Trial Outcomes & Findings for Safety, Tolerability, and Pharmacokinetics of Oral Treprostinil in Pediatric PAH Patients Aged 7 to 17 Years (NCT NCT02276872)

NCT ID: NCT02276872

Last Updated: 2025-03-30

Results Overview

A successful transition was defined as a subject from Cohort 1 or Cohort 2 who was receiving oral treprostinil and no longer receiving IV/SC Remodulin or inhaled prostacyclin, respectively, at Week 4 and clinically maintained on oral treprostinil treatment through Week 24. A successful initiation of oral treprostinil for Cohort 3 was defined as a subject who was clinically maintained on oral treprostinil through Week 24.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 32 participants
• Primary outcome timeframe: Up to 24 weeks
• Results posted on: 2025-03-30

Participant Flow

Participant milestones

Measure	Cohort 1 (Transitioning From Parental) Transitioned from IV or SC Remodulin to oral treprostinil	Cohort 2 (Transitioning From Inhaled) Transitioned from inhaled prostacyclin to oral treprostinil	Cohort 3 (Add-on to Current PAH Therapy) Treated with oral treprostinil as a de novo add-on to current PAH therapy
Overall Study STARTED	10	10	12
Overall Study COMPLETED	9	10	12
Overall Study NOT COMPLETED	1	0	0

Reasons for withdrawal

Measure	Cohort 1 (Transitioning From Parental) Transitioned from IV or SC Remodulin to oral treprostinil	Cohort 2 (Transitioning From Inhaled) Transitioned from inhaled prostacyclin to oral treprostinil	Cohort 3 (Add-on to Current PAH Therapy) Treated with oral treprostinil as a de novo add-on to current PAH therapy
Overall Study Adverse Event	1	0	0

Baseline Characteristics

Safety, Tolerability, and Pharmacokinetics of Oral Treprostinil in Pediatric PAH Patients Aged 7 to 17 Years

Baseline characteristics by cohort

Measure	Cohort 1 (Transitioning From Parental) n=10 Participants Transitioned from IV or SC Remodulin to oral treprostinil	Cohort 2 (Transitioning From Inhaled) n=10 Participants Transitioned from inhaled prostacyclin to oral treprostinil	Cohort 3 (Add-on to Current PAH Therapy) n=12 Participants Treated with oral treprostinil as a de novo add-on to current PAH therapy	Total n=32 Participants Total of all reporting groups
Age, Categorical <=18 years	10 Participants n=93 Participants	10 Participants n=4 Participants	12 Participants n=27 Participants	32 Participants n=483 Participants
Age, Categorical Between 18 and 65 years	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants
Age, Categorical >=65 years	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants
Age, Continuous	10.0 years n=93 Participants	13.5 years n=4 Participants	13.5 years n=27 Participants	12 years n=483 Participants
Sex: Female, Male Female	9 Participants n=93 Participants	7 Participants n=4 Participants	7 Participants n=27 Participants	23 Participants n=483 Participants
Sex: Female, Male Male	1 Participants n=93 Participants	3 Participants n=4 Participants	5 Participants n=27 Participants	9 Participants n=483 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	4 Participants n=93 Participants	2 Participants n=4 Participants	1 Participants n=27 Participants	7 Participants n=483 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	6 Participants n=93 Participants	8 Participants n=4 Participants	11 Participants n=27 Participants	25 Participants n=483 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants
Race (NIH/OMB) American Indian or Alaska Native	1 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	1 Participants n=483 Participants
Race (NIH/OMB) Asian	1 Participants n=93 Participants	1 Participants n=4 Participants	2 Participants n=27 Participants	4 Participants n=483 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	0 Participants n=483 Participants
Race (NIH/OMB) Black or African American	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants
Race (NIH/OMB) White	7 Participants n=93 Participants	9 Participants n=4 Participants	10 Participants n=27 Participants	26 Participants n=483 Participants
Race (NIH/OMB) More than one race	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	1 Participants n=483 Participants
Region of Enrollment United States	10 Participants n=93 Participants	10 Participants n=4 Participants	12 Participants n=27 Participants	32 Participants n=483 Participants

PRIMARY outcome

Timeframe: Up to 24 weeks

Population: Safety Population

A successful transition was defined as a subject from Cohort 1 or Cohort 2 who was receiving oral treprostinil and no longer receiving IV/SC Remodulin or inhaled prostacyclin, respectively, at Week 4 and clinically maintained on oral treprostinil treatment through Week 24. A successful initiation of oral treprostinil for Cohort 3 was defined as a subject who was clinically maintained on oral treprostinil through Week 24.

Outcome measures

Measure	Cohort 1 (Transitioning From Parental) n=10 Participants Transitioned from IV or SC Remodulin to oral treprostinil	Cohort 2 (Transitioning From Inhaled) n=10 Participants Transitioned from inhaled prostacyclin to oral treprostinil	Cohort 3 (Add-on to Current PAH Therapy) n=12 Participants Treated with oral treprostinil as a de novo add-on to current PAH therapy
Number of Participants With Successful Transition From IV/SC Remodulin to Oral Treprostinil (Cohort 1), From Inhaled Prostacyclin to Oral Treprostinil (Cohort 2), or as an add-on to Current PAH Therapy in de Novo Prostacyclin Subjects (Cohort 3). Successfully transitioned/initiated within 4 weeks	10 participants	10 participants	12 participants
Number of Participants With Successful Transition From IV/SC Remodulin to Oral Treprostinil (Cohort 1), From Inhaled Prostacyclin to Oral Treprostinil (Cohort 2), or as an add-on to Current PAH Therapy in de Novo Prostacyclin Subjects (Cohort 3). Successfully maintained through 24 weeks	9 participants	10 participants	12 participants

SECONDARY outcome

Timeframe: Baseline and Week 24

Population: Safety Population - Number of Subjects that Completed Testing at Week 24

Cardiopulmonary Exercise Testing (CPET) was performed with progressive cycle ergometry and ventilatory expired gas analysis obtained using a metabolic cart at Baseline and Week 24/Premature Termination. CPET consisted of measuring oxygen uptake (VO2), carbon dioxide output (VCO2), minute ventilation (VE), and other variables in addition to a 12-lead ECG, blood pressure (BP) monitoring, and pulse oximetry.

Outcome measures

Measure	Cohort 1 (Transitioning From Parental) n=5 Participants Transitioned from IV or SC Remodulin to oral treprostinil	Cohort 2 (Transitioning From Inhaled) n=9 Participants Transitioned from inhaled prostacyclin to oral treprostinil	Cohort 3 (Add-on to Current PAH Therapy) n=12 Participants Treated with oral treprostinil as a de novo add-on to current PAH therapy
Cardiopulmonary Exercise Testing - Change From Baseline in Peak Oxygen Uptake (VO2) at Week 24	-3.26 mL/kg/min Standard Deviation 7.34	2.18 mL/kg/min Standard Deviation 8.01	2.00 mL/kg/min Standard Deviation 3.47

SECONDARY outcome

Timeframe: Baseline and Week 24

Population: Safety Population - Number of Subjects that Completed Testing at Week 24

Cardiopulmonary Exercise Testing (CPET) was performed with progressive cycle ergometry and ventilatory expired gas analysis obtained using a metabolic cart at Baseline and Week 24/Premature Termination. CPET consisted of measuring oxygen uptake (VO2), carbon dioxide output (VCO2), minute ventilation (VE), and other variables in addition to a 12-lead ECG, blood pressure (BP) monitoring, and pulse oximetry.

