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

NCT01841762 | Completed Phase 3 Results

• 1 other identifier: AC-055-401
• Study Type: interventional
• Target: 284
• Locations: 1 country
• Sites: 81

Brief Summary

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.

Conditions

Pulmonary Arterial Hypertension

Keywords

PAH-SYMPACT; Pulmonary Arterial Hypertension; psychometric instrument

Outcome Measures

Primary Outcomes (3)

• Development and Refinement of the Patient-reported Outcome Measure of Symptoms and Their Impact in PAH (the PAH-SYMPACT)

  Content validity of the PAH-SYMPACT was assessed using item performance, exploratory and confirmatory factor analysis. The final item content and domain structure of PAH-SYMPACT was determined based on these analyses from the Steering Committee (expert clinicians) and findings from the qualitative research done with patients previously.

  From Screening Visit (Day -14) to End of Treatment (EOT) Visit (Visit 4, Week 16)

• Validation of the Patient-reported Outcome Measure of Symptoms and Their Impact in PAH (the PAH-SYMPACT), With Reliability Assessed Via Test-retest Reliability.

  The reliability of the PAH-SYMPACT is assessed by test-retest reliability. Intra-class correlation coefficients (ICCs) assess test-retest reliability for the symptom and impact part scores as well as domains. ICCs equal to or greater than 0.70 are considered to demonstrate good test-retest reliability for total and domain scores.

  From ePRO period 1 (Days -14 to -8) to ePRO period 2 (Days -7 to -1) in screening period.

• Validation of the Patient-reported Outcome Measure of Symptoms and Their Impact in PAH (the PAH-SYMPACT), Assessing Internal Consistency Reliability.

  The reliability of the PAH-SYMPACT is assessed by internal consistency reliability. This was determined using Cronbach's alpha-a value on an internal level scale from 0 to 1.0 with higher scores indicating a more-reliable (precise) instrument.

  From ePRO period 1 (Days -14 to -8) to ePRO period 2 (Days -7 to -1) in screening period.

Secondary Outcomes (1)

• Number of Participants With Treatment-emergent Adverse Events, Serious Adverse Events, and Adverse Events Resulting in Patient Study Drug Discontinuation Between Time Periods, BL to End of Study Visit (EoS, Week 16+30 Days for Follow-up Safety Visits)

  From Day 1 (Baseline Visit) to End of Study visit (EoS).

Other Outcomes (1)

• Assessment of the Sensitivity to Detect Change in the Symptoms and Impacts Domain Scores of the PAH-SYMPACT From Baseline to Week 16.

  From Screening period (Days -7 to -1) to Week 16 (7-day period prior to Week 16 visit).

Study Arms (1)

Macitentan

EXPERIMENTAL

Macitentan tablet, dose of 10 mg, once daily

Drug: Macitentan

Interventions

Macitentan DRUG

Macitentan tablet, dose of 10 mg, once daily

Also known as: Macitentan / ACT-064992

Macitentan

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed informed consent prior to initiation of any study mandated procedure
• Patients with symptomatic PAH in World Health Organization (WHO) Functional Class (FC) II to IV
• Patients with PAH belonging to one of the following subgroups of the Dana Point Clinical Classification Group 1:
• Idiopathic, or
• Heritable, or
• Drug or toxin induced, or
• 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
• Documented hemodynamic diagnosis of PAH by right heart catheterization - performed at any time prior to Screening showing:
• Resting mean pulmonary arterial pressure (mPAP) ≥ 25 mmHg and
• Resting pulmonary vascular resistance (PVR) \> 240 dyn•s•cm-5 and
• Pulmonary capillary wedge pressure (PCWP) or left ventricular end diastolic pressure (LVEDP) ≤ 15 mmHg
• minute walk distance (6MWD) ≥ 150 m at Screening
• Able to fluently speak and read English
• 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

You may not qualify if:

