Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Multicenter, Double-blind, Placebo-controlled Phase 3 Study Assessing the Safety and Efficacy of Selexipag on Morbidity and Mortality in Patients With Pulmonary Arterial Hypertension
Brief Summary: The AC-065A302 (GRIPHON) study is an event-driven Phase 3 study to demonstrate the effect of selexipag on time to first morbidity or mortality event in patients with pulmonary arterial hypertension.


Options:
A: Inclusion Criteria:

* Subjects aged 18 and over above with PAH and for which bosentan therapy is indicated according to national license
* Subjects with a mean pulmonary artery pressure of \>25mmHg and a pulmonary artery wedge pressure of \<15mmHg at rest via right heart catheterization within 3 years prior to randomization.
* Subjects whose baseline 6 Minute Walk Test distance is \>100m and \< 450m.

Exclusion Criteria:

* PAH secondary to any aetiology including congenital heart disease other than those specified in the inclusion criteria
* Subjects whose 6 Minute Walk Test may be limited by conditions other than PAH related dyspnoea or fatigue eg. claudication from vascular insufficiency or arthritis.
B: Inclusion Criteria:

* Eisenmenger syndrome
* Negative pregnancy test

Exclusion Criteria:

* Elevated liver enzymes to more than 3´times normal value
* Hypotension (SBP \< 90 mmhg).
* Mandatory treatment with nitrates
* Myocardial infarction within 3 months
* Stroke within 3 months
* Known allergy to Bosentan or Sildenafil
* inherited degenerative diseases in retina
* Breast feeding
* Suspicion of risc of noncompliance.
C: Inclusion Criteria:

* Must have participated and discontinued in the previous PAH placebo controlled study due to clinical worsening on placebo or tadalafil 2.5 mg, 10mg, or 20 mg
* Must have completed Week 16 of the previous PAH study and had either no clinical worsening or became clinically worse at the Week 16 visit on placebo or tadalafil 2.5 mg, 10mg, or 20 mg
* Females who have a negative urine pregnancy test and are willing to use 2 types of birth control
* Be 12 years or older (country specific regulations apply) with parental approval

Exclusion Criteria:

* Participated in the placebo controlled study and had clinical worsening on 40 mg tadalafil
* Have left-sided heart disease
* Have a musculoskeletal disorder that limits being able to get around
* Nitrate use
* Certain current systemic treatments
D: 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

Answer: D