Trial Outcomes & Findings for EXPEDITE: A Study of Remodulin Induction Followed by Orenitram Optimization to Treat Pulmonary Arterial Hypertension (NCT NCT03497689)

Last Updated: 2023-08-07

Results Overview

The number of subjects that achieved an oral treprostinil dose of ≥4 mg TID (or a total daily dose \[TDD\] of 12 mg) at Week 16 (or a dose of ≥0.057 mg/kg TID \[TDD of 0.171 mg/kg\] for subjects \<70 kg).

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

36 participants

Primary outcome timeframe

Assessed at Week 16

Results posted on

2023-08-07

Participant Flow

There were 36 subjects enrolled but only 35 subjects started treatment with Remodulin (Safety Population). One subject was enrolled but did not receive study drug due to a violation of entry criteria (CD4 lymphocyte count for HIV-positive subjects).

Participant milestones

Participant milestones
Measure	Intravenous/Subcutaneous Treprostinil; Oral Treprostinil IV or SC treprostinil induction followed by transition to oral treprostinil Intravenous/Subcutaneous Treprostinil; Oral Treprostinil: Short-term course of IV or SC treprostinil continuous infusion followed by transition to oral treprostinil XR tablets taken TID
Overall Study STARTED	35
Overall Study COMPLETED	28
Overall Study NOT COMPLETED	7

Reasons for withdrawal

Reasons for withdrawal
Measure	Intravenous/Subcutaneous Treprostinil; Oral Treprostinil IV or SC treprostinil induction followed by transition to oral treprostinil Intravenous/Subcutaneous Treprostinil; Oral Treprostinil: Short-term course of IV or SC treprostinil continuous infusion followed by transition to oral treprostinil XR tablets taken TID
Overall Study Adverse Event	2
Overall Study Death	1
Overall Study Physician Decision	1
Overall Study Withdrawal by Subject	1
Overall Study Protocol Violation	2

Baseline Characteristics

EXPEDITE: A Study of Remodulin Induction Followed by Orenitram Optimization to Treat Pulmonary Arterial Hypertension

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Intravenous/Subcutaneous Treprostinil; Oral Treprostinil n=35 Participants IV or SC treprostinil induction followed by transition to oral treprostinil Intravenous/Subcutaneous Treprostinil; Oral Treprostinil: Short term course of IV/SC treprostinil continuous infusion followed by transition to oral treprostinil extended-release (XR) tablets taken three times daily (TID)
Age, Continuous	56.0 years n=93 Participants
Sex: Female, Male Female	24 Participants n=93 Participants
Sex: Female, Male Male	11 Participants n=93 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	3 Participants n=93 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	32 Participants n=93 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=93 Participants
Race (NIH/OMB) American Indian or Alaska Native	1 Participants n=93 Participants
Race (NIH/OMB) Asian	0 Participants n=93 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=93 Participants
Race (NIH/OMB) Black or African American	4 Participants n=93 Participants
Race (NIH/OMB) White	29 Participants n=93 Participants
Race (NIH/OMB) More than one race	0 Participants n=93 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=93 Participants
PAH Etiology Idiopathic PAH	15 Participants n=93 Participants
PAH Etiology Associated with connective tissue disease	9 Participants n=93 Participants
PAH Etiology Associated with appetite suppressant or toxin use	7 Participants n=93 Participants
PAH Etiology Associated with HIV infection	1 Participants n=93 Participants
PAH Etiology Heritable PAH	1 Participants n=93 Participants
PAH Etiology Other	2 Participants n=93 Participants
PAH Etiology Associated with repaired congenital systemic-to-pulmonary shunts	0 Participants n=93 Participants
Days Since Initial PAH Diagnosis	245.0 days n=93 Participants

PRIMARY outcome

Timeframe: Assessed at Week 16

Population: Per-protocol Population

Outcome measures

Outcome measures
Measure	Intravenous/Subcutaneous Treprostinil; Oral Treprostinil n=29 Participants IV or SC treprostinil induction followed by transition to oral treprostinil Intravenous/Subcutaneous Treprostinil; Oral Treprostinil: Short term course of IV/SC treprostinil continuous infusion followed by transition to oral treprostinil extended-release (XR) tablets taken three times daily (TID)
Number of Subjects Achieving Oral Treprostinil Dose	23 Participants

SECONDARY outcome

Timeframe: From Baseline to Week 16

Population: Per-protocol Population. Only Subjects with Baseline and Week 16 are included.

The 6-Minute Walk Test (6MWT) is used to measure exercise ability in patients with chronic respiratory diseases. The distance walked on a predetermined course over 6 minutes was recorded.

Outcome measures

Outcome measures
Measure	Intravenous/Subcutaneous Treprostinil; Oral Treprostinil n=27 Participants IV or SC treprostinil induction followed by transition to oral treprostinil Intravenous/Subcutaneous Treprostinil; Oral Treprostinil: Short term course of IV/SC treprostinil continuous infusion followed by transition to oral treprostinil extended-release (XR) tablets taken three times daily (TID)
Change in 6-minute Walk Distance (6MWD)	25.00 meters Interval -210.0 to 112.0

SECONDARY outcome

Timeframe: From Baseline to Week 16

Population: Per-protocol Population. Only Subjects with Baseline and Week 16 are included.

The Borg dyspnea score is a 10-point scale rating the maximum level of dyspnea experienced during the 6MWT. Scores range from 0 (no shortness of breath) to 10 (worst shortness of breath you have ever had).

Outcome measures

Outcome measures
Measure	Intravenous/Subcutaneous Treprostinil; Oral Treprostinil n=27 Participants IV or SC treprostinil induction followed by transition to oral treprostinil Intravenous/Subcutaneous Treprostinil; Oral Treprostinil: Short term course of IV/SC treprostinil continuous infusion followed by transition to oral treprostinil extended-release (XR) tablets taken three times daily (TID)
Change in Borg Dyspnea Score	-1.00 score on a scale Interval -5.0 to 4.0

SECONDARY outcome

Timeframe: From Baseline to Week 16

Population: Per-protocol Population. Only Subjects with Baseline and Week 16 are included.

WHO FC ranges from I (subjects with PH but without resulting limitation of physical activity) to IV (subjects with PH with inability to carry out any physical activities without symptoms). A lower WHO FC was considered "improved"; a higher WHO FC was considered "worsened."

Outcome measures

Outcome measures
Measure	Intravenous/Subcutaneous Treprostinil; Oral Treprostinil n=28 Participants IV or SC treprostinil induction followed by transition to oral treprostinil Intravenous/Subcutaneous Treprostinil; Oral Treprostinil: Short term course of IV/SC treprostinil continuous infusion followed by transition to oral treprostinil extended-release (XR) tablets taken three times daily (TID)
Number of Subjects With Changes in WHO FC Improved	19 Participants
Number of Subjects With Changes in WHO FC Worsened	1 Participants
Number of Subjects With Changes in WHO FC No Change	8 Participants

SECONDARY outcome

Timeframe: From Baseline to Week 16

Population: Per-protocol Population. Only Subjects with Baseline and Week 16 are included.

NT-proBNP is a hormone produced by the heart. NT-proBNP concentration is associated with changes in right heart morphology and function. The main purpose of NT-proBNP testing is to see if the blood levels of this protein are within the expected range for a healthy person. Normal levels of NT-proBNP are less than 125 pg/mL for people under 75 years old and less than 450 pg/mL for people over age 75. NT-proBNP levels over 900 pg/mL may be a sign of heart failure. The higher the level, the more serious the condition.

