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

• Status: Terminated
• Trial end date: 2014-09-08
• Target enrollment: 0
• Participant gender: All

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).

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Merck Sharp & Dohme Corp.

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