Trial Outcomes & Findings for Dose-response Study of the Safety and Efficacy of Beraprost Sodium Modified Release (BPS-MR) in Patients With Pulmonary Arterial Hypertension (PAH) (NCT NCT00989963)

Last Updated: 2020-09-30

Results Overview

The change in Pulmonary Vascular Resistance (PVR) was evaluated from Baseline to Week 12. PVR is expressed in Wood Units or millimeters of Mercury per Liter per minute (mmHG/L/min)

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

36 participants

Primary outcome timeframe

Week 12

Results posted on

2020-09-30

Participant Flow

Participant milestones

Participant milestones
Measure	Low Fixed Dose Group (60 ug) Participants in the low dose group received 60 microgram of Beraprost sodium modified release tablets, orally twice daily up to maximum duration of Week 12.	High Fixed Dose (FD) Group (240 ug) Participants in the high dose group received starting dose of 60 microgram of Beraprost sodium modified release tablets twice daily which was escalated until they reached the fixed maximum dose of 240 microgram twice daily up to a maximum duration of Week 12	Maximum Tolerated Dose (MTD) Participants in this group received starting dose of 60 microgram of Beraprost sodium modified release tablets twice daily which was escalated until they reached the fixed maximum dose of 600 microgram twice daily up to a maximum duration of Week 12 or they reached an intolerable dose which required them to down-titrate by 60 microgram twice daily in these instances and at the Investigator's discretion, further attempts at dose escalation may have been made.
Overall Study STARTED	12	12	12
Overall Study Safety Population	13	12	11
Overall Study Per-Protocol Population	12	11	10
Overall Study COMPLETED	11	11	11
Overall Study NOT COMPLETED	1	1	1

Reasons for withdrawal

Reasons for withdrawal
Measure	Low Fixed Dose Group (60 ug) Participants in the low dose group received 60 microgram of Beraprost sodium modified release tablets, orally twice daily up to maximum duration of Week 12.	High Fixed Dose (FD) Group (240 ug) Participants in the high dose group received starting dose of 60 microgram of Beraprost sodium modified release tablets twice daily which was escalated until they reached the fixed maximum dose of 240 microgram twice daily up to a maximum duration of Week 12	Maximum Tolerated Dose (MTD) Participants in this group received starting dose of 60 microgram of Beraprost sodium modified release tablets twice daily which was escalated until they reached the fixed maximum dose of 600 microgram twice daily up to a maximum duration of Week 12 or they reached an intolerable dose which required them to down-titrate by 60 microgram twice daily in these instances and at the Investigator's discretion, further attempts at dose escalation may have been made.
Overall Study Adverse Event	1	1	1

Baseline Characteristics

Randomized participants (actual treatment received) who had completed the study and had received the required protocol processing for the study, i.e., no major protocol deviations (Per-Protocol Population).

Baseline characteristics by cohort

PRIMARY outcome

Timeframe: Week 12

The change in Pulmonary Vascular Resistance (PVR) was evaluated from Baseline to Week 12. PVR is expressed in Wood Units or millimeters of Mercury per Liter per minute (mmHG/L/min)

Outcome measures

Outcome measures
Measure	Low Fixed Dose Group (60 ug) n=12 Participants Participants in the low dose group received 60 microgram of Beraprost sodium modified release tablets, orally twice daily up to maximum duration of Week 12.	High Fixed Dose Group (240 ug) n=11 Participants Participants in the high dose group received starting dose of 60 microgram of Beraprost sodium modified release tablets twice daily which was escalated until they reached the fixed maximum dose of 240 microgram twice daily up to a maximum duration of Week 12	Maximum Tolerated Dose (MTD) n=10 Participants Participants in this group received starting dose of 60 microgram of Beraprost sodium modified release tablets twice daily which was escalated until they reached the fixed maximum dose of 600 microgram twice daily up to a maximum duration of Week 12 or they reached an intolerable dose which required them to down-titrate by 60 microgram twice daily in these instances and at the Investigator's discretion, further attempts at dose escalation may have been made.
Change From Baseline in Pulmonary Vascular Resistance at Week 12	0.37 Wood Units (mmHg/L/min) Standard Deviation 3.08	0.00 Wood Units (mmHg/L/min) Standard Deviation 1.57	0.13 Wood Units (mmHg/L/min) Standard Deviation 3.21

PRIMARY outcome

Timeframe: Week 12

The change in Cardiac Output was evaluated from Baseline to Week 12.