Outcome measures

Measure	Cohort 1 (Transitioning From Parental) n=5 Participants Transitioned from IV or SC Remodulin to oral treprostinil	Cohort 2 (Transitioning From Inhaled) n=9 Participants Transitioned from inhaled prostacyclin to oral treprostinil	Cohort 3 (Add-on to Current PAH Therapy) n=12 Participants Treated with oral treprostinil as a de novo add-on to current PAH therapy
Cardiopulmonary Exercise Testing - Change From Baseline in Minute Ventilation (VE)/Carbon Dioxide Output (VCO2) Slope at Week 24	-1.066 VE/VCO2 Slope Standard Deviation 3.169	2.170 VE/VCO2 Slope Standard Deviation 5.111	1.531 VE/VCO2 Slope Standard Deviation 3.821

SECONDARY outcome

Timeframe: Baseline and Week 24

Population: Safety Population - Number of Subjects that Completed Testing at Week 24

Cardiopulmonary Exercise Testing (CPET) was performed with progressive cycle ergometry and ventilatory expired gas analysis obtained using a metabolic cart at Baseline and Week 24/Premature Termination. CPET consisted of measuring oxygen uptake (VO2), carbon dioxide output (VCO2), minute ventilation (VE), and other variables in addition to a 12-lead ECG, blood pressure (BP) monitoring, and pulse oximetry.

Outcome measures

Measure	Cohort 1 (Transitioning From Parental) n=6 Participants Transitioned from IV or SC Remodulin to oral treprostinil	Cohort 2 (Transitioning From Inhaled) n=9 Participants Transitioned from inhaled prostacyclin to oral treprostinil	Cohort 3 (Add-on to Current PAH Therapy) n=11 Participants Treated with oral treprostinil as a de novo add-on to current PAH therapy
Cardiopulmonary Exercise Testing - Change From Baseline in Peak Watts at Week 24	4.8 Watts Standard Deviation 10.3	-2.8 Watts Standard Deviation 11.9	6.5 Watts Standard Deviation 12.9

SECONDARY outcome

Timeframe: Baseline and Week 24

Population: Safety Population - Number of Subjects that Completed Study Week 24

PAH symptoms (fatigue, dyspnea, edema, dizziness, syncope, chest pain, orthopnea) were assessed at the Baseline Visit prior to the initiation of oral treprostinil dosing and at Week 24. Scores range from 0 (for the best condition) to 3 (for the worst condition).

Outcome measures

Measure	Cohort 1 (Transitioning From Parental) n=9 Participants Transitioned from IV or SC Remodulin to oral treprostinil	Cohort 2 (Transitioning From Inhaled) n=10 Participants Transitioned from inhaled prostacyclin to oral treprostinil	Cohort 3 (Add-on to Current PAH Therapy) n=12 Participants Treated with oral treprostinil as a de novo add-on to current PAH therapy
Change in Symptoms of PAH From Baseline to Week 24 Chest Pain - Improved - Week 24	0 Participants	0 Participants	2 Participants
Change in Symptoms of PAH From Baseline to Week 24 Chest Pain - No Change - Week 24	8 Participants	9 Participants	8 Participants
Change in Symptoms of PAH From Baseline to Week 24 Chest Pain - Deteriorated - Week 24	1 Participants	1 Participants	2 Participants
Change in Symptoms of PAH From Baseline to Week 24 Dizziness - Improved - Week 24	0 Participants	0 Participants	4 Participants
Change in Symptoms of PAH From Baseline to Week 24 Dizziness - No Change - Week 24	9 Participants	8 Participants	8 Participants
Change in Symptoms of PAH From Baseline to Week 24 Dizziness - Deteriorated - Week 24	0 Participants	2 Participants	0 Participants
Change in Symptoms of PAH From Baseline to Week 24 Dyspnea - Improved - Week 24	3 Participants	0 Participants	5 Participants
Change in Symptoms of PAH From Baseline to Week 24 Dyspnea - No Change - Week 24	4 Participants	8 Participants	6 Participants
Change in Symptoms of PAH From Baseline to Week 24 Dyspnea - Deteriorated - Week 24	2 Participants	2 Participants	1 Participants
Change in Symptoms of PAH From Baseline to Week 24 Edema - Improved - Week 24	0 Participants	0 Participants	1 Participants
Change in Symptoms of PAH From Baseline to Week 24 Edema - No Change - Week 24	8 Participants	10 Participants	10 Participants
Change in Symptoms of PAH From Baseline to Week 24 Edema - Deteriorated - Week 24	1 Participants	0 Participants	1 Participants
Change in Symptoms of PAH From Baseline to Week 24 Fatigue - Improved - Week 24	0 Participants	3 Participants	2 Participants
Change in Symptoms of PAH From Baseline to Week 24 Fatigue - No Change - Week 24	5 Participants	6 Participants	9 Participants
Change in Symptoms of PAH From Baseline to Week 24 Fatigue - Deteriorated - Week 24	4 Participants	1 Participants	1 Participants
Change in Symptoms of PAH From Baseline to Week 24 Orthopnea - Improved - Week 24	0 Participants	0 Participants	3 Participants
Change in Symptoms of PAH From Baseline to Week 24 Orthopnea - No Change - Week 24	9 Participants	10 Participants	9 Participants
Change in Symptoms of PAH From Baseline to Week 24 Orthopnea - Deteriorated - Week 24	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Baseline and Week 24

Population: Safety Population - Number of Subjects that Completed Study Week 24

Change from Baseline in subject clinical status was recorded according to the Panama Functional Class.

Outcome measures

Measure	Cohort 1 (Transitioning From Parental) n=9 Participants Transitioned from IV or SC Remodulin to oral treprostinil	Cohort 2 (Transitioning From Inhaled) n=10 Participants Transitioned from inhaled prostacyclin to oral treprostinil	Cohort 3 (Add-on to Current PAH Therapy) n=12 Participants Treated with oral treprostinil as a de novo add-on to current PAH therapy
Change in Panama Functional Class From Baseline to Week 24 Improved - Week 24	0 Participants	2 Participants	3 Participants
Change in Panama Functional Class From Baseline to Week 24 No Change - Week 24	9 Participants	7 Participants	9 Participants
Change in Panama Functional Class From Baseline to Week 24 Deteriorated - Week 24	0 Participants	1 Participants	0 Participants

SECONDARY outcome

Timeframe: Baseline and Week 24

Population: Safety Population - Number of Subjects that Completed Study Week 24

Change from Baseline in subject clinical status was recorded according to the WHO Functional Class.

Outcome measures

Measure	Cohort 1 (Transitioning From Parental) n=9 Participants Transitioned from IV or SC Remodulin to oral treprostinil	Cohort 2 (Transitioning From Inhaled) n=10 Participants Transitioned from inhaled prostacyclin to oral treprostinil	Cohort 3 (Add-on to Current PAH Therapy) n=12 Participants Treated with oral treprostinil as a de novo add-on to current PAH therapy
Change in WHO Functional Class From Baseline to Week 24 Improved - Week 24	0 Participants	1 Participants	3 Participants
Change in WHO Functional Class From Baseline to Week 24 No Change - Week 24	9 Participants	8 Participants	9 Participants
Change in WHO Functional Class From Baseline to Week 24 Deteriorated - Week 24	0 Participants	1 Participants	0 Participants

SECONDARY outcome

Timeframe: Baseline and Week 24

Population: Safety Population - Number of Subjects that Completed Study Week 24

The intent of the 6MWT was to evaluate exercise capacity associated with carrying out activities of daily living. Total distance covered in a total of 6 minutes was measured. Oxygen saturation and heart rate (HR) were measured at rest prior to the 6MWT and monitored continuously during the walk. Recovery monitoring (HR and oxygen saturation) was performed and documented at Minute 0 (immediately upon stopping the 6MWT), Minute 1, Minute 2, and Minute 3 post walk.

