A Study of Selexipag Assessing Right Ventricular Remodeling in Pulmonary Arterial Hypertension by Cardiac Magnetic Resonance Imaging

Change from baseline to Week 26 in RVEDV assessed by MRI was reported.

Change from baseline to Week 26 in RVESV assessed by MRI was reported.

Change from baseline to Week 26 in RVEF assessed by MRI was reported. RVEF was the fraction of the end-diastolic volume (EDV) that is ejected out of right ventricle with each contraction. EDV is the volume of blood within a ventricle immediately before a contraction.

Change from baseline to Week 26 in RV mass index assessed by MRI was reported.

Change in RVGLS was a measure of longitudinal percent change in length of endocardium at Week 26 from baseline length assessed by MRI.

WHO functional classification for PAH ranged from Class I (no limitation in physical activity, ordinary physical activity does not cause undue dyspnea or fatigue, chest pain or near syncope), Class II (slight limitation of physical activity, ordinary physical activity cause undue dyspnea or fatigue, chest pain or near syncope), Class III (marked limitation of physical activity, less than ordinary activity cause undue dyspnea or fatigue, chest pain or near syncope) and Class IV (cannot perform a physical activity without any symptoms, dyspnea and/or fatigue may even be present at rest). Change from baseline in WHO functional class was classified into "Improved", "No change" and "Worsened". Improvement =reduction in functional class; worsened =increase in functional class; and no change = no change in functional class.

NT pro-BNP is a cardiac biomarker that is released in the blood in response to changes in the pressure inside of the heart. Levels go up when heart failure develops or gets worse, and levels go down when heart failure is stable or improves. This biomarker helps to measure the changes in the severity of heart failure over time in response to therapy.

6MWD was the distance that a participant could walk in 6 minutes. Participants were asked to perform the test at a pace that was comfortable to them, with as many breaks as they needed.

An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Serious adverse event (SAE) was any untoward medical occurrence that at any dose resulted in death, was life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, was a suspected transmission of any infectious agent via a medicinal product. Any AE occurring at or after the initial administration of study intervention up to 3 days after last dose of study intervention was considered as treatment-emergent.

Number of participants with AEs leading to premature discontinuation of study drug were reported. An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship.

Number of participants with AESI were reported. An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. AESI were anaemia, bleeding events, gastrointestinal disturbances denoting intestinal intussusception (manifested as ileus or obstruction), hyperthyroidism, hypotension, light-dependent non-melanoma skin malignancies, major adverse cardiovascular events (MACE), medication errors, ophthalmological effects associated to retinal vascular system, pregnancy, pulmonary venoocclusive disease associated with pulmonary oedema, renal function impairment / acute renal failure.

Number of participants with treatment-emergent marked laboratory abnormalities in alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, total bilirubin, creatinine, sodium, potassium, hemoglobin, hematocrit; EVF; PCV (male), hematocrit; EVF; PCV (female), platelets (assuming no platelet cluster), leukocytes; white blood cells, Neutrophils (Abs), Eosinophils (Abs), lymphocytes (Abs) were reported. Abnormalities that occurred after study treatment start and up to 3 days after study treatment discontinuation, that were not present at baseline, were treatment-emergent. Treatment-emergent marked laboratory abnormalities were determined at the investigator's discretion.

The risk score is derived for each participant considering the following non-invasive low-risk criteria among the 8 variables: absence of clinical signs of right heart failure, absence of symptoms progression, absence of syncope, WHO FC I-II, 6MWD greater than (>) 440 meter, NT-proBNP less than (<) 300 ng/L, Right atrial (RA) area <18 centimeter square (cm^2) as determined by echocardiography (Echo), absence of pericardial effusion, as determined by Echo. Number of low-risk criteria at baseline and Week 26 constitutes risk score and were derived for each participant by adding '1' for each of above criteria met. Number of low-risk criteria among the 8 variables for each participant can vary from 0 (worse participants) to 8 (healthier participants). Higher score indicated healthier participants.

The risk score is derived for each participant considering the following non-invasive low-risk criteria among the 3 variables: WHO FC I-II, 6MWD >440 m, NT-proBNP < 300 ng/L. Number of low-risk criteria at baseline and Week 26 constitutes risk score and were derived for each participant by adding '1' for each of above criteria met. Number of low-risk criteria among the 3 variables for each participant can vary from 0 (worse participants) to 3 (healthier participants). Higher score indicated healthier participants.