Outcome measures

Outcome measures
Measure	Low Fixed Dose Group (60 ug) n=12 Participants Participants in the low dose group received 60 microgram of Beraprost sodium modified release tablets, orally twice daily up to maximum duration of Week 12.	High Fixed Dose Group (240 ug) n=11 Participants Participants in the high dose group received starting dose of 60 microgram of Beraprost sodium modified release tablets twice daily which was escalated until they reached the fixed maximum dose of 240 microgram twice daily up to a maximum duration of Week 12	Maximum Tolerated Dose (MTD) n=10 Participants Participants in this group received starting dose of 60 microgram of Beraprost sodium modified release tablets twice daily which was escalated until they reached the fixed maximum dose of 600 microgram twice daily up to a maximum duration of Week 12 or they reached an intolerable dose which required them to down-titrate by 60 microgram twice daily in these instances and at the Investigator's discretion, further attempts at dose escalation may have been made.
Change From Baseline in Cardiac Output (CO) at Week 12	0.16 Liters per minute (L/min) Standard Deviation 1.17	0.07 Liters per minute (L/min) Standard Deviation 0.84	0.35 Liters per minute (L/min) Standard Deviation 1.15

PRIMARY outcome

Timeframe: 12 weeks

The change in mean Pulmonary Arterial Pressure (mPAP) was evaluated from Baseline to Week 12.

Outcome measures

Outcome measures
Measure	Low Fixed Dose Group (60 ug) n=12 Participants Participants in the low dose group received 60 microgram of Beraprost sodium modified release tablets, orally twice daily up to maximum duration of Week 12.	High Fixed Dose Group (240 ug) n=11 Participants Participants in the high dose group received starting dose of 60 microgram of Beraprost sodium modified release tablets twice daily which was escalated until they reached the fixed maximum dose of 240 microgram twice daily up to a maximum duration of Week 12	Maximum Tolerated Dose (MTD) n=10 Participants Participants in this group received starting dose of 60 microgram of Beraprost sodium modified release tablets twice daily which was escalated until they reached the fixed maximum dose of 600 microgram twice daily up to a maximum duration of Week 12 or they reached an intolerable dose which required them to down-titrate by 60 microgram twice daily in these instances and at the Investigator's discretion, further attempts at dose escalation may have been made.
Change From Baseline in Pulmonary Arterial Pressure at Week 12	0.42 mmHg Standard Deviation 5.76	-1.45 mmHg Standard Deviation 11.96	4.10 mmHg Standard Deviation 5.15

SECONDARY outcome

Timeframe: Baseline, Week 6 and 12

Area used for the Six Minute Walk Test (6MWT) was pre-measured at 30 meters in length. Rest periods were allowed if patient could no longer continue. If patient needed to rest, he/she could stand or sit and then begin again when rested but the clock continued to run. At the end of 6 minutes, the tester called "stop" while stopping the watch and then measured the distance walked. For purposes of the 6MWT, if patient was assessed at Baseline using oxygen therapy, all future 6MWT were conducted in the same manner. All efficacy results are descriptive; no statistical analysis was conducted.

