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

Inclusion Criteria:

• Pulmonary arterial hypertension (PAH) in one of the following groups:

• Idiopathic PAH

• Heritable PAH

• Drug and toxin-induced PAH

• PAH associated with connective tissue disease, HIV infection, or congenitalheart disease.

• Diagnosis of PAH documented by right heart catheterization (RHC).

• Eligibility RHC meeting all of the following criteria:

• Mean pulmonary artery pressure (mPAP) ≥25 mmHg

• Pulmonary vascular resistance (PVR) of ≥3 Wood units

• Pulmonary capillary wedge pressure (PCWP) or left ventricular end diastolicpressure (LVEDP) ≤15 mmHg.

• World Health Organization functional class (WHO-FC) symptoms between Class II andIV.

• Two 6-Minute walk distance (6MWD) measurements between 150 and 500 meters, one atscreening and one at randomization.

• Stable concomitant background PAH-specific therapy.

• Body Mass Index (BMI) between 18.5 kg/m² and 40 kg/m² .

• Agree to be abstinent from heterosexual intercourse or use contraception during theintervention period and for at least 14 days after the last dose of studyintervention.

• Female participants may not be pregnant or breastfeeding.

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 stenosisor regurgitation)

• Significant left ventricular diastolic dysfunction on echocardiographicevaluation

• Presence of 3 or more of the following risk factors for heart failure with preservedejection fraction: BMI>30 kg/m², essential systemic hypertension, diabetes mellitusof any type, or coronary artery disease.

• Oxygen saturation measured by pulse oximetry (SpO₂) <90%, despite supplementaloxygen therapy.

• Chronic renal insufficiency (eGFR <30 mL/min)

• Chronic liver disease (i.e., Child-Pugh B or C), portal hypertension, cirrhosis, orsignificant hepatic laboratory abnormalities.

• Current smoker or currently uses electronic cigarettes (vapes).

• History of cancer, except: nonmelanomatous skin carcinoma or carcinoma in situ ofthe cervix or other malignancies which have been successfully treated, withappropriate follow up, and unlikely to recur for the duration of the study.