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

August 30, 2013
April 4, 2014
November 2013
August 2014   (final data collection date for primary outcome measure)
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 ]
Same as current
Complete list of historical versions of study NCT01934647 on ClinicalTrials.gov Archive Site
Not Provided
Not Provided
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Acute Dosing of MK-8892 in Participants With Pulmonary Arterial Hypertension (PAH) (MK-8892-003)
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

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).

Not Provided
Interventional
Phase 1
Allocation: Non-Randomized
Endpoint Classification: Pharmacodynamics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Pulmonary Arterial Hypertension
Drug: MK-8892
Single oral capsule with up to 14 mg of MK-8892
  • Experimental: Dose Escalation
    MK-8892 doses starting at 1 mg, are sequentially escalated, stopping at the HAT dose or a maximum of 14 mg.
    Intervention: Drug: MK-8892
  • Experimental: HAT Dose
    Dose of MK-8892 that is highest acutely tolerated or a maximum of 14 mg.
    Intervention: Drug: MK-8892
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
20
August 2014
August 2014   (final data collection date for primary outcome measure)

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
Both
18 Years to 70 Years
No
Contact: Toll Free Number 1-888-577-8839
Germany
 
NCT01934647
8892-003, 2013-001680-23
No
Merck Sharp & Dohme Corp.
Merck Sharp & Dohme Corp.
Not Provided
Study Director: Medical Director Merck Sharp & Dohme Corp.
Merck Sharp & Dohme Corp.
April 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP