Please select the eligibility criteria that correspond to the clinical trial below.
Title: ARTEMIS-IPF: A Phase 3, Randomized, Double-Blind, Placebo-Controlled, Multi-Center, Parallel-Group, Event Driven Study to Evaluate the Efficacy and Safety of Ambrisentan in Subjects With Early Idiopathic Pulmonary Fibrosis (IPF)
Brief Summary: The ARTEMIS-IPF study was conducted to determine if ambrisentan was effective in delaying disease progression and death in participants with idiopathic pulmonary fibrosis (IPF), to evaluate its safety, and to evaluate its effect on development of pulmonary hypertension, quality of life, and dyspnea (shortness of breath) symptoms in this participant population. Participants were randomized in a 2:1 ratio to receive ambrisentan or placebo, respectively. Participation in the study was to be up to 4 years, depending on how long it would take to enroll participants and observe study events. After randomization, visits to the clinic took place every 3 months, and laboratory procedures were performed every month.


Options:
A: * INCLUSION CRITERIA
* Completion of the 16-week treatment period in the double-blind ASSET study
* Women of childbearing potential must have a negative result on their serum pregnancy test and use reliable methods of contraception during study treatment and for 3 months after study treatment termination.

Reliable methods of contraception are:

1. Barrier type devices (e.g., female condom, diaphragm, contraceptive sponge) only in combination with a spermicide.
2. Intra-uterine devices.
3. Oral, injectable, transdermal or implantable contraceptives only in combination with a barrier method.

Hormone-based contraceptives alone, regardless of the route of administration, are not considered to be reliable methods of contraception.

Abstention, rhythm method, and contraception by the partner alone are not acceptable methods of contraception.

Women not of childbearing potential are defined as prepubescent, postmenopausal (i.e., amenorrhea for at least 1 year), or surgically or naturally sterile.

Signed written informed consent is obtained from the patient or patient's parent/ legal representative prior to initiation of any study-related procedure.

EXCLUSION CRITERIA

All patients (Groups A and B):

1. Any major protocol violation in the preceding double-blind ASSET study\*.
2. Hemoglobin concentration less than 6.0 g/dL.
3. Pregnancy or breast-feeding.

   \* Protocol violations will be reviewed by the monitor during site visits and discussed with the study staff on an ongoing basis and at the patient's completion of the double-blind study.

   Group B only:
4. Acute liver disease.
5. Newly diagnosed cirrhosis or portal hypertension.
6. ALT greater than or equal to 3 times ULN and/or albumin greater than 20% below LLN.
7. Newly diagnosed psychotic, addictive or other disorder limiting the ability to provide informed consent or to comply with study requirements.
B: Inclusion Criteria:

* Between 18 and 60 years of age inclusive, at the time of signing the informed consent.
* Healthy as determined by a responsible and experienced physician, based on a medical evaluation including medical history, physical examination, laboratory tests, vital signs and cardiac monitoring (ECG and 24 hour Holter). A subject with a clinical abnormality or laboratory parameter(s) which is/are not specifically listed in the inclusion or exclusion criteria, outside the reference range for the population being studied may be included only if the Investigator, in consultation with Medical Monitor if required, judges and documents that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures.
* Body weight \>= 50 Kilogram (kg) (110 pounds \[lbs\]) for men and \>= 45 kg (99lbs) for women and body mass index (BMI) within the range 18 - 30 kg per square metre (m\^2) (inclusive)
* Male or Female. Female with non-reproductive potential defined as, Pre-menopausal females with one of the following: Documented tubal ligation or Documented hysteroscopic tubal occlusion procedure with follow-up confirmation of bilateral tubal occlusion or Hysterectomy or Documented Bilateral Oophorectomy, Documented Postmenopausal defined as 12 months of spontaneous amenorrhea
* Capable of giving signed informed consent.

Exclusion Criteria:

* A blood pressure \<100/55 millimetre of Mercury (mm Hg).
* Haemoglobin (Hb) below normal range: Hb \<133 (gram per litre) g/L for males and Hb \<114 g/L for females
* Alanine amino transferase (ALT) and bilirubin \>1.5 x upper limit of normal (ULN) (isolated bilirubin \>1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin is \<35 percentage \[%\]).
* Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones)
* Corrected QT (QTc) \>450 milliseconds (msec). The QTc is the QT interval corrected for heart rate according to Bazett's formula (QTcB), Fridericia's formula (QTcF), and/or another method, machine-read or manually over-read.
* Use of prescription or non-prescription drugs, including vitamins, herbal and dietary supplements (including St John's Wort) within 7 days (or 14 days if the drug is a potential enzyme inducer) or 5 half-lives (whichever is longer) prior to the first dose of study medication, unless in the opinion of the Investigator and Medical Monitor the medication will not interfere with the study procedures or compromise subject safety.
* History of regular alcohol consumption within 6 months of the study defined as: An average weekly intake of \>21 units for males or \>14 units for females. One unit is equivalent to 8 gram (g) of alcohol: a half-pint (\~240 millilitre \[mL\]) of beer, 1 glass (125 mL) of wine or 1 (25 mL) measure of spirits.
* Smoking more than 5 cigarettes per week and subjects must be able to abstain from smoking for a 24 hour period prior to dose and any time whilst in the clinical unit.
* History of sensitivity to any of the study medications, or components thereof or a history of drug or other allergy that, in the opinion of the Investigator or Medical Monitor, contraindicates their participation.
* Presence of hepatitis B surface antigen (HBsAg), positive hepatitis C antibody test result at Screening or within 3 months prior to first dose of study treatment.
* A positive test for human immuno-deficiency virus (HIV) antibody
* A positive pre-study drug/alcohol screen.
* Where participation in the study would result in donation of blood or blood products in excess of 500 mL within previous 3 months
* The subject has participated in a clinical trial and has received an investigational product within the following time period prior to the first dosing day in the current study: 3 months, 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is longer).
* Exposure to more than four new chemical entities within 12 months prior to the first dosing day.
C: Inclusion Criteria:

