SYMPHONY: A Study of Macitentan in Pulmonary Arterial Hypertension to Validate the PAH-SYMPACT

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Actelion
ClinicalTrials.gov Identifier:
NCT01841762
First received: March 27, 2013
Last updated: May 14, 2015
Last verified: May 2015
  Purpose

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.


Condition Intervention Phase
Pulmonary Arterial Hypertension
Drug: Macitentan
Phase 3

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Multi-center, Open-label, Single-arm, Phase 3b Study of Macitentan in Patients With Pulmonary Arterial Hypertension to Psychometrically Validate the PAH-SYMPACT Instrument

Resource links provided by NLM:


Further study details as provided by Actelion:

Primary Outcome Measures:
  • Development of patient-reported outcome measure of symptoms and their impact in PAH (the PAH-SYMPACT) [ Time Frame: From Screening Visit (Visit 1) to End of Treatment (EOT) Visit (Visit 4, Week 16) ] [ Designated as safety issue: No ]
    Assessed through item analyses, factor analyses, and Rasch analyses.


Secondary Outcome Measures:
  • To assess the frequency of treatment-emergent adverse events, serious adverse events, and adverse events leading to study drug discontinuation from Baseline to Week 16. [ Time Frame: From Baseline Visit (Visit 2, Day 1) to End of Treatment (EOT) Visit (Visit 4, Week 16) ] [ Designated as safety issue: Yes ]

Other Outcome Measures:
  • Change from Baseline to Week 16 in the symptom and impact scales of the PAH-SYMPACT. [ Time Frame: From Baseline Visit (Visit 2, Day 1) to End of Treatment (EOT) Visit (Visit 4, Week 16) ] [ Designated as safety issue: No ]
    Assessed by the PAH-SYMPACT questionnaire.


Estimated Enrollment: 275
Study Start Date: April 2013
Estimated Study Completion Date: September 2015
Estimated Primary Completion Date: September 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Macitentan
Macitentan tablet, dose of 10 mg, once daily
Drug: Macitentan
Macitentan tablet, dose of 10 mg, once daily
Other Name: Macitentan / ACT-064992

