Pulmonary Arterial Hypertension
Conditions
Keywords
daily life, physical activity, actigraphy, PAH-SYMPACT
Brief summary
The primary objective of this study is to evaluate the effect of selexipag on the physical activity of patients with pulmonary arterial hypertension (PAH) in their daily life, by using a wearable wrist device (actigraph). The actigraph will collect data on daily life physical activity in the patient's real environment. In addition, the PAH symptoms and their impacts will be assessed by using an electronic patient reported outcome measure in the patient's real environment. Patients will be assigned randomly to either selexipag or placebo.
Detailed description
This study is designed as exploratory with the purpose to generate hypotheses on new endpoints
Interventions
DRUGSelexipag
Film-coated tablets for oral use; one tablet (200 mcg) to eight tablets (1600 mcg) are administered depending on the individual tolerability.
DRUGPlacebo
Matching film coated tablets
Sponsors
Actelion
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline to Week 24 in Sleep Efficiency (SE) | Baseline and Week 24 (data collection was done during 14-Days each for Baseline and for Week 24) | 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. |
| Change From Baseline to Week 24 in Actigraphy DLPA for Variable Expressed in Step Counts | 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 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. |
| Change From Baseline to Week 24 in Actigraphy DLPA for Variables Expressed in 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) | 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. |
| Change From Baseline to Week 24 in Total Sleep Time (TST) | Baseline and Week 24 (data analysis was done during 14-Days each for Baseline and for Week 24 and mean value reported) | TST (in minutes) was assessed by actigraphy. |
| Change From Baseline to Week 24 in Wake After Sleep Onset (WASO) | Baseline and Week 24 (data collection was done during 14-Days each for Baseline and for Week 24) | WASO (in minutes) was assessed by actigraphy. |
| Change From Baseline to Week 24 in Number of Awakenings | Baseline and Week 24 (data collection was done during 14-Days each for Baseline and for Week 24) | Number of awakenings was assessed by actigraphy. |
| Change From Baseline to Week 24 in Actigraphy Assessed Daily Life Physical Activity (DLPA) for Variables Expressed in Minutes | 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 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. |
| Change From Baseline to Week 24 in Actigraphy DLPA for Variables Expressed in Percentage (%) | 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 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. |
| Change From Baseline to Week 24 in Actigraphy DLPA for Variables Expressed in Counts Per Minute (Counts/Minute) | 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 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. |
| Change From Baseline to Week 24 in Actigraphy DLPA for Variables Expressed in Counts | 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 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Change From Baseline to Week 24 in World Health Organization Functional Class (WHO FC) | Baseline and Week 24 | 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. |
| Change From Baseline to Week 24 in 6-Minute Walk Distance (6MWD) | Baseline and Week 24 | 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. |
| Change From Baseline to Week 24 in Borg Dyspnea Score | Baseline and Week 24 | 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. |
| Change From Baseline to Week 24 in N-Terminal Pro B-type Natriuretic Peptide (NT-proBNP) | Baseline and Week 24 | Change from baseline to Week 24 in NT-pro BNP levels was reported. The negative change from baseline means improvement. |
| Change From Baseline to Week 24 in Pulmonary Arterial Hypertension-Symptoms and Impact (PAH-SYMPACT) Score | Baseline and Week 24 | 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. |
Countries
Austria, France, Germany, Ireland, Norway, Portugal, Sweden, Switzerland, United Kingdom, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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. | 53 |
| 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. | 55 |
| Total | 108 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 2 | 0 |
| Overall Study | Other | 1 | 0 |
| Overall Study | Protocol Violation | 0 | 1 |
Baseline characteristics
| Characteristic | Selexipag | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 49 years STANDARD_DEVIATION 14.75 | 49.8 years STANDARD_DEVIATION 13.63 | 49.4 years STANDARD_DEVIATION 14.13 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 4 Participants | 3 Participants | 7 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 3 Participants | 0 Participants | 3 Participants |
| Race (NIH/OMB) White | 44 Participants | 52 Participants | 96 Participants |
| Region of Enrollment AUSTRIA | 0 participants | 1 participants | 1 participants |
| Region of Enrollment FRANCE | 2 participants | 0 participants | 2 participants |
| Region of Enrollment GERMANY | 6 participants | 5 participants | 11 participants |
| Region of Enrollment IRELAND | 1 participants | 1 participants | 2 participants |
| Region of Enrollment NORWAY | 0 participants | 1 participants | 1 participants |
| Region of Enrollment PORTUGAL | 3 participants | 3 participants | 6 participants |
| Region of Enrollment SWEDEN | 4 participants | 0 participants | 4 participants |
| Region of Enrollment SWITZERLAND | 0 participants | 1 participants | 1 participants |
| Region of Enrollment UNITED KINGDOM | 31 participants | 35 participants | 66 participants |
| Region of Enrollment UNITED STATES | 6 participants | 8 participants | 14 participants |
| Sex: Female, Male Female | 35 Participants | 42 Participants | 77 Participants |
| Sex: Female, Male Male | 18 Participants | 13 Participants | 31 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 53 | 0 / 55 |
| other Total, other adverse events | 52 / 53 | 52 / 55 |
| serious Total, serious adverse events | 3 / 53 | 6 / 55 |
Outcome results
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.
