acute dosing of mk-8892 in participants with pulmonary arterial hypertension (pah) (mk-8892-003)

Conditions: Pulmonary Arterial Hypertension

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) \ 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