Acute Dosing of MK-8892 in Participants With Pulmonary Arterial Hypertension (PAH) (MK-8892-003)
Condition: Pulmonary Arterial Hypertension
MeSH terms: Pulmonary Arterial Hypertension; Familial Primary Pulmonary Hypertension; Hypertension
Intervention: MK-8892
Intervention description: Single oral capsule with 1 mg, 4 mg, or 8 mg of MK-8892
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 7.0
Sex: All
Minimum age: 18 Years
Maximum age: 70 Years
Healthy volunteers: No

Summary:

      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).
    

Eligibility criteria:

        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