Outcome measures

Outcome measures
Measure	Low Fixed Dose Group (60 ug) n=12 Participants Participants in the low dose group received 60 microgram of Beraprost sodium modified release tablets, orally twice daily up to maximum duration of Week 12.	High Fixed Dose Group (240 ug) n=11 Participants Participants in the high dose group received starting dose of 60 microgram of Beraprost sodium modified release tablets twice daily which was escalated until they reached the fixed maximum dose of 240 microgram twice daily up to a maximum duration of Week 12	Maximum Tolerated Dose (MTD) n=10 Participants Participants in this group received starting dose of 60 microgram of Beraprost sodium modified release tablets twice daily which was escalated until they reached the fixed maximum dose of 600 microgram twice daily up to a maximum duration of Week 12 or they reached an intolerable dose which required them to down-titrate by 60 microgram twice daily in these instances and at the Investigator's discretion, further attempts at dose escalation may have been made.
Change in Six Minute Walk Distance From Baseline to Week 6 and Week 12 Week 12 Trough	44.00 meters Standard Deviation 50.74	47.67 meters Standard Deviation 92.20	11.67 meters Standard Deviation 72.25
Change in Six Minute Walk Distance From Baseline to Week 6 and Week 12 Week 6 Peak	2.17 meters Standard Deviation 112.63	29.91 meters Standard Deviation 46.83	39.90 meters Standard Deviation 47.59
Change in Six Minute Walk Distance From Baseline to Week 6 and Week 12 Week 12 Peak	52.82 meters Standard Deviation 70.53	42.18 meters Standard Deviation 83.08	47.10 meters Standard Deviation 48.39

SECONDARY outcome

Timeframe: Week 6 and Week 12

Population: Randomized participants (actual treatment received) who had completed the study and had received the required protocol processing for the study, i.e., no major protocol deviations (Per-Protocol Population). Here, number analyzed signifies number of participants evaluable at specified time points only.

WHO functional classification for PAH range from Class I (no limitation in physical activity, no dyspnea with normal activity), Class II (slight limitation of physical activity), Class III (marked limitation of physical activity) and Class IV (cannot perform a physical activity without any symptoms, dyspnea at rest).

Outcome measures

Outcome measures
Measure	Low Fixed Dose Group (60 ug) n=12 Participants Participants in the low dose group received 60 microgram of Beraprost sodium modified release tablets, orally twice daily up to maximum duration of Week 12.	High Fixed Dose Group (240 ug) n=11 Participants Participants in the high dose group received starting dose of 60 microgram of Beraprost sodium modified release tablets twice daily which was escalated until they reached the fixed maximum dose of 240 microgram twice daily up to a maximum duration of Week 12	Maximum Tolerated Dose (MTD) n=10 Participants Participants in this group received starting dose of 60 microgram of Beraprost sodium modified release tablets twice daily which was escalated until they reached the fixed maximum dose of 600 microgram twice daily up to a maximum duration of Week 12 or they reached an intolerable dose which required them to down-titrate by 60 microgram twice daily in these instances and at the Investigator's discretion, further attempts at dose escalation may have been made.
Number of Participants in Each World Health Organization (WHO) Functional Class for Pulmonary Arterial Hypertension (PAH) at Week 6 and 12 Week 6: Class I	1 Participants	0 Participants	0 Participants
Number of Participants in Each World Health Organization (WHO) Functional Class for Pulmonary Arterial Hypertension (PAH) at Week 6 and 12 Week 6: Class II	6 Participants	3 Participants	3 Participants
Number of Participants in Each World Health Organization (WHO) Functional Class for Pulmonary Arterial Hypertension (PAH) at Week 6 and 12 Week 6: Class III	5 Participants	8 Participants	7 Participants
Number of Participants in Each World Health Organization (WHO) Functional Class for Pulmonary Arterial Hypertension (PAH) at Week 6 and 12 Week 6: Class IV	0 Participants	0 Participants	0 Participants
Number of Participants in Each World Health Organization (WHO) Functional Class for Pulmonary Arterial Hypertension (PAH) at Week 6 and 12 Week 12: Class I	1 Participants	1 Participants	0 Participants
Number of Participants in Each World Health Organization (WHO) Functional Class for Pulmonary Arterial Hypertension (PAH) at Week 6 and 12 Week 12: Class II	5 Participants	4 Participants	3 Participants
Number of Participants in Each World Health Organization (WHO) Functional Class for Pulmonary Arterial Hypertension (PAH) at Week 6 and 12 Week 12: Class III	6 Participants	6 Participants	7 Participants
Number of Participants in Each World Health Organization (WHO) Functional Class for Pulmonary Arterial Hypertension (PAH) at Week 6 and 12 Week 12: Class IV	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Up to Week 12

Population: Randomized participants (per actual treatment received) who received ≥1 dose of study drug (Safety Population). Overall number of participants analyzed signifies those who were evaluable for this outcome measure.

