Macitentan Use in an Idiopathic Pulmonary Fibrosis Clinical Study (MUSIC)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00903331
Recruitment Status : Completed
First Posted : May 18, 2009
Results First Posted : February 17, 2014
Last Update Posted : February 17, 2014
Information provided by (Responsible Party):

Brief Summary:

The AC-055B201/MUSIC study is a Phase II study, comparing one dose of ACT-064922 (macitentan) 10 mg with placebo in patients with idiopathic pulmonary fibrosis (IPF). The main study objective is to demonstrate that macitentan positively affects the forced vital capacity (FVC) in comparison with placebo in patients with idiopathic pulmonary fibrosis (IPF).

The secondary objectives are to evaluate the effect of macitentan on the time to disease worsening or death in patients with IPF, and to evaluate the benefit/risk profile of macitentan in the treatment of patients with IPF.

Condition or disease Intervention/treatment Phase
Idiopathic Pulmonary Fibrosis Drug: ACT-064992 (macitentan) Drug: Placebo Phase 2

Detailed Description:
The study included two treatment periods: Period 1 (fixed duration) from randomization up to the primary endpoint evaluation (Month 12 or earlier in case of premature discontinuation of study drug) and Period 2 (variable duration) from the primary endpoint evaluation visit up to the end of study (EOS). EOS occurred when the last patient randomized and not prematurely discontinued completed Period 1.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 178 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Double-blind, Randomized, Placebo-controlled, Multicenter, Parallel Group Study to Evaluate the Efficacy, Safety, and Tolerability of Macitentan in Patients With Idiopathic Pulmonary Fibrosis
Study Start Date : May 2009
Actual Primary Completion Date : June 2011
Actual Study Completion Date : August 2011

Arm Intervention/treatment
Experimental: ACT-064922
ACT-064922 tablet (macitentan), 10 mg, once daily
Drug: ACT-064992 (macitentan)
ACT-064992 (macitentan) tablet, 10 mg, once daily
Other Name: macitentan

Placebo Comparator: Placebo
Matching placebo, once daily
Drug: Placebo
matching placebo, once daily

Primary Outcome Measures :
  1. Forced Vital Capacity (FVC) at Baseline and End of Period 1 [ Time Frame: 12 months ]
    FVC was measured at baseline and at the end of Period 1. The same equipment and tester were used during the course of the study. The equipment was calibrated and the calibration documented prior to each patient's measurement. The person responsible for conducting the pulmonary function tests was required to comply with the study guidelines and the American Thoracic Society/European Respiratory Society joint criteria on lung function testing.

Secondary Outcome Measures :
  1. Number of Patients at Risk of Event of Disease Worsening or Death up to the End of Study [ Time Frame: Up to end of study (Up to 24 months) ]

    Disease worsening was indicated by pulmonary function test/idiopathic pulmonary fibrosis worsening (PFT/IPF) or acute respiratory decompensation of IPF.

    PFT/IPF worsening was indicated by the occurrence of both of the following: confirmed by two tests at least 4 weeks apart, as defined by the occurrence of both of the following: decrease from baseline ≥ 10% in forced vital capacity and decrease from baseline ≥ 15% in corrected diffusing capacity of the lung for carbon monoxide.

    Acute respiratory decompensation of IPF was defined as an unexplained rapid deterioration (over a period of less than 4 weeks) of the patient's condition with increasing shortness of breath requiring oxygen supplementation ≥ 5 L/min to maintain a resting oxygen saturation ≥ 90% or arterial oxygen pressure ≥ 55 mmHg (sea level) or 50 mmHg (high altitude).

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  1. Signed informed consent.
  2. Male or female patients of at least 18 years of age (females of child-bearing potential must use a reliable method of contraception).
  3. IPF diagnosis within 3 years prior to randomization, proven according to the American Thoracic Society/European Respiratory Society consensus conference criteria, with surgical lung biopsy.

