Please select the eligibility criteria that correspond to the clinical trial below.
Title: A 12-Week, International, Multicenter, Double-Blind, Randomized, Placebo-Controlled Comparison of the Efficacy and Safety of Oral UT-15C Sustained Release Tablets in Subjects With Pulmonary Arterial Hypertension
Brief Summary: This study was an international, multicenter, randomized (2:1 active:placebo), double-blind, placebo-controlled study in subjects with PAH who were NOT currently receiving approved therapy for their PAH. Study visits occurred at 4 week intervals for 12 weeks (with an additional visit at Week 11) with the key measure of efficacy being the 6-minute walk test. Study procedures included routine blood tests, medical history, physical exams, disease evaluation, and exercise tests. Two optional substudies were also a part of FREEDOM-M at select centers - a hemodynamic substudy with a right heart catheterization at Baseline and Week 12 and a genetics and biomarkers substudy with blood samples collected at Baseline and Week 12.

Patients who completed all assessments for 12 weeks were also eligible to enter an open-label, extension phase study (FREEDOM - EXT).


Options:
A: Inclusion Criteria:

* Between 12 and 75 years of age, inclusive.
* Body weight at least 40 kg with a Body Mass Index \< 45
* PAH that is either idiopathic/heritable; associated with repaired congenital systemic-to-pulmonary shunts (repaired ≥ 5 years); associated with collagen vascular disease; associated with HIV.
* Previous testing (e.g., right heart catheterization, echocardiography) consistent with the diagnosis of PAH.
* Baseline 6-minute walk distance between 200 and 425 meters, inclusive.
* Reliable and cooperative with protocol requirements.

Exclusion Criteria:

* Nursing or pregnant.
* Currently receiving an endothelin receptor antagonist, a phosphodiesterase-5 inhibitor, or prostacyclin within 30 days of Baseline.
* PAH due to conditions other than noted in the above inclusion criteria.
* History of uncontrolled sleep apnea, renal insufficiency, anemia, left sided heart disease, uncontrolled systemic hypertension, or parenchymal lung disease.
* Use of an investigational drug within 30 days of Baseline.
B: Inclusion Criteria:

* Clinically stable, pulmonary arterial hypertension diagnosed as either idiopathic or familial PAH, collagen vascular disease associated PAH, HIV PAH, or PAH induced by anorexigens, New York Heart Association (NYHA) Class III or Class IV.
* Been on a stable dose of 125 mg twice daily (bid) of bosentan OR any stable dose of sildenafil for at least three months prior to study start
* An unencouraged six minute walk test (6MWT) of between 200 and 450 meters at screening
* Cardiac catheterization within the past 13 months consistent with PAH, specifically mean pulmonary artery pressure (PAPm) ≥25 mmHg (at rest), pulmonary capillary wedge pressure (PCWP) (or left ventricular end diastolic pressure) ≤15 mmHg, and pulmonary vascular resistance (PVR) \>3 mmHg/L/min
* Within the past 12 months, patients must have had a chest radiograph consistent with the diagnosis of PAH
* Willing and able to follow all study procedures

Exclusion Criteria:

* Considering pregnancy, are pregnant and/or lactating
* PAH due to conditions other than noted in the above inclusion criteria.
* Have had any change in or discontinued any PAH medication within the last three months, including but not limited to endothelin receptor antagonist (ERA), or calcium channel blockers (CCB) (with the exception of anticoagulants)
* Have received any prostanoid within the 30 days before screening or are scheduled to receive any during the course of the study
* Have received any investigational medication within 30 days prior to the start of this study or are scheduled to receive another investigational drug during the course of this study
* Have a known intolerance to any drug, especially to treprostinil sodium or prostanoids
* Have an increased risk of hemorrhage
* Have a new type of chronic therapy (e.g., a different category of vasodilator, diuretic) for PAH added within the last month, except anticoagulants
* Have any musculoskeletal disease or any other disease that would limit ambulation.
C: Inclusion Criteria:

* Male and female patients 18-75 years old, with symptomatic PAH
* PAH belonging to the following subgroups of the updated Dana Point Clinical Classification Group 1 (Idiopathic, or Heritable, or Drug or toxin induced, or Associated (APAH) with Connective tissue disease, Congenital heart disease with simple systemic-to-pulmonary shunt at least 1 year after surgical repair, or HIV infection)
* Documented hemodynamic diagnosis of PAH by right heart catheterization, performed at any time prior to Screening
* Six minute walk distance (6MWD) between 50 and 450 m at Screening within 2 weeks prior to the Baseline Visit
* Signed informed consent

Exclusion Criteria:

* Patients with pulmonary hypertension (PH) in the Updated Dana Point Classification Groups 2-5, and PAH Group 1 subgroups that are not covered by the inclusion criteria
* Patients who have received prostacyclin or its analogs within 1 month before Baseline Visit, or are scheduled to receive any of these compounds during the trial
* Patients with moderate or severe obstructive lung disease
* Patients with moderate or severe restrictive lung disease
* Patients with moderate or severe hepatic impairment (Child-Pugh B and C)
* Patients with documented left ventricular dysfunction
* Patients with severe renal insufficiency
* Patients with BMI \<18.5 Kg/m2
* Patients who are receiving or have been receiving any investigational drugs within 1 month before the Baseline Visit
* Acute or chronic impairment (other than dyspnea), limiting the ability to comply with study requirements, in particular with 6MWT
* Recently conducted or planned cardio-pulmonary rehabilitation program based on exercise training
* Psychotic, addictive or other disorder limiting the ability to provide informed consent or to comply with study requirements
* Life expectancy less than 12 months
* Females who are lactating or pregnant or plan to become pregnant during the study
* Known hypersensitivity to any of the excipients of the drug formulations
D: Inclusion Criteria: Patients Must

