Please select the eligibility criteria that correspond to the clinical trial below.
Title: A 16-Week, International, Multicenter, Double-Blind, Randomized, Placebo-Controlled Study of the Efficacy and Safety of Oral UT-15C Sustained Release Tablets in Subjects With Pulmonary Arterial Hypertension
Brief Summary: This study is an international, multi-center, randomized, double-blind, placebo-controlled study in subjects with PAH who are currently receiving approved therapy for their PAH (i.e., endothelin receptor antagonist and/or phosphodiesterase-5 inhibitor). Study visits will occur at 4 week intervals for 16 weeks with the key measure of efficacy being the 6-minute walk test. Study procedures include routine blood tests, medical history, physical exams, disease evaluation, and exercise tests.

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


Options:
A: 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
B: 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.
C: Inclusion Criteria:

* A subject is eligible for inclusion in this study if all of the following criteria apply:
* Between 18 and 75 years of age, inclusive.
* Body weight at least 40 kg (approximately 90 lbs.)
* PAH that is either idiopathic/heritable; associated with appetite suppressant or toxin use; associated with collagen vascular disease; associated with repaired congenital shunts; associated with HIV.
* 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.
* Baseline six-minute walk distance (6MWD) between 150-425 meters
* Previous testing (e.g., right heart catheterization, echocardiography) consistent with the diagnosis of PAH.
* Reliable and cooperative with protocol requirements.
D: Inclusion Criteria:

1. Male and female subjects 18 years of age or older with symptomatic PAH despite treatment with anticoagulants, calcium channel blockers, diuretics, cardiac glycosides, supplemental oxygen, endothelin-receptor antagonists and/or phosphodiesterase inhibitors. Endothelin receptor antagonists and phosphodiesterase inhibitors must have been used at a stable dose for more than 12 weeks before screening.
2. Subjects with idiopathic PAH, familial pulmonary arterial hypertension and PAH associated with collagen vascular disease, corrected congenital vitium (congenital systemic to pulmonary shunts surgically repaired at least five years before) or anorexigen use.
3. Diagnosis of PAH established according to the standard criteria:

   1. Resting mean pulmonary arterial pressure \> 25 mmHg.
   2. PVR \> 240 dynes s/cm5.
   3. Pulmonary capillary wedge pressure or left ventricular end diastolic pressure \< 15 mmHg.
4. PVR \> 400 dynes s/cm5.
5. Two 6MWTs between 150 and 500 m (inclusive) with the variation in 6MWT within ± 15% between the two tests despite other treatments for PAH.

   - Two 6MWT values are needed. Only one 6MWT should be performed at screening for confirmation of eligibility if 6MWT has been previously conducted within six weeks of the screening visit unless the subject was taking another investigational drug or participating in a specific training and exercise programme at the time of the previous test.
6. Subjects who are able and willing to refrain from sunbathing, prolonged sun exposure, and solarium use, and to limit skin and eye exposure to sunlight using appropriate precautions (protective clothing, sunscreen and sunglasses) from the first dose until 14 days after study drug discontinuation.

Exclusion Criteria:

Subjects will not be entered in the study for any of the following reasons:

1. Subjects with clinically unstable right heart failure within the last three months (NYHA Class IV).
2. Subjects who have received or have been scheduled to receive long-term treatment with epoprostenol within three months before screening.
3. Hypotensive subjects (systemic systolic blood pressure \< 85 mmHg).
4. Subjects with PAH associated with portal hypertension, Human Immunodeficiency Virus infection or unrepaired congenital systemic to pulmonary shunts.
5. Subjects with ventilation-perfusion lung scan or pulmonary angiography indicative of thromboembolic disease.
6. Subjects with significant obstructive (forced expiratory volume in one second \[FEV1\]/forced vital capacity \[FVC\] \< 70% predicted) or restrictive (total lung capacity \< 70% predicted) lung disease.
7. In collagen vascular diseases, subjects with significant interstitial disease (FVC \< 70% predicted).
8. Subjects with evidence of left sided heart disease.
9. Subjects with moderate or severe hepatic impairment (Child-Pugh B and C).
10. Subjects with clinically significant chronic renal insufficiency (estimated creatinine clearance \< 30 mL/minute, or serum creatinine \> 2.5 mg/dL).
11. Subjects who are receiving or have been receiving any investigational drugs within 30 days before screening.
12. Subjects with musculoskeletal disorder limiting ambulation.
13. Females who are breast-feeding, pregnant or plan to become pregnant during the study and females who are not using a highly effective method of birth control (failure rate less than 1% per year) such as implants, injectables, combined oral contraceptives, some intrauterine devices, sexual abstinence or vasectomised partner.

Answer: C