
n=93 Participants
|
8 participants
n=4 Participants
|
14 participants
n=27 Participants
|
PRIMARY outcome
Timeframe: Baseline and Week 24 (data analysis was done during 14-Days each for Baseline and for Week 24 and mean value reported)Population: The Full Analysis Set (FAS) included all participants randomly assigned to a study treatment.
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.
Outcome measures
| Measure |
Selexipag
n=53 Participants
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.
|
Placebo
n=55 Participants
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.
|
|---|---|---|
|
Change From Baseline to Week 24 in Actigraphy Assessed Daily Life Physical Activity (DLPA) for Variables Expressed in Minutes
Daily time spent in NSA (Freedson '98)
|
-15.2 minutes
Standard Deviation 79.78
|
-25.2 minutes
Standard Deviation 72.47
|
|
Change From Baseline to Week 24 in Actigraphy Assessed Daily Life Physical Activity (DLPA) for Variables Expressed in Minutes
Daily time spent in MVPA (Freedson '98)
|
0.2 minutes
Standard Deviation 34.48
|
-1.9 minutes
Standard Deviation 34.26
|
|
Change From Baseline to Week 24 in Actigraphy Assessed Daily Life Physical Activity (DLPA) for Variables Expressed in Minutes
Daily time spent in NSA (Koster'16)
|
-0.7 minutes
Standard Deviation 72.50
|
-15.0 minutes
Standard Deviation 62.27
|
PRIMARY outcome
Timeframe: Baseline and Week 24 (data analysis was done during 14-Days each for Baseline and for Week 24 and mean value reported)Population: The Full Analysis Set (FAS) included all participants randomly assigned to a study treatment.
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.
Outcome measures
| Measure |
Selexipag
n=53 Participants
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.
|
Placebo
n=55 Participants
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.
|
|---|---|---|
|
Change From Baseline to Week 24 in Actigraphy DLPA for Variables Expressed in Percentage (%)
Daily time spent in NSA (%), Freedson '98
|
0.08 Percentage of daily time spent
Standard Deviation 7.265
|
-0.10 Percentage of daily time spent
Standard Deviation 6.439
|
|
Change From Baseline to Week 24 in Actigraphy DLPA for Variables Expressed in Percentage (%)
Daily time spent in MVPA (%), Freedson '98
|
0.23 Percentage of daily time spent
Standard Deviation 3.342
|
0.32 Percentage of daily time spent
Standard Deviation 3.513
|
|
Change From Baseline to Week 24 in Actigraphy DLPA for Variables Expressed in Percentage (%)
Daily time spent in NSA (%), Koster '16
|
0.80 Percentage of daily time spent
Standard Deviation 7.158
|
0.00 Percentage of daily time spent
Standard Deviation 6.269
|
PRIMARY outcome
Timeframe: Baseline and Week 24 (data analysis was done during 14-Days each for Baseline and for Week 24 and mean value reported)Population: The Full Analysis Set (FAS) included all participants randomly assigned to a study treatment.
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.
Outcome measures
| Measure |
Selexipag
n=53 Participants
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.
|
Placebo
n=55 Participants
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.
|
|---|---|---|
|
Change From Baseline to Week 24 in Actigraphy DLPA for Variables Expressed in Counts Per Minute (Counts/Minute)
Total daily activities
|
29.3 counts/minute
Standard Deviation 337.18
|
18.8 counts/minute
Standard Deviation 342.77
|
|
Change From Baseline to Week 24 in Actigraphy DLPA for Variables Expressed in Counts Per Minute (Counts/Minute)
NSA, Koster '16
|
36.1 counts/minute
Standard Deviation 342.11
|
16.8 counts/minute
Standard Deviation 351.08
|
PRIMARY outcome
Timeframe: Baseline and Week 24 (data analysis was done during 14-Days each for Baseline and for Week 24 and mean value reported)Population: The Full Analysis Set (FAS) included all participants randomly assigned to a study treatment.
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.