Post-baseline clinically significant values, as defined by the Investigator, for hematology, serum chemistry, coagulation and urinalysis parameters were summarized.

Outcome measures

Outcome measures
Measure	Low Fixed Dose Group (60 ug) n=12 Participants Participants in the low dose group received 60 microgram of Beraprost sodium modified release tablets, orally twice daily up to maximum duration of Week 12.	High Fixed Dose Group (240 ug) n=11 Participants Participants in the high dose group received starting dose of 60 microgram of Beraprost sodium modified release tablets twice daily which was escalated until they reached the fixed maximum dose of 240 microgram twice daily up to a maximum duration of Week 12	Maximum Tolerated Dose (MTD) n=11 Participants Participants in this group received starting dose of 60 microgram of Beraprost sodium modified release tablets twice daily which was escalated until they reached the fixed maximum dose of 600 microgram twice daily up to a maximum duration of Week 12 or they reached an intolerable dose which required them to down-titrate by 60 microgram twice daily in these instances and at the Investigator's discretion, further attempts at dose escalation may have been made.
Number of Participants With at Least One Post-baseline Clinically Significant Laboratory Value	5 participants	3 participants	3 participants

SECONDARY outcome

Timeframe: Up to 12 weeks

Clinically significant ECG abnormalities at Baseline only are excluded.

Outcome measures

Outcome measures
Measure	Low Fixed Dose Group (60 ug) n=13 Participants Participants in the low dose group received 60 microgram of Beraprost sodium modified release tablets, orally twice daily up to maximum duration of Week 12.	High Fixed Dose Group (240 ug) n=12 Participants Participants in the high dose group received starting dose of 60 microgram of Beraprost sodium modified release tablets twice daily which was escalated until they reached the fixed maximum dose of 240 microgram twice daily up to a maximum duration of Week 12	Maximum Tolerated Dose (MTD) n=11 Participants Participants in this group received starting dose of 60 microgram of Beraprost sodium modified release tablets twice daily which was escalated until they reached the fixed maximum dose of 600 microgram twice daily up to a maximum duration of Week 12 or they reached an intolerable dose which required them to down-titrate by 60 microgram twice daily in these instances and at the Investigator's discretion, further attempts at dose escalation may have been made.
Number of Participants With Newly Occurring Clinically Significant ECG Abnormalities Right Atrial Abnormality	0 Participants	2 Participants	0 Participants
Number of Participants With Newly Occurring Clinically Significant ECG Abnormalities Chronic Pulmonary Disease Pattern	0 Participants	1 Participants	0 Participants
Number of Participants With Newly Occurring Clinically Significant ECG Abnormalities Low QRS Voltage	0 Participants	0 Participants	1 Participants
Number of Participants With Newly Occurring Clinically Significant ECG Abnormalities Non-Specific ST-T Changes	0 Participants	0 Participants	1 Participants

SECONDARY outcome

Timeframe: Baseline, Week 6 and 12

The modified 0-10 category-ratio Borg scale consists of an 11-point scale rating the maximum level of dyspnea experienced during the 6MWT. Scores range from 0 (for the best condition) and 10 (for the worst condition) with nonlinear spacing of verbal descriptors of severity corresponding to specific numbers. The participant chose the number or the verbal descriptor to reflect presumed ratio properties of sensation or symptom intensity. Only participants with both a measurement at baseline and at the given visit are presented. All efficacy results are descriptive; no statistical analysis was conducted.

