A Multiple Dose Titration Study of MK-8892 in Participants With Pulmonary Hypertension and Left Heart Disease (MK-8892-007)

This study will assess multiple doses of MK-8892 administered to participants with pulmonary hypertension "out of proportion" (PHOOP) and heart failure with reduced left ventricular ejection fraction (rEF). It is hypothesized that generally safe and well tolerated multiple doses of MK-8892 will achieve a true reduction from baseline in pulmonary vascular resistance (PVR) greater than 12%.

Sixteen participants with PHOOP/rEF were to receive multiple doses of MK-8892 titrated to the highest tolerated dose for each participant (up to 4 mg daily), and to undergo evaluation for safety and systemic hemodynamics and cardiac function. Only 4 participants were enrolled and completed the study due to a strategic business decision by the sponsor to terminate the clinical conduct of all MK-8892 ongoing trials including this trial.


Eligibility Criteria:
Inclusion Criteria:

* Pulmonary hypertension (out of proportion, PHOOP) and heart failure with reduced left ventricular ejection fraction (PHOOP/rEF)
* If female, cannot be pregnant or breastfeeding. Females of reproductive potential must agree to agree to use (and/or have their partner use) two (2) acceptable methods of birth control throughout the study and until 2 weeks after the last dose of study drug is administered
* Body mass index (BMI) \<=35 kg/m\^2 and and \<=18 kg/m\^2
* Has World Health Organization (WHO) Group 2 pulmonary hypertension (PAH)
* Stable heart failure on optimal medical therapy with no hospitalizations for congestion due to heart failure within the previous 3 months

Exclusion Criteria:

* Primary pulmonary arterial hypertension or veno-occlusive disease (WHO Group 1), or pulmonary hypertension secondary to other causes (WHO Groups 3 -5) including but not limited to autoimmune disease, connective tissue disease, and Eisenmenger syndrome
* Currently treatment with or anticipates use of nitrate, phosphodiesterase type 5 (PDE5) inhibitor, or medications known to induce or inhibit cytochrome P450 3A4 (CYP3A4) metabolism, and cannot be transitioned off of this therapy for \>=7 days prior to dosing and through completion of this study
* Symptoms of coronary artery disease requiring therapy with nitrates, within the past 3 months
* Severe aortic or mitral stenosis, or severe aortic, mitral, or tricuspid insufficiency.
* Significant carotid artery disease
* Restrictive, infiltrative (e.g., amyloidosis) or hypertrophic cardiomyopathy
* Mentally or legally institutionalized or incapacitated, has significant emotional problems at the time of pre study (screening) visit or expected during the conduct of the study or has a history of a clinically significant psychiatric disorder over the last 5 years. Subjects who have had situational depression may be enrolled in the study at the discretion of the investigator.
* History of stroke, chronic seizures, or major neurological disorder
* History of clinically significant endocrine (not including diabetes mellitus), gastrointestinal, hematological, hepatic (not including chronic Hepatitis C), immunological (not including chronic human immunodeficiency virus \[HIV\]), respiratory, or genitourinary abnormalities or diseases. Participants with a history of childhood asthma may be enrolled in the study at the discretion of the investigator. Participants with controlled hypertension are allowed to be enrolled.
* Unable to refrain from or anticipates the use of any medication, including prescription and non-prescription drugs or herbal remedies (such as St. John's Wort \[hypericum perforatum\]) beginning approximately 2 weeks (or 5 half-lives) prior to administration of the dose of study drug, throughout the study (including washout intervals between treatment periods), until the post study visit. There may be certain medications that will be permitted.
* Consumes excessive amounts of alcohol, defined as greater than 5 glasses of alcoholic beverages (1 glass is approximately equivalent to: beer \[284 mL/10 ounces\], wine \[125 mL/4 ounces\], or distilled spirits \[25 mL/1 ounce\]) per day
* Major surgery or donated blood within 8 weeks prior to the pre study (screening) visit
* Participated in another investigational study within 4 weeks prior to the pre study (screening) visit
* History of significant multiple and/or severe allergies (including latex allergy), or has had an anaphylactic reaction or significant intolerability to prescription or nonprescription drugs or food
* Uses illicit drugs or has a history of drug (including alcohol) abuse within the past 6 months