Outcome measures
| Measure |
Selexipag
n=53 Participants
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.
|
Placebo
n=55 Participants
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.
|
|---|---|---|
|
Change From Baseline to Week 24 in Actigraphy DLPA for Variables Expressed in Counts
|
3898 counts
Standard Deviation 345872
|
-49187 counts
Standard Deviation 343402.2
|
PRIMARY outcome
Timeframe: Baseline and Week 24 (data analysis was done during 14-Days each for Baseline and for Week 24 and mean value reported)Population: The Full Analysis Set (FAS) included all participants randomly assigned to a study treatment.
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.
Outcome measures
| Measure |
Selexipag
n=53 Participants
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.
|
Placebo
n=55 Participants
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.
|
|---|---|---|
|
Change From Baseline to Week 24 in Actigraphy DLPA for Variable Expressed in Step Counts
|
-32.4 step counts
Standard Deviation 1288.64
|
-170.9 step counts
Standard Deviation 1076.87
|
PRIMARY outcome
Timeframe: Baseline and Week 24 (data analysis was done during 14-Days each for Baseline and for Week 24 and mean value reported)Population: The Full Analysis Set (FAS) included all participants randomly assigned to a study treatment.
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/minute. Positive change from baseline means improvement.
Outcome measures
| Measure |
Selexipag
n=53 Participants
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.
|
Placebo
n=55 Participants
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.
|
|---|---|---|
|
Change From Baseline to Week 24 in Actigraphy DLPA for Variables Expressed in Step Counts/Minute
|
0.0 step counts/minute
Standard Deviation 1.25
|
0.0 step counts/minute
Standard Deviation 1.04
|
PRIMARY outcome
Timeframe: Baseline and Week 24 (data analysis was done during 14-Days each for Baseline and for Week 24 and mean value reported)Population: 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.
TST (in minutes) was assessed by actigraphy.
Outcome measures
Outcome data not reported
PRIMARY outcome
Timeframe: Baseline and Week 24 (data collection was done during 14-Days each for Baseline and for Week 24)Population: 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.
WASO (in minutes) was assessed by actigraphy.
Outcome measures
Outcome data not reported
PRIMARY outcome
Timeframe: Baseline and Week 24 (data collection was done during 14-Days each for Baseline and for Week 24)Population: 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.
Number of awakenings was assessed by actigraphy.
Outcome measures
Outcome data not reported
PRIMARY outcome
Timeframe: Baseline and Week 24 (data collection was done during 14-Days each for Baseline and for Week 24)Population: 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.
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.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Baseline and Week 24Population: 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.
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.
Outcome measures
| Measure |
Selexipag
n=44 Participants
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.
|
Placebo
n=52 Participants
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.
|
|---|---|---|
|
Change From Baseline to Week 24 in Pulmonary Arterial Hypertension-Symptoms and Impact (PAH-SYMPACT) Score
Cardiopulmonary symptoms
|
-0.030 units on a scale
Standard Deviation 0.4160
|
-0.080 units on a scale
Standard Deviation 0.2564
|
|
Change From Baseline to Week 24 in Pulmonary Arterial Hypertension-Symptoms and Impact (PAH-SYMPACT) Score
Cardiovascular symptoms
|
0.010 units on a scale
Standard Deviation 0.3522
|
-0.045 units on a scale
Standard Deviation 0.3029
|
|
Change From Baseline to Week 24 in Pulmonary Arterial Hypertension-Symptoms and Impact (PAH-SYMPACT) Score
Physical impact
|
-0.043 units on a scale
Standard Deviation 0.5932
|
-0.074 units on a scale
Standard Deviation 0.5470
|
|
Change From Baseline to Week 24 in Pulmonary Arterial Hypertension-Symptoms and Impact (PAH-SYMPACT) Score
Cognitive/emotional impact
|
0.000 units on a scale
Standard Deviation 0.5311
|
-0.090 units on a scale
Standard Deviation 0.5992
|
SECONDARY outcome
Timeframe: Baseline and Week 24Population: 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.
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.
Outcome measures
| Measure |
Selexipag
n=44 Participants
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.
|
Placebo
n=52 Participants
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.
|
|---|---|---|
|
Number of Participants With Change From Baseline to Week 24 in World Health Organization Functional Class (WHO FC)
Deterioration
|
2 Participants
|
1 Participants
|
|
Number of Participants With Change From Baseline to Week 24 in World Health Organization Functional Class (WHO FC)
No change
|
33 Participants
|
43 Participants
|
|
Number of Participants With Change From Baseline to Week 24 in World Health Organization Functional Class (WHO FC)
Improvement
|
9 Participants
|
10 Participants
|
SECONDARY outcome
Timeframe: Baseline and Week 24Population: 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.