Outcome measures

Outcome measures
Measure	Low Fixed Dose Group (60 ug) n=12 Participants Participants in the low dose group received 60 microgram of Beraprost sodium modified release tablets, orally twice daily up to maximum duration of Week 12.	High Fixed Dose Group (240 ug) n=11 Participants Participants in the high dose group received starting dose of 60 microgram of Beraprost sodium modified release tablets twice daily which was escalated until they reached the fixed maximum dose of 240 microgram twice daily up to a maximum duration of Week 12	Maximum Tolerated Dose (MTD) n=10 Participants Participants in this group received starting dose of 60 microgram of Beraprost sodium modified release tablets twice daily which was escalated until they reached the fixed maximum dose of 600 microgram twice daily up to a maximum duration of Week 12 or they reached an intolerable dose which required them to down-titrate by 60 microgram twice daily in these instances and at the Investigator's discretion, further attempts at dose escalation may have been made.
Change in Borg Dyspnea Score From Baseline to Week 6 and Week 12 Week 6	0.71 scores on a scale Standard Deviation 1.29	0.68 scores on a scale Standard Deviation 1.65	0.80 scores on a scale Standard Deviation 3.13
Change in Borg Dyspnea Score From Baseline to Week 6 and Week 12 Week 12 at peak	0.50 scores on a scale Standard Deviation 0.81	0.64 scores on a scale Standard Deviation 2.16	0.40 scores on a scale Standard Deviation 2.69
Change in Borg Dyspnea Score From Baseline to Week 6 and Week 12 Week 12 at trough	0.45 scores on a scale Standard Deviation 0.83	1.11 scores on a scale Standard Deviation 0.78	0.67 scores on a scale Standard Deviation 3.00

SECONDARY outcome

Timeframe: Week 6 and Week 12

Population: Randomized participants (actual treatment received) who completed the study and received required protocol processing, ie, no major protocol deviations (PP Population). Overall number of participants analyzed signifies those who were evaluable for the outcome measure; number analyzed signifies those who were evaluable at specified timepoint only.

NT-proBNP functions as a strong indicator of prognosis in patients with pulmonary arterial hypertension.

Outcome measures

Outcome measures
Measure	Low Fixed Dose Group (60 ug) n=11 Participants Participants in the low dose group received 60 microgram of Beraprost sodium modified release tablets, orally twice daily up to maximum duration of Week 12.	High Fixed Dose Group (240 ug) n=10 Participants Participants in the high dose group received starting dose of 60 microgram of Beraprost sodium modified release tablets twice daily which was escalated until they reached the fixed maximum dose of 240 microgram twice daily up to a maximum duration of Week 12	Maximum Tolerated Dose (MTD) n=10 Participants Participants in this group received starting dose of 60 microgram of Beraprost sodium modified release tablets twice daily which was escalated until they reached the fixed maximum dose of 600 microgram twice daily up to a maximum duration of Week 12 or they reached an intolerable dose which required them to down-titrate by 60 microgram twice daily in these instances and at the Investigator's discretion, further attempts at dose escalation may have been made.
N-Terminal ProB-type Natriuretic Peptide Level at Week 6 and Week 12 Week 6	6.38 nanograms per Liter (ng/L) Standard Deviation 1.28	5.82 nanograms per Liter (ng/L) Standard Deviation 0.72	6.83 nanograms per Liter (ng/L) Standard Deviation 1.18
N-Terminal ProB-type Natriuretic Peptide Level at Week 6 and Week 12 Week 12	6.33 nanograms per Liter (ng/L) Standard Deviation 1.41	6.06 nanograms per Liter (ng/L) Standard Deviation 1.08	6.85 nanograms per Liter (ng/L) Standard Deviation 1.55

Adverse Events

Low Fixed Dose Group (60 ug)

Serious events: 3 serious events

Other events: 13 other events

Deaths: 0 deaths

High Fixed Dose Group (240 ug)

Serious events: 0 serious events

Other events: 11 other events

Deaths: 0 deaths

Maximum Tolerated Dose (MTD)

