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

NCT ID: NCT01934647

Last Updated: 2018-10-22

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1
• Total Enrollment: 7 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-11-22
• Study Completion Date: 2014-09-08

Brief 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).

Conditions

Pulmonary Arterial Hypertension

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

1 mg MK-8892

Participants will receive a single oral dose of 1 mg MK-8892.

Group Type: EXPERIMENTAL

MK-8892

Intervention Type: DRUG

Single oral capsule with 1 mg, 4 mg, or 8 mg of MK-8892

4 mg MK-8892

Participants will receive a single oral dose of 4 mg MK-8892.

Group Type: EXPERIMENTAL

MK-8892

Intervention Type: DRUG

Single oral capsule with 1 mg, 4 mg, or 8 mg of MK-8892

8 mg MK-8892

Participants will receive a single oral dose of 8 mg MK-8892.

Group Type: EXPERIMENTAL

MK-8892

Intervention Type: DRUG

Single oral capsule with 1 mg, 4 mg, or 8 mg of MK-8892

Interventions

MK-8892

Single oral capsule with 1 mg, 4 mg, or 8 mg of MK-8892

Intervention Type: DRUG

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Medical Director

Role: STUDY_DIRECTOR

Merck Sharp & Dohme LLC

Other Identifiers

2013-001680-23

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

MK-8892-003

Identifier Type: OTHER

Identifier Source: secondary_id

8892-003

Identifier Type: -

Identifier Source: org_study_id