1. Between 16- 75 years of age.
2. Male or, if female, physiologically incapable of childbearing or utilizing birth control.
3. Have current diagnosis of symptom-limited NYHA Functional Class III/IV PAH that is:

   * PPH ("idiopathic" or familial PAH); or
   * PAH associated with collagen vascular disease (confirmed by antinuclear antibody titer or acceptable test); or
   * PAH associated with HIV infection (confirmed by serological test).
4. If HIV positive, have CD4 lymphocyte count ≥ 200 at baseline and receiving current SOC anti-retroviral or effective medication for HIV infection.
5. Optimally treated with conventional PH therapy and clinically stable for at least 1 month prior to baseline.
6. Have ventilation/perfusion scan, contrast-enhanced CT scan, or pulmonary angiogram after onset of PAH that rules out pulmonary embolism.
7. Have cardiac catheterization in last 3 months (or at Baseline) showing:

   * PAPm \> 35 mmHg (at rest) \&
   * PCWPm (or LV end diastolic pressure) \< 16 mmHg \&
   * PVR \> 5 mmHg/L/min.
8. Have echocardiogram in last 3 months consistent with PH, specifically:

   * evidence of RV hypertrophy or dilation \&
   * evidence of normal LV function \&
   * absence of mitral valve stenosis.
9. Have chest radiograph consistent with PH performed in last 3 months. Radiograph must show clear lung fields or no more than patchy interstitial infiltrates.
10. Unless contraindicated, able to receive one of following anticoagulants: warfarin to achieve INR between 1.5-2.5 or heparin to produce aPTT between 1.3-1.5 times control, unless higher levels clinically indicated.
11. Mentally and physically capable of learning to administer Study Drug using ambulatory intravenous infusion pump and central venous access, or have trained caregiver.
12. If on corticosteroids, receiving stable dose of 20 mg/day of prednisone (or equivalent dose of another steroid) for at least 1 month prior to entry.

Exclusion Criteria: Patients must not:

1. Nursing or pregnant (women of childbearing potential have negative pregnancy test).
2. Have had new type of chronic therapy (including but not limited to oxygen, different category of vasodilator, diuretic, digoxin) for PH, except for anticoagulants, added in last month.
3. Be scheduled for heart-lung transplant.
4. Have any PH medication except for anticoagulants discontinued in week prior to study entry.
5. Have received any chronic prostaglandin or prostaglandin analogue (including intravenous/inhaled/oral: epoprostenol, iloprost, beraprost, etc.), any phosphodiesterase inhibitor therapy such as sildenafil, or any endothelin antagonist therapy such as bosentan, in past 30 days.
6. Have PH associated with chronic thromboembolic disease; or chronic obstructive lung diseases or hypoxemia; or evidence of significant parenchymal lung disease as evidenced by PFTs in last 3 months as follows (any one of following):

   * TLC \< 60% (predicted) or high resolution CT documenting diffuse interstitial fibrosis or alveolitis
   * FEV1/FVC ratio \< 50%
7. Have Portal Hypertension.
8. Have history of uncontrolled Sleep Apnea, defined as oxygen desaturation less than 90% at night, in past 3 months.
9. Have history of left-sided heart disease including:

   * Aortic or mitral valve disease or
   * Pericardial constriction or
   * Restrictive or congestive cardiomyopathy; or have evidence of current left-sided heart disease defined by:
   * PCWPm or LV end diastolic pressure \> 16 mmHg or
   * LVEF \< 40% by MUGA, angiography or echocardiography or
   * LV Shortening Fraction \< 22% by echocardiography or
   * Symptomatic coronary disease (demonstrable ischemia).
10. Have any disease other than HIV or connective tissue disease associated with PH (e.g. sickle cell anemia, schistosomiasis).
11. Have active AIDS or tuberculosis.
12. Have musculoskeletal disorder (e.g. arthritis, artificial leg, etc.) or any other disease thought to limit ambulation, or connected to machine which is not portable.
13. Have baseline exercise capacity of \<50 m or \>325 m as measured by 6-Minute Walk Test.
14. Have uncontrolled systemic hypertension as evidenced by systolic blood pressure \>160 mmHg or diastolic blood pressure \>100 mmHg.
15. Have used prescription appetite suppressants in 3 months of study entry.
16. Have chronic renal insufficiency defined by creatinine \>2.5 mg/dL or requiring dialysis.
17. Receiving an investigational drug (other than acute challenge with epoprostenol), have in place an investigational device, or have participated in investigational drug/device study in past 30 days.
18. Have presence of any physiological or mental condition which contraindicates administration of Remodulin.

Answer: A