Outcome measures

Measure	Cohort 1 (Transitioning From Parental) n=9 Participants Transitioned from IV or SC Remodulin to oral treprostinil	Cohort 2 (Transitioning From Inhaled) n=10 Participants Transitioned from inhaled prostacyclin to oral treprostinil	Cohort 3 (Add-on to Current PAH Therapy) n=12 Participants Treated with oral treprostinil as a de novo add-on to current PAH therapy
Change in 6-Minute Walk Distance (6MWD) From Baseline to Week 24	2.7 meters Standard Deviation 94.2	22.1 meters Standard Deviation 86.5	12.8 meters Standard Deviation 49.6

SECONDARY outcome

Timeframe: Baseline and Week 24

Population: Safety Population - Number of Subjects that Completed Study Week 24

The Borg dyspnea score was assessed prior to and following the completion of the 6MWT at Week 24. The Borg dyspnea score is a 10-point scale rating the maximum level of dyspnea experienced during the 6MWT. Scores range from 0 (for the best condition) to 10 (for the worst condition).

Outcome measures

Measure	Cohort 1 (Transitioning From Parental) n=9 Participants Transitioned from IV or SC Remodulin to oral treprostinil	Cohort 2 (Transitioning From Inhaled) n=10 Participants Transitioned from inhaled prostacyclin to oral treprostinil	Cohort 3 (Add-on to Current PAH Therapy) n=12 Participants Treated with oral treprostinil as a de novo add-on to current PAH therapy
Change in Borg Dyspnea Score From Baseline to Week 24	-1.56 score on a scale Standard Deviation 3.51	0.05 score on a scale Standard Deviation 1.50	-0.83 score on a scale Standard Deviation 1.59

SECONDARY outcome

Timeframe: Baseline and Week 24

Population: Safety Population - Number of Subjects that Completed Study Week 24

Four subscales [items]: (Physical [8], Emotional [5], Social [5], School Functioning [5]). Subjects and subjects' parent(s) completed PedsQL at Week 24. Response to each item on the subscales were graded 0-4 (0=never a problem, 1=almost never a problem, 2=sometimes a problem, 3=often a problem, 4=almost always a problem). Response to each item was transformed from the 0-4 scale to a 0-100 scale as follows: 0=100, 1=75, 2=50, 3=25, 4=0. Using transformed values, mean was computed as sum of the items in each subscale over number of items answered in the same subscale. Two summary scores (Psychosocial Health Summary Score and Total Scale Score) were calculated with a range of 0-100 (higher values indicating better outcome). Psychosocial Health Summary Score was mean computed as sum of the items over the number of items answered in the Emotional, Social, and School Functioning Scales. Total Score was calculated as sum of all items over number of items answered on all the scales.

Outcome measures

Measure	Cohort 1 (Transitioning From Parental) n=9 Participants Transitioned from IV or SC Remodulin to oral treprostinil	Cohort 2 (Transitioning From Inhaled) n=10 Participants Transitioned from inhaled prostacyclin to oral treprostinil	Cohort 3 (Add-on to Current PAH Therapy) n=12 Participants Treated with oral treprostinil as a de novo add-on to current PAH therapy
Change in Quality of Life Assessed Via the Pediatric Quality of Life Inventory (PedsQL) Questionnaire From Baseline to Week 24 Total Scale Score - Parent - Week 24	1.93 score on a scale Standard Deviation 11.79	-2.84 score on a scale Standard Deviation 12.29	5.17 score on a scale Standard Deviation 12.78
Change in Quality of Life Assessed Via the Pediatric Quality of Life Inventory (PedsQL) Questionnaire From Baseline to Week 24 Physical Functioning - Child - Week 24	5.57 score on a scale Standard Deviation 22.14	-2.82 score on a scale Standard Deviation 11.09	5.48 score on a scale Standard Deviation 13.40
Change in Quality of Life Assessed Via the Pediatric Quality of Life Inventory (PedsQL) Questionnaire From Baseline to Week 24 Emotional Functioning - Child - Week 24	8.33 score on a scale Standard Deviation 11.46	3.00 score on a scale Standard Deviation 13.98	2.92 score on a scale Standard Deviation 13.05
Change in Quality of Life Assessed Via the Pediatric Quality of Life Inventory (PedsQL) Questionnaire From Baseline to Week 24 Social Functioning - Child - Week 24	9.44 score on a scale Standard Deviation 16.85	0.00 score on a scale Standard Deviation 15.09	1.25 score on a scale Standard Deviation 11.31
Change in Quality of Life Assessed Via the Pediatric Quality of Life Inventory (PedsQL) Questionnaire From Baseline to Week 24 School Functioning - Child - Week 24	3.89 score on a scale Standard Deviation 23.29	-6.50 score on a scale Standard Deviation 11.56	7.92 score on a scale Standard Deviation 21.37
Change in Quality of Life Assessed Via the Pediatric Quality of Life Inventory (PedsQL) Questionnaire From Baseline to Week 24 Psychosocial Health - Child - Week 24	7.23 score on a scale Standard Deviation 13.52	-1.17 score on a scale Standard Deviation 11.11	4.04 score on a scale Standard Deviation 11.85
Change in Quality of Life Assessed Via the Pediatric Quality of Life Inventory (PedsQL) Questionnaire From Baseline to Week 24 Total Scale Score - Child - Week 24	6.64 score on a scale Standard Deviation 15.08	-1.76 score on a scale Standard Deviation 8.54	4.53 score on a scale Standard Deviation 11.46
Change in Quality of Life Assessed Via the Pediatric Quality of Life Inventory (PedsQL) Questionnaire From Baseline to Week 24 Physical Functioning - Parent - Week 24	1.72 score on a scale Standard Deviation 12.31	-2.81 score on a scale Standard Deviation 14.98	1.29 score on a scale Standard Deviation 14.67
Change in Quality of Life Assessed Via the Pediatric Quality of Life Inventory (PedsQL) Questionnaire From Baseline to Week 24 Emotional Functioning - Parent - Week 24	-2.22 score on a scale Standard Deviation 15.63	2.50 score on a scale Standard Deviation 10.07	5.00 score on a scale Standard Deviation 18.95
Change in Quality of Life Assessed Via the Pediatric Quality of Life Inventory (PedsQL) Questionnaire From Baseline to Week 24 Social Functioning - Parent - Week 24	-1.11 score on a scale Standard Deviation 14.53	-5.50 score on a scale Standard Deviation 18.92	11.67 score on a scale Standard Deviation 16.28
Change in Quality of Life Assessed Via the Pediatric Quality of Life Inventory (PedsQL) Questionnaire From Baseline to Week 24 School Functioning - Parent - Week 24	9.44 score on a scale Standard Deviation 16.85	-5.50 score on a scale Standard Deviation 11.65	5.00 score on a scale Standard Deviation 13.14
Change in Quality of Life Assessed Via the Pediatric Quality of Life Inventory (PedsQL) Questionnaire From Baseline to Week 24 Psychosocial Health - Parent - Week 24	2.04 score on a scale Standard Deviation 13.80	-2.81 score on a scale Standard Deviation 11.48	7.22 score on a scale Standard Deviation 13.21

SECONDARY outcome

Timeframe: Baseline and Week 24

Population: Safety Population - Number of Subjects that Completed Study Week 24

Plasma NT-proBNP concentration is a useful biomarker for PAH as it is associated with changes in right heart morphology and function.

Outcome measures

Measure	Cohort 1 (Transitioning From Parental) n=9 Participants Transitioned from IV or SC Remodulin to oral treprostinil	Cohort 2 (Transitioning From Inhaled) n=10 Participants Transitioned from inhaled prostacyclin to oral treprostinil	Cohort 3 (Add-on to Current PAH Therapy) n=12 Participants Treated with oral treprostinil as a de novo add-on to current PAH therapy
Change in Plasma N-terminal Pro-B-type Natriuretic Peptide (NT-Pro BNP) From Baseline to Week 24	87.156 pg/mL Standard Deviation 281.664	81.930 pg/mL Standard Deviation 245.534	160.617 pg/mL Standard Deviation 549.953

SECONDARY outcome

Timeframe: Baseline and Week 24

Population: Safety Population - Number of Subjects with both Baseline and Week 24 Measurements

Cardiac MRI imaging was performed in all subjects aged 10 years and older at Baseline and Week 24/Premature Termination; imaging was optionally performed in subjects under the age of 10 years. The subject's BP was taken immediately prior to the cMRI assessment in the supine position to measure vascular parameters.

