A Study of the Efficacy and Safety of Frespaciguat (MK-5475) in Participants With Pulmonary Arterial Hypertension (INSIGNIA-PAH: Phase 2/3 Study of an Inhaled sGC Stimulator in PAH) (MK-5475-007)

Exclusion Criteria

• •Group 2 to 5 pulmonary hypertension.
• •PAH in one of the following groups:
• •* Long term responders to calcium channel blockers
• •* Overt features of venous/capillary involvement
• •Evidence of more-than-mild obstructive lung disease.
• •Evidence of more-than-mild parenchymal lung disease.
• •Evidence of more-than-mild obstructive sleep apnea (OSA) that is untreated.
• •Evidence or history of left heart disease, including any of the following:
• •* Left ventricular ejection fraction (LVEF) ≤45%
• •* Moderate or severe left-sided valvular disease (aortic or mitral valve stenosis or regurgitation)
• •* Significant left ventricular diastolic dysfunction on echocardiographic evaluation
• •Presence of 3 or more of the following risk factors for heart failure with preserved ejection fraction: BMI\>30 kg/m², essential systemic hypertension, diabetes mellitus of any type, or coronary artery disease.
• •Oxygen saturation measured by pulse oximetry (SpO₂) \<90%, despite supplemental oxygen therapy.
• •Chronic renal insufficiency (eGFR \<30 mL/min)
• •Chronic liver disease (i.e., Child-Pugh B or C), portal hypertension, cirrhosis, or significant hepatic laboratory abnormalities.
• •Current smoker or currently uses electronic cigarettes (vapes).
• •History of cancer, except: nonmelanomatous skin carcinoma or carcinoma in situ of the cervix or other malignancies which have been successfully treated, with appropriate follow up, and unlikely to recur for the duration of the study.