Exclusion Criteria:

  1. Interstitial lung disease due to conditions other than IPF.
  2. Presence of extensive honeycombing on Baseline high-resolution computed tomography (HRCT) scan performed within 3 months prior to randomization.
  3. Severe concomitant illness limiting life expectancy (< 1 year).
  4. Severe restrictive lung disease: forced vital capacity (FVC) < 50% predicted, or FVC < 1.2 liter.
  5. Diffusing capacity of the lung for carbon monoxide (DLCO) < 30% predicted.
  6. Residual volume ≥ 120% predicted.
  7. Obstructive lung disease: forced expiratory volume in 1 second (FEV1)/FVC) < 0.70.
  8. Documented sustained improvement of the patient's IPF condition up to 12 months prior to randomization with or without IPF-specific therapy.
  9. Recent pulmonary or upper respiratory tract infection (up to 4 weeks prior to randomization).
  10. Acute or chronic impairment (other than dyspnea) limiting the ability to comply with study requirements (e.g., pulmonary function tests).
  11. Chronic heart failure with New York Heart Association class III/IV or known left ventricular ejection fraction < 25%.
  12. Moderate to severe hepatic impairment, i.e., Child-Pugh Class B or C.
  13. Estimated creatinine clearance < 30 mL/min.
  14. Aspartate aminotransferase (AST) and/or alanine aminotransferase > 1.5 x upper limit of normal.
  15. Hemoglobin < 75% of the lower limit of the normal range.
  16. Systolic blood pressure < 100 mmHg.
  17. Pregnant or breast-feeding.
  18. Current drug or alcohol dependence.
  19. Chronic treatment with the following drugs (within 4 weeks of randomization):

    • Oral corticosteroids (> 20 mg/day of prednisone or equivalent),
    • Immunosuppressive or cytotoxic drugs including cyclophosphamide and azathioprine,
    • Antifibrotic drugs including pirfenidone, D penicillamine, colchicine, tumor necrosis factor α blockers, imatinib and interferon γ,
    • Chronic use of N-acetylcysteine prescribed for IPF (> 600 mg/day).
    • Oral anticoagulants prescribed for IPF.
  20. Treatment with endothelin receptor antagonists within 4 weeks prior to randomization.
  21. Systemic treatment within 4 weeks prior to randomization with cyclosporine A or tacrolimus, everolimus, sirolimus (calcineurin or mammalian target of rapamycin (mTOR) inhibitors).
  22. Treatment with Cytochrome P450 3A inducers within 4 weeks prior to randomization.
  23. Known hypersensitivity to drugs of the same class as the study drug, or any of their excipients.
  24. Planned treatment, or treatment with another investigational drug within 4 weeks prior to randomization.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00903331

