A Study of Single Doses of MK -5475 on Pulmonary Vascular Resistance (MK-5475-002)

This study of MK-5475 in participants with Group 1 pulmonary arterial hypertension (PAH) will assess the safety, tolerability and pharmacokinetics (PK) of inhaled MK-5475. There is no formal hypothesis to be tested.

In Part 1, one panel (Panel A) of up to 8 participants will dose in up to 3 dosing periods, with a minimum washout of 7 days between dosing periods. In each dosing period, 6 participants will receive MK-5475 and 2 will receive placebo, with 2 different participants receiving placebo in each of the dosing periods. Review of available safety data will occur prior to escalating to the next dose level.

Participants from Part 1 may continue into Part 2, which will assess safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of single-dose inhaled MK-5475. Three additional panels of participants (Panels B, C and D) will be enrolled into Part 2. Participants in Panel A will participate in 2 open-label dosing periods to assess PD measures associated with right heart catherization (RHC) \[Period 2\] and functional respiratory imaging (FRI) \[Period 3\]. Participants in Panels B, C, and D will participate in 3 dosing periods: Period 1 (open-label assessment of safety/tolerability and PK), Period 2 (FRI period) and Period 3 (RHC period).

Eligibility Criteria:
Inclusion Criteria:

* Be or have suspected Group 1 pulmonary hypertension as defined by the Nice 2013 Clinical Classification, including: idiopathic PAH, heritable PAH, drug- or toxin-induced PAH, or PAH associated with connective tissue disease or congenital heart disease
* Have a Body Mass Index (BMI) ≤35 kg/m2,
* Female participant is eligible to participate if she is not pregnant or breastfeeding, and at least one of the following conditions applies: She is a woman of nonchildbearing potential (WONCBP) or is a WOCBP and using a contraceptive method that is highly effective (with a failure rate of \<1% per year), with low user dependency or be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis)
* Male participants are eligible to participate if they agree to the following during the intervention period and for at least 14 days, corresponding to time needed to eliminate study intervention(s) after the last dose of study intervention: Be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis) and agree to remain abstinent or must agree to use contraception unless confirmed to be azoospermic (Vasectomized) or secondary to medical cause.
* Have a clinical indication for right heart catheterization (RHC) as part of initial work-up or ongoing medical management
* Panel A: Have history of RHC within 3 years of starting study medication demonstrating mean pulmonary artery pressure of ≥ 27 mmHg and pulmonary vascular resistance (PVR) of ≥ 300 dynes/sec/cm5
* Panels B/C/D: Have history of RHC within 3 years of starting study medication demonstrating mean pulmonary artery pressure of ≥ 27 mmHg and PVR of ≥ 300 dynes/sec/cm5 OR have an echocardiogram performed by the investigator at screening or within 1 year of screening demonstrating pulmonary artery systolic pressure ≥ 50 mmHg in conjunction with 1 or more of the following: tricuspid regurgitation velocity \> 3.0 m/s and or significant right heart enlargement and or reduced right heart function.

Exclusion Criteria:

* Has pulmonary hypertension subtypes including the following according to Nice 2013 Clinical Classification: human immunodeficiency (HIV) infection, portal hypertension, schistosomiasis, chronic hemolytic anemia, pulmonary veno-occlusive disease (PVOD) and or pulmonary capillary hemangiomatosis (PCH), persistent pulmonary hypertension of the newborn (PPHN), pulmonary hypertension owing to left heart diseases, left ventricular systolic dysfunction, left ventricular diastolic dysfunction, valvular disease, congenital/acquired left heart inflow/outflow tract obstruction and congenital cardiomyopathies, pulmonary hypertension owing to lung diseases and/or hypoxia, Chronic obstructive pulmonary disease, Interstitial lung disease, other pulmonary diseases with mixed restrictive and obstructive pattern, sleep-disordered breathing, alveolar hypoventilation disorders, chronic exposure to high altitude, developmental abnormalities, pulmonary hypertension defined as chronic thromboembolic pulmonary hypertension \[CTEPH\]), pulmonary hypertension with unclear multifactorial mechanisms, hematologic disorders: chronic hemolytic anemia, myeloproliferative disorders, splenectomy, systemic disorders: sarcoidosis, pulmonary Langerhans cell histiocytosis, lymphangioleiomyomatosis, neurofibromatosis, vasculitis, metabolic disorders: glycogen storage disease, Gaucher disease, thyroid disorders, others: tumoral obstruction, fibrosing mediastinitis, chronic renal failure, segmental pulmonary hypertension
* Has a history of clinically significant endocrine (not including stable diabetes mellitus), gastrointestinal, cardiovascular, hematological, hepatic (not including chronic stable Hepatitis B and Hepatitis C), immunological, renal, respiratory, genitourinary, or major neurological (including stroke and chronic seizures) abnormalities or diseases
* Is mentally or legally incapacitated, has significant emotional problems
* History of cancer (malignancy) except nonmelanomatous skin carcinoma or carcinoma in situ of the cervix or other malignancies which have been successfully treated 10 years prior to screening
* History of significant multiple and/or severe allergies
* Known hypersensitivity to iodine or iodine containing products
* Positive for HIV
* Had major surgery, donated or lost 1 unit of blood (approximately 500 mL) within 4 weeks of screening
* Has persistent or permanent atrial fibrillation with an uncontrolled ventricular rate
* Has significantly impaired gas exchange
* Has an active respiratory infection (e.g. common cold, bronchitis, influenza, pneumonia) with lung function outside of the normal range
* Is currently on monotherapy calcium channel blockers as a specific treatment for pulmonary hypertension
* Has taken nitrates within 24 hours of anticipated dosing
* Has taken inhaled prostacyclin within 24 hours of anticipated dosing (iloprost or treprostinil)
* Has taken diltiazem immediate release taken within 24 hours or extended release taken within 48 hours of anticipated dosing
* Has taken sildenafil or vardenafil within 24 hours or tadalafil within 7 days of anticipated dosing
* Has taken soluble guanylate cyclase (sGC) activator for PAH within 24 hours of anticipated dosing
* Is unable to refrain from or anticipates the use of any medication, including prescription and nonprescription drugs or herbal remedies beginning approximately 2 weeks (or 5 half-lives) prior to administration of the initial dose of study drug, throughout the study (including washout intervals between treatment periods), until the poststudy visit
* Has participated in another investigational study within 4 weeks
* Does not agree to follow the smoking restrictions
* Part 2 only: Suffers from claustrophobia and would be unable to undergo computerized tomography (CT) scan
* Part 2 only: Has participated in a positron-emission tomography (PET) research study or other study involving administration of a radioactive substance or ionizing radiation within 12 months prior to the screening visit, or has undergone or plans to have extensive radiological examination within this period
* Consumes greater than 3 glasses of alcoholic beverages (1 glass is approximately equivalent to: beer \[354 mL/12 ounces\], wine \[118 mL/4 ounces\], or distilled spirits \[29.5 mL/1 ounce\]) per day
* Consumes excessive amounts, defined as greater than 6 servings (1 serving is approximately equivalent to 120 mg of caffeine) of coffee, tea, cola, energy drinks, or other caffeinated beverages per day
* Is a regular user of cannabis, any illicit drugs or has a history of drug (including alcohol) abuse within approximately 12 months. Participants must have a negative urine drug screen (UDS) prior to randomization