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.
Outcome measures
| Measure |
Selexipag
n=50 Participants
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.
|
Placebo
n=54 Participants
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.
|
|---|---|---|
|
Change From Baseline to Week 24 in 6-Minute Walk Distance (6MWD)
|
18.3 meters
Standard Deviation 54.47
|
9.8 meters
Standard Deviation 60.72
|
SECONDARY outcome
Timeframe: Baseline and Week 24Population: 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.
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.
Outcome measures
| Measure |
Selexipag
n=50 Participants
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.
|
Placebo
n=54 Participants
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.
|
|---|---|---|
|
Change From Baseline to Week 24 in Borg Dyspnea Score
|
-0.25 units on a scale
Standard Deviation 2.122
|
0.37 units on a scale
Standard Deviation 1.869
|
SECONDARY outcome
Timeframe: Baseline and Week 24Population: 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.
Change from baseline to Week 24 in NT-pro BNP levels was reported. The negative change from baseline means improvement.
Outcome measures
| Measure |
Selexipag
n=51 Participants
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.
|
Placebo
n=53 Participants
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.
|
|---|---|---|
|
Change From Baseline to Week 24 in N-Terminal Pro B-type Natriuretic Peptide (NT-proBNP)
|
-153.8 nanogram per liter (ng/L)
Standard Deviation 609.32
|
81.8 nanogram per liter (ng/L)
Standard Deviation 316.54
|
Adverse Events
Selexipag
Placebo
Serious adverse events
| Measure |
Selexipag
n=53 participants at risk
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.
|
Placebo
n=55 participants at risk
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.
|
|---|---|---|
|
Cardiac disorders
Atrial Flutter
|
1.9%
1/53 • Up to 28 weeks
Safety Analysis Set included the participants who were who were randomized and received at least 1 dose of study treatment.
|
1.8%
1/55 • Up to 28 weeks
Safety Analysis Set included the participants who were who were randomized and received at least 1 dose of study treatment.
|
|
Cardiac disorders
Right Ventricular Failure
|
1.9%
1/53 • Up to 28 weeks
Safety Analysis Set included the participants who were who were randomized and received at least 1 dose of study treatment.
|
0.00%
0/55 • Up to 28 weeks
Safety Analysis Set included the participants who were who were randomized and received at least 1 dose of study treatment.
|
|
Eye disorders
Vision Blurred
|
0.00%
0/53 • Up to 28 weeks
Safety Analysis Set included the participants who were who were randomized and received at least 1 dose of study treatment.
|
1.8%
1/55 • Up to 28 weeks
Safety Analysis Set included the participants who were who were randomized and received at least 1 dose of study treatment.
|
|
Gastrointestinal disorders
Glossitis
|
0.00%
0/53 • Up to 28 weeks
Safety Analysis Set included the participants who were who were randomized and received at least 1 dose of study treatment.
|
1.8%
1/55 • Up to 28 weeks
Safety Analysis Set included the participants who were who were randomized and received at least 1 dose of study treatment.
|
|
Infections and infestations
Pneumonia
|
0.00%
0/53 • Up to 28 weeks
Safety Analysis Set included the participants who were who were randomized and received at least 1 dose of study treatment.
|
1.8%
1/55 • Up to 28 weeks
Safety Analysis Set included the participants who were who were randomized and received at least 1 dose of study treatment.
|
|
Nervous system disorders
Migraine
|
1.9%
1/53 • Up to 28 weeks
Safety Analysis Set included the participants who were who were randomized and received at least 1 dose of study treatment.
|
0.00%
0/55 • Up to 28 weeks
Safety Analysis Set included the participants who were who were randomized and received at least 1 dose of study treatment.
|
|
Nervous system disorders
Multiple Sclerosis Relapse
|
0.00%
0/53 • Up to 28 weeks
Safety Analysis Set included the participants who were who were randomized and received at least 1 dose of study treatment.
