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

Primary Purpose

Pulmonary Arterial Hypertension

Status
Terminated
Phase
Phase 1
Locations
Study Type
Interventional
Intervention
MK-8892
Sponsored by
Merck Sharp & Dohme LLC
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Pulmonary Arterial Hypertension

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm 3

    Arm Type

    Experimental

    Experimental

    Experimental

    Arm Label

    1 mg MK-8892

    4 mg MK-8892

    8 mg MK-8892

    Arm Description

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

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

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

    Outcomes

    Primary Outcome Measures

    Peak Percent Change From Baseline in Pulmonary Vascular Resistance (PVR) at the Highest Acutely Tolerated (HAT) Dose of MK-8892
    PVR assessments were performed throughout the right heart catheterization (RHC). Peak PVR reduction was determined to occur if 2 consecutive PVR measurements were at least 20% greater than the nadir PVR measurement.

    Secondary Outcome Measures

    Full Information

    First Posted
    August 30, 2013
    Last Updated
    March 27, 2018
    Sponsor
    Merck Sharp & Dohme LLC
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    1. Study Identification

    Unique Protocol Identification Number
    NCT01934647
    Brief Title
    Acute Dosing of MK-8892 in Participants With Pulmonary Arterial Hypertension (PAH) (MK-8892-003)
    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 Type
    Interventional

    2. Study Status

    Record Verification Date
    March 2018
    Overall Recruitment Status
    Terminated
    Study Start Date
    November 22, 2013 (Actual)
    Primary Completion Date
    September 8, 2014 (Actual)
    Study Completion Date
    September 8, 2014 (Actual)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    Merck Sharp & Dohme LLC

    4. Oversight

    Data Monitoring Committee
    No

    5. Study Description

    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).

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Pulmonary Arterial Hypertension

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 1
    Interventional Study Model
    Parallel Assignment
    Masking
    None (Open Label)
    Allocation
    Non-Randomized
    Enrollment
    7 (Actual)

    8. Arms, Groups, and Interventions

    Arm Title
    1 mg MK-8892
    Arm Type
    Experimental
    Arm Description
    Participants will receive a single oral dose of 1 mg MK-8892.
    Arm Title
    4 mg MK-8892
    Arm Type
    Experimental
    Arm Description
    Participants will receive a single oral dose of 4 mg MK-8892.
    Arm Title
    8 mg MK-8892
    Arm Type
    Experimental
    Arm Description
    Participants will receive a single oral dose of 8 mg MK-8892.
    Intervention Type
    Drug
    Intervention Name(s)
    MK-8892
    Intervention Description
    Single oral capsule with 1 mg, 4 mg, or 8 mg of MK-8892
    Primary Outcome Measure Information:
    Title
    Peak Percent Change From Baseline in Pulmonary Vascular Resistance (PVR) at the Highest Acutely Tolerated (HAT) Dose of MK-8892
    Description
    PVR assessments were performed throughout the right heart catheterization (RHC). Peak PVR reduction was determined to occur if 2 consecutive PVR measurements were at least 20% greater than the nadir PVR measurement.
    Time Frame
    Baseline and up to 5 hours post-dose

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Maximum Age & Unit of Time
    70 Years
    Accepts Healthy Volunteers
    No
    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
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Medical Director
    Organizational Affiliation
    Merck Sharp & Dohme LLC
    Official's Role
    Study Director

    12. IPD Sharing Statement

    Learn more about this trial

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

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