Time frame: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Selexipag | 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 |
| Selexipag | 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 |
| Selexipag | 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 72.5 |
| Placebo | 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) | -25.2 minutes | Standard Deviation 72.47 |
| Placebo | 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) | -1.9 minutes | Standard Deviation 34.26 |
| Placebo | 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) | -15.0 minutes | Standard Deviation 62.27 |
Comparison: Daily time spent in non-sedentary activity (minutes), Freedson '9895% CI: [13.366, 40.944]ANCOVA
Comparison: Daily time spent in MVPA (minutes), Freedson '9895% CI: [-10.782, 15.396]ANCOVA
Comparison: Daily time spent in non-sedentary activity (minutes), Koster '1695% CI: [-6.003, 41.619]ANCOVA
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.
Time frame: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Selexipag | Change From Baseline to Week 24 in Actigraphy DLPA for Variable Expressed in Step Counts | -32.4 step counts | Standard Deviation 1288.64 |
| Placebo | Change From Baseline to Week 24 in Actigraphy DLPA for Variable Expressed in Step Counts | -170.9 step counts | Standard Deviation 1076.87 |
95% CI: [-242.977, 646.163]ANCOVA
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.
Time frame: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Selexipag | Change From Baseline to Week 24 in Actigraphy DLPA for Variables Expressed in Counts | 3898 counts | Standard Deviation 345872 |
| Placebo | Change From Baseline to Week 24 in Actigraphy DLPA for Variables Expressed in Counts | -49187 counts | Standard Deviation 343402.2 |
95% CI: [-70444, 187263]ANCOVA
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.
Time frame: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Selexipag | 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 |
| Selexipag | 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 |
| Placebo | Change From Baseline to Week 24 in Actigraphy DLPA for Variables Expressed in Counts Per Minute (Counts/Minute) | Total daily activities | 18.8 counts/minute | Standard Deviation 342.77 |
| Placebo | Change From Baseline to Week 24 in Actigraphy DLPA for Variables Expressed in Counts Per Minute (Counts/Minute) | NSA, Koster '16 | 16.8 counts/minute | Standard Deviation 351.08 |
Comparison: Volume of total daily activities (counts / minute)95% CI: [-105.632, 146.958]ANCOVA
Comparison: Volume of non-sedentary activity (counts/minute), Koster '1695% CI: [-101.945, 156.976]ANCOVA
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.
Time frame: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Selexipag | 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 |
| Selexipag | 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 |
| Selexipag | 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 |
| Placebo | Change From Baseline to Week 24 in Actigraphy DLPA for Variables Expressed in Percentage (%) | Daily time spent in NSA (%), Freedson '98 | -0.10 Percentage of daily time spent | Standard Deviation 6.439 |
| Placebo | Change From Baseline to Week 24 in Actigraphy DLPA for Variables Expressed in Percentage (%) | Daily time spent in MVPA (%), Freedson '98 | 0.32 Percentage of daily time spent | Standard Deviation 3.513 |
| Placebo | Change From Baseline to Week 24 in Actigraphy DLPA for Variables Expressed in Percentage (%) | Daily time spent in NSA (%), Koster '16 | 0.00 Percentage of daily time spent | Standard Deviation 6.269 |
Comparison: Percentage of daily time spent in non-sedentary activity (%), Freedson '9895% CI: [-1.713, 3.06]ANCOVA
Comparison: Percentage of daily time spent in MVPA (%), Freedson '9895% CI: [-1.351, 1.258]ANCOVA
Comparison: Percentage of daily time spent in non-sedentary activity (%), Koster '1695% CI: [-1.104, 3.618]ANCOVA
Primary
Change From Baseline to Week 24 in Actigraphy DLPA for Variables Expressed in Step Counts/Minute
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.