|
1.8%
1/55 • Up to 28 weeks
Safety Analysis Set included the participants who were who were randomized and received at least 1 dose of study treatment.
|
|
Nervous system disorders
Syncope
|
0.00%
0/53 • Up to 28 weeks
Safety Analysis Set included the participants who were who were randomized and received at least 1 dose of study treatment.
|
1.8%
1/55 • Up to 28 weeks
Safety Analysis Set included the participants who were who were randomized and received at least 1 dose of study treatment.
|
|
Respiratory, thoracic and mediastinal disorders
Pleural Effusion
|
0.00%
0/53 • Up to 28 weeks
Safety Analysis Set included the participants who were who were randomized and received at least 1 dose of study treatment.
|
1.8%
1/55 • Up to 28 weeks
Safety Analysis Set included the participants who were who were randomized and received at least 1 dose of study treatment.
|
|
Surgical and medical procedures
Thyroid Nodule Removal
|
0.00%
0/53 • Up to 28 weeks
Safety Analysis Set included the participants who were who were randomized and received at least 1 dose of study treatment.
|
1.8%
1/55 • Up to 28 weeks
Safety Analysis Set included the participants who were who were randomized and received at least 1 dose of study treatment.
|
Other adverse events
| Measure |
Selexipag
n=53 participants at risk
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.
|
Placebo
n=55 participants at risk
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.
|
|---|---|---|
|
Cardiac disorders
Palpitations
|
3.8%
2/53 • Up to 28 weeks
Safety Analysis Set included the participants who were who were randomized and received at least 1 dose of study treatment.
|
7.3%
4/55 • Up to 28 weeks
Safety Analysis Set included the participants who were who were randomized and received at least 1 dose of study treatment.
|
|
Gastrointestinal disorders
Abdominal Distension
|
1.9%
1/53 • Up to 28 weeks
Safety Analysis Set included the participants who were who were randomized and received at least 1 dose of study treatment.
|
5.5%
3/55 • Up to 28 weeks
Safety Analysis Set included the participants who were who were randomized and received at least 1 dose of study treatment.
|
|
Gastrointestinal disorders
Abdominal Pain Upper
|
3.8%
2/53 • Up to 28 weeks
Safety Analysis Set included the participants who were who were randomized and received at least 1 dose of study treatment.
|
5.5%
3/55 • Up to 28 weeks
Safety Analysis Set included the participants who were who were randomized and received at least 1 dose of study treatment.
|
|
Gastrointestinal disorders
Diarrhoea
|
52.8%
28/53 • Up to 28 weeks
Safety Analysis Set included the participants who were who were randomized and received at least 1 dose of study treatment.
|
41.8%
23/55 • Up to 28 weeks
Safety Analysis Set included the participants who were who were randomized and received at least 1 dose of study treatment.
|
|
Gastrointestinal disorders
Dyspepsia
|
11.3%
6/53 • Up to 28 weeks
Safety Analysis Set included the participants who were who were randomized and received at least 1 dose of study treatment.
|
0.00%
0/55 • Up to 28 weeks
Safety Analysis Set included the participants who were who were randomized and received at least 1 dose of study treatment.
|
|
Gastrointestinal disorders
Nausea
|
41.5%
22/53 • Up to 28 weeks
Safety Analysis Set included the participants who were who were randomized and received at least 1 dose of study treatment.
|
27.3%
15/55 • Up to 28 weeks
Safety Analysis Set included the participants who were who were randomized and received at least 1 dose of study treatment.
|
|
Gastrointestinal disorders
Vomiting
|
24.5%
13/53 • Up to 28 weeks
Safety Analysis Set included the participants who were who were randomized and received at least 1 dose of study treatment.
|
7.3%
4/55 • Up to 28 weeks
Safety Analysis Set included the participants who were who were randomized and received at least 1 dose of study treatment.
|
|
General disorders
Fatigue
|
9.4%
5/53 • Up to 28 weeks
Safety Analysis Set included the participants who were who were randomized and received at least 1 dose of study treatment.
|
7.3%
4/55 • Up to 28 weeks
Safety Analysis Set included the participants who were who were randomized and received at least 1 dose of study treatment.
