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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01934647
Recruitment Status : Terminated
First Posted : September 4, 2013
Last Update Posted : January 25, 2016
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.

Brief Summary:
This clinical trial will study the safety, tolerability, and pharmacodynamics of single doses of MK-8892 in participants with 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).

Condition or disease Intervention/treatment Phase
Pulmonary Arterial Hypertension Drug: MK-8892 Phase 1

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 20 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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
Study Start Date : November 2013
Actual Primary Completion Date : September 2014
Actual Study Completion Date : September 2014

Arm Intervention/treatment
Experimental: Dose Escalation
MK-8892 doses starting at 1 mg, are sequentially escalated, stopping at the HAT dose or a maximum of 14 mg.
Drug: MK-8892
Single oral capsule with up to 14 mg of MK-8892
Experimental: HAT Dose
Dose of MK-8892 that is highest acutely tolerated or a maximum of 14 mg.
Drug: MK-8892
Single oral capsule with up to 14 mg of MK-8892

Primary Outcome Measures :
  1. Peak percent reduction from baseline in PVR at the HAT single oral dose of MK-8892 [ Time Frame: Baseline and up to 5 hours post-dose ]

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

Ages Eligible for Study:   18 Years to 70 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01934647

Sponsors and Collaborators
Merck Sharp & Dohme Corp.
Study Director: Medical Director Merck Sharp & Dohme Corp.

Responsible Party: Merck Sharp & Dohme Corp. Identifier: NCT01934647     History of Changes
Other Study ID Numbers: 8892-003
2013-001680-23 ( EudraCT Number )
First Posted: September 4, 2013    Key Record Dates
Last Update Posted: January 25, 2016
Last Verified: January 2016

Additional relevant MeSH terms:
Familial Primary Pulmonary Hypertension
Vascular Diseases
Cardiovascular Diseases
Hypertension, Pulmonary
Lung Diseases
Respiratory Tract Diseases