Phase III Clinical Worsening Study of UT-15C in Subjects With PAH Receiving Background Oral Monotherapy

Subject Inclusion Criteria:

1. Voluntarily gave informed consent to participate in the study.

2. Are 18 to 75 years of age (inclusive) at Screening.

3. Women of childbearing potential must practice abstinence from intercourse when in linewith their preferred and usual lifestyle, or use 2 different forms of highly effectivecontraception for the duration of the study, and for at least 30 days afterdiscontinuing study medication. A negative urine pregnancy test is required atScreening and Baseline prior to initiating study medication.

4. Male subjects must consent to use a condom during intercourse for the duration of thestudy, and for at least 48 hours after discontinuing study medication.

5. Have a diagnosis of symptomatic idiopathic or heritable PAH, PAH associated withconnective tissue disease (CTD), PAH associated with HIV infection, PAH associatedwith repaired congenital systemic-to-pulmonary shunt, or PAH associated with appetitesuppressant or toxin use.

6. If known to be positive for HIV infection, have a CD4 lymphocyte count of at least 200cells/mm^3 assessed at Screening and are receiving current standard of care antiretroviral or other effective medication for the treatment of HIV infection.

7. Have a baseline 6MWD greater than or equal to 150 m in the absence of a concurrentinjury, illness, or other confounding factor including, but not limited to, use of anaid for ambulation or connection to a nonportable machine, that would have preventedthe accurate assessment of the subject's exercise capacity.

8. Are optimally treated with conventional pulmonary hypertension therapy with noadditions, discontinuations, or dose changes for a minimum of 10 days prior torandomization. The exceptions are the discontinuation or dose changes ofanticoagulants and/or dose change of diuretics.

9. Are receiving a PAH-approved oral monotherapy at a minimum dose that complies with theapproved prescribing information for the product for at least 30 days prior torandomization and are receiving a stable dose for at least 10 days prior torandomization.

10. Have had previously undergone a cardiac catheterization within 3 years prior to thestart of Screening or during the Screening Period, and the most recent assessmentdocumented a pulmonary artery pressure mean of at least 25 mmHg, a pulmonary capillarywedge pressure (PCWP) (or in the event a PCWP could not be reliably obtained, a leftventricular end diastolic pressure [LVEDP]) less than or equal to 15 mmHg, and absenceof unrepaired congenital heart disease (other than patent foramen ovale). If areliable PCWP or LVEDP are unable to be obtained during cardiac catheterization,subjects with clinically normal left heart function and absence of clinically relevantmitral valve disease on echocardiography are eligible for enrollment.

11. Undergo echocardiography with evidence of clinically normal systolic and diastolicleft ventricular function and absence of any clinically significant left sided heartdisease (eg, mitral valve disease). Subjects with clinically insignificant leftventricular diastolic dysfunction due to the effects of right ventricular overload (ie, right ventricular hypertrophy and/or dilatation) are eligible.

12. Have a previous ventilation perfusion lung scan, high-resolution computerizedtomography scan of the chest, and/or pulmonary angiography that are consistent withthe diagnosis of PAH.

13. Have pulmonary function tests conducted within 6 months before Screening or during theScreening Period to confirm the following:

14. Total lung capacity is at least 60%

15. Forced expiratory volume at 1 second is at least 50%

16. In the opinion of the Principal Investigator, is able to communicate effectively withstudy personnel and is considered reliable, willing, and likely to cooperate withprotocol requirements, including attending all study visits.

Subject Exclusion Criteria:

1. Is pregnant or lactating.

2. Have previously received oral treprostinil.

3. Have received a PGI2 (except if used during acute vasoreactivity testing) within 30days prior to randomization or have previous intolerance or significant lack ofefficacy to any PGI2 or PGI2 analogue that resulted in discontinuation or inability totitrate that therapy effectively.

4. Have any background conventional therapies for PAH added, removed, or dose-adjustedwithin 10 days prior to randomization. The exceptions are removal or dose adjustmentsof anticoagulants and/or dose adjustments of diuretics.

5. Receive their first dose of a PAH-approved oral monotherapy less than 30 days prior torandomization, or have their PAH-approved oral monotherapy dose changed within 10 daysprior to randomization, or the subject discontinues any PAH approved therapy within 30days prior to Screening, or the subject has previously received 2 PAH approved oraltherapies at the same time (specifically, a PDE5-I, an ERA, or a sGC stimulator)concomitantly for more than 90 days cumulatively.

6. Have any disease associated with PAH other than CTD, HIV infection, repaired (for atleast 1 year) congenital systemic-to-pulmonary shunt, PAH associated with appetitesuppressant/toxin use, or have an atrial septostomy.

7. Have a current diagnosis of uncontrolled sleep apnea as defined by their physician.

8. Have a history of ischemic heart disease, including a previous myocardial infarctionor symptomatic coronary artery disease within 6 months prior to Screening or a historyof left-sided myocardial disease as evidenced by a mean PCWP (or a LVEDP) greater than 15 mmHg or left ventricular ejection fraction less than 40% as assessed by eithermultigated angiogram, angiography, or echocardiography.

9. Have uncontrolled systemic hypertension as evidenced by systolic blood pressure (BP)greater than 160 mmHg or diastolic BP greater than 100 mmHg.

10. Have alanine aminotransferase or aspartate aminotransferase levels at least 3 timesgreater than the upper limit of normal, clinically significant liverdisease/dysfunction, or known Child-Pugh Class C hepatic disease at Screening.

11. Have any other disease or condition that would interfere with the interpretation ofstudy assessments.

12. Have a musculoskeletal disorder, is using a device to assist walking, or any diseasethat is likely to limit ambulation, or is connected to a machine that is nonportable.

13. Have an unstable psychiatric condition or is mentally incapable of understanding theobjectives, nature, or consequences of the study, or has any condition which in theInvestigator's opinion would constitute an unacceptable risk to the subject's safety.

14. Is receiving an investigational drug, have an investigational device in place, or haveparticipated in an investigational drug or device study within 30 days prior toScreening.

15. Have chronic renal insufficiency as defined by either a Screening creatinine valuegreater than 2.5 mg/dL or the requirement for dialysis.

16. Does not have 3 or more of the following left ventricular disease/dysfunction riskfactors:

17. Body mass index at least 30 kg/m^2

18. History of essential hypertension

19. Diabetes mellitus (any type)

20. Historical evidence of significant coronary artery disease established by any 1of the following: history of myocardial infarction, percutaneous coronaryintervention, or angiographic evidence of coronary artery disease; positivestress test with imaging; previous coronary artery bypass graft; or stableangina.