Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Multicenter, Non-randomized, Non-blinded, Noncontrolled Study to Investigate the Impact of Multiple Doses of BAY 63-2521 on Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics in Patients With Pulmonary Hypertension in a 12-week 3 Times a Day Individual Dose Titration Scheme
Brief Summary: This is a study to demonstrate the feasibility of an individual dose titration scheme based on the systolic blood pressure with a dose range from 1.0 mg TID to 2.5 mg TID. Patients suffering from chronic thromboembolic pulmonary hypertension (CTEPH) or pulmonary arterial hypertension (PAH) will be included. After diagnosis by an expert center, patients receive medication three times a day starting with 1.0 mg TID. The first tablets are given in the hospital, then the patients are allowed to go home and take the medication at home. After 2 weeks, patients return to the hospital for an ambulatory visit and the dose may be increased based on the actual condition of the patient (blood pressure and adverse events). Several measurements will be performed to test the efficacy of the drug and whether there are any unwanted reactions to the drug (blood tests, ECG, 6 minute walk test, imaging by Echo, quality of life scores). The dose of the drug will then be increased further until unwanted effects may occur or the blood pressure drops to low. The highest dose tested will be 2.5 mg TID. After 12 weeks the patient is going to stay in the hospital again and a right heart catheter is performed to examine the changes in hemodynamics after 12 weeks of treatment with the drug. If the patients give their consent they can enter a long-term extension trial continuing on BAY63-2521 with the dose reached after 12 weeks. Every 3 months an ambulatory visit at the specialist center will be performed including measurements of safety (blood tests, ECG, clinical assessment) and efficacy (6 minute walk test, Borg dyspnea scale, NT-pro BNP). Blood tests and ECG have been removed begin of 2013 as safety parameter by amendment 7; furthermore Borg dyspnea score and NT-proBNP have been removed as efficacy parameter.

Initially the inclusion of ten patients suffering from chronic thromboembolic pulmonary hypertension (CTEPH) or pulmonary arterial hypertension (PAH) was planned. Later on the patient number was amended and 75 patients entered the trial.

Furthermore the trial duration was extended and a long term treatment with BAY63-2521 was offered to the patients. Finally 68 patients moved over to the long term extension period of the trial.


Options:
A: Inclusion Criteria:

* Patients with CTEPH or PAH in NYHA class II or III

Exclusion Criteria:

* Patients with PDE 5 inhibitor or prostacycline pretreatment, relevant pulmonary diseases, relevant cardiac diseases, severe coagulation disorders, moderate to severe hepatic or renal insufficiency, pregnancy, hypotension
B: Inclusion Criteria:

* Patients who have completed 12 weeks of treatment in the double blind trial PATENT 1

Exclusion Criteria:

* Patients who have an ongoing serious adverse event from PATENT 1 that is assessed as related to BAY63-2521 are not allowed to participate in the extension trial.
C: Inclusion Criteria:

* 18 to 75 years of age at Visit 1
* Male and female subjects with symptomatic PAH (Group I Dana Point Updated Clinical Classification 2008), a 6-min walking distance (6MWD) of more than 150 m, a pulmonary vascular resistance (PVR) \>300 dyn\*s\*cm-5, and a mean pulmonary artery pressure (PAPmean) ≥ 25 mmHg
* For Study Part 1: subjects on stable pretreatment with sildenafil at a dose of 20 mg tid
* Unspecific treatments which may also be used for the treatment of PAH such as oral anticoagulants, diuretics, digitalis, calcium channel blockers or oxygen supplementation are permitted. However, treatment with anticoagulants (if indicated) must have been started at least 30 days before Visit 1 and treatment with diuretics needs to be stable for at least 30 days before Visit 1
* Subjects with supplemental long-term oxygen therapy may be included, if the amount of supplemental oxygen and the delivery method was stable on average for at least 90 days before Visit 1
* SBP \>/=95 mmHg and heart rate (HR) \</=105 beats per minute (BPM) in the first 2 h after intake of sildenafil (measured at Visits 0 and 1)
* Women without child-bearing potential
* Subjects who are able to understand and follow instructions and who are able to participate in the study for the entire period
* Subjects must have given their written informed consent to participate in the study after having received adequate previous information and prior to any study-specific procedures

Exclusion Criteria:

* Subject's participating in another clinical trial or who have done so within 30 days before Visit 1
* Previous assignment to treatment during this study
* Pregnant women
* Subjects with a medical disorder, condition, or history of such that would impair the subject's ability to participate or complete this study in the opinion of the investigator
* Subjects with substance abuse (eg alcohol or drug abuse) within the previous 180 days before Visit 1
* Subjects with underlying medical disorders with an anticipated life expectancy below 2 years (eg active cancer disease with localized and/or metastasized tumor mass)
* Subjects with a history of severe allergies or multiple drug allergies
* Subjects with hypersensitivity to the investigational drug or any of the excipients
* Subjects unable to perform a valid 6MWD test, eg subjects with a severe peripheral artery occlusive disease
* Subjects with a relative difference (ie absolute difference/mean) of more than 15% between the eligibility- and the baseline 6MWD test
* All types of pulmonary hypertension except subtypes of Updated Clinical Classification of pulmonary hypertension (PH) (Dana Point 2008) Group I specified in the inclusion criteria
* Moderate to severe obstructive lung disease (forced expiratory volume \<60% predicted). The predicted forced expiratory volume in 1 second (FEV1) is a calculated value
* Severe restrictive lung disease (total lung capacity \<70% predicted). The predicted total lung capacity (TLC) is a calculated value
* Severe congenital abnormalities of the lungs, thorax, and diaphragm
* Oxygen saturation (SaO2) \<88% despite supplemental oxygen therapy
* Arterial partial oxygen pressure (PaO2) \<55 mmHg despite supplemental oxygen therapy
* Arterial partial pressure of carbon dioxide (PaCO2) \>45 mmHg
* Uncontrolled arterial hypertension (SBP \>180 mmHg and /or diastolic blood pressure \>110 mmHg
* Atrial fibrillation within the last 90 days before Visit 1
* Pulmonary venous hypertension with pulmonary capillary wedge pressure 15 mmHg
* Hypertrophic obstructive cardiomyopathy
* Severe proven or suspected coronary artery disease
* Clinical evidence of symptomatic atherosclerotic disease
* Congenital or acquired valvular or myocardial disease if clinically significant apart from tricuspid valvular insufficiency due to pulmonary hypertension
* Clinical relevant hepatic dysfunction indicated by:

  * Bilirubin \>2 times upper limit normal (ULN)
  * and/or ALT (alanine aminotransferase) or AST (aspartate aminotransferase) \>3 times ULN
  * and/or signs of severe hepatic insufficiency (eg impaired albumin synthesis with an albumin \<32 g/L, hepatic encephalopathy \> grade 1
* Renal insufficiency (glomerular filtration rate \<30 mL/min, eg calculated based on the Cockcroft-Gault or Modification of Diet in Renal Disease (MDRD) formulas
D: Inclusion Criteria:

* Male and female patients with symptomatic pulmonary hypertension due to left ventricular diastolic dysfunction

Exclusion Criteria:

* Types of pulmonary hypertension other than group 2.2 of Dana Point Classification

Answer: A