Outcome measures

Measure	Cohort 1 (Transitioning From Parental) n=4 Participants Transitioned from IV or SC Remodulin to oral treprostinil	Cohort 2 (Transitioning From Inhaled) n=9 Participants Transitioned from inhaled prostacyclin to oral treprostinil	Cohort 3 (Add-on to Current PAH Therapy) n=9 Participants Treated with oral treprostinil as a de novo add-on to current PAH therapy
Change From Baseline in Left Ventricular Ejection Fraction (LVEF) at Week 24	-1.0 percentage of LVEF Standard Deviation 1.4	2.4 percentage of LVEF Standard Deviation 6.0	-2.4 percentage of LVEF Standard Deviation 3.1

SECONDARY outcome

Timeframe: Baseline and Week 24

Population: Safety Population - Number of Subjects with both Baseline and Week 24 Measurements

Cardiac MRI imaging was performed in all subjects aged 10 years and older at Baseline and Week 24/Premature Termination; imaging was optionally performed in subjects under the age of 10 years. The subject's BP was taken immediately prior to the cMRI assessment in the supine position to measure vascular parameters.

Outcome measures

Measure	Cohort 1 (Transitioning From Parental) n=4 Participants Transitioned from IV or SC Remodulin to oral treprostinil	Cohort 2 (Transitioning From Inhaled) n=9 Participants Transitioned from inhaled prostacyclin to oral treprostinil	Cohort 3 (Add-on to Current PAH Therapy) n=9 Participants Treated with oral treprostinil as a de novo add-on to current PAH therapy
Change From Baseline in Left Ventricular (LV) Stroke Volume Index at Week 24	-4.003 mL/beat/m2 Standard Error 2.688	6.336 mL/beat/m2 Standard Error 8.448	1.113 mL/beat/m2 Standard Error 5.539

SECONDARY outcome

Timeframe: Baseline and Week 24

Population: Safety Population - Number of Subjects with both Baseline and Week 24 Measurements

Cardiac MRI imaging was performed in all subjects aged 10 years and older at Baseline and Week 24/Premature Termination; imaging was optionally performed in subjects under the age of 10 years. The subject's BP was taken immediately prior to the cMRI assessment in the supine position to measure vascular parameters.

Outcome measures

Measure	Cohort 1 (Transitioning From Parental) n=4 Participants Transitioned from IV or SC Remodulin to oral treprostinil	Cohort 2 (Transitioning From Inhaled) n=9 Participants Transitioned from inhaled prostacyclin to oral treprostinil	Cohort 3 (Add-on to Current PAH Therapy) n=9 Participants Treated with oral treprostinil as a de novo add-on to current PAH therapy
Change From Baseline in Right Ventricular (RV) Cardiac Output Index at Week 24	0.303 L/min/m2 Standard Error 0.209	0.767 L/min/m2 Standard Error 1.010	0.121 L/min/m2 Standard Error 1.047

SECONDARY outcome

Timeframe: Baseline and Week 24

Population: Safety Population - Number of Subjects with both Baseline and Week 24 Measurements

Cardiac MRI imaging was performed in all subjects aged 10 years and older at Baseline and Week 24/Premature Termination; imaging was optionally performed in subjects under the age of 10 years. The subject's BP was taken immediately prior to the cMRI assessment in the supine position to measure vascular parameters.

Outcome measures

Measure	Cohort 1 (Transitioning From Parental) n=4 Participants Transitioned from IV or SC Remodulin to oral treprostinil	Cohort 2 (Transitioning From Inhaled) n=9 Participants Transitioned from inhaled prostacyclin to oral treprostinil	Cohort 3 (Add-on to Current PAH Therapy) n=9 Participants Treated with oral treprostinil as a de novo add-on to current PAH therapy
Change From Baseline in Right Ventricular End-diastolic Volume (RVEDV) Index at Week 24	-8.190 mL/m^2 Standard Error 12.887	12.131 mL/m^2 Standard Error 14.382	10.601 mL/m^2 Standard Error 26.115

SECONDARY outcome

Timeframe: Baseline and Week 24

Population: Safety Population - Number of Subjects with both Baseline and Week 24 Measurements

Cardiac MRI imaging was performed in all subjects aged 10 years and older at Baseline and Week 24/Premature Termination; imaging was optionally performed in subjects under the age of 10 years. The subject's BP was taken immediately prior to the cMRI assessment in the supine position to measure vascular parameters.

Outcome measures

Measure	Cohort 1 (Transitioning From Parental) n=4 Participants Transitioned from IV or SC Remodulin to oral treprostinil	Cohort 2 (Transitioning From Inhaled) n=9 Participants Transitioned from inhaled prostacyclin to oral treprostinil	Cohort 3 (Add-on to Current PAH Therapy) n=9 Participants Treated with oral treprostinil as a de novo add-on to current PAH therapy
Change From Baseline in Right Ventricular Ejection Fraction (RVEF) at Week 24	4.0 percentage of RVEF Standard Error 7.6	0.4 percentage of RVEF Standard Error 7.1	-0.7 percentage of RVEF Standard Error 2.7

SECONDARY outcome

Timeframe: Baseline and Week 24

Population: Safety Population - Number of Subjects with both Baseline and Week 24 Measurements

Cardiac MRI imaging was performed in all subjects aged 10 years and older at Baseline and Week 24/Premature Termination; imaging was optionally performed in subjects under the age of 10 years. The subject's BP was taken immediately prior to the cMRI assessment in the supine position to measure vascular parameters.

Outcome measures

Measure	Cohort 1 (Transitioning From Parental) n=4 Participants Transitioned from IV or SC Remodulin to oral treprostinil	Cohort 2 (Transitioning From Inhaled) n=9 Participants Transitioned from inhaled prostacyclin to oral treprostinil	Cohort 3 (Add-on to Current PAH Therapy) n=9 Participants Treated with oral treprostinil as a de novo add-on to current PAH therapy
Change From Baseline in Right Ventricular End-systolic Volume (RVESV) Index at Week 24	-7.975 mL/m2 Standard Error 12.614	5.884 mL/m2 Standard Error 12.965	5.722 mL/m2 Standard Error 13.807

SECONDARY outcome

Timeframe: Baseline and Week 24

Population: Safety Population - Number of Subjects with both Baseline and Week 24 Measurements

Cardiac MRI imaging was performed in all subjects aged 10 years and older at Baseline and Week 24/Premature Termination; imaging was optionally performed in subjects under the age of 10 years. The subject's BP was taken immediately prior to the cMRI assessment in the supine position to measure vascular parameters.

Outcome measures

Measure	Cohort 1 (Transitioning From Parental) n=4 Participants Transitioned from IV or SC Remodulin to oral treprostinil	Cohort 2 (Transitioning From Inhaled) n=9 Participants Transitioned from inhaled prostacyclin to oral treprostinil	Cohort 3 (Add-on to Current PAH Therapy) n=9 Participants Treated with oral treprostinil as a de novo add-on to current PAH therapy
Change From Baseline in Right Ventricular (RV) Mass Index at Week 24	2.375 g/m2 Standard Error 6.226	3.041 g/m2 Standard Error 7.890	0.614 g/m2 Standard Error 3.450

SECONDARY outcome

Timeframe: Baseline and Week 24

Population: Safety Population - Number of Subjects with both Baseline and Week 24 Measurements

Cardiac MRI imaging was performed in all subjects aged 10 years and older at Baseline and Week 24/Premature Termination; imaging was optionally performed in subjects under the age of 10 years. The subject's BP was taken immediately prior to the cMRI assessment in the supine position to measure vascular parameters.

