Acute Dosing of MK-8892 in Participants With Pulmonary Arterial Hypertension (PAH) (MK-8892-003)

Study Overview
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Brief Summary
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This clinical trial will study the safety, tolerability, and pharmacodynamics of single doses of MK-8892 in participants with pulmonary arterial hypertension (PAH). The primary objective is to estimate the measured peak effect of the highest acutely tolerated (HAT) single oral dose of MK-8892 on pulmonary vascular resistance (PVR).

Official Title
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A Non-randomized, Single-Panel, Open-Label Trial to Study the Safety, Tolerability and Pharmacodynamics of MK-8892 Acute Dosing in Subjects With Moderate to Severe Pulmonary Arterial Hypertension

Conditions
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Pulmonary Arterial Hypertension

Intervention / Treatment
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* Drug: MK-8892


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: postmenopausal female or if female of reproductive potential, remains abstinent or uses two acceptable methods of birth control during 14 days after dosing with MK-8892 has suspected PAH classified in one of the following sub-groups: idiopathic, heritable, drug- or toxin-induced, or associated with connective tissue disease, as defined by the Dana Point 2008 Clinical Classification has a clinical indication for right heart catheterization PAH classified as World Health Organization (WHO) functional class II or III Exclusion Criteria: has a medical history indicating a secondary cause of Pulmonary Hypertension (PH) or a non-included etiology of PAH including the following tests within 6 months of Visit 1: Echo indicating significant left heart disease, valvular disease, or structural defects; function test indicating significant pulmonary disease; imaging test indicating veno-occlusive disease; perfusion scan indicating thromboembolic disease; abdominal ultrasound indicating cirrhosis; positive test for human immunodeficiency virus (HIV) has persistent or permanent atrial fibrillation, significantly impaired gas exchange, history of radiation of the lung or mediastinum, hepatic or hepatobiliary disease, immunodeficiencies or latent bleeding risk has estimated Glomerular Filtration Rate (GFR) <45 mL/min has alanine aminotransferase test (ALT) serum glutamic pyruvic transaminase (SGPT) or aspartate aminotransferase test (AST) serum glutamic oxaloacetic transaminase (SGOT) >= 3 x upper limit of normal (ULN) at Visit 1 has a systolic blood pressure (BP) <105 mmHg, or heart rate (HR) > 100 beats/min at Visit 1 (Day -7 to -1) has previously received specific therapy for PAH within 4 weeks prior to Visit 1 has taken sildenafil, valdenafil or a nitrate within 24 hours prior to Visit 2 date has taken tadalafil within 7 days prior to Visit 2 date has taken 2 or more specific PAH medications concomitantly within 4 weeks of anticipated Visit 2 date. Only treatment naïve subjects or subjects on stable PAH-specific monotherapy with an endothelin receptor antagonist ([ERA]; bosentan, ambrisentan, or macitentan) or a prostacyclin analog ([PCA]; treprostinil, epoprostenol, or iloprost) are eligible. PAH monotherapy with one of these medications may continue without interruption during this study has taken a soluble guanylate cyclase (sGC) activator (riociguat) within 24 hours of anticipated Visit 2 date. has taken diltiazem immediate release within 1 day or diltiazem extended release within 2 days prior to Visit 2 date is currently taking potent inhibitors or inducers of Cytochrome P450 3A4 (CYPA4), or is consuming >1 liter of grapefruit juice per day is pregnant or breastfeeding or expecting to conceive during study or post study follow-up period has donated 500 mL of blood within prior 60 days is currently participating in or has within the prior three months participated in a study with an investigational compound or device

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1 mg MK-8892<br>Participants will receive a single oral dose of 1 mg MK-8892. | Drug: MK-8892<br>* Single oral capsule with 1 mg, 4 mg, or 8 mg of MK-8892<br>|
| Experimental: 4 mg MK-8892<br>Participants will receive a single oral dose of 4 mg MK-8892. | Drug: MK-8892<br>* Single oral capsule with 1 mg, 4 mg, or 8 mg of MK-8892<br>|
| Experimental: 8 mg MK-8892<br>Participants will receive a single oral dose of 8 mg MK-8892. | Drug: MK-8892<br>* Single oral capsule with 1 mg, 4 mg, or 8 mg of MK-8892<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Peak Percent Change From Baseline in Pulmonary Vascular Resistance (PVR) at the Highest Acutely Tolerated (HAT) Dose of MK-8892 | PVR assessments were performed throughout the right heart catheterization (RHC). Peak PVR reduction was determined to occur if 2 consecutive PVR measurements were at least 20% greater than the nadir PVR measurement. | Baseline and up to 5 hours post-dose |