Serious events: 1 serious events

Other events: 11 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Low Fixed Dose Group (60 ug) n=13 participants at risk Participants in the low dose group received 60 microgram of Beraprost sodium modified release tablets, orally twice daily up to maximum duration of Week 12.	High Fixed Dose Group (240 ug) n=12 participants at risk Participants in the high dose group received starting dose of 60 microgram of Beraprost sodium modified release tablets twice daily which was escalated until they reached the fixed maximum dose of 240 microgram twice daily up to a maximum duration of Week 12	Maximum Tolerated Dose (MTD) n=11 participants at risk Participants in this group received starting dose of 60 microgram of Beraprost sodium modified release tablets twice daily which was escalated until they reached the fixed maximum dose of 600 microgram twice daily up to a maximum duration of Week 12 or they reached an intolerable dose which required them to down-titrate by 60 microgram twice daily in these instances and at the Investigator's discretion, further attempts at dose escalation may have been made.
Cardiac disorders Right ventricular failure	7.7% 1/13 • Baseline up to 30 days after last dose of study drug (up to Week 12). Randomized participants (per actual treatment received) who received ≥1 dose of study drug (Safety Population).	0.00% 0/12 • Baseline up to 30 days after last dose of study drug (up to Week 12). Randomized participants (per actual treatment received) who received ≥1 dose of study drug (Safety Population).	0.00% 0/11 • Baseline up to 30 days after last dose of study drug (up to Week 12). Randomized participants (per actual treatment received) who received ≥1 dose of study drug (Safety Population).
Nervous system disorders Headache	7.7% 1/13 • Baseline up to 30 days after last dose of study drug (up to Week 12). Randomized participants (per actual treatment received) who received ≥1 dose of study drug (Safety Population).	0.00% 0/12 • Baseline up to 30 days after last dose of study drug (up to Week 12). Randomized participants (per actual treatment received) who received ≥1 dose of study drug (Safety Population).	0.00% 0/11 • Baseline up to 30 days after last dose of study drug (up to Week 12). Randomized participants (per actual treatment received) who received ≥1 dose of study drug (Safety Population).
Infections and infestations Pneumonia	7.7% 1/13 • Baseline up to 30 days after last dose of study drug (up to Week 12). Randomized participants (per actual treatment received) who received ≥1 dose of study drug (Safety Population).	0.00% 0/12 • Baseline up to 30 days after last dose of study drug (up to Week 12). Randomized participants (per actual treatment received) who received ≥1 dose of study drug (Safety Population).	0.00% 0/11 • Baseline up to 30 days after last dose of study drug (up to Week 12). Randomized participants (per actual treatment received) who received ≥1 dose of study drug (Safety Population).
Cardiac disorders Coronary artery stenosis	0.00% 0/13 • Baseline up to 30 days after last dose of study drug (up to Week 12). Randomized participants (per actual treatment received) who received ≥1 dose of study drug (Safety Population).	0.00% 0/12 • Baseline up to 30 days after last dose of study drug (up to Week 12). Randomized participants (per actual treatment received) who received ≥1 dose of study drug (Safety Population).	9.1% 1/11 • Baseline up to 30 days after last dose of study drug (up to Week 12). Randomized participants (per actual treatment received) who received ≥1 dose of study drug (Safety Population).
Cardiac disorders Cardiac arrest	0.00% 0/13 • Baseline up to 30 days after last dose of study drug (up to Week 12). Randomized participants (per actual treatment received) who received ≥1 dose of study drug (Safety Population).	0.00% 0/12 • Baseline up to 30 days after last dose of study drug (up to Week 12). Randomized participants (per actual treatment received) who received ≥1 dose of study drug (Safety Population).	9.1% 1/11 • Baseline up to 30 days after last dose of study drug (up to Week 12). Randomized participants (per actual treatment received) who received ≥1 dose of study drug (Safety Population).