• 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
• Moderate to severe restrictive lung disease: total lung capacity \< 60% of predicted value
• Hemoglobin \< 75% of the lower limit of the normal range at screening
• Serum aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) \> 3 times the upper limit of normal (ULN) at screening
• Estimated creatinine clearance \< 30 mL/min at screening
• Systolic blood pressure (SBP) \< 90 mmHg at screening
• Body weight \< 40 kg at screening
• Known concomitant life-threatening diseases with a life expectancy of \< 12 months
• Any condition that prevents compliance with the protocol or adherence to therapy
• 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
• 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
• Treatment with riociguat within 3 months prior to Visit 2, or scheduled to receive riociguat during the trial
• Treatment with strong cytochrome P450 (CYP) 3A4 inducers or inhibitors within 4 weeks prior to Visit 2
• Recently started (\< 8 weeks prior to Visit 2) or planned cardio-pulmonary rehabilitation program based on exercise
• Females who are lactating or pregnant (positive Screening or Baseline pregnancy test) or plan to become pregnant during the study

Sponsors & Collaborators

• Actelion: lead

Study Sites (81)

Cardiovascular Associates of the Southeast, LLC

Birmingham, Alabama, 35243, United States

Location

University of Alabama at Birmingham

Birmingham, Alabama, 35294, United States

Location

Pulmonary Associates, PA

Phoenix, Arizona, 85006-2611, United States

Location

Mayo Clinic Arizona

Phoenix, Arizona, 85054-4502, United States

Location

Cedars-Sinai Medical Center

Beverly Hills, California, 90211, United States

Location

UCSF Fresno

Fresno, California, 93701, United States

Location

UCSD Medical Center, Pulmonary Department

La Jolla, California, 92093, United States

Location

VAGLAHS, VA Greater LA Healthcare System

Los Angeles, California, 90073, United States

Location

University of California Los Angeles

Los Angeles, California, 90095, United States

Location

University of California San Francisco Medical Center

San Francisco, California, 94143, United States

Location

Stanford University

Stanford, California, 94305-2200, United States

Location

Los Angeles Biomedical Research Institute

Torrance, California, 90502, United States

Location

University of Colorado

Aurora, Colorado, 80045, United States

Location

MedStar Georgetown University Hospital

Washington D.C., District of Columbia, 20007, United States

Location

Medstar Washington Hospital Center

Washington D.C., District of Columbia, 20010, United States

Location

Bay Area Cardiology Associates, P.A.

Brandon, Florida, 33511, United States

Location

University of Florida Academic Health Center

Gainesville, Florida, 32610, United States

Location

University of Florida College of Medicine, Jacksonville

Jacksonville, Florida, 32209, United States

Location

Mayo Clinic

Jacksonville, Florida, 32224-1865, United States

Location

Cleveland Clinic Florida

Weston, Florida, 33331-3609, United States

Location

Georgia Regents University

Augusta, Georgia, 30912, United States

Location

Georgia Clinical Research

Austell, Georgia, 30106, United States

Location

Northwestern University

Chicago, Illinois, 60611, United States

Location

University of Chicago Medical

Chicago, Illinois, 60637, United States

Location

Advocate Health and Hospitals Corporation

Oakbrook Terrace, Illinois, 60181, United States

Location

Chest Infectious Diseases and Critical Care Associates, PC

Des Moines, Iowa, 50325-7046, United States

Location

University of Iowa Hospitals & Clinics

Iowa City, Iowa, 52242, United States

Location

Iowa City Heart Center

Iowa City, Iowa, 52245, United States

Location

University of Kansas Medical Center

Kansas City, Kansas, 66160-0001, United States

Location

Veritas Clinical Specialties

Topeka, Kansas, 66606, United States

Location

Kentuckiana Pulmonary Associates

Louisville, Kentucky, 40202, United States

Location

University of Louisville

Louisville, Kentucky, 40202, United States

Location

University of Maryland Medical Center

Baltimore, Maryland, 21201, United States

Location

Johns Hopkins University

Baltimore, Maryland, 21205, United States

Location

Tufts Medical Center

Boston, Massachusetts, 02111, United States

Location

Boston University Medical Center

Boston, Massachusetts, 02118, United States

Location

University of Michigan

Ann Arbor, Michigan, 48109-5644, United States

Location

Beaumont Hospital

Troy, Michigan, 48085, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Midwest Pulmonary Consultants

Kansas City, Missouri, 64111, United States

Location

Ferrell-Duncan Clinic

Springfield, Missouri, 65807, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Mercy Clinic Pulmonology