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01841762

  Hide Study Locations
Locations
United States, Alabama
Cardiovascular Associates of the Southeast, LLC
Birmingham, Alabama, United States, 35243
University of Alabama at Birmingham
Birmingham, Alabama, United States, 35294
United States, Arizona
Mayo Clinic Arizona
Phoenix, Arizona, United States, 85054-4502
Pulmonary Associates, PA
Phoenix, Arizona, United States, 85006-2611
United States, California
Cedars-Sinai Medical Center
Beverly Hills, California, United States, 90211
UCSF Fresno
Fresno, California, United States, 93701
UCSD Medical Center, Pulmonary Department
La Jolla, California, United States, 92093
University of California Los Angeles
Los Angeles, California, United States, 90095
VAGLAHS, VA Greater LA Healthcare System
Los Angeles, California, United States, 90073
University of California San Francisco Medical Center
San Francisco, California, United States, 94143
Stanford University
Stanford, California, United States, 94305-2200
Los Angeles Biomedical Research Institute
Torrance, California, United States, 90502
United States, Colorado
University of Colorado
Aurora, Colorado, United States, 80045
United States, District of Columbia
Medstar Washington Hospital Center
Washington, District of Columbia, United States, 20010
MedStar Georgetown University Hospital
Washington, District of Columbia, United States, 20007
United States, Florida
Bay Area Cardiology Associates, P.A.
Brandon, Florida, United States, 33511
University of Florida Academic Health Center
Gainesville, Florida, United States, 32610
Mayo Clinic
Jacksonville, Florida, United States, 32224-1865
University of Florida College of Medicine, Jacksonville
Jacksonville, Florida, United States, 32209
Cleveland Clinic Florida
Weston, Florida, United States, 33331-3609
United States, Georgia
Georgia Regents University
Augusta, Georgia, United States, 30912
Georgia Clinical Research
Austell, Georgia, United States, 30106
United States, Illinois
Northwestern University
Chicago, Illinois, United States, 60611
University of Chicago Medical
Chicago, Illinois, United States, 60637
Advocate Health and Hospitals Corporation
Oakbrook Terrace, Illinois, United States, 60181
United States, Iowa
Chest Infectious Diseases and Critical Care Associates, PC
Des Moines, Iowa, United States, 50325-7046
Iowa City Heart Center
Iowa City, Iowa, United States, 52245
University of Iowa Hospitals & Clinics
Iowa City, Iowa, United States, 52242
United States, Kansas
University of Kansas Medical Center
Kansas City, Kansas, United States, 66160-0001
Veritas Clinical Specialties
Topeka, Kansas, United States, 66606
United States, Kentucky
Kentuckiana Pulmonary Associates
Louisville, Kentucky, United States, 40202
University of Louisville
Louisville, Kentucky, United States, 40202
United States, Maryland
University of Maryland Medical Center
Baltimore, Maryland, United States, 21201
Johns Hopkins University
Baltimore, Maryland, United States, 21205
United States, Massachusetts
Boston University Medical Center
Boston, Massachusetts, United States, 02118
Tufts Medical Center
Boston, Massachusetts, United States, 02111
United States, Michigan
University of Michigan
Ann Arbor, Michigan, United States, 48109-5644
Beaumont Hospital
Troy, Michigan, United States, 48085
United States, Minnesota
Mayo Clinic
Rochester, Minnesota, United States, 55905
United States, Missouri
Midwest Pulmonary Consultants
Kansas City, Missouri, United States, 64111
Clayton Sleep Institute
Saint Louis, Missouri, United States, 63143
Ferrell-Duncan Clinic
Springfield, Missouri, United States, 65807
Mercy Clinic Pulmonology
St. Louis, Missouri, United States, 63141
Washington University School of Medicine
St. Louis, Missouri, United States, 63110
United States, Nebraska
Nebraska Pulmonary Specialties
Lincoln, Nebraska, United States, 68506
University of Nebraska Medical Center
Omaha, Nebraska, United States, 68198
United States, New Jersey
Pulmonary and Critical Care Associates
Union, New Jersey, United States, 07083
United States, New York
Montefiore Medical Center, Weiler Division
Bronx, New York, United States, 10461
Buffalo General Medical Center
Buffalo, New York, United States, 14203
Winthrop University Hospital
Mineola, New York, United States, 11501
North Shore-LIJ/Advance Lung Disease Clinic
New Hyde Park, New York, United States, 11040
Beth Israel Medical Center
New York, New York, United States, 10003
Columbia University Medical Center
New York, New York, United States, 10032
United States, North Carolina
University of North Carolina at Chapel Hill
Chapel Hill, North Carolina, United States, 27599
Novant Health Pulmonary and Critical Care
Matthews, North Carolina, United States, 28105
United States, Ohio
The Christ Hospital
Cincinnati, Ohio, United States, 45219
UC Health/University of Cincinnati
Cincinnati, Ohio, United States, 45267
Cleveland Clinic
Cleveland, Ohio, United States, 45219
The Ohio State University
Columbus, Ohio, United States, 43221
Davis Heart & Lung Research Institute
Columbus, Ohio, United States, 43210-1252
United States, Oklahoma
University of Oklahoma Health Sciences Center
Oklahoma City, Oklahoma, United States, 73104
United States, Oregon
CDA for Oregon Pulmonary Associate
Portland, Oregon, United States, 97225
Oregon Health and Science University
Portland, Oregon, United States, 97239
The Oregon Clinic
Portland, Oregon, United States, 97220
United States, Pennsylvania
Temple Lung Center
Philadelphia, Pennsylvania, United States, 19140
Thomas Jefferson University, Division on Pulmonary and Critical Care
Philadelphia, Pennsylvania, United States, 19107-5109
UPMC
Pittsburgh, Pennsylvania, United States, 15123
Allegheny General Hospital
Pittsburgh, Pennsylvania, United States, 15212-4756
Berks Schuylkill Respiratory Specialists, Ltd.
Wyomissing, Pennsylvania, United States, 19610
Wellspan Lung, Sleep and Critical Care
York, Pennsylvania, United States, 17402-8200
United States, South Dakota
Sioux Falls Cardiovascular, PC
Sioux Falls, South Dakota, United States, 57108
United States, Texas
Baylor Research Institute (BRI)
Dallas, Texas, United States, 75204
UT Southwestern Medical Center
Dallas, Texas, United States, 75390-8550
Baylor College of Medicine
Houston, Texas, United States, 77030-2348
The University of Texas Health Science Center at Houston
Houston, Texas, United States, 77030
Scott & White Memorial Hospital
Temple, Texas, United States, 76508
United States, Virginia
Inova Heart and Vascular Institue / Inova Fairfax Hospital
Falls Church, Virginia, United States, 22042-3307
Sentara Norfolk General Hospital
Norfolk, Virginia, United States, 23507
United States, Washington
Pulmonary & Sleep Research
Spokane, Washington, United States, 99204
United States, Wisconsin
University of Wisconsin School of Medicine and Public Health
Madison, Wisconsin, United States, 53792
Aurora Cardiovascular Services
Milwaukee, Wisconsin, United States, 53215
Sponsors and Collaborators
Actelion
Investigators
Study Chair: Alain Romero, PharmD, PhD Actelion Pharmaceuticals US, Inc
  More Information

No publications provided

Responsible Party: Actelion
ClinicalTrials.gov Identifier: NCT01841762     History of Changes
Other Study ID Numbers: AC-055-401
Study First Received: March 27, 2013
Last Updated: May 14, 2015
Health Authority: United States: Food and Drug Administration

Keywords provided by Actelion:
Pulmonary Arterial Hypertension

Additional relevant MeSH terms:
Hypertension
Cardiovascular Diseases
Vascular Diseases

ClinicalTrials.gov processed this record on July 28, 2015