Time frame: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Selexipag | 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 |
| Placebo | Change From Baseline to Week 24 in Actigraphy DLPA for Variables Expressed in Step Counts/Minute | 0.0 step counts/minute | Standard Deviation 1.04 |
95% CI: [-0.366, 0.51]ANCOVA
Primary
Change From Baseline to Week 24 in Number of Awakenings
Number of awakenings was assessed by actigraphy.
Time frame: 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.
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.
Time frame: 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.
Primary
Change From Baseline to Week 24 in Total Sleep Time (TST)
TST (in minutes) was assessed by actigraphy.
Time frame: 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.
Primary
Change From Baseline to Week 24 in Wake After Sleep Onset (WASO)
WASO (in minutes) was assessed by actigraphy.
Time frame: 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.
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.
Time frame: Baseline and Week 24
Population: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Selexipag | Change From Baseline to Week 24 in 6-Minute Walk Distance (6MWD) | 18.3 meters | Standard Deviation 54.47 |
| Placebo | Change From Baseline to Week 24 in 6-Minute Walk Distance (6MWD) | 9.8 meters | Standard Deviation 60.72 |
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.
Time frame: Baseline and Week 24
Population: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Selexipag | Change From Baseline to Week 24 in Borg Dyspnea Score | -0.25 units on a scale | Standard Deviation 2.122 |
| Placebo | Change From Baseline to Week 24 in Borg Dyspnea Score | 0.37 units on a scale | Standard Deviation 1.869 |
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.
Time frame: Baseline and Week 24
Population: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Selexipag | 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 |
| Placebo | Change From Baseline to Week 24 in N-Terminal Pro B-type Natriuretic Peptide (NT-proBNP) | 81.8 nanogram per liter (ng/L) | Standard Deviation 316.54 |
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.
Time frame: Baseline and Week 24
Population: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Selexipag | 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 0.416 |
| Selexipag | 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 |
| Selexipag | 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 |
| Selexipag | 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 |
| Placebo | Change From Baseline to Week 24 in Pulmonary Arterial Hypertension-Symptoms and Impact (PAH-SYMPACT) Score | Cognitive/emotional impact | -0.090 units on a scale | Standard Deviation 0.5992 |
| Placebo | Change From Baseline to Week 24 in Pulmonary Arterial Hypertension-Symptoms and Impact (PAH-SYMPACT) Score | Cardiopulmonary symptoms | -0.080 units on a scale | Standard Deviation 0.2564 |
| Placebo | Change From Baseline to Week 24 in Pulmonary Arterial Hypertension-Symptoms and Impact (PAH-SYMPACT) Score | Physical impact | -0.074 units on a scale | Standard Deviation 0.547 |
| Placebo | Change From Baseline to Week 24 in Pulmonary Arterial Hypertension-Symptoms and Impact (PAH-SYMPACT) Score | Cardiovascular symptoms | -0.045 units on a scale | Standard Deviation 0.3029 |
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.
Time frame: Baseline and Week 24
Population: 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.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Selexipag | Number of Participants With Change From Baseline to Week 24 in World Health Organization Functional Class (WHO FC) | Deterioration | 2 Participants |
| Selexipag | Number of Participants With Change From Baseline to Week 24 in World Health Organization Functional Class (WHO FC) | No change | 33 Participants |
| Selexipag | Number of Participants With Change From Baseline to Week 24 in World Health Organization Functional Class (WHO FC) | Improvement | 9 Participants |
| Placebo | Number of Participants With Change From Baseline to Week 24 in World Health Organization Functional Class (WHO FC) | Deterioration | 1 Participants |
| Placebo | Number of Participants With Change From Baseline to Week 24 in World Health Organization Functional Class (WHO FC) | No change | 43 Participants |
| Placebo | Number of Participants With Change From Baseline to Week 24 in World Health Organization Functional Class (WHO FC) | Improvement | 10 Participants |