St Louis, Missouri, 63141, United States

Location

Clayton Sleep Institute

St Louis, Missouri, 63143, United States

Location

Nebraska Pulmonary Specialties

Lincoln, Nebraska, 68506, United States

Location

University of Nebraska Medical Center

Omaha, Nebraska, 68198, United States

Location

Pulmonary and Critical Care Associates

Union, New Jersey, 07083, United States

Location

Buffalo General Medical Center

Buffalo, New York, 14203, United States

Location

Winthrop University Hospital

Mineola, New York, 11501, United States

Location

North Shore-LIJ/Advance Lung Disease Clinic

New Hyde Park, New York, 11040, United States

Location

Beth Israel Medical Center

New York, New York, 10003, United States

Location

Columbia University Medical Center

New York, New York, 10032, United States

Location

Montefiore Medical Center, Weiler Division

The Bronx, New York, 10461, United States

Location

University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, 27599, United States

Location

Novant Health Pulmonary and Critical Care

Matthews, North Carolina, 28105, United States

Location

The Christ Hospital

Cincinnati, Ohio, 45219, United States

Location

UC Health/University of Cincinnati

Cincinnati, Ohio, 45267, United States

Location

Cleveland Clinic

Cleveland, Ohio, 45219, United States

Location

Davis Heart & Lung Research Institute

Columbus, Ohio, 43210-1252, United States

Location

The Ohio State University

Columbus, Ohio, 43221, United States

Location

University of Oklahoma Health Sciences Center

Oklahoma City, Oklahoma, 73104, United States

Location

The Oregon Clinic

Portland, Oregon, 97220, United States

Location

CDA for Oregon Pulmonary Associate

Portland, Oregon, 97225, United States

Location

Oregon Health and Science University

Portland, Oregon, 97239, United States

Location

Thomas Jefferson University, Division on Pulmonary and Critical Care

Philadelphia, Pennsylvania, 19107-5109, United States

Location

Temple Lung Center

Philadelphia, Pennsylvania, 19140, United States

Location

UPMC

Pittsburgh, Pennsylvania, 15123, United States

Location

Allegheny General Hospital

Pittsburgh, Pennsylvania, 15212-4756, United States

Location

Berks Schuylkill Respiratory Specialists, Ltd.

Wyomissing, Pennsylvania, 19610, United States

Location

Wellspan Lung, Sleep and Critical Care

York, Pennsylvania, 17402-8200, United States

Location

Sioux Falls Cardiovascular, PC

Sioux Falls, South Dakota, 57108, United States

Location

Baylor Research Institute (BRI)

Dallas, Texas, 75204, United States

Location

UT Southwestern Medical Center

Dallas, Texas, 75390-8550, United States

Location

Baylor College of Medicine

Houston, Texas, 77030-2348, United States

Location

The University of Texas Health Science Center at Houston

Houston, Texas, 77030, United States

Location

Scott & White Memorial Hospital

Temple, Texas, 76508, United States

Location

Inova Heart and Vascular Institue / Inova Fairfax Hospital

Falls Church, Virginia, 22042-3307, United States

Location

Sentara Norfolk General Hospital

Norfolk, Virginia, 23507, United States

Location

Pulmonary & Sleep Research

Spokane, Washington, 99204, United States

Location

University of Wisconsin School of Medicine and Public Health

Madison, Wisconsin, 53792, United States

Location

Aurora Cardiovascular Services

Milwaukee, Wisconsin, 53215, United States

Location

Related Publications (1)

• 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.

  PMID: 29705220 DERIVED

MeSH Terms

Conditions

Pulmonary Arterial Hypertension

Interventions

macitentan

Condition Hierarchy (Ancestors)

Hypertension, Pulmonary; Lung Diseases; Respiratory Tract Diseases

Results Point of Contact

• Title: Scott Tsurutani / Associate Director, Clinical Operations
• Organization: Actelion Pharmaceuticals US, Inc.

scott.tsurutani@actelion.com

6508086586

Study Officials

• Alain Romero, PharmD, PhD

  Actelion Pharmaceuticals US, Inc

  STUDY CHAIR

• Gary Palmer, MD, MBA

  Actelion Pharmaceuticals US, Inc.

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 27, 2013
• First Posted: April 29, 2013
• Study Start: April 1, 2013
• Primary Completion: November 1, 2015
• Study Completion: November 1, 2015
• Last Updated: February 26, 2019
• Results First Posted: October 31, 2018

Record last verified: 2019-02

Locations

US (81)