|
|
General disorders
Non-Cardiac Chest Pain
|
3.8%
2/53 • Up to 28 weeks
Safety Analysis Set included the participants who were who were randomized and received at least 1 dose of study treatment.
|
12.7%
7/55 • Up to 28 weeks
Safety Analysis Set included the participants who were who were randomized and received at least 1 dose of study treatment.
|
|
General disorders
Oedema Peripheral
|
5.7%
3/53 • Up to 28 weeks
Safety Analysis Set included the participants who were who were randomized and received at least 1 dose of study treatment.
|
5.5%
3/55 • Up to 28 weeks
Safety Analysis Set included the participants who were who were randomized and received at least 1 dose of study treatment.
|
|
Infections and infestations
Lower Respiratory Tract Infection
|
3.8%
2/53 • Up to 28 weeks
Safety Analysis Set included the participants who were who were randomized and received at least 1 dose of study treatment.
|
5.5%
3/55 • Up to 28 weeks
Safety Analysis Set included the participants who were who were randomized and received at least 1 dose of study treatment.
|
|
Infections and infestations
Nasopharyngitis
|
9.4%
5/53 • Up to 28 weeks
Safety Analysis Set included the participants who were who were randomized and received at least 1 dose of study treatment.
|
25.5%
14/55 • Up to 28 weeks
Safety Analysis Set included the participants who were who were randomized and received at least 1 dose of study treatment.
|
|
Infections and infestations
Respiratory Tract Infection
|
1.9%
1/53 • Up to 28 weeks
Safety Analysis Set included the participants who were who were randomized and received at least 1 dose of study treatment.
|
5.5%
3/55 • Up to 28 weeks
Safety Analysis Set included the participants who were who were randomized and received at least 1 dose of study treatment.
|
|
Infections and infestations
Tonsillitis
|
0.00%
0/53 • Up to 28 weeks
Safety Analysis Set included the participants who were who were randomized and received at least 1 dose of study treatment.
|
5.5%
3/55 • Up to 28 weeks
Safety Analysis Set included the participants who were who were randomized and received at least 1 dose of study treatment.
|
|
Infections and infestations
Upper Respiratory Tract Infection
|
11.3%
6/53 • Up to 28 weeks
Safety Analysis Set included the participants who were who were randomized and received at least 1 dose of study treatment.
|
10.9%
6/55 • Up to 28 weeks
Safety Analysis Set included the participants who were who were randomized and received at least 1 dose of study treatment.
|
|
Infections and infestations
Urinary Tract Infection
|
0.00%
0/53 • Up to 28 weeks
Safety Analysis Set included the participants who were who were randomized and received at least 1 dose of study treatment.
|
7.3%
4/55 • Up to 28 weeks
Safety Analysis Set included the participants who were who were randomized and received at least 1 dose of study treatment.
|
|
Metabolism and nutrition disorders
Decreased Appetite
|
7.5%
4/53 • Up to 28 weeks
Safety Analysis Set included the participants who were who were randomized and received at least 1 dose of study treatment.
|
1.8%
1/55 • Up to 28 weeks
Safety Analysis Set included the participants who were who were randomized and received at least 1 dose of study treatment.
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
20.8%
11/53 • Up to 28 weeks
Safety Analysis Set included the participants who were who were randomized and received at least 1 dose of study treatment.
|
14.5%
8/55 • Up to 28 weeks
Safety Analysis Set included the participants who were who were randomized and received at least 1 dose of study treatment.
|
|
Musculoskeletal and connective tissue disorders
Back Pain
|
7.5%
4/53 • Up to 28 weeks
Safety Analysis Set included the participants who were who were randomized and received at least 1 dose of study treatment.
|
10.9%
6/55 • Up to 28 weeks
Safety Analysis Set included the participants who were who were randomized and received at least 1 dose of study treatment.