Outcome measures

Outcome measures
Measure	Intravenous/Subcutaneous Treprostinil; Oral Treprostinil n=28 Participants IV or SC treprostinil induction followed by transition to oral treprostinil Intravenous/Subcutaneous Treprostinil; Oral Treprostinil: Short term course of IV/SC treprostinil continuous infusion followed by transition to oral treprostinil extended-release (XR) tablets taken three times daily (TID)
Change in Serum N-terminal Pro-brain Natriuretic Peptide (NT-proBNP) Levels	-134.0 ng/L Interval -3896.0 to 556.0

SECONDARY outcome

Timeframe: At Baseline and Week 16

Population: Per-protocol Population. Only Subjects with Baseline and Week 16 are included.

ECHOs provide information regarding cardiac structure and function. Cardiac output was summarized at each time point listed.

Outcome measures

Outcome measures
Measure	Intravenous/Subcutaneous Treprostinil; Oral Treprostinil n=22 Participants IV or SC treprostinil induction followed by transition to oral treprostinil Intravenous/Subcutaneous Treprostinil; Oral Treprostinil: Short term course of IV/SC treprostinil continuous infusion followed by transition to oral treprostinil extended-release (XR) tablets taken three times daily (TID)
Change in Echocardiogram Parameters (Change in Cardiac Output)	0.55 L/min Interval -1.7 to 3.1

SECONDARY outcome

Timeframe: At Baseline and Week 16

Population: Per-protocol Population. Only Subjects with Baseline and Week 16 are included.

ECHOs provide information regarding cardiac structure and function. Heart rate was summarized at each time point listed.

Outcome measures

Outcome measures
Measure	Intravenous/Subcutaneous Treprostinil; Oral Treprostinil n=22 Participants IV or SC treprostinil induction followed by transition to oral treprostinil Intravenous/Subcutaneous Treprostinil; Oral Treprostinil: Short term course of IV/SC treprostinil continuous infusion followed by transition to oral treprostinil extended-release (XR) tablets taken three times daily (TID)
Change in Echocardiogram Parameters (Heart Rate)	1.50 beats/min Interval -17.0 to 23.0

SECONDARY outcome

Timeframe: At Baseline and Week 16

Population: Per-protocol Population. Only Subjects with Baseline and Week 16 are included.

ECHOs provide information regarding cardiac structure and function. Left ventricular outflow track (LVOT) dimension was summarized at each time point listed.

Outcome measures

Outcome measures
Measure	Intravenous/Subcutaneous Treprostinil; Oral Treprostinil n=23 Participants IV or SC treprostinil induction followed by transition to oral treprostinil Intravenous/Subcutaneous Treprostinil; Oral Treprostinil: Short term course of IV/SC treprostinil continuous infusion followed by transition to oral treprostinil extended-release (XR) tablets taken three times daily (TID)
Change in Echocardiogram Parameters (Left Ventricular Outflow Track Dimension)	0.42 mm Interval -1.1 to 2.6

SECONDARY outcome

Timeframe: At Baseline and Week 16

Population: Per-protocol Population. Only Subjects with Baseline and Week 16 are included.

ECHOs provide information regarding cardiac structure and function. LVOT velocity time integral was summarized at each time point listed.

Outcome measures

Outcome measures
Measure	Intravenous/Subcutaneous Treprostinil; Oral Treprostinil n=22 Participants IV or SC treprostinil induction followed by transition to oral treprostinil Intravenous/Subcutaneous Treprostinil; Oral Treprostinil: Short term course of IV/SC treprostinil continuous infusion followed by transition to oral treprostinil extended-release (XR) tablets taken three times daily (TID)
Change in Echocardiogram Parameters (LVOT Velocity Time Integral)	0.93 cm Interval -6.8 to 7.7

SECONDARY outcome

Timeframe: At Baseline and Week 16

Population: Per-protocol Population. Only Subjects with Baseline and Week 16 are included.

ECHOs provide information regarding cardiac structure and function. LV diameter was summarized at each time point listed.

Outcome measures

Outcome measures
Measure	Intravenous/Subcutaneous Treprostinil; Oral Treprostinil n=21 Participants IV or SC treprostinil induction followed by transition to oral treprostinil Intravenous/Subcutaneous Treprostinil; Oral Treprostinil: Short term course of IV/SC treprostinil continuous infusion followed by transition to oral treprostinil extended-release (XR) tablets taken three times daily (TID)
Change in Echocardiogram Parameters (LV Diameter)	3.52 mm Interval -4.4 to 14.1

SECONDARY outcome

Timeframe: At Baseline and Week 16

Population: Per-protocol Population. Only Subjects with Baseline and Week 16 are included.

ECHOs provide information regarding cardiac structure and function. LV Eccentricity Index (Diastole) was summarized at each time point listed. Diastole LV Eccentricity Index is measured during ECHOs to assess how much the shape of the LV deviates from normal while the heart is relaxing (full of blood prior to contraction). A lower Diastole LV Eccentricity Index indicates that the LV is closer to a normal shape during diastole. A higher Diastole LV Eccentricity Index indicates that the LV is more elongated/stretched during diastole, indicating potential heart problems. There is no theoretical minimum or maximum value for the index range.

Outcome measures

Outcome measures
Measure	Intravenous/Subcutaneous Treprostinil; Oral Treprostinil n=22 Participants IV or SC treprostinil induction followed by transition to oral treprostinil Intravenous/Subcutaneous Treprostinil; Oral Treprostinil: Short term course of IV/SC treprostinil continuous infusion followed by transition to oral treprostinil extended-release (XR) tablets taken three times daily (TID)
Change in Echocardiogram Parameters (LV Eccentricity Index [Diastole])	0.04 Eccentricity Index Interval -0.3 to 0.3

SECONDARY outcome

Timeframe: At Baseline and Week 16

Population: Per-protocol Population. Only Subjects with Baseline and Week 16 are included.

ECHOs provide information regarding cardiac structure and function. LV Eccentricity Index (Systole) was summarized at each time point listed. Systole LV Eccentricity Index is measured during ECHOs to assess how much the shape of the LV deviates from normal while the heart is contracting (pumping blood to the body). A lower Systole LV Eccentricity Index indicates that the LV is closer to a normal shape during systole. A higher Systole LV Eccentricity Index indicates that the LV is more elongated/stretched during systole, indicating potential heart problems. There is no theoretical minimum or maximum value for the index range.

Outcome measures

Outcome measures
Measure	Intravenous/Subcutaneous Treprostinil; Oral Treprostinil n=22 Participants IV or SC treprostinil induction followed by transition to oral treprostinil Intravenous/Subcutaneous Treprostinil; Oral Treprostinil: Short term course of IV/SC treprostinil continuous infusion followed by transition to oral treprostinil extended-release (XR) tablets taken three times daily (TID)
Change in Echocardiogram Parameters (LV Eccentricity Index [Systole])	0.09 Eccentricity Index Interval -1.0 to 0.7

SECONDARY outcome

Timeframe: At Baseline and Week 16

Population: Per-protocol Population. Only Subjects with Baseline and Week 16 are included.

ECHOs provide information regarding cardiac structure and function. Pulmonary valve acceleration time was summarized at each time point listed.=.

Outcome measures

Outcome measures
Measure	Intravenous/Subcutaneous Treprostinil; Oral Treprostinil n=20 Participants IV or SC treprostinil induction followed by transition to oral treprostinil Intravenous/Subcutaneous Treprostinil; Oral Treprostinil: Short term course of IV/SC treprostinil continuous infusion followed by transition to oral treprostinil extended-release (XR) tablets taken three times daily (TID)
Change in Echocardiogram Parameters (Pulmonary Valve Acceleration Time)	4.43 msec Interval -22.0 to 41.2

SECONDARY outcome

Timeframe: At Baseline and Week 16

Population: Per-protocol Population. Only Subjects with Baseline and Week 16 are included.