  Hide Study Locations
United States, Alabama
University of Alabama at Birmingham
Birmingham, Alabama, United States, 35294
United States, Arizona
Pulmonary Associates, P.A.
Phoenix, Arizona, United States, 85006
Mayo Clinic - Arizona
Scottsdale, Arizona, United States, 85259
United States, California
U.C. Davis University of California
Sacramento, California, United States, 95817
UCSD Pulmonary Critical Care
San Diego, California, United States, 92103
University of California - San Francisco
San Francisco, California, United States, 94143
Stanford University Medical Center - Chest Clinic
Stanford, California, United States, 94305
United States, Colorado
National Jewish Medical & Research Center
Denver, Colorado, United States, 80206
United States, Connecticut
Yale University School of Medicine
New Haven, Connecticut, United States, 06520
United States, Kansas
Wichita Clinic P.A
Wichita, Kansas, United States, 67208
United States, Missouri
St. Luke's Medical Group
Chesterfield, Missouri, United States, 63017
United States, Ohio
The Cleveland Clinic Foundation
Cleveland, Ohio, United States, 44195
United States, Pennsylvania
Temple University Hospital - Lung Center
Philadelphia, Pennsylvania, United States, 19140
United States, Texas
Baylor College of Medicine - Baylor Clinic
Houston, Texas, United States, 77030
United States, Wisconsin
University of Wisconsin - Madison
Madison, Wisconsin, United States, 53792
Prince Charles Hospital Lung Transplant
Chermside, Australia
St. Vincent's Public Hospital
Darlinghurst, Australia
The Alfred Hospital
Melbourne, Australia
Royal Perth Hospital
Perth, Australia
Canada, Alberta
University of Alberta - Health Sciences Center
Edmonton, Alberta, Canada, T6G2B7
Canada, British Columbia
Kelowna General Hospital
Kelowna, British Columbia, Canada, V1W3T1
St. Paul's Hospital
Vancouver, British Columbia, Canada, V6Z1Y6
Canada, Ontario
St. Joseph's Healthcare
Hamilton, Ontario, Canada, L8N4A6
Toronto General Hospital
Toronto, Ontario, Canada, M5G2N2
Canada, Quebec
Hospital Notre-Dame du CHUM
Montreal, Quebec, Canada, H2L4M1
Hopital Avicenne
Bobigny, France
Hôpital Cardiologique et Pneumologique Louis Pradel
Bron, France
CHRU - Hopital Calmette Clinique des Maladies Respiratoires
Lille, France
Helios Klinikum Emil von Behring
Berlin, Germany
Justus-Liebig-Universität Gießen
Giessen, Germany
Fachklinik fur Lungenerkrankungen
Immenhausen, Germany
Universität zu Köln
Koln, Germany
Ludwig-Maximilian-Universität München
Munchen, Germany
Hadassah Ein Kerem Medical Center
Jerusalem, Israel
Rabin Medical Center, Beilinson Hospital
Petach Tikvah, Israel
Kaplan Medical Center
Rehovot, Israel
Tel-Aviv Sourasky Medical Center
Tel Aviv, Israel
The Chaim Sheba Medical Center
Tel Hashomer, Israel
Ospedale San Giuseppe Milanocuore
Milan, Italy
Università degli Studi di Torino Clinica di Malattie dell'Apparato Respiratorio
Orbassano, Italy
A.O.U Policlinico Tor Vergata
Roma, Italy
Ospedale di Cattinara
Trieste, Italy
Bolnišnica Golnik
Golnik, Slovenia
South Africa
Centre for Chest Diseases, Milpark Hospital
Johannesburg, South Africa
Pretoria East Hospital
Pretoria, South Africa
Hospital Clinic I Provincial de Barcelona
Barcelona, Spain
Hospital General Vall d'Hebron
Barcelona, Spain
Fundación Hospital Alcorcón
Madrid, Spain
Hospital Clinico San Carlos
Madrid, Spain
Hospital Universitario Ramón y Cajal
Madrid, Spain
Karolinska Universitetssjukhuset Lung Allergi kliniken
Stockholm, Sweden
Ankara University School of Medicine
Ankara, Turkey
Ege University School of Medicine
Izmir, Turkey
Sponsors and Collaborators
Study Chair: Loic Perchenet, Ph.D. Actelion

Publications automatically indexed to this study by Identifier (NCT Number):
Responsible Party: Actelion Identifier: NCT00903331     History of Changes
Other Study ID Numbers: AC-055B201
First Posted: May 18, 2009    Key Record Dates
Results First Posted: February 17, 2014
Last Update Posted: February 17, 2014
Last Verified: January 2014

Keywords provided by Actelion:
idiopathic pulmonary fibrosis

Additional relevant MeSH terms:
Pulmonary Fibrosis
Idiopathic Pulmonary Fibrosis
Idiopathic Interstitial Pneumonias
Pathologic Processes
Lung Diseases
Respiratory Tract Diseases
Lung Diseases, Interstitial
Endothelin A Receptor Antagonists
Endothelin Receptor Antagonists
Molecular Mechanisms of Pharmacological Action
Endothelin B Receptor Antagonists