Clinical Study of Macitentan in Patients With Pulmonary Arterial Hypertension to Psychometrically Validate the PAH-SYMPACT Instrument

NCT ID: NCT01841762

Last Updated: 2019-02-26

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

284 participants

Study Classification

INTERVENTIONAL

Study Start Date

2013-04-01

Study Completion Date

2015-11-01

Brief Summary

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SYMPHONY is prospective, multi-center, open-label, single-arm, Phase 3b psychometric validation study of the PAH-SYMPACT, a new quality of life questionnaire for patients with pulmonary arterial hypertension. Patients will be in the study for 5 1/2 months, 4 months of which they will receive macitentan, 10 mg, once daily.

The primary objectives are to demonstrate the final content validity of the PAH SYMPACT instrument, to demonstrate the psychometric characteristics of reliability and construct validity of the PAH-SYMPACT instrument, and to demonstrate the ability of the PAH SYMPACT instrument to detect change. The secondary objective is to assess the safety of macitentan in patients with pulmonary arterial hypertension. The exploratory objective is to explore the effects of macitentan on PAH symptoms and their impact (as measured by the PAH-SYMPACT) in patients with pulmonary arterial hypertension.

Detailed Description

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Conditions

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Pulmonary Arterial Hypertension

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Macitentan

Macitentan tablet, dose of 10 mg, once daily

Group Type EXPERIMENTAL

Macitentan

Intervention Type DRUG

Macitentan tablet, dose of 10 mg, once daily

Interventions

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Macitentan

Macitentan tablet, dose of 10 mg, once daily

Intervention Type DRUG

Other Intervention Names

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Macitentan / ACT-064992

Eligibility Criteria

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Inclusion Criteria

1. Signed informed consent prior to initiation of any study mandated procedure
2. Patients with symptomatic PAH in World Health Organization (WHO) Functional Class (FC) II to IV
3. Patients with PAH belonging to one of the following subgroups of the Dana Point Clinical Classification Group 1:

1. Idiopathic, or
2. Heritable, or
3. Drug or toxin induced, or
4. Associated with one of the following:

i. Connective tissue disease ii. Congenital heart disease with simple systemic-to-pulmonary shunt at least one year after surgical repair iii. HIV infection
4. Documented hemodynamic diagnosis of PAH by right heart catheterization - performed at any time prior to Screening showing:

1. Resting mean pulmonary arterial pressure (mPAP) ≥ 25 mmHg and
2. Resting pulmonary vascular resistance (PVR) \> 240 dyn•s•cm-5 and
3. Pulmonary capillary wedge pressure (PCWP) or left ventricular end diastolic pressure (LVEDP) ≤ 15 mmHg
5. 6-minute walk distance (6MWD) ≥ 150 m at Screening
6. Able to fluently speak and read English
7. For patients on phosphodiesterase type-5 inhibitors (PDE5i), inhaled prostacyclin analogues, or calcium channel blockers, stable doses for at least 3 months prior to Visit 2
8. For patients on oral diuretics, stable doses for at least 4 weeks prior to Visit 2
9. Men or women aged 18 or older

1. A woman is considered to be of childbearing potential unless she:

* Has not yet entered puberty, or
* Does not have a uterus, or
* Has gone through menopause (has not had a period for at least 12 months for natural reasons, or who has had their ovaries removed)
2. A women of childbearing potential is eligible only if she meets both criteria below:

* Has a negative serum pregnancy test at Screening and a negative urine pregnancy test at Baseline and agree to perform monthly urine pregnancy tests, and
* Agrees to use two methods of contraception (one method for patients with a progesterone implant or an intrauterine device or tubal sterilization) from the Screening Visit 1 until one month after study drug discontinuation