ECHOs provide information regarding cardiac structure and function. RV/LV (diastole) ratio was summarized at each time point listed. RV/LV Ratio is the ratio of right ventricular to left ventricular diameter. A normal RV/LV Ratio is 0.6 to 1.0. When the ratio exceeds 1.0 it is indicative of high pulmonary artery pressure or right ventricular hypertrophy.

Outcome measures

Outcome measures
Measure	Intravenous/Subcutaneous Treprostinil; Oral Treprostinil n=20 Participants IV or SC treprostinil induction followed by transition to oral treprostinil Intravenous/Subcutaneous Treprostinil; Oral Treprostinil: Short term course of IV/SC treprostinil continuous infusion followed by transition to oral treprostinil extended-release (XR) tablets taken three times daily (TID)
Change in Echocardiogram Parameters (RV/LV Ratio)	-0.6 Ratio Interval -0.6 to 0.3

SECONDARY outcome

Timeframe: At Baseline and Week 16

Population: Per-protocol Population. Only Subjects with Baseline and Week 16 are included.

ECHOs provide information regarding cardiac structure and function. Right atrial area was summarized at each time point listed.

Outcome measures

Outcome measures
Measure	Intravenous/Subcutaneous Treprostinil; Oral Treprostinil n=23 Participants IV or SC treprostinil induction followed by transition to oral treprostinil Intravenous/Subcutaneous Treprostinil; Oral Treprostinil: Short term course of IV/SC treprostinil continuous infusion followed by transition to oral treprostinil extended-release (XR) tablets taken three times daily (TID)
Change in Echocardiogram Parameters (Right Atrial Area)	-2.88 cm^2 Interval -15.8 to 5.3

SECONDARY outcome

Timeframe: At Baseline and Week 16

Population: Per-protocol Population. Only Subjects with Baseline and Week 16 are included.

ECHOs provide information regarding cardiac structure and function. RV diameter was summarized at each time point.

Outcome measures

Outcome measures
Measure	Intravenous/Subcutaneous Treprostinil; Oral Treprostinil n=20 Participants IV or SC treprostinil induction followed by transition to oral treprostinil Intravenous/Subcutaneous Treprostinil; Oral Treprostinil: Short term course of IV/SC treprostinil continuous infusion followed by transition to oral treprostinil extended-release (XR) tablets taken three times daily (TID)
Change in Echocardiogram Parameters (RV Diameter)	-2.61 mm Interval -16.6 to 18.8

SECONDARY outcome

Timeframe: At Baseline and Week 16

Population: Per-protocol Population. Only Subjects with Baseline and Week 16 are included.

ECHOs provide information regarding cardiac structure and function. RV free wall strain was summarized at each time point listed .

Outcome measures

Outcome measures
Measure	Intravenous/Subcutaneous Treprostinil; Oral Treprostinil n=18 Participants IV or SC treprostinil induction followed by transition to oral treprostinil Intravenous/Subcutaneous Treprostinil; Oral Treprostinil: Short term course of IV/SC treprostinil continuous infusion followed by transition to oral treprostinil extended-release (XR) tablets taken three times daily (TID)
Change in Echocardiogram Parameters (RV Free Wall Strain)	1.28 percent Interval -8.2 to 15.4

SECONDARY outcome

Timeframe: At Baseline and Week 16

Population: Per-protocol Population. Only Subjects with Baseline and Week 16 are included.

ECHOs provide information regarding cardiac structure and function. RV myocardial performance index (MPI) was summarized at each time point listed. RV MPI is a measurement used to assess RV systolic function in patients with PH. MPI correlates with pulmonary arterial pressure. Normal MPI is approximately 0.35. Higher MPI values indicate higher pulmonary arterial pressure.

Outcome measures

Outcome measures
Measure	Intravenous/Subcutaneous Treprostinil; Oral Treprostinil n=22 Participants IV or SC treprostinil induction followed by transition to oral treprostinil Intravenous/Subcutaneous Treprostinil; Oral Treprostinil: Short term course of IV/SC treprostinil continuous infusion followed by transition to oral treprostinil extended-release (XR) tablets taken three times daily (TID)
Change in Echocardiogram Parameters (RV Myocardial Performance Index)	-0.08 MPI Interval -0.6 to 0.5

SECONDARY outcome

Timeframe: At Baseline and Week 16

Population: Per-protocol Population. Only Subjects with Baseline and Week 16 are included.

ECHOs provide information regarding cardiac structure and function. Tricuspid annular plane systolic excursion was summarized at each time point listed.

Outcome measures

Outcome measures
Measure	Intravenous/Subcutaneous Treprostinil; Oral Treprostinil n=22 Participants IV or SC treprostinil induction followed by transition to oral treprostinil Intravenous/Subcutaneous Treprostinil; Oral Treprostinil: Short term course of IV/SC treprostinil continuous infusion followed by transition to oral treprostinil extended-release (XR) tablets taken three times daily (TID)
Change in Echocardiogram Parameters (Tricuspid Annular Plane Systolic Excursion)	1.20 mm Interval -5.0 to 7.8

SECONDARY outcome

Timeframe: At Baseline and Week 16

Population: Per-protocol Population. The Count of Participants analyzed in each row differs from the Overall Number of Participants since only subjects with Baseline and Week 16 values were measured and analyzed (ie, contributed data reported in the table).

PAH symptoms included fatigue, dyspnea, lower extremity edema, dizziness, syncope, chest pain, and orthopnea. Symptoms were scored (Grades 0 \[none\], 1 \[mild\], 2 \[moderate\], to 3 \[severe\]) except for syncope (0 \[No\], 1 \[Infrequent; 1 episode\], 2 \[Somewhat frequent; 2 to 3 episodes\], and 3 \[Often; \>4 episodes). A lower score was considered "improved"; a higher score was considered "worsened."

Outcome measures

Outcome measures
Measure	Intravenous/Subcutaneous Treprostinil; Oral Treprostinil n=28 Participants IV or SC treprostinil induction followed by transition to oral treprostinil Intravenous/Subcutaneous Treprostinil; Oral Treprostinil: Short term course of IV/SC treprostinil continuous infusion followed by transition to oral treprostinil extended-release (XR) tablets taken three times daily (TID)
Change in PAH Symptom Score Fatigue · Improved	11 Participants
Change in PAH Symptom Score Fatigue · Worsened	3 Participants
Change in PAH Symptom Score Fatigue · No Change	14 Participants
Change in PAH Symptom Score Dyspnea · Improved	17 Participants
Change in PAH Symptom Score Dyspnea · Worsened	1 Participants
Change in PAH Symptom Score Dizziness · Improved	7 Participants
Change in PAH Symptom Score Dizziness · Worsened	4 Participants
Change in PAH Symptom Score Dizziness · No Change	17 Participants
Change in PAH Symptom Score Syncope · Improved	1 Participants
Change in PAH Symptom Score Syncope · Worsened	1 Participants
Change in PAH Symptom Score Syncope · No Change	26 Participants
Change in PAH Symptom Score Chest Pain · Improved	3 Participants
Change in PAH Symptom Score Chest Pain · Worsened	2 Participants
Change in PAH Symptom Score Chest Pain · No Change	23 Participants
Change in PAH Symptom Score Orthopnea · Improved	8 Participants
Change in PAH Symptom Score Orthopnea · Worsened	2 Participants
Change in PAH Symptom Score Orthopnea · No Change	18 Participants
Change in PAH Symptom Score Dyspnea · No Change	10 Participants
Change in PAH Symptom Score Lower Extremity Edema · Improved	8 Participants
Change in PAH Symptom Score Lower Extremity Edema · Worsened	4 Participants
Change in PAH Symptom Score Lower Extremity Edema · No Change	16 Participants

SECONDARY outcome

Timeframe: At Baseline and Week 16

Population: Per-protocol Population. Only Subjects with Baseline and Week 16 are included.

