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

This study is currently recruiting participants. (see Contacts and Locations)
Verified April 2014 by Merck Sharp & Dohme Corp.
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:
NCT01934647
First received: August 30, 2013
Last updated: April 4, 2014
Last verified: April 2014
  Purpose

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 Intervention Phase
Pulmonary Arterial Hypertension
Drug: MK-8892
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Pharmacodynamics Study
Intervention Model: Single Group Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by Merck Sharp & Dohme Corp.:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]

Estimated Enrollment: 20
Study Start Date: November 2013
Estimated Study Completion Date: August 2014
Estimated Primary Completion Date: August 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01934647

Contacts
Contact: Toll Free Number 1-888-577-8839

Locations
Germany
Merck Sharp & Dohme GmbH Recruiting
Haar, Germany
Contact: German Medical Information Center    49 800 673 673 673      
Sponsors and Collaborators
Merck Sharp & Dohme Corp.
Investigators
Study Director: Medical Director Merck Sharp & Dohme Corp.
  More Information

No publications provided

Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT01934647     History of Changes
Other Study ID Numbers: 8892-003, 2013-001680-23
Study First Received: August 30, 2013
Last Updated: April 4, 2014
Health Authority: Germany: Federal Institute for Drugs and Medical Devices

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

ClinicalTrials.gov processed this record on July 22, 2014