Other adverse events

Additional Information

Lung Biotechnology PBC Study Director

Lung Biotechnology PBC

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: GT60

Measure	Low Fixed Dose Group (60 ug) n=12 Participants Participants in the low dose group received 60 microgram of Beraprost sodium modified release tablets, orally twice daily up to maximum duration of Week 12.	High Fixed Dose Group (240 ug) n=12 Participants Participants in the high dose group received starting dose of 60 microgram of Beraprost sodium modified release tablets twice daily which was escalated until they reached the fixed maximum dose of 240 microgram twice daily up to a maximum duration of Week 12	Maximum Tolerated Dose (MTD) n=12 Participants Participants in this group received starting dose of 60 microgram of Beraprost sodium modified release tablets twice daily which was escalated until they reached the fixed maximum dose of 600 microgram twice daily up to a maximum duration of Week 12 or they reached an intolerable dose which required them to down-titrate by 60 microgram twice daily in these instances and at the Investigator's discretion, further attempts at dose escalation may have been made.	Total n=36 Participants Total of all reporting groups
Age, Continuous	46.0 years STANDARD_DEVIATION 14.19 • n=12 Participants	45.1 years STANDARD_DEVIATION 15.2 • n=12 Participants	51.1 years STANDARD_DEVIATION 14.71 • n=12 Participants	47.4 years STANDARD_DEVIATION 14.53 • n=36 Participants
Sex: Female, Male Female	10 Participants n=12 Participants	10 Participants n=12 Participants	10 Participants n=12 Participants	30 Participants n=36 Participants
Sex: Female, Male Male	2 Participants n=12 Participants	2 Participants n=12 Participants	2 Participants n=12 Participants	6 Participants n=36 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=12 Participants	2 Participants n=12 Participants	4 Participants n=12 Participants	6 Participants n=36 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	12 Participants n=12 Participants	10 Participants n=12 Participants	8 Participants n=12 Participants	30 Participants n=36 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=12 Participants	0 Participants n=12 Participants	0 Participants n=12 Participants	0 Participants n=36 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=12 Participants	0 Participants n=12 Participants	0 Participants n=12 Participants	0 Participants n=36 Participants
Race (NIH/OMB) Asian	0 Participants n=12 Participants	1 Participants n=12 Participants	0 Participants n=12 Participants	1 Participants n=36 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=12 Participants	0 Participants n=12 Participants	0 Participants n=12 Participants	0 Participants n=36 Participants
Race (NIH/OMB) Black or African American	0 Participants n=12 Participants	0 Participants n=12 Participants	0 Participants n=12 Participants	0 Participants n=36 Participants
Race (NIH/OMB) White	12 Participants n=12 Participants	11 Participants n=12 Participants	12 Participants n=12 Participants	35 Participants n=36 Participants
Race (NIH/OMB) More than one race	0 Participants n=12 Participants	0 Participants n=12 Participants	0 Participants n=12 Participants	0 Participants n=36 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=12 Participants	0 Participants n=12 Participants	0 Participants n=12 Participants	0 Participants n=36 Participants
Pulmonary Vascular Resistance (PVR)	9.74 Wood Units (mmHg/L/min) STANDARD_DEVIATION 5.35 • n=12 Participants • Randomized participants (actual treatment received) who had completed the study and had received the required protocol processing for the study, i.e., no major protocol deviations (Per-Protocol Population).	9.39 Wood Units (mmHg/L/min) STANDARD_DEVIATION 4.05 • n=11 Participants • Randomized participants (actual treatment received) who had completed the study and had received the required protocol processing for the study, i.e., no major protocol deviations (Per-Protocol Population).	10.19 Wood Units (mmHg/L/min) STANDARD_DEVIATION 5.61 • n=10 Participants • Randomized participants (actual treatment received) who had completed the study and had received the required protocol processing for the study, i.e., no major protocol deviations (Per-Protocol Population).	9.76 Wood Units (mmHg/L/min) STANDARD_DEVIATION 4.89 • n=33 Participants • Randomized participants (actual treatment received) who had completed the study and had received the required protocol processing for the study, i.e., no major protocol deviations (Per-Protocol Population).