The Health-related Quality of Life in Pulmonary Hypertension Questionnaire (emPHasis-10) is a 10-question questionnaire used during clinical assessments that measures quality of life by the patients participating in the study. The patients graded their response to each of the 10 health-related questions on a scale of 0 to 5 based on how they were feeling that day. The most favorable score for each question is 0, and the least favorable score for each question is 5. A total score was then summed for each subject based on their responses to the 10 questions. The lower the total score was (best possible total score was 0), the less living with PH was negatively affecting the quality of the patient's life. The higher the total score (worst possible score was 50), the more living with PH was negatively affecting the quality of the patient's life.

Outcome measures

Outcome measures
Measure	Intravenous/Subcutaneous Treprostinil; Oral Treprostinil n=27 Participants IV or SC treprostinil induction followed by transition to oral treprostinil Intravenous/Subcutaneous Treprostinil; Oral Treprostinil: Short term course of IV/SC treprostinil continuous infusion followed by transition to oral treprostinil extended-release (XR) tablets taken three times daily (TID)
Change in Patient-reported Outcomes (Health-related Quality of Life)	-3.0 score on a scale Interval -33.0 to 16.0

SECONDARY outcome

Timeframe: At Baseline and Week 16

The Treatment Satisfaction Questionnaire for Medication (TSQM) is a 14-question questionnaire that measures the level of satisfaction or dissatisfaction patients have with their study medication in 4 areas: effectiveness (3 questions), side effects (5 questions), convenience (3 questions), and global satisfaction (3 questions). With the exception of the first side effects question (a yes or no question), all items have 5 or 7 responses which are scored from 1 (least satisfied) to 5 or 7 (most satisfied). A total score is then summed for each domain on the following scales: effectiveness 1-21, side effects 1-20, convenience 1-21, and global satisfaction 1-17. Lower total scores in each domain indicate dissatisfaction with the study medication and higher total scores indicate satisfaction.

Outcome measures

Outcome measures
Measure	Intravenous/Subcutaneous Treprostinil; Oral Treprostinil n=28 Participants IV or SC treprostinil induction followed by transition to oral treprostinil Intravenous/Subcutaneous Treprostinil; Oral Treprostinil: Short term course of IV/SC treprostinil continuous infusion followed by transition to oral treprostinil extended-release (XR) tablets taken three times daily (TID)
Change in Treatment Satisfaction Effectiveness	4.76 score on a scale Interval -28.6 to 42.9
Change in Treatment Satisfaction Side Effects	5.00 score on a scale Interval -50.0 to 35.0
Change in Treatment Satisfaction Convenience	-4.76 score on a scale Interval -52.4 to 28.6
Change in Treatment Satisfaction Global Satisfaction	0.00 score on a scale Interval -47.1 to 35.3

SECONDARY outcome

Timeframe: At Baseline and Week 16

6MWD low risk: \>440 m, intermediate risk: 165-440 m, high risk: \<165 m; NT-proBNP low risk: \<300 ng/L, intermediate risk: 300-1400 ng/L, high risk: \>1400 ng/L; WHO FC: low risk: I or II, intermediate risk: III, high risk: IV; and Right Atrial Area: low risk: \<18 cm², intermediate risk: 18-26 cm², high risk: \>26 cm². Moving from a higher risk category to a low risk category was considered "improved;" moving from a lower risk category to a higher risk category was considered "worsened."

Outcome measures

Outcome measures
Measure	Intravenous/Subcutaneous Treprostinil; Oral Treprostinil n=29 Participants IV or SC treprostinil induction followed by transition to oral treprostinil Intravenous/Subcutaneous Treprostinil; Oral Treprostinil: Short term course of IV/SC treprostinil continuous infusion followed by transition to oral treprostinil extended-release (XR) tablets taken three times daily (TID)
Improvement From Baseline in Clinical Risk Category 6MWD · Improved	4 Participants
Improvement From Baseline in Clinical Risk Category 6MWD · Worsened	1 Participants
Improvement From Baseline in Clinical Risk Category 6MWD · No Change	22 Participants
Improvement From Baseline in Clinical Risk Category NT-proBNP · Improved	11 Participants
Improvement From Baseline in Clinical Risk Category NT-proBNP · Worsened	1 Participants
Improvement From Baseline in Clinical Risk Category NT-proBNP · No Change	16 Participants
Improvement From Baseline in Clinical Risk Category WHO FC · Improved	11 Participants
Improvement From Baseline in Clinical Risk Category WHO FC · Worsened	1 Participants
Improvement From Baseline in Clinical Risk Category WHO FC · No Change	16 Participants
Improvement From Baseline in Clinical Risk Category Right Atrial Area · Improved	8 Participants
Improvement From Baseline in Clinical Risk Category Right Atrial Area · Worsened	1 Participants
Improvement From Baseline in Clinical Risk Category Right Atrial Area · No Change	14 Participants

SECONDARY outcome

Timeframe: At Week 16

Low risk categories for the 4 selected parameters were: 6MWD \>440 m, serum NT-proBNP \<300 ng/L, WHO FC I or II, and right atrial area \<18cm². The rows of the table indicate the count of participants that were in the low risk category for the parameter at Week 16.

Outcome measures

Outcome measures
Measure	Intravenous/Subcutaneous Treprostinil; Oral Treprostinil n=29 Participants IV or SC treprostinil induction followed by transition to oral treprostinil Intravenous/Subcutaneous Treprostinil; Oral Treprostinil: Short term course of IV/SC treprostinil continuous infusion followed by transition to oral treprostinil extended-release (XR) tablets taken three times daily (TID)
Achievement of Low Risk Category in Clinical Parameters 6MWD	10 Participants
Achievement of Low Risk Category in Clinical Parameters NT-proBNP	19 Participants
Achievement of Low Risk Category in Clinical Parameters WHO FC	24 Participants
Achievement of Low Risk Category in Clinical Parameters Right Atrial Area	14 Participants

SECONDARY outcome

Timeframe: At Week 16

Population: Per-protocol Population. Only Subjects with Baseline and Week 16 are included.

The percentage of subjects that ended the study in achievement Class 1 (either achieved an Orenitram dose of ≥4 mg TID \[or TDD of 12 mg\] at Week 16 or a dose of ≥0.057 mg/kg TID \[or a TDD of 0.171 mg/kg\] for subjects \<70 kg), Class 2 (achieved a prescribed Orenitram dose ≥2 mg TID and \<4 mg TID \[or a TDD ≥6 mg and \<12 mg\] at specific visit, with at least 2 of the following 3 clinical parameters: 6MWD increase by ≥10% or ≥30 m from baseline, serum NT-proBNP reduction \>30% from baseline, or WHO FC I or II), or Class 3 (were not Class 1 or Class 2, or with class undetermined).

Outcome measures

Outcome measures
Measure	Intravenous/Subcutaneous Treprostinil; Oral Treprostinil n=29 Participants IV or SC treprostinil induction followed by transition to oral treprostinil Intravenous/Subcutaneous Treprostinil; Oral Treprostinil: Short term course of IV/SC treprostinil continuous infusion followed by transition to oral treprostinil extended-release (XR) tablets taken three times daily (TID)
Overall Achievement Class 3	4 Participants
Overall Achievement Class 1	23 Participants
Overall Achievement Class 2	2 Participants

SECONDARY outcome

Timeframe: At Week 16

Population: Per-protocol Population. Only Subjects with Baseline and Week 16 are included.