Outcome measures

Measure	Cohort 1 (Transitioning From Parental) n=4 Participants Transitioned from IV or SC Remodulin to oral treprostinil	Cohort 2 (Transitioning From Inhaled) n=9 Participants Transitioned from inhaled prostacyclin to oral treprostinil	Cohort 3 (Add-on to Current PAH Therapy) n=9 Participants Treated with oral treprostinil as a de novo add-on to current PAH therapy
Change From Baseline in Right Ventricular (RV) Stroke Volume Index at Week 24	-0.215 mL/beat//m2 Standard Error 1.557	6.193 mL/beat//m2 Standard Error 8.015	1.458 mL/beat//m2 Standard Error 6.719

SECONDARY outcome

Timeframe: Baseline (Cohort 1 only; 0, 4, 8 hours while receiving IV/SC Remodulin) and Week 24 (all cohorts; 0, 2, 4, 6, 8 hours post-dose oral treprostinil)

Population: PK Population. To provide a larger sample size for PK analysis, data for Cohorts 1, 2, and 3 following oral treprostinil administration were combined and compared to parenteral infusion (Cohort 1 Baseline data; Remodulin IV/SC).

Cohort 1 had three blood samples obtained at 'Time 0' and at 4 and 8 hours at the Baseline visit. All cohorts had five blood samples obtained from at 'Time 0' and at 2, 4, 6, and 8 hours at the Week 24 visit. Plasma samples were analyzed for treprostinil using a validated bioanalytical plasma assay. Individual and mean treprostinil plasma concentration data and treprostinil pharmacokinetic parameters, such as peak observed plasma concentration (Cmax), time to peak plasma concentration (Tmax), area under the plasma concentration-time curve (AUC0-inf), were determined as able. For the purposes of PK analysis, data for Cohorts 1, 2, and 3 following oral treprostinil administration were combined and compared to parenteral infusion (Cohort 1 Baseline data; Remodulin IV/SC).

Outcome measures

Measure	Cohort 1 (Transitioning From Parental) n=10 Participants Transitioned from IV or SC Remodulin to oral treprostinil	Cohort 2 (Transitioning From Inhaled) n=32 Participants Transitioned from inhaled prostacyclin to oral treprostinil	Cohort 3 (Add-on to Current PAH Therapy) Treated with oral treprostinil as a de novo add-on to current PAH therapy
Maximum Observed Drug Concentration in Plasma (Cmax)	5.14 ng/mL Geometric Coefficient of Variation 39.4	4.91 ng/mL Geometric Coefficient of Variation 50.5	—

SECONDARY outcome

Timeframe: Baseline (Cohort 1 only; 0, 4, 8 hours while receiving IV/SC Remodulin) and Week 24 (all cohorts; 0, 2, 4, 6, 8 hours post-dose oral treprostinil)

Population: PK Population. To provide a larger sample size for PK analysis, data for Cohorts 1, 2, and 3 following oral treprostinil administration were combined and compared to parenteral infusion (Cohort 1 Baseline data; Remodulin IV/SC).

Cohort 1 had three blood samples obtained at 'Time 0' and at 4 and 8 hours at the Baseline visit. All cohorts had five blood samples obtained from at 'Time 0' and at 2, 4, 6, and 8 hours at the Week 24 visit. Plasma samples were analyzed for treprostinil using a validated bioanalytical plasma assay. Individual and mean treprostinil plasma concentration data and treprostinil pharmacokinetic parameters, such as peak observed plasma concentration (Cmax), time to peak plasma concentration (Tmax), area under the plasma concentration-time curve (AUC0-inf), were determined as able.

Outcome measures

Measure	Cohort 1 (Transitioning From Parental) n=10 Participants Transitioned from IV or SC Remodulin to oral treprostinil	Cohort 2 (Transitioning From Inhaled) n=32 Participants Transitioned from inhaled prostacyclin to oral treprostinil	Cohort 3 (Add-on to Current PAH Therapy) Treated with oral treprostinil as a de novo add-on to current PAH therapy
Last Observed Drug Concentration in Plasma (Clast)	4.66 ng/mL Geometric Coefficient of Variation 38.6	0.985 ng/mL Geometric Coefficient of Variation 104	—

SECONDARY outcome

Timeframe: Baseline (Cohort 1 only; 0, 4, 8 hours while receiving IV/SC Remodulin) and Week 24 (all cohorts; 0, 2, 4, 6, 8 hours post-dose oral treprostinil)

Population: PK Population. To provide a larger sample size for PK analysis, data for Cohorts 1, 2, and 3 following oral treprostinil administration were combined and compared to parenteral infusion (Cohort 1 Baseline data; Remodulin IV/SC).

Cohort 1 had three blood samples obtained at 'Time 0' and at 4 and 8 hours at the Baseline visit. All cohorts had five blood samples obtained from at 'Time 0' and at 2, 4, 6, and 8 hours at the Week 24 visit. Plasma samples were analyzed for treprostinil using a validated bioanalytical plasma assay. Individual and mean treprostinil plasma concentration data and treprostinil pharmacokinetic parameters, such as peak observed plasma concentration (Cmax), time to peak plasma concentration (Tmax), area under the plasma concentration-time curve (AUC0-inf), were determined as able.

Outcome measures

Measure	Cohort 1 (Transitioning From Parental) n=10 Participants Transitioned from IV or SC Remodulin to oral treprostinil	Cohort 2 (Transitioning From Inhaled) n=32 Participants Transitioned from inhaled prostacyclin to oral treprostinil	Cohort 3 (Add-on to Current PAH Therapy) Treated with oral treprostinil as a de novo add-on to current PAH therapy
Average Drug Concentration in Plasma (Cavg)	4.28 ng/mL Geometric Coefficient of Variation 37.7	2.80 ng/mL Geometric Coefficient of Variation 54.5	—

SECONDARY outcome

Timeframe: Baseline (Cohort 1 only; 0, 4, 8 hours while receiving IV/SC Remodulin) and Week 24 (all cohorts; 0, 2, 4, 6, 8 hours post-dose oral treprostinil)

Population: PK Population. To provide a larger sample size for PK analysis, data for Cohorts 1, 2, and 3 following oral treprostinil administration were combined and compared to parenteral infusion (Cohort 1 Baseline data; Remodulin IV/SC).

Cohort 1 had three blood samples obtained at 'Time 0' and at 4 and 8 hours at the Baseline visit. All cohorts had five blood samples obtained from at 'Time 0' and at 2, 4, 6, and 8 hours at the Week 24 visit. Plasma samples were analyzed for treprostinil using a validated bioanalytical plasma assay. Individual and mean treprostinil plasma concentration data and treprostinil pharmacokinetic parameters, such as peak observed plasma concentration (Cmax), time to peak plasma concentration (Tmax), area under the plasma concentration-time curve (AUC0-inf), were determined as able.

Outcome measures

Measure	Cohort 1 (Transitioning From Parental) n=10 Participants Transitioned from IV or SC Remodulin to oral treprostinil	Cohort 2 (Transitioning From Inhaled) n=32 Participants Transitioned from inhaled prostacyclin to oral treprostinil	Cohort 3 (Add-on to Current PAH Therapy) Treated with oral treprostinil as a de novo add-on to current PAH therapy
Observed Minimum Drug Concentration in Plasma (Cmin)	3.45 ng/mL Geometric Coefficient of Variation 47.9	0.799 ng/mL Geometric Coefficient of Variation 88.5	—

SECONDARY outcome

Timeframe: Baseline (Cohort 1 only; 0, 4, 8 hours while receiving IV/SC Remodulin) and Week 24 (all cohorts; 0, 2, 4, 6, 8 hours post-dose oral treprostinil)

Population: PK Population. To provide a larger sample size for PK analysis, data for Cohorts 1, 2, and 3 following oral treprostinil administration were combined and compared to parenteral infusion (Cohort 1 Baseline data; Remodulin IV/SC).