Exclusion Criteria

1. Moderate to severe obstructive lung disease: forced expiratory volume in one second (FEV1) / forced vital capacity \< 70% and FEV1 \< 65% of predicted value after bronchodilator administration
2. Moderate to severe restrictive lung disease: total lung capacity \< 60% of predicted value
3. Hemoglobin \< 75% of the lower limit of the normal range at screening
4. Serum aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) \> 3 times the upper limit of normal (ULN) at screening
5. Estimated creatinine clearance \< 30 mL/min at screening
6. Systolic blood pressure (SBP) \< 90 mmHg at screening
7. Body weight \< 40 kg at screening
8. Known concomitant life-threatening diseases with a life expectancy of \< 12 months
9. Any condition that prevents compliance with the protocol or adherence to therapy
10. Treatment with endothelin receptor antagonists (ERAs) within 3 months prior to Visit 2, or scheduled to receive any of these compounds, other than macitentan, during the trial
11. Treatment with intravenous or subcutaneous prostacyclin or prostacyclin analogs within 3 months prior to Visit 2, or scheduled to receive any of these compounds during the trial
12. Treatment with riociguat within 3 months prior to Visit 2, or scheduled to receive riociguat during the trial
13. Treatment with strong cytochrome P450 (CYP) 3A4 inducers or inhibitors within 4 weeks prior to Visit 2
14. Recently started (\< 8 weeks prior to Visit 2) or planned cardio-pulmonary rehabilitation program based on exercise
15. Females who are lactating or pregnant (positive Screening or Baseline pregnancy test) or plan to become pregnant during the study
16. Known hypersensitivity to macitentan or its excipients or drugs of the same class
17. Treatment with another investigational drug within 3 months prior to Visit 2
18. Any known factor or disease that might interfere with treatment compliance, study conduct or interpretation of the results such as drug or alcohol dependence or psychiatric disease
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Actelion

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Alain Romero, PharmD, PhD

Role: STUDY_CHAIR

Actelion Pharmaceuticals US, Inc

Gary Palmer, MD, MBA

Role: STUDY_CHAIR

Actelion Pharmaceuticals US, Inc.

Locations

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Cardiovascular Associates of the Southeast, LLC

Birmingham, Alabama, United States

Site Status

University of Alabama at Birmingham

Birmingham, Alabama, United States

Site Status

Pulmonary Associates, PA

Phoenix, Arizona, United States

Site Status

Mayo Clinic Arizona

Phoenix, Arizona, United States

Site Status

Cedars-Sinai Medical Center

Beverly Hills, California, United States

Site Status

UCSF Fresno

Fresno, California, United States

Site Status

UCSD Medical Center, Pulmonary Department

La Jolla, California, United States

Site Status

VAGLAHS, VA Greater LA Healthcare System

Los Angeles, California, United States

Site Status

University of California Los Angeles

Los Angeles, California, United States

Site Status

University of California San Francisco Medical Center

San Francisco, California, United States

Site Status

Stanford University

Stanford, California, United States

Site Status

Los Angeles Biomedical Research Institute

Torrance, California, United States

Site Status

University of Colorado

Aurora, Colorado, United States

Site Status

MedStar Georgetown University Hospital

Washington D.C., District of Columbia, United States

Site Status

Medstar Washington Hospital Center

Washington D.C., District of Columbia, United States

Site Status

Bay Area Cardiology Associates, P.A.