The percentage of subjects that transitioned to oral treprostinil at any dose and were maintained on therapy at Week 16 (considered a "successful" result).

Outcome measures

Outcome measures
Measure	Intravenous/Subcutaneous Treprostinil; Oral Treprostinil n=29 Participants IV or SC treprostinil induction followed by transition to oral treprostinil Intravenous/Subcutaneous Treprostinil; Oral Treprostinil: Short term course of IV/SC treprostinil continuous infusion followed by transition to oral treprostinil extended-release (XR) tablets taken three times daily (TID)
Transition and Maintenance of Orenitram Therapy	28 Participants

Adverse Events

Intravenous/Subcutaneous Treprostinil; Oral Treprostinil

Serious events: 10 serious events

Other events: 35 other events

Deaths: 1 deaths

Serious adverse events

Serious adverse events
Measure	Intravenous/Subcutaneous Treprostinil; Oral Treprostinil n=35 participants at risk IV or SC treprostinil induction followed by transition to oral treprostinil Intravenous/Subcutaneous Treprostinil; Oral Treprostinil: Short term course of IV/SC treprostinil continuous infusion followed by transition to oral treprostinil extended-release (XR) tablets taken three times daily (TID)
Respiratory, thoracic and mediastinal disorders Acute respiratory failure	2.9% 1/35 • Number of events 1 • Adverse events (AEs) were captured from when the subject signed the informed consent form until the subject completed the study or was withdrawn from the study, up to 20 weeks. AEs were followed until either resolution (or return to normal or baseline values), until they were judged by the Investigator to no longer be clinically significant, or for at least 4 weeks if the AE extended beyond the final study visit (Week 16). All serious adverse events (SAEs) that occurred during the study were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 4 weeks after completion of the final study visit.
Respiratory, thoracic and mediastinal disorders Dyspnoea	2.9% 1/35 • Number of events 1 • Adverse events (AEs) were captured from when the subject signed the informed consent form until the subject completed the study or was withdrawn from the study, up to 20 weeks. AEs were followed until either resolution (or return to normal or baseline values), until they were judged by the Investigator to no longer be clinically significant, or for at least 4 weeks if the AE extended beyond the final study visit (Week 16). All serious adverse events (SAEs) that occurred during the study were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 4 weeks after completion of the final study visit.
Respiratory, thoracic and mediastinal disorders Pulmonary arterial hypertension	2.9% 1/35 • Number of events 1 • Adverse events (AEs) were captured from when the subject signed the informed consent form until the subject completed the study or was withdrawn from the study, up to 20 weeks. AEs were followed until either resolution (or return to normal or baseline values), until they were judged by the Investigator to no longer be clinically significant, or for at least 4 weeks if the AE extended beyond the final study visit (Week 16). All serious adverse events (SAEs) that occurred during the study were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 4 weeks after completion of the final study visit.
Respiratory, thoracic and mediastinal disorders Respiratory failure	2.9% 1/35 • Number of events 1 • Adverse events (AEs) were captured from when the subject signed the informed consent form until the subject completed the study or was withdrawn from the study, up to 20 weeks. AEs were followed until either resolution (or return to normal or baseline values), until they were judged by the Investigator to no longer be clinically significant, or for at least 4 weeks if the AE extended beyond the final study visit (Week 16). All serious adverse events (SAEs) that occurred during the study were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 4 weeks after completion of the final study visit.
Product Issues Device dislocation	5.7% 2/35 • Number of events 2 • Adverse events (AEs) were captured from when the subject signed the informed consent form until the subject completed the study or was withdrawn from the study, up to 20 weeks. AEs were followed until either resolution (or return to normal or baseline values), until they were judged by the Investigator to no longer be clinically significant, or for at least 4 weeks if the AE extended beyond the final study visit (Week 16). All serious adverse events (SAEs) that occurred during the study were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 4 weeks after completion of the final study visit.
Blood and lymphatic system disorders Febrile neutropenia	2.9% 1/35 • Number of events 1 • Adverse events (AEs) were captured from when the subject signed the informed consent form until the subject completed the study or was withdrawn from the study, up to 20 weeks. AEs were followed until either resolution (or return to normal or baseline values), until they were judged by the Investigator to no longer be clinically significant, or for at least 4 weeks if the AE extended beyond the final study visit (Week 16). All serious adverse events (SAEs) that occurred during the study were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 4 weeks after completion of the final study visit.
Cardiac disorders Right ventricular failure	2.9% 1/35 • Number of events 1 • Adverse events (AEs) were captured from when the subject signed the informed consent form until the subject completed the study or was withdrawn from the study, up to 20 weeks. AEs were followed until either resolution (or return to normal or baseline values), until they were judged by the Investigator to no longer be clinically significant, or for at least 4 weeks if the AE extended beyond the final study visit (Week 16). All serious adverse events (SAEs) that occurred during the study were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 4 weeks after completion of the final study visit.
Gastrointestinal disorders Upper gastrointestinal haemorrhage	2.9% 1/35 • Number of events 1 • Adverse events (AEs) were captured from when the subject signed the informed consent form until the subject completed the study or was withdrawn from the study, up to 20 weeks. AEs were followed until either resolution (or return to normal or baseline values), until they were judged by the Investigator to no longer be clinically significant, or for at least 4 weeks if the AE extended beyond the final study visit (Week 16). All serious adverse events (SAEs) that occurred during the study were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 4 weeks after completion of the final study visit.
Infections and infestations Bacterial sepsis	2.9% 1/35 • Number of events 1 • Adverse events (AEs) were captured from when the subject signed the informed consent form until the subject completed the study or was withdrawn from the study, up to 20 weeks. AEs were followed until either resolution (or return to normal or baseline values), until they were judged by the Investigator to no longer be clinically significant, or for at least 4 weeks if the AE extended beyond the final study visit (Week 16). All serious adverse events (SAEs) that occurred during the study were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 4 weeks after completion of the final study visit.
Infections and infestations Endocarditis	2.9% 1/35 • Number of events 1 • Adverse events (AEs) were captured from when the subject signed the informed consent form until the subject completed the study or was withdrawn from the study, up to 20 weeks. AEs were followed until either resolution (or return to normal or baseline values), until they were judged by the Investigator to no longer be clinically significant, or for at least 4 weeks if the AE extended beyond the final study visit (Week 16). All serious adverse events (SAEs) that occurred during the study were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 4 weeks after completion of the final study visit.
Infections and infestations Pneumonia	2.9% 1/35 • Number of events 1 • Adverse events (AEs) were captured from when the subject signed the informed consent form until the subject completed the study or was withdrawn from the study, up to 20 weeks. AEs were followed until either resolution (or return to normal or baseline values), until they were judged by the Investigator to no longer be clinically significant, or for at least 4 weeks if the AE extended beyond the final study visit (Week 16). All serious adverse events (SAEs) that occurred during the study were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 4 weeks after completion of the final study visit.
Infections and infestations Septic embolus	2.9% 1/35 • Number of events 1 • Adverse events (AEs) were captured from when the subject signed the informed consent form until the subject completed the study or was withdrawn from the study, up to 20 weeks. AEs were followed until either resolution (or return to normal or baseline values), until they were judged by the Investigator to no longer be clinically significant, or for at least 4 weeks if the AE extended beyond the final study visit (Week 16). All serious adverse events (SAEs) that occurred during the study were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 4 weeks after completion of the final study visit.
Musculoskeletal and connective tissue disorders Pain in extremity	2.9% 1/35 • Number of events 1 • Adverse events (AEs) were captured from when the subject signed the informed consent form until the subject completed the study or was withdrawn from the study, up to 20 weeks. AEs were followed until either resolution (or return to normal or baseline values), until they were judged by the Investigator to no longer be clinically significant, or for at least 4 weeks if the AE extended beyond the final study visit (Week 16). All serious adverse events (SAEs) that occurred during the study were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 4 weeks after completion of the final study visit.
Psychiatric disorders Suicidal ideation	2.9% 1/35 • Number of events 1 • Adverse events (AEs) were captured from when the subject signed the informed consent form until the subject completed the study or was withdrawn from the study, up to 20 weeks. AEs were followed until either resolution (or return to normal or baseline values), until they were judged by the Investigator to no longer be clinically significant, or for at least 4 weeks if the AE extended beyond the final study visit (Week 16). All serious adverse events (SAEs) that occurred during the study were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 4 weeks after completion of the final study visit.
Vascular disorders Hypotension	2.9% 1/35 • Number of events 1 • Adverse events (AEs) were captured from when the subject signed the informed consent form until the subject completed the study or was withdrawn from the study, up to 20 weeks. AEs were followed until either resolution (or return to normal or baseline values), until they were judged by the Investigator to no longer be clinically significant, or for at least 4 weeks if the AE extended beyond the final study visit (Week 16). All serious adverse events (SAEs) that occurred during the study were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 4 weeks after completion of the final study visit.