Cohort 1 had three blood samples obtained at 'Time 0' and at 4 and 8 hours at the Baseline visit. All cohorts had five blood samples obtained from at 'Time 0' and at 2, 4, 6, and 8 hours at the Week 24 visit. Plasma samples were analyzed for treprostinil using a validated bioanalytical plasma assay. Individual and mean treprostinil plasma concentration data and treprostinil pharmacokinetic parameters, such as peak observed plasma concentration (Cmax), time to peak plasma concentration (Tmax), area under the plasma concentration-time curve (AUC0-inf), were determined as able.

Outcome measures

Measure	Cohort 1 (Transitioning From Parental) n=10 Participants Transitioned from IV or SC Remodulin to oral treprostinil	Cohort 2 (Transitioning From Inhaled) n=32 Participants Transitioned from inhaled prostacyclin to oral treprostinil	Cohort 3 (Add-on to Current PAH Therapy) Treated with oral treprostinil as a de novo add-on to current PAH therapy
Area Under the Concentration-Time Curve From Zero to Tau Hours Post-dose (AUCtau)	34.3 h*ng/mL Geometric Coefficient of Variation 37.7	22.2 h*ng/mL Geometric Coefficient of Variation 53.8	—

SECONDARY outcome

Timeframe: Baseline (Cohort 1 only; 0, 4, 8 hours while receiving IV/SC Remodulin) and Week 24 (all cohorts; 0, 2, 4, 6, 8 hours post-dose oral treprostinil)

Population: PK Population. To provide a larger sample size for PK analysis, data for Cohorts 1, 2, and 3 following oral treprostinil administration were combined and compared to parenteral infusion (Cohort 1 Baseline data; Remodulin IV/SC).

Cohort 1 had three blood samples obtained at 'Time 0' and at 4 and 8 hours at the Baseline visit. All cohorts had five blood samples obtained from at 'Time 0' and at 2, 4, 6, and 8 hours at the Week 24 visit. Plasma samples were analyzed for treprostinil using a validated bioanalytical plasma assay. Individual and mean treprostinil plasma concentration data and treprostinil pharmacokinetic parameters, such as peak observed plasma concentration (Cmax), time to peak plasma concentration (Tmax), area under the plasma concentration-time curve (AUC0-inf), were determined as able.

Outcome measures

Measure	Cohort 1 (Transitioning From Parental) n=10 Participants Transitioned from IV or SC Remodulin to oral treprostinil	Cohort 2 (Transitioning From Inhaled) n=32 Participants Transitioned from inhaled prostacyclin to oral treprostinil	Cohort 3 (Add-on to Current PAH Therapy) Treated with oral treprostinil as a de novo add-on to current PAH therapy
Area Under the Concentration-Time Curve From Zero to 8 Hours Post-dose (AUC0-8)	34.3 h*ng/mL Geometric Coefficient of Variation 37.7	22.4 h*ng/mL Geometric Coefficient of Variation 54.3	—

Adverse Events

Cohort 1 (Transitioning From Parental)

Serious events: 5 serious events

Other events: 10 other events

Deaths: 0 deaths

Cohort 2 (Transitioning From Inhaled)

Serious events: 0 serious events

Other events: 10 other events

Deaths: 0 deaths

Cohort 3 (Add-on to Current PAH Therapy)

Serious events: 4 serious events

Other events: 12 other events

Deaths: 0 deaths

Serious adverse events

Measure	Cohort 1 (Transitioning From Parental) n=10 participants at risk Transitioned from IV or SC Remodulin to oral treprostinil	Cohort 2 (Transitioning From Inhaled) n=10 participants at risk Transitioned from inhaled prostacyclin to oral treprostinil	Cohort 3 (Add-on to Current PAH Therapy) n=12 participants at risk Treated with oral treprostinil as a de novo add-on to current PAH therapy
Cardiac disorders Tachycardia	0.00% 0/10 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.	0.00% 0/10 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.	8.3% 1/12 • Number of events 1 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.
General disorders Chest pain	0.00% 0/10 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.	0.00% 0/10 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.	16.7% 2/12 • Number of events 2 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.
Infections and infestations Device related infection	10.0% 1/10 • Number of events 1 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.	0.00% 0/10 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.	0.00% 0/12 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.
Infections and infestations Pneumonia	0.00% 0/10 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.	0.00% 0/10 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.	8.3% 1/12 • Number of events 1 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.
Infections and infestations Stoma site infection	10.0% 1/10 • Number of events 1 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.	0.00% 0/10 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.	0.00% 0/12 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.
Nervous system disorders Seizure	20.0% 2/10 • Number of events 2 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.	0.00% 0/10 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.	0.00% 0/12 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.
Nervous system disorders Syncope	10.0% 1/10 • Number of events 2 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.	0.00% 0/10 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.	0.00% 0/12 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.
Respiratory, thoracic and mediastinal disorders Bronchial hyperreactivity	0.00% 0/10 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.	0.00% 0/10 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.	8.3% 1/12 • Number of events 1 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.00% 0/10 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.	0.00% 0/10 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.	8.3% 1/12 • Number of events 1 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.