Brandon, Florida, United States

Site Status

University of Florida Academic Health Center

Gainesville, Florida, United States

Site Status

University of Florida College of Medicine, Jacksonville

Jacksonville, Florida, United States

Site Status

Mayo Clinic

Jacksonville, Florida, United States

Site Status

Cleveland Clinic Florida

Weston, Florida, United States

Site Status

Georgia Regents University

Augusta, Georgia, United States

Site Status

Georgia Clinical Research

Austell, Georgia, United States

Site Status

Northwestern University

Chicago, Illinois, United States

Site Status

University of Chicago Medical

Chicago, Illinois, United States

Site Status

Advocate Health and Hospitals Corporation

Oakbrook Terrace, Illinois, United States

Site Status

Chest Infectious Diseases and Critical Care Associates, PC

Des Moines, Iowa, United States

Site Status

University of Iowa Hospitals & Clinics

Iowa City, Iowa, United States

Site Status

Iowa City Heart Center

Iowa City, Iowa, United States

Site Status

University of Kansas Medical Center

Kansas City, Kansas, United States

Site Status

Veritas Clinical Specialties

Topeka, Kansas, United States

Site Status

Kentuckiana Pulmonary Associates

Louisville, Kentucky, United States

Site Status

University of Louisville

Louisville, Kentucky, United States

Site Status

University of Maryland Medical Center

Baltimore, Maryland, United States

Site Status

Johns Hopkins University

Baltimore, Maryland, United States

Site Status

Tufts Medical Center

Boston, Massachusetts, United States

Site Status

Boston University Medical Center

Boston, Massachusetts, United States

Site Status

University of Michigan

Ann Arbor, Michigan, United States

Site Status

Beaumont Hospital

Troy, Michigan, United States

Site Status

Mayo Clinic

Rochester, Minnesota, United States

Site Status

Midwest Pulmonary Consultants

Kansas City, Missouri, United States

Site Status

Ferrell-Duncan Clinic

Springfield, Missouri, United States

Site Status

Washington University School of Medicine

St Louis, Missouri, United States

Site Status

Mercy Clinic Pulmonology

St Louis, Missouri, United States

Site Status

Clayton Sleep Institute

St Louis, Missouri, United States

Site Status

Nebraska Pulmonary Specialties

Lincoln, Nebraska, United States

Site Status

University of Nebraska Medical Center

Omaha, Nebraska, United States

Site Status

Pulmonary and Critical Care Associates

Union, New Jersey, United States

Site Status

Buffalo General Medical Center

Buffalo, New York, United States

Site Status

Winthrop University Hospital

Mineola, New York, United States

Site Status

North Shore-LIJ/Advance Lung Disease Clinic

New Hyde Park, New York, United States

Site Status

Beth Israel Medical Center

New York, New York, United States

Site Status

Columbia University Medical Center

New York, New York, United States

Site Status

Montefiore Medical Center, Weiler Division

The Bronx, New York, United States

Site Status

University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, United States

Site Status

Novant Health Pulmonary and Critical Care

Matthews, North Carolina, United States

Site Status

The Christ Hospital

Cincinnati, Ohio, United States

Site Status

UC Health/University of Cincinnati

Cincinnati, Ohio, United States

Site Status

Cleveland Clinic

Cleveland, Ohio, United States

Site Status

Davis Heart & Lung Research Institute

Columbus, Ohio, United States

Site Status

The Ohio State University

Columbus, Ohio, United States

Site Status

University of Oklahoma Health Sciences Center

Oklahoma City, Oklahoma, United States

Site Status

The Oregon Clinic

Portland, Oregon, United States

Site Status

CDA for Oregon Pulmonary Associate

Portland, Oregon, United States

Site Status

Oregon Health and Science University

Portland, Oregon, United States

Site Status

Thomas Jefferson University, Division on Pulmonary and Critical Care

Philadelphia, Pennsylvania, United States

Site Status

Temple Lung Center

Philadelphia, Pennsylvania, United States

Site Status

UPMC

Pittsburgh, Pennsylvania, United States

Site Status

Allegheny General Hospital

Pittsburgh, Pennsylvania, United States

Site Status

Berks Schuylkill Respiratory Specialists, Ltd.

Wyomissing, Pennsylvania, United States

Site Status

Wellspan Lung, Sleep and Critical Care

York, Pennsylvania, United States

Site Status

Sioux Falls Cardiovascular, PC

Sioux Falls, South Dakota, United States

Site Status

Baylor Research Institute (BRI)

Dallas, Texas, United States

Site Status

UT Southwestern Medical Center

Dallas, Texas, United States

Site Status

Baylor College of Medicine

Houston, Texas, United States

Site Status

The University of Texas Health Science Center at Houston

Houston, Texas, United States

Site Status

Scott & White Memorial Hospital

Temple, Texas, United States

Site Status

Inova Heart and Vascular Institue / Inova Fairfax Hospital

Falls Church, Virginia, United States

Site Status

Sentara Norfolk General Hospital

Norfolk, Virginia, United States

Site Status

Pulmonary & Sleep Research

Spokane, Washington, United States

Site Status

University of Wisconsin School of Medicine and Public Health

Madison, Wisconsin, United States

Site Status

Aurora Cardiovascular Services

Milwaukee, Wisconsin, United States

Site Status

Countries

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United States

References

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Chin KM, Gomberg-Maitland M, Channick RN, Cuttica MJ, Fischer A, Frantz RP, Hunsche E, Kleinman L, McConnell JW, McLaughlin VV, Miller CE, Zamanian RT, Zastrow MS, Badesch DB. Psychometric Validation of the Pulmonary Arterial Hypertension-Symptoms and Impact (PAH-SYMPACT) Questionnaire: Results of the SYMPHONY Trial. Chest. 2018 Oct;154(4):848-861. doi: 10.1016/j.chest.2018.04.027. Epub 2018 Apr 26.

Reference Type DERIVED
PMID: 29705220 (View on PubMed)

Other Identifiers

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AC-055-401

Identifier Type: -

Identifier Source: org_study_id

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