Please select the eligibility criteria that correspond to the clinical trial below.
Title: A 16-Week, International, Multicenter, Double-Blind, Randomized, Placebo-Controlled Comparison of the Efficacy and Safety of Oral UT-15C Sustained Release Tablets in Combination With an Endothelin Receptor Antagonist and/or a Phosphodiesterase-5 Inhibitor in Subjects With Pulmonary Arterial Hypertension
Brief Summary: This study was an international, multi-center, randomized, double-blind, placebo-controlled study in subjects with PAH who were currently receiving approved therapy for their PAH (i.e., endothelin receptor antagonist and/or phosphodiesterase-5 inhibitor). Study visits occurred at 4 week intervals for 16 weeks; the key measure of efficacy was the 6-minute walk test. Study procedures included routine blood tests, medical history, physical exams, disease evaluation, and exercise tests. One optional substudy was also a part of FREEDOM-C at select centers - a hemodynamic substudy with a right heart catheterization at Baseline and Week 16.

Patients who completed all assessments for 16-weeks were also eligible to enter an open-label, extension phase study (FREEDOM - EXT).


Options:
A: 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.
B: Inclusion Criteria:

* Between 12 and 70 years of age, inclusive.
* Body weight at least 45 kg (approximately 100 pounds).
* PAH that is either idiopathic/heritable (including PAH associated with appetite suppressant/toxin use); PAH associated with repaired congenital systemic-to-pulmonary shunts (repaired ≥ 5 years); PAH associated with collagen vascular disease; or PAH associated with HIV.
* Baseline 6-minute walk distance between 150 and 450 meters, inclusive.
* Currently receiving an approved endothelin receptor antagonist and/or an approved phosphodiesterase-5 inhibitor for at least 90 days and on a stable dose for at least the last 30 days.
* Previous testing (e.g., right heart catheterization, echocardiography) consistent with the diagnosis of PAH.
* Reliable and cooperative with protocol requirements.

Exclusion Criteria:

* Nursing or pregnant.
* Received a prostacyclin within the past 30 days.
* 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.
C: 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.
D: Inclusion Criteria:

* Male or female patients
* Secondary pulmonary hypertension
* Mean pulmonary artery pressure equal or above 40 mmHg or primary pulmonary hypertension with a pressure equal or above 30 mmHg while resting during appropriate conventional treatment
* Written informed consent after having been duly informed about all diagnostic and therapeutic measures involved in the study

Exclusion Criteria:

* Clinical Instability at baseline
* Pulmonary venous obstruction
* Global respiratory insufficiency
* Obstructive ventilation disorders, Interstitial pulmonary disease
* Cerebrovascular events
* Myocardial infarction or major cardiac surgery within 3 months prior to baseline
* Bleeding disorders or bleeding risk
* Severe hepatic insufficiency or renal insufficiency
* Malignant diseases
* HIV positive
* Pregnancy, female patients of child-bearing potential without adequate contraception and nursing mothers
* Congenital or acquired valvular defects and myocardial function disorders not related to pulmonary hypertension
* Prior pulmonary embolism
* Collagenosis
* Pulmonary arterial or valvular stenosis

Answer: B