Other adverse events

Measure	Cohort 1 (Transitioning From Parental) n=10 participants at risk Transitioned from IV or SC Remodulin to oral treprostinil	Cohort 2 (Transitioning From Inhaled) n=10 participants at risk Transitioned from inhaled prostacyclin to oral treprostinil	Cohort 3 (Add-on to Current PAH Therapy) n=12 participants at risk Treated with oral treprostinil as a de novo add-on to current PAH therapy
Respiratory, thoracic and mediastinal disorders Pulmonary hypertension	0.00% 0/10 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.	0.00% 0/10 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.	8.3% 1/12 • Number of events 1 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.
Respiratory, thoracic and mediastinal disorders Rhinorrhoea	0.00% 0/10 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.	0.00% 0/10 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.	8.3% 1/12 • Number of events 1 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.
Respiratory, thoracic and mediastinal disorders Snoring	0.00% 0/10 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.	0.00% 0/10 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.	8.3% 1/12 • Number of events 1 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.
Skin and subcutaneous tissue disorders Rash	20.0% 2/10 • Number of events 2 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.	0.00% 0/10 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.	0.00% 0/12 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.
Skin and subcutaneous tissue disorders Eczema	0.00% 0/10 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.	10.0% 1/10 • Number of events 1 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.	0.00% 0/12 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.
Cardiac disorders Arrhythmia	10.0% 1/10 • Number of events 1 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.	0.00% 0/10 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.	0.00% 0/12 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.
Cardiac disorders Cyanosis	0.00% 0/10 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.	10.0% 1/10 • Number of events 1 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.	0.00% 0/12 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.
Cardiac disorders Palpitations	0.00% 0/10 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.	0.00% 0/10 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.	8.3% 1/12 • Number of events 1 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.
Cardiac disorders Pericardial effusion	10.0% 1/10 • Number of events 1 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.	0.00% 0/10 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.	0.00% 0/12 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.
Cardiac disorders Right atrial enlargement	0.00% 0/10 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.	0.00% 0/10 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.	8.3% 1/12 • Number of events 1 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.
Cardiac disorders Right ventricular hypertrophy	0.00% 0/10 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.	0.00% 0/10 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.	8.3% 1/12 • Number of events 1 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.
Cardiac disorders Tachycardia	0.00% 0/10 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.	0.00% 0/10 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.	8.3% 1/12 • Number of events 1 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.
Eye disorders Excessive eye blinking	10.0% 1/10 • Number of events 1 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.	0.00% 0/10 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.	0.00% 0/12 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.
Eye disorders Eye pain	0.00% 0/10 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.	10.0% 1/10 • Number of events 1 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.	0.00% 0/12 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.
Eye disorders Perioribital oedema	10.0% 1/10 • Number of events 1 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.	0.00% 0/10 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.	0.00% 0/12 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.
Gastrointestinal disorders Diarrhoea	60.0% 6/10 • Number of events 6 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.	70.0% 7/10 • Number of events 7 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.	75.0% 9/12 • Number of events 10 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.
Gastrointestinal disorders Nausea	70.0% 7/10 • Number of events 7 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.	50.0% 5/10 • Number of events 6 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.	75.0% 9/12 • Number of events 9 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.
Gastrointestinal disorders Vomiting	90.0% 9/10 • Number of events 9 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.	50.0% 5/10 • Number of events 6 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.	58.3% 7/12 • Number of events 7 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.
Gastrointestinal disorders Abdominal pain upper	40.0% 4/10 • Number of events 4 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.	40.0% 4/10 • Number of events 4 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.	41.7% 5/12 • Number of events 6 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.
Gastrointestinal disorders Abdominal pain	0.00% 0/10 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.	20.0% 2/10 • Number of events 2 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.	16.7% 2/12 • Number of events 2 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.
Gastrointestinal disorders Gastrooesophageal reflux disease	10.0% 1/10 • Number of events 2 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.	10.0% 1/10 • Number of events 1 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.	8.3% 1/12 • Number of events 1 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.
Gastrointestinal disorders Dyspepsia	10.0% 1/10 • Number of events 1 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.	10.0% 1/10 • Number of events 1 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.	0.00% 0/12 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.
Gastrointestinal disorders Anorectal discomfort	10.0% 1/10 • Number of events 1 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.	0.00% 0/10 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.	0.00% 0/12 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.
Gastrointestinal disorders Dyschezia	0.00% 0/10 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.	0.00% 0/10 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.	8.3% 1/12 • Number of events 1 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.
Gastrointestinal disorders Faeces soft	10.0% 1/10 • Number of events 1 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.	0.00% 0/10 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.	0.00% 0/12 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.
Gastrointestinal disorders Flatulence	0.00% 0/10 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.	0.00% 0/10 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.	8.3% 1/12 • Number of events 1 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.
Gastrointestinal disorders Gingival bleeding	0.00% 0/10 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.	10.0% 1/10 • Number of events 1 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.	0.00% 0/12 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.
Gastrointestinal disorders Haematochezia	0.00% 0/10 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.	0.00% 0/10 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.	8.3% 1/12 • Number of events 1 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.
General disorders Chest pain	10.0% 1/10 • Number of events 1 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.	0.00% 0/10 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.	41.7% 5/12 • Number of events 6 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.
General disorders Fatigue	20.0% 2/10 • Number of events 2 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.	10.0% 1/10 • Number of events 1 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.	25.0% 3/12 • Number of events 3 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.
General disorders Pyrexia	10.0% 1/10 • Number of events 1 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.	10.0% 1/10 • Number of events 1 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.	16.7% 2/12 • Number of events 2 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.
General disorders Pain	0.00% 0/10 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.	0.00% 0/10 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.	16.7% 2/12 • Number of events 2 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.
General disorders Facial pain	0.00% 0/10 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.	0.00% 0/10 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.	8.3% 1/12 • Number of events 1 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.
General disorders Feeling hot	0.00% 0/10 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.	10.0% 1/10 • Number of events 1 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.	0.00% 0/12 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.
General disorders Influenza like illness	0.00% 0/10 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.	0.00% 0/10 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.	8.3% 1/12 • Number of events 1 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.
General disorders Malaise	0.00% 0/10 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.	10.0% 1/10 • Number of events 1 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.	0.00% 0/12 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.
General disorders Oedema	0.00% 0/10 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.	0.00% 0/10 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.	8.3% 1/12 • Number of events 1 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.
Immune system disorders Hypersensitivity	0.00% 0/10 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.	10.0% 1/10 • Number of events 1 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.	0.00% 0/12 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.
Infections and infestations Viral upper respiratory tract infection	20.0% 2/10 • Number of events 2 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.	40.0% 4/10 • Number of events 5 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.	16.7% 2/12 • Number of events 2 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.
Infections and infestations Ear infection	20.0% 2/10 • Number of events 2 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.	0.00% 0/10 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.	0.00% 0/12 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.
Infections and infestations Gastroenteritis	10.0% 1/10 • Number of events 1 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.	10.0% 1/10 • Number of events 1 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.	0.00% 0/12 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.
Infections and infestations Gastroenteritis viral	20.0% 2/10 • Number of events 2 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.	0.00% 0/10 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.	0.00% 0/12 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.
Infections and infestations Pharyngitis streptococcal	10.0% 1/10 • Number of events 1 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.	10.0% 1/10 • Number of events 1 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.	0.00% 0/12 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.
Infections and infestations Sinusitis	0.00% 0/10 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.	0.00% 0/10 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.	16.7% 2/12 • Number of events 2 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.
Infections and infestations Upper respiratory tract infection	10.0% 1/10 • Number of events 1 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.	0.00% 0/10 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.	8.3% 1/12 • Number of events 1 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.
Infections and infestations Device related infection	10.0% 1/10 • Number of events 1 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.	0.00% 0/10 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.	0.00% 0/12 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.
Infections and infestations Hand-foot-and-mouth disease	0.00% 0/10 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.	10.0% 1/10 • Number of events 1 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.	0.00% 0/12 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.
Infections and infestations Impetigo	10.0% 1/10 • Number of events 1 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.	0.00% 0/10 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.	0.00% 0/12 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.
Infections and infestations Kidney infection	10.0% 1/10 • Number of events 1 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.	0.00% 0/10 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.	0.00% 0/12 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.
Infections and infestations Nasopharyngitis	0.00% 0/10 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.	10.0% 1/10 • Number of events 1 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.	0.00% 0/12 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.
Infections and infestations Pneumonia	0.00% 0/10 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.	0.00% 0/10 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.	8.3% 1/12 • Number of events 1 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.
Infections and infestations Stoma site infection	10.0% 1/10 • Number of events 2 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.	0.00% 0/10 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.	0.00% 0/12 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.
Injury, poisoning and procedural complications Heat exhaustion	0.00% 0/10 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.	10.0% 1/10 • Number of events 1 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.	0.00% 0/12 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.
Investigations N-terminal prohormone brain natriuretic peptide increased	20.0% 2/10 • Number of events 2 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.	10.0% 1/10 • Number of events 2 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.	8.3% 1/12 • Number of events 1 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.