* Male or females from 40 to 80 years of age
* Diagnosis of IPF
* Honeycombing (fibrosis in the lung) on high-resolution computerised tomography (HRCT) scan of less than or equal to 5%
* Willing and able to have 2 right heart catheterizations performed
* Willing to have monthly lab tests to monitor liver function
* Able to perform the 6 minute walk test (indicated adequate physical function)
* Must have meet lung function requirements
* Normal liver function tests
* Negative serum pregnancy test
* Willing to use at least 2 reliable methods of contraception
* Able to understand and willing to sign informed consent form

Exclusion Criteria:

* No restrictive lung disease (other than usual interstitial pneumonia or IPF)
* No obstructive lung disease
* No recent or active respiratory exacerbations
* No recent hospitalization for an IPF exacerbation
* No recent history of alcohol abuse
* Chronic sildenafil (or same drug class) use for pulmonary hypertension
* Chronic treatment with certain medications for IPF within 30 days of randomization
* No other serious medical conditions
D: Inclusion Criteria:

1. mPAP 21-24 mmHg, TPG \> 11mmHg, PAWP \<15 mmHg and/or
2. Exercise induced elevated mPAP-values \>30 mmHg, PAWP \<18 mmHg; TPG \>15 mmHg, as defined in Saggar et al. (2012) without left heart or severe lung disease or systemic arterial hypertension
3. Adult patients having completed his/her 18th birthday
4. Patients with definite diagnosis of Systemic Sclerosis using the scleroderma criteria of the American Rheumatism Association
5. SSc-disease duration \>3 years
6. Able to understand and willing to sign the Informed Consent Form
7. Negative pregnancy test at the start of the trial and appropriate contraception throughout the study for women with child-bearing potential.

Exclusion Criteria:

1. Any connective tissue diseases (CTD) other than SSc
2. Pulmonary hypertension (PH) confirmed by right heart catheter (RHC) before enrolment, i.e. mPAP ≥25 mmHg at rest
3. Patients presenting normal mPAP values, that is mPAP\<21 mmHg at rest, ≤30 mmHg during exercise, PAWP \>=15 mmHg at rest or \<=18 mmHg during exercise
4. Ongoing or a history of \>2 weeks of continued use of therapies that are considered definitive PH treatment: endothelin receptor antagonists (ERA; e.g. bosentan, ambrisentan), phosphodiesterase type 5 inhibitors (PDE5; e.g. sildenafil, tadalafil, vardenafil), prostanoids (e.g. epoprostenol, treprostinil, iloprost, beraprost) and soluble guanylate cyclase stimulator (e.g. Riociguat). Intermittent use of PDE5 inhibitors for male erectile dysfunction is permitted.
5. Except for diuretics and corticosteroids medical treatment should not be expected to change 4 weeks prior inclusion into the study and during the entire 12-week study period.
6. Known intolerance to ambrisentan or one of its excipients
7. Clinically significant anemia (hemoglobin concentration of less than 75% of the lower limit of normal, LLN)
8. Forced vital capacity (FVC) \<60%, forced expiratory volume in first second (FEV1) \<65%
9. Severe interstitial lung disease, idiopathic pulmonary fibrosis
10. Renal insufficiency (glomerular filtration rate \[GFR\] \<60 mL/min/1.73m2 for at least 3 months)
11. Baseline values of hepatic aminotransferases (ALT and/or AST) \>3 x upper limit of normal (ULN)
12. Systolic blood pressure \<85 mmHg;
13. evidence of inadequately treated blood pressure \>160/90 mmHg and/or blood pressure during exercise \>220/120 mmHg
14. Patients referred with clinically significant overt heart failure
15. Clinically significant fluid retention
16. Previous evidence or diagnosis of clinically relevant left heart disease, i.e. at least one of the following: Previous echocardiography with estimated left ventricular (LV) ejection fraction \<50%, previous history of cardiogenic pulmonary edema, increased size of left atrium (\>50 mm)
17. Known significant diastolic dysfunction associated with clinical heart failure
18. Known coronary disease or significant valvular heart disease
19. Known congenital heart defects such as single ventricle, transposition, Eisenmenger
20. Known hypertrophic cardiomyopathy or left ventricular hypertrophy (interventricular septum thickness (IVS) or posterior wall thickness (PWD) \>1.2 cm)
21. Participation in any clinical drug trial within 4 weeks prior to screening of this study and/or who is scheduled to receive another investigational medicinal product (IMP) during the course of this study
22. Pregnancy or lactation

Answer: C