A Phase 2/3, Multicenter, Randomized, Double-blind, Placebo-Controlled, Adaptive Design Study to Evaluate the Efficacy and Safety of MK-5475 in Adults With Pulmonary Arterial Hypertension

  • End date
    Oct 29, 2026
  • participants needed
  • sponsor
    Merck Sharp & Dohme LLC
Updated on 20 October 2022
body mass index
heart disease
pulmonary arterial hypertension
right heart catheterization
left ventricular end-diastolic pressure


This is a two-part (Phase 2/Phase 3) study of MK-5475, an inhaled soluble guanylate cyclase stimulator, in participants with pulmonary arterial hypertension (PAH).

The first part (Phase 2) will assess three different doses of MK-5475 compared to placebo in a base period of 12 weeks, followed by comparison of three different doses of MK-5475 during an optional 24 month extension period. The treatment dose with the best efficacy and safety profile in the phase 2 cohort base period will be selected for use in the second part (Phase 3) of the study. The primary hypothesis of Phase 2 is that at least one MK-5475 dose is superior to placebo in reducing pulmonary vascular resistance (PVR) from baseline at week 12.

The purpose of the second part (Phase 3) of the study is to confirm the efficacy, safety, and tolerability of MK-5475 at the selected dose compared to placebo during a 12 week base period followed by an extension period of up to 5 years. The primary hypothesis of Phase 3 is that MK-5475 is superior to placebo in increasing 6-minute walk distance (6MWD) from baseline at week 12.

Condition Pulmonary Arterial Hypertension, Hypertension, Pulmonary
Treatment MK-5475, Placebo to MK-5475
Clinical Study IdentifierNCT04732221
SponsorMerck Sharp & Dohme LLC
Last Modified on20 October 2022


Yes No Not Sure

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 congenital heart 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 diastolic pressure (LVEDP) ≤15 mmHg
World Health Organization functional class (WHO-FC) symptoms between Class II and IV
Two 6-Minute walk distance (6MWD) measurements between 150 and 500 meters, one at screening 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 the intervention period and for at least 14 days after the last dose of study intervention
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 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
Chronic renal insufficiency (eGFR <30 mL/min)
mellitus of any type, or coronary artery disease
Chronic liver disease (i.e., Child-Pugh B or C), portal hypertension, cirrhosis, or significant hepatic laboratory abnormalities
Oxygen saturation measured by pulse oximetry (SpO₂) <90%, despite supplemental oxygen therapy
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
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