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
11.3%
6/53 • Up to 28 weeks
Safety Analysis Set included the participants who were who were randomized and received at least 1 dose of study treatment.
|
5.5%
3/55 • Up to 28 weeks
Safety Analysis Set included the participants who were who were randomized and received at least 1 dose of study treatment.
|
|
Musculoskeletal and connective tissue disorders
Pain in Extremity
|
20.8%
11/53 • Up to 28 weeks
Safety Analysis Set included the participants who were who were randomized and received at least 1 dose of study treatment.
|
1.8%
1/55 • Up to 28 weeks
Safety Analysis Set included the participants who were who were randomized and received at least 1 dose of study treatment.
|
|
Musculoskeletal and connective tissue disorders
Pain in Jaw
|
37.7%
20/53 • Up to 28 weeks
Safety Analysis Set included the participants who were who were randomized and received at least 1 dose of study treatment.
|
9.1%
5/55 • Up to 28 weeks
Safety Analysis Set included the participants who were who were randomized and received at least 1 dose of study treatment.
|
|
Nervous system disorders
Dizziness
|
13.2%
7/53 • Up to 28 weeks
Safety Analysis Set included the participants who were who were randomized and received at least 1 dose of study treatment.
|
12.7%
7/55 • Up to 28 weeks
Safety Analysis Set included the participants who were who were randomized and received at least 1 dose of study treatment.
|
|
Nervous system disorders
Headache
|
77.4%
41/53 • Up to 28 weeks
Safety Analysis Set included the participants who were who were randomized and received at least 1 dose of study treatment.
|
47.3%
26/55 • Up to 28 weeks
Safety Analysis Set included the participants who were who were randomized and received at least 1 dose of study treatment.
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
5.7%
3/53 • Up to 28 weeks
Safety Analysis Set included the participants who were who were randomized and received at least 1 dose of study treatment.
|
5.5%
3/55 • Up to 28 weeks
Safety Analysis Set included the participants who were who were randomized and received at least 1 dose of study treatment.
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
7.5%
4/53 • Up to 28 weeks
Safety Analysis Set included the participants who were who were randomized and received at least 1 dose of study treatment.
|
10.9%
6/55 • Up to 28 weeks
Safety Analysis Set included the participants who were who were randomized and received at least 1 dose of study treatment.
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
5.7%
3/53 • Up to 28 weeks
Safety Analysis Set included the participants who were who were randomized and received at least 1 dose of study treatment.
|
5.5%
3/55 • Up to 28 weeks
Safety Analysis Set included the participants who were who were randomized and received at least 1 dose of study treatment.
|
|
Respiratory, thoracic and mediastinal disorders
Nasal Congestion
|
9.4%
5/53 • Up to 28 weeks
Safety Analysis Set included the participants who were who were randomized and received at least 1 dose of study treatment.
|
3.6%
2/55 • Up to 28 weeks
Safety Analysis Set included the participants who were who were randomized and received at least 1 dose of study treatment.
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal Pain
|
3.8%
2/53 • Up to 28 weeks
Safety Analysis Set included the participants who were who were randomized and received at least 1 dose of study treatment.
|
7.3%
4/55 • Up to 28 weeks
Safety Analysis Set included the participants who were who were randomized and received at least 1 dose of study treatment.
|
|
Skin and subcutaneous tissue disorders
Rash
|
3.8%
2/53 • Up to 28 weeks
Safety Analysis Set included the participants who were who were randomized and received at least 1 dose of study treatment.
|
5.5%
3/55 • Up to 28 weeks
Safety Analysis Set included the participants who were who were randomized and received at least 1 dose of study treatment.
|
|
Vascular disorders
Flushing
|
9.4%
5/53 • Up to 28 weeks
Safety Analysis Set included the participants who were who were randomized and received at least 1 dose of study treatment.
|
10.9%
6/55 • Up to 28 weeks
Safety Analysis Set included the participants who were who were randomized and received at least 1 dose of study treatment.
|
|
Vascular disorders
Hot Flush
|
0.00%
0/53 • Up to 28 weeks
Safety Analysis Set included the participants who were who were randomized and received at least 1 dose of study treatment.
|
5.5%
3/55 • Up to 28 weeks
Safety Analysis Set included the participants who were who were randomized and received at least 1 dose of study treatment.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee Any study-related publication written independently by investigators must be submitted to Actelion for review at least 30 days prior to submission for publication or presentation at a congress. Upon review, Actelion may provide comments and may also request alterations and/or deletions for the sole purpose of protecting its confidential information or patent rights.
- Publication restrictions are in place
Restriction type: OTHER