Cardiac Output (CO)	4.44 Liters per minute (L/min) STANDARD_DEVIATION 1.12 • n=12 Participants • Randomized participants (actual treatment received) who had completed the study and had received the required protocol processing for the study, i.e., no major protocol deviations (Per-Protocol Population).	5.53 Liters per minute (L/min) STANDARD_DEVIATION 1.79 • n=11 Participants • Randomized participants (actual treatment received) who had completed the study and had received the required protocol processing for the study, i.e., no major protocol deviations (Per-Protocol Population).	4.52 Liters per minute (L/min) STANDARD_DEVIATION 1.20 • n=10 Participants • Randomized participants (actual treatment received) who had completed the study and had received the required protocol processing for the study, i.e., no major protocol deviations (Per-Protocol Population).	4.83 Liters per minute (L/min) STANDARD_DEVIATION 1.45 • n=33 Participants • Randomized participants (actual treatment received) who had completed the study and had received the required protocol processing for the study, i.e., no major protocol deviations (Per-Protocol Population).
Mean Pulmonary Arterial Pressure (mPAP)	49.58 Millimeters of Mercury (mmHg) STANDARD_DEVIATION 18.72 • n=12 Participants • Randomized participants (actual treatment received) who had completed the study and had received the required protocol processing for the study, i.e., no major protocol deviations (Per-Protocol Population).	57.91 Millimeters of Mercury (mmHg) STANDARD_DEVIATION 19.03 • n=11 Participants • Randomized participants (actual treatment received) who had completed the study and had received the required protocol processing for the study, i.e., no major protocol deviations (Per-Protocol Population).	52.40 Millimeters of Mercury (mmHg) STANDARD_DEVIATION 15.54 • n=10 Participants • Randomized participants (actual treatment received) who had completed the study and had received the required protocol processing for the study, i.e., no major protocol deviations (Per-Protocol Population).	53.21 Millimeters of Mercury (mmHg) STANDARD_DEVIATION 17.73 • n=33 Participants • Randomized participants (actual treatment received) who had completed the study and had received the required protocol processing for the study, i.e., no major protocol deviations (Per-Protocol Population).
Six Minute Walk Distance	362.92 meters (m) STANDARD_DEVIATION 51.01 • n=12 Participants • Randomized participants (actual treatment received) who had completed the study and had received the required protocol processing for the study, i.e., no major protocol deviations (Per-Protocol Population).	388.73 meters (m) STANDARD_DEVIATION 74.21 • n=11 Participants • Randomized participants (actual treatment received) who had completed the study and had received the required protocol processing for the study, i.e., no major protocol deviations (Per-Protocol Population).	327.70 meters (m) STANDARD_DEVIATION 94.48 • n=10 Participants • Randomized participants (actual treatment received) who had completed the study and had received the required protocol processing for the study, i.e., no major protocol deviations (Per-Protocol Population).	360.85 meters (m) STANDARD_DEVIATION 75.75 • n=33 Participants • Randomized participants (actual treatment received) who had completed the study and had received the required protocol processing for the study, i.e., no major protocol deviations (Per-Protocol Population).
Borg Dyspnea Score	2.71 scores on a scale STANDARD_DEVIATION 1.48 • n=12 Participants • Randomized participants (actual treatment received) who had completed the study and had received the required protocol processing for the study, i.e., no major protocol deviations (Per-Protocol Population).	3.36 scores on a scale STANDARD_DEVIATION 2.34 • n=11 Participants • Randomized participants (actual treatment received) who had completed the study and had received the required protocol processing for the study, i.e., no major protocol deviations (Per-Protocol Population).	3.10 scores on a scale STANDARD_DEVIATION 2.27 • n=10 Participants • Randomized participants (actual treatment received) who had completed the study and had received the required protocol processing for the study, i.e., no major protocol deviations (Per-Protocol Population).	3.05 scores on a scale STANDARD_DEVIATION 2.00 • n=33 Participants • Randomized participants (actual treatment received) who had completed the study and had received the required protocol processing for the study, i.e., no major protocol deviations (Per-Protocol Population).