Investigations Weight decreased	0.00% 0/10 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.	10.0% 1/10 • Number of events 1 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.	8.3% 1/12 • Number of events 1 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.
Investigations Aspartate aminotransferase increased	0.00% 0/10 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.	0.00% 0/10 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.	8.3% 1/12 • Number of events 1 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.
Investigations Blood creatinine increased	0.00% 0/10 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.	10.0% 1/10 • Number of events 1 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.	0.00% 0/12 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.
Investigations Blood iron decreased	0.00% 0/10 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.	0.00% 0/10 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.	8.3% 1/12 • Number of events 1 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.
Investigations Platelet count decreased	0.00% 0/10 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.	10.0% 1/10 • Number of events 1 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.	0.00% 0/12 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.
Metabolism and nutrition disorders Decreased appetite	10.0% 1/10 • Number of events 1 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.	10.0% 1/10 • Number of events 1 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.	16.7% 2/12 • Number of events 2 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.
Metabolism and nutrition disorders Dehydration	0.00% 0/10 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.	10.0% 1/10 • Number of events 1 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.	0.00% 0/12 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.
Metabolism and nutrition disorders Hyperkalaemia	0.00% 0/10 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.	0.00% 0/10 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.	8.3% 1/12 • Number of events 1 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.
Musculoskeletal and connective tissue disorders Pain in jaw	10.0% 1/10 • Number of events 1 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.	10.0% 1/10 • Number of events 1 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.	50.0% 6/12 • Number of events 6 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.
Musculoskeletal and connective tissue disorders Pain in extremity	10.0% 1/10 • Number of events 1 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.	10.0% 1/10 • Number of events 1 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.	41.7% 5/12 • Number of events 7 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.
Musculoskeletal and connective tissue disorders Arthralgia	10.0% 1/10 • Number of events 1 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.	0.00% 0/10 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.	8.3% 1/12 • Number of events 1 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.
Musculoskeletal and connective tissue disorders Back pain	10.0% 1/10 • Number of events 1 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.	10.0% 1/10 • Number of events 1 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.	0.00% 0/12 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.
Musculoskeletal and connective tissue disorders Muscle spasms	0.00% 0/10 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.	0.00% 0/10 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.	16.7% 2/12 • Number of events 2 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.
Musculoskeletal and connective tissue disorders Musculoskeletal pain	0.00% 0/10 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.	10.0% 1/10 • Number of events 1 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.	0.00% 0/12 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.
Musculoskeletal and connective tissue disorders Musculoskeletal stiffness	0.00% 0/10 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.	0.00% 0/10 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.	8.3% 1/12 • Number of events 1 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.
Nervous system disorders Headache	60.0% 6/10 • Number of events 6 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.	80.0% 8/10 • Number of events 9 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.	100.0% 12/12 • Number of events 12 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.
Nervous system disorders Dizziness	30.0% 3/10 • Number of events 3 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.	10.0% 1/10 • Number of events 1 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.	33.3% 4/12 • Number of events 4 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.
Nervous system disorders Syncope	20.0% 2/10 • Number of events 3 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.	10.0% 1/10 • Number of events 1 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.	0.00% 0/12 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.
Nervous system disorders Presyncope	0.00% 0/10 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.	10.0% 1/10 • Number of events 1 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.	8.3% 1/12 • Number of events 1 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.
Nervous system disorders Seizure	20.0% 2/10 • Number of events 2 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.	0.00% 0/10 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.	0.00% 0/12 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.
Skin and subcutaneous tissue disorders Night sweats	10.0% 1/10 • Number of events 1 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.	0.00% 0/10 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.	0.00% 0/12 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.
Nervous system disorders Disturbance in attention	0.00% 0/10 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.	10.0% 1/10 • Number of events 1 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.	0.00% 0/12 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.
Nervous system disorders Migraine	0.00% 0/10 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.	0.00% 0/10 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.	8.3% 1/12 • Number of events 1 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.
Nervous system disorders Paraesthesia	0.00% 0/10 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.	0.00% 0/10 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.	8.3% 1/12 • Number of events 1 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.
Nervous system disorders Periodic limb movement disorder	0.00% 0/10 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.	0.00% 0/10 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.	8.3% 1/12 • Number of events 1 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.
Psychiatric disorders Depression	0.00% 0/10 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.	10.0% 1/10 • Number of events 1 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.	8.3% 1/12 • Number of events 1 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.
Psychiatric disorders Anxiety	0.00% 0/10 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.	0.00% 0/10 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.	8.3% 1/12 • Number of events 1 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.
Psychiatric disorders Enuresis	10.0% 1/10 • Number of events 1 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.	0.00% 0/10 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.	0.00% 0/12 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.
Psychiatric disorders Intentional self injury	0.00% 0/10 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.	0.00% 0/10 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.	8.3% 1/12 • Number of events 1 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.
Psychiatric disorders Stress	0.00% 0/10 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.	0.00% 0/10 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.	8.3% 1/12 • Number of events 1 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.
Renal and urinary disorders Dysuria	0.00% 0/10 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.	0.00% 0/10 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.	8.3% 1/12 • Number of events 1 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.
Reproductive system and breast disorders Erection increased	0.00% 0/10 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.	0.00% 0/10 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.	8.3% 1/12 • Number of events 1 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.
Reproductive system and breast disorders Menorrhagia	0.00% 0/10 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.	10.0% 1/10 • Number of events 1 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.	0.00% 0/12 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.
Reproductive system and breast disorders Metrorrhagia	0.00% 0/10 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.	0.00% 0/10 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.	8.3% 1/12 • Number of events 1 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.
Reproductive system and breast disorders Pelvic pain	0.00% 0/10 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.	0.00% 0/10 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.	8.3% 1/12 • Number of events 1 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.
Reproductive system and breast disorders Vaginal haemorrhage	0.00% 0/10 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.	0.00% 0/10 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.	8.3% 1/12 • Number of events 1 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.
Respiratory, thoracic and mediastinal disorders Cough	10.0% 1/10 • Number of events 1 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.	50.0% 5/10 • Number of events 5 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.	16.7% 2/12 • Number of events 2 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.00% 0/10 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.	10.0% 1/10 • Number of events 1 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.	33.3% 4/12 • Number of events 5 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	10.0% 1/10 • Number of events 1 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.	20.0% 2/10 • Number of events 2 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.	16.7% 2/12 • Number of events 2 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.
Respiratory, thoracic and mediastinal disorders Epistaxis	10.0% 1/10 • Number of events 1 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.	10.0% 1/10 • Number of events 1 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.	8.3% 1/12 • Number of events 1 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.
Respiratory, thoracic and mediastinal disorders Nasal congestion	0.00% 0/10 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.	10.0% 1/10 • Number of events 1 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.	8.3% 1/12 • Number of events 1 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.
Respiratory, thoracic and mediastinal disorders Asthma	0.00% 0/10 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.	10.0% 1/10 • Number of events 1 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.	0.00% 0/12 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.
Respiratory, thoracic and mediastinal disorders Bronchial hyperreactivity	0.00% 0/10 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.	0.00% 0/10 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.	8.3% 1/12 • Number of events 1 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.
Respiratory, thoracic and mediastinal disorders Dysphonia	0.00% 0/10 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.	0.00% 0/10 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.	8.3% 1/12 • Number of events 1 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.
Respiratory, thoracic and mediastinal disorders Pulmonary congestion	0.00% 0/10 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.	0.00% 0/10 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.	8.3% 1/12 • Number of events 1 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.
Skin and subcutaneous tissue disorders Swelling face	10.0% 1/10 • Number of events 1 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.	0.00% 0/10 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.	0.00% 0/12 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.
Vascular disorders Flushing	60.0% 6/10 • Number of events 6 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.	40.0% 4/10 • Number of events 4 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.	66.7% 8/12 • Number of events 8 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.
Vascular disorders Hypotension	0.00% 0/10 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.	10.0% 1/10 • Number of events 1 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.	16.7% 2/12 • Number of events 2 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.
Vascular disorders Pallor	10.0% 1/10 • Number of events 1 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.	0.00% 0/10 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.	8.3% 1/12 • Number of events 1 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.
Vascular disorders Hypertension	0.00% 0/10 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.	0.00% 0/10 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.	8.3% 1/12 • Number of events 1 • Adverse events were recorded from the time that each subject and/or caregiver signed the ICF until the time screen failure was documented, or until the subject was either discontinued from the study or all Week 24 study assessments were completed.

Additional Information

Derek Solum, PhD

United Therapeutics

Phone: 919-425-8122

Email: dsolum@unither.com

Results disclosure agreements

• Principal investigator is a sponsor employee Institution and/or Principal Investigator agree not to publish or publicly present any interim results of the Study without the prior written consent of Sponsor, not to be unreasonably withheld or delayed. Institution and/or Principal Investigator further agree to provide Sponsor with drafts of any such publication or presentation for review and approval no less than 30 days prior to submission for publication or the date of public presentation.
• Publication restrictions are in place

Restriction type: OTHER