Other adverse events

Other adverse events
Measure	Intravenous/Subcutaneous Treprostinil; Oral Treprostinil n=35 participants at risk IV or SC treprostinil induction followed by transition to oral treprostinil Intravenous/Subcutaneous Treprostinil; Oral Treprostinil: Short term course of IV/SC treprostinil continuous infusion followed by transition to oral treprostinil extended-release (XR) tablets taken three times daily (TID)
Gastrointestinal disorders Nausea	71.4% 25/35 • Number of events 27 • Adverse events (AEs) were captured from when the subject signed the informed consent form until the subject completed the study or was withdrawn from the study, up to 20 weeks. AEs were followed until either resolution (or return to normal or baseline values), until they were judged by the Investigator to no longer be clinically significant, or for at least 4 weeks if the AE extended beyond the final study visit (Week 16). All serious adverse events (SAEs) that occurred during the study were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 4 weeks after completion of the final study visit.
Gastrointestinal disorders Diarrhoea	60.0% 21/35 • Number of events 22 • Adverse events (AEs) were captured from when the subject signed the informed consent form until the subject completed the study or was withdrawn from the study, up to 20 weeks. AEs were followed until either resolution (or return to normal or baseline values), until they were judged by the Investigator to no longer be clinically significant, or for at least 4 weeks if the AE extended beyond the final study visit (Week 16). All serious adverse events (SAEs) that occurred during the study were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 4 weeks after completion of the final study visit.
Gastrointestinal disorders Vomiting	42.9% 15/35 • Number of events 17 • Adverse events (AEs) were captured from when the subject signed the informed consent form until the subject completed the study or was withdrawn from the study, up to 20 weeks. AEs were followed until either resolution (or return to normal or baseline values), until they were judged by the Investigator to no longer be clinically significant, or for at least 4 weeks if the AE extended beyond the final study visit (Week 16). All serious adverse events (SAEs) that occurred during the study were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 4 weeks after completion of the final study visit.
Gastrointestinal disorders Abdominal pain	11.4% 4/35 • Number of events 4 • Adverse events (AEs) were captured from when the subject signed the informed consent form until the subject completed the study or was withdrawn from the study, up to 20 weeks. AEs were followed until either resolution (or return to normal or baseline values), until they were judged by the Investigator to no longer be clinically significant, or for at least 4 weeks if the AE extended beyond the final study visit (Week 16). All serious adverse events (SAEs) that occurred during the study were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 4 weeks after completion of the final study visit.
Gastrointestinal disorders Dyspepsia	11.4% 4/35 • Number of events 4 • Adverse events (AEs) were captured from when the subject signed the informed consent form until the subject completed the study or was withdrawn from the study, up to 20 weeks. AEs were followed until either resolution (or return to normal or baseline values), until they were judged by the Investigator to no longer be clinically significant, or for at least 4 weeks if the AE extended beyond the final study visit (Week 16). All serious adverse events (SAEs) that occurred during the study were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 4 weeks after completion of the final study visit.
Gastrointestinal disorders Flatulence	5.7% 2/35 • Number of events 2 • Adverse events (AEs) were captured from when the subject signed the informed consent form until the subject completed the study or was withdrawn from the study, up to 20 weeks. AEs were followed until either resolution (or return to normal or baseline values), until they were judged by the Investigator to no longer be clinically significant, or for at least 4 weeks if the AE extended beyond the final study visit (Week 16). All serious adverse events (SAEs) that occurred during the study were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 4 weeks after completion of the final study visit.
Nervous system disorders Headache	85.7% 30/35 • Number of events 33 • Adverse events (AEs) were captured from when the subject signed the informed consent form until the subject completed the study or was withdrawn from the study, up to 20 weeks. AEs were followed until either resolution (or return to normal or baseline values), until they were judged by the Investigator to no longer be clinically significant, or for at least 4 weeks if the AE extended beyond the final study visit (Week 16). All serious adverse events (SAEs) that occurred during the study were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 4 weeks after completion of the final study visit.
Nervous system disorders Dizziness	20.0% 7/35 • Number of events 10 • Adverse events (AEs) were captured from when the subject signed the informed consent form until the subject completed the study or was withdrawn from the study, up to 20 weeks. AEs were followed until either resolution (or return to normal or baseline values), until they were judged by the Investigator to no longer be clinically significant, or for at least 4 weeks if the AE extended beyond the final study visit (Week 16). All serious adverse events (SAEs) that occurred during the study were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 4 weeks after completion of the final study visit.
Nervous system disorders Syncope	5.7% 2/35 • Number of events 2 • Adverse events (AEs) were captured from when the subject signed the informed consent form until the subject completed the study or was withdrawn from the study, up to 20 weeks. AEs were followed until either resolution (or return to normal or baseline values), until they were judged by the Investigator to no longer be clinically significant, or for at least 4 weeks if the AE extended beyond the final study visit (Week 16). All serious adverse events (SAEs) that occurred during the study were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 4 weeks after completion of the final study visit.
Nervous system disorders Tremor	5.7% 2/35 • Number of events 2 • Adverse events (AEs) were captured from when the subject signed the informed consent form until the subject completed the study or was withdrawn from the study, up to 20 weeks. AEs were followed until either resolution (or return to normal or baseline values), until they were judged by the Investigator to no longer be clinically significant, or for at least 4 weeks if the AE extended beyond the final study visit (Week 16). All serious adverse events (SAEs) that occurred during the study were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 4 weeks after completion of the final study visit.
General disorders Fatigue	40.0% 14/35 • Number of events 14 • Adverse events (AEs) were captured from when the subject signed the informed consent form until the subject completed the study or was withdrawn from the study, up to 20 weeks. AEs were followed until either resolution (or return to normal or baseline values), until they were judged by the Investigator to no longer be clinically significant, or for at least 4 weeks if the AE extended beyond the final study visit (Week 16). All serious adverse events (SAEs) that occurred during the study were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 4 weeks after completion of the final study visit.
General disorders Infusion site pain	25.7% 9/35 • Number of events 9 • Adverse events (AEs) were captured from when the subject signed the informed consent form until the subject completed the study or was withdrawn from the study, up to 20 weeks. AEs were followed until either resolution (or return to normal or baseline values), until they were judged by the Investigator to no longer be clinically significant, or for at least 4 weeks if the AE extended beyond the final study visit (Week 16). All serious adverse events (SAEs) that occurred during the study were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 4 weeks after completion of the final study visit.
General disorders Pain	25.7% 9/35 • Number of events 9 • Adverse events (AEs) were captured from when the subject signed the informed consent form until the subject completed the study or was withdrawn from the study, up to 20 weeks. AEs were followed until either resolution (or return to normal or baseline values), until they were judged by the Investigator to no longer be clinically significant, or for at least 4 weeks if the AE extended beyond the final study visit (Week 16). All serious adverse events (SAEs) that occurred during the study were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 4 weeks after completion of the final study visit.
General disorders Oedema peripheral	17.1% 6/35 • Number of events 6 • Adverse events (AEs) were captured from when the subject signed the informed consent form until the subject completed the study or was withdrawn from the study, up to 20 weeks. AEs were followed until either resolution (or return to normal or baseline values), until they were judged by the Investigator to no longer be clinically significant, or for at least 4 weeks if the AE extended beyond the final study visit (Week 16). All serious adverse events (SAEs) that occurred during the study were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 4 weeks after completion of the final study visit.
