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

This study is currently recruiting participants.
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
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 April 23, 2014