Table 1.

Endpoints for the main study objectives for ELEVATE 2

Endpoints for the primary objective
Percent change from baseline to 24 weeks of pulmonary vascular resistance between an active cohort and the placebo arm
Endpoints for the Secondary Objectives
Change from baseline in World Health Organization Functional Class Change from baseline in the 6‐min walk distance Change from baseline in N‐terminal probrain natriuretic peptide Change in safety parameters including adverse events, vital signs, laboratory values, and electrocardiogram assessments Change from baseline in cardiac index, mean pulmonary artery pressure, mean right atrial pressure, mixed venous oxygen saturation, and pulmonary artery compliance Time to clinical worsening defined as the first occurrence of a composite endpoint of: 1. Death from any cause, OR 2. Hospitalization for worsening pulmonary arterial hypertension (any hospitalization for worsening PAH, lung or heart transplantation, atrial septostomy, or initiation of parenteral prostanoid therapy), OR 3. Disease progression defined as a decrease of more than 15% from baseline in the 6‐min walk distance combined with World Health Organization Functional Class III or IV symptoms at two consecutive visits separated by at least 14 days (adjudicated) Death from any cause Change from baseline in right atrial size and right ventricle function (tricuspid annular plane systolic excursion, tricuspid annular systolic velocity, and right ventricle fractional area change) Change from baseline in Pulmonary Arterial Hypertension‐Symptoms and Impact (PAH‐SYMPACT®) Questionnaire Change from baseline in Register to Evaluate Early and Long‐Term Pulmonary Arterial Hypertension Disease Management Lite 2 score Population pharmacokinetic parameters of rodatristat ethyl, and its active metabolite rodatristat Change from baseline in 5‐hydroxyindoleacetic acid (plasma and spot‐urine concentrations and creatinine‐corrected urinary 5‐hydroxyindoleacetic acid)
Endpoints for the exploratory objectives
Time to clinical improvement defined as a >10% increase in the 6‐min walk distance or 30 m and an improvement to or maintenance of World Health Organization Functional Class II symptomatology, in the absence of a deterioration in clinical condition or death during the 24 weeks of the Main Study Change from baseline in actual daily activity (counts/minute) as determined by actigraphy: o Light to vigorous activity/day o Moderate to vigorous activity/day o Total movement/day o Best 6‐min walk effort Plasma selexipag and its active metabolite, ACT‐333679 trough concentrations at baseline and Week 4 for patients receiving selexipag as part of background therapy