General disorders Infusion site irritation	14.3% 5/35 • Number of events 5 • Adverse events (AEs) were captured from when the subject signed the informed consent form until the subject completed the study or was withdrawn from the study, up to 20 weeks. AEs were followed until either resolution (or return to normal or baseline values), until they were judged by the Investigator to no longer be clinically significant, or for at least 4 weeks if the AE extended beyond the final study visit (Week 16). All serious adverse events (SAEs) that occurred during the study were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 4 weeks after completion of the final study visit.
General disorders Chills	5.7% 2/35 • Number of events 2 • Adverse events (AEs) were captured from when the subject signed the informed consent form until the subject completed the study or was withdrawn from the study, up to 20 weeks. AEs were followed until either resolution (or return to normal or baseline values), until they were judged by the Investigator to no longer be clinically significant, or for at least 4 weeks if the AE extended beyond the final study visit (Week 16). All serious adverse events (SAEs) that occurred during the study were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 4 weeks after completion of the final study visit.
General disorders Infusion site swelling	5.7% 2/35 • Number of events 2 • Adverse events (AEs) were captured from when the subject signed the informed consent form until the subject completed the study or was withdrawn from the study, up to 20 weeks. AEs were followed until either resolution (or return to normal or baseline values), until they were judged by the Investigator to no longer be clinically significant, or for at least 4 weeks if the AE extended beyond the final study visit (Week 16). All serious adverse events (SAEs) that occurred during the study were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 4 weeks after completion of the final study visit.
General disorders Non-cardiac chest pain	5.7% 2/35 • Number of events 2 • Adverse events (AEs) were captured from when the subject signed the informed consent form until the subject completed the study or was withdrawn from the study, up to 20 weeks. AEs were followed until either resolution (or return to normal or baseline values), until they were judged by the Investigator to no longer be clinically significant, or for at least 4 weeks if the AE extended beyond the final study visit (Week 16). All serious adverse events (SAEs) that occurred during the study were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 4 weeks after completion of the final study visit.
Musculoskeletal and connective tissue disorders Pain in jaw	51.4% 18/35 • Number of events 18 • Adverse events (AEs) were captured from when the subject signed the informed consent form until the subject completed the study or was withdrawn from the study, up to 20 weeks. AEs were followed until either resolution (or return to normal or baseline values), until they were judged by the Investigator to no longer be clinically significant, or for at least 4 weeks if the AE extended beyond the final study visit (Week 16). All serious adverse events (SAEs) that occurred during the study were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 4 weeks after completion of the final study visit.
Musculoskeletal and connective tissue disorders Pain in extremity	42.9% 15/35 • Number of events 17 • Adverse events (AEs) were captured from when the subject signed the informed consent form until the subject completed the study or was withdrawn from the study, up to 20 weeks. AEs were followed until either resolution (or return to normal or baseline values), until they were judged by the Investigator to no longer be clinically significant, or for at least 4 weeks if the AE extended beyond the final study visit (Week 16). All serious adverse events (SAEs) that occurred during the study were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 4 weeks after completion of the final study visit.
Musculoskeletal and connective tissue disorders Muscle spasms	17.1% 6/35 • Number of events 7 • Adverse events (AEs) were captured from when the subject signed the informed consent form until the subject completed the study or was withdrawn from the study, up to 20 weeks. AEs were followed until either resolution (or return to normal or baseline values), until they were judged by the Investigator to no longer be clinically significant, or for at least 4 weeks if the AE extended beyond the final study visit (Week 16). All serious adverse events (SAEs) that occurred during the study were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 4 weeks after completion of the final study visit.
Musculoskeletal and connective tissue disorders Back pain	14.3% 5/35 • Number of events 5 • Adverse events (AEs) were captured from when the subject signed the informed consent form until the subject completed the study or was withdrawn from the study, up to 20 weeks. AEs were followed until either resolution (or return to normal or baseline values), until they were judged by the Investigator to no longer be clinically significant, or for at least 4 weeks if the AE extended beyond the final study visit (Week 16). All serious adverse events (SAEs) that occurred during the study were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 4 weeks after completion of the final study visit.
Musculoskeletal and connective tissue disorders Arthralgia	11.4% 4/35 • Number of events 4 • Adverse events (AEs) were captured from when the subject signed the informed consent form until the subject completed the study or was withdrawn from the study, up to 20 weeks. AEs were followed until either resolution (or return to normal or baseline values), until they were judged by the Investigator to no longer be clinically significant, or for at least 4 weeks if the AE extended beyond the final study visit (Week 16). All serious adverse events (SAEs) that occurred during the study were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 4 weeks after completion of the final study visit.
Musculoskeletal and connective tissue disorders Musculoskeletal stiffness	5.7% 2/35 • Number of events 2 • Adverse events (AEs) were captured from when the subject signed the informed consent form until the subject completed the study or was withdrawn from the study, up to 20 weeks. AEs were followed until either resolution (or return to normal or baseline values), until they were judged by the Investigator to no longer be clinically significant, or for at least 4 weeks if the AE extended beyond the final study visit (Week 16). All serious adverse events (SAEs) that occurred during the study were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 4 weeks after completion of the final study visit.
Vascular disorders Flushing	57.1% 20/35 • Number of events 20 • Adverse events (AEs) were captured from when the subject signed the informed consent form until the subject completed the study or was withdrawn from the study, up to 20 weeks. AEs were followed until either resolution (or return to normal or baseline values), until they were judged by the Investigator to no longer be clinically significant, or for at least 4 weeks if the AE extended beyond the final study visit (Week 16). All serious adverse events (SAEs) that occurred during the study were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 4 weeks after completion of the final study visit.
Vascular disorders Hot flush	5.7% 2/35 • Number of events 2 • Adverse events (AEs) were captured from when the subject signed the informed consent form until the subject completed the study or was withdrawn from the study, up to 20 weeks. AEs were followed until either resolution (or return to normal or baseline values), until they were judged by the Investigator to no longer be clinically significant, or for at least 4 weeks if the AE extended beyond the final study visit (Week 16). All serious adverse events (SAEs) that occurred during the study were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 4 weeks after completion of the final study visit.
Respiratory, thoracic and mediastinal disorders Dyspnoea	17.1% 6/35 • Number of events 6 • Adverse events (AEs) were captured from when the subject signed the informed consent form until the subject completed the study or was withdrawn from the study, up to 20 weeks. AEs were followed until either resolution (or return to normal or baseline values), until they were judged by the Investigator to no longer be clinically significant, or for at least 4 weeks if the AE extended beyond the final study visit (Week 16). All serious adverse events (SAEs) that occurred during the study were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 4 weeks after completion of the final study visit.
Respiratory, thoracic and mediastinal disorders Cough	8.6% 3/35 • Number of events 3 • Adverse events (AEs) were captured from when the subject signed the informed consent form until the subject completed the study or was withdrawn from the study, up to 20 weeks. AEs were followed until either resolution (or return to normal or baseline values), until they were judged by the Investigator to no longer be clinically significant, or for at least 4 weeks if the AE extended beyond the final study visit (Week 16). All serious adverse events (SAEs) that occurred during the study were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 4 weeks after completion of the final study visit.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	8.6% 3/35 • Number of events 3 • Adverse events (AEs) were captured from when the subject signed the informed consent form until the subject completed the study or was withdrawn from the study, up to 20 weeks. AEs were followed until either resolution (or return to normal or baseline values), until they were judged by the Investigator to no longer be clinically significant, or for at least 4 weeks if the AE extended beyond the final study visit (Week 16). All serious adverse events (SAEs) that occurred during the study were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 4 weeks after completion of the final study visit.
Respiratory, thoracic and mediastinal disorders Nasal congestion	5.7% 2/35 • Number of events 2 • Adverse events (AEs) were captured from when the subject signed the informed consent form until the subject completed the study or was withdrawn from the study, up to 20 weeks. AEs were followed until either resolution (or return to normal or baseline values), until they were judged by the Investigator to no longer be clinically significant, or for at least 4 weeks if the AE extended beyond the final study visit (Week 16). All serious adverse events (SAEs) that occurred during the study were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 4 weeks after completion of the final study visit.
Infections and infestations Pneumonia	8.6% 3/35 • Number of events 3 • Adverse events (AEs) were captured from when the subject signed the informed consent form until the subject completed the study or was withdrawn from the study, up to 20 weeks. AEs were followed until either resolution (or return to normal or baseline values), until they were judged by the Investigator to no longer be clinically significant, or for at least 4 weeks if the AE extended beyond the final study visit (Week 16). All serious adverse events (SAEs) that occurred during the study were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 4 weeks after completion of the final study visit.
Infections and infestations Bronchitis	5.7% 2/35 • Number of events 2 • Adverse events (AEs) were captured from when the subject signed the informed consent form until the subject completed the study or was withdrawn from the study, up to 20 weeks. AEs were followed until either resolution (or return to normal or baseline values), until they were judged by the Investigator to no longer be clinically significant, or for at least 4 weeks if the AE extended beyond the final study visit (Week 16). All serious adverse events (SAEs) that occurred during the study were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 4 weeks after completion of the final study visit.
Infections and infestations Infusion site infection	5.7% 2/35 • Number of events 3 • Adverse events (AEs) were captured from when the subject signed the informed consent form until the subject completed the study or was withdrawn from the study, up to 20 weeks. AEs were followed until either resolution (or return to normal or baseline values), until they were judged by the Investigator to no longer be clinically significant, or for at least 4 weeks if the AE extended beyond the final study visit (Week 16). All serious adverse events (SAEs) that occurred during the study were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 4 weeks after completion of the final study visit.
Infections and infestations Urinary tract infection	5.7% 2/35 • Number of events 2 • Adverse events (AEs) were captured from when the subject signed the informed consent form until the subject completed the study or was withdrawn from the study, up to 20 weeks. AEs were followed until either resolution (or return to normal or baseline values), until they were judged by the Investigator to no longer be clinically significant, or for at least 4 weeks if the AE extended beyond the final study visit (Week 16). All serious adverse events (SAEs) that occurred during the study were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 4 weeks after completion of the final study visit.
Injury, poisoning and procedural complications Ligament sprain	5.7% 2/35 • Number of events 2 • Adverse events (AEs) were captured from when the subject signed the informed consent form until the subject completed the study or was withdrawn from the study, up to 20 weeks. AEs were followed until either resolution (or return to normal or baseline values), until they were judged by the Investigator to no longer be clinically significant, or for at least 4 weeks if the AE extended beyond the final study visit (Week 16). All serious adverse events (SAEs) that occurred during the study were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 4 weeks after completion of the final study visit.
Metabolism and nutrition disorders Decreased appetite	11.4% 4/35 • Number of events 4 • Adverse events (AEs) were captured from when the subject signed the informed consent form until the subject completed the study or was withdrawn from the study, up to 20 weeks. AEs were followed until either resolution (or return to normal or baseline values), until they were judged by the Investigator to no longer be clinically significant, or for at least 4 weeks if the AE extended beyond the final study visit (Week 16). All serious adverse events (SAEs) that occurred during the study were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 4 weeks after completion of the final study visit.
Metabolism and nutrition disorders Hypokalaemia	8.6% 3/35 • Number of events 3 • Adverse events (AEs) were captured from when the subject signed the informed consent form until the subject completed the study or was withdrawn from the study, up to 20 weeks. AEs were followed until either resolution (or return to normal or baseline values), until they were judged by the Investigator to no longer be clinically significant, or for at least 4 weeks if the AE extended beyond the final study visit (Week 16). All serious adverse events (SAEs) that occurred during the study were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 4 weeks after completion of the final study visit.
Psychiatric disorders Anxiety	8.6% 3/35 • Number of events 3 • Adverse events (AEs) were captured from when the subject signed the informed consent form until the subject completed the study or was withdrawn from the study, up to 20 weeks. AEs were followed until either resolution (or return to normal or baseline values), until they were judged by the Investigator to no longer be clinically significant, or for at least 4 weeks if the AE extended beyond the final study visit (Week 16). All serious adverse events (SAEs) that occurred during the study were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 4 weeks after completion of the final study visit.
Psychiatric disorders Insomnia	5.7% 2/35 • Number of events 2 • Adverse events (AEs) were captured from when the subject signed the informed consent form until the subject completed the study or was withdrawn from the study, up to 20 weeks. AEs were followed until either resolution (or return to normal or baseline values), until they were judged by the Investigator to no longer be clinically significant, or for at least 4 weeks if the AE extended beyond the final study visit (Week 16). All serious adverse events (SAEs) that occurred during the study were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 4 weeks after completion of the final study visit.
Skin and subcutaneous tissue disorders Rash	5.7% 2/35 • Number of events 4 • Adverse events (AEs) were captured from when the subject signed the informed consent form until the subject completed the study or was withdrawn from the study, up to 20 weeks. AEs were followed until either resolution (or return to normal or baseline values), until they were judged by the Investigator to no longer be clinically significant, or for at least 4 weeks if the AE extended beyond the final study visit (Week 16). All serious adverse events (SAEs) that occurred during the study were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 4 weeks after completion of the final study visit.
Product Issues Device dislocation	8.6% 3/35 • Number of events 3 • Adverse events (AEs) were captured from when the subject signed the informed consent form until the subject completed the study or was withdrawn from the study, up to 20 weeks. AEs were followed until either resolution (or return to normal or baseline values), until they were judged by the Investigator to no longer be clinically significant, or for at least 4 weeks if the AE extended beyond the final study visit (Week 16). All serious adverse events (SAEs) that occurred during the study were followed until resolution, death, or the subject was lost to follow-up, even if they were ongoing more than 4 weeks after completion of the final study visit.

Additional Information

Global Medical Information

United Therapeutics Corp.

Phone: 919-485-8350

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Institution and/or Principal Investigator agree not to publish or publicly present any 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