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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Actelion
ClinicalTrials.gov Identifier:
NCT00903331
First received: May 14, 2009
Last updated: January 2, 2014
Last verified: January 2014
  Purpose

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 Intervention Phase
Idiopathic Pulmonary Fibrosis
Drug: ACT-064992 (macitentan)
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, 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

Resource links provided by NLM:


Further study details as provided by Actelion:

Primary Outcome Measures:
  • Forced Vital Capacity (FVC) at Baseline and End of Period 1 [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    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:
  • 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) ] [ Designated as safety issue: No ]

    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).



Enrollment: 178
Study Start Date: May 2009
Study Completion Date: August 2011
Primary Completion Date: June 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.

  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.
  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.
  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: NCT00903331

  Hide Study Locations
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
Australia
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
France
Hopital Avicenne
Bobigny, France
Hôpital Cardiologique et Pneumologique Louis Pradel
Bron, France
CHRU - Hopital Calmette Clinique des Maladies Respiratoires
Lille, France
Germany
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
Israel
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
Italy
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
Slovenia
Bolnišnica Golnik
Golnik, Slovenia
South Africa
Centre for Chest Diseases, Milpark Hospital
Johannesburg, South Africa
Pretoria East Hospital
Pretoria, South Africa
Spain
Hospital General Vall d'Hebron
Barcelona, Spain
Hospital Clinic I Provincial de Barcelona
Barcelona, Spain
Hospital Clinico San Carlos
Madrid, Spain
Hospital Universitario Ramón y Cajal
Madrid, Spain
Fundación Hospital Alcorcón
Madrid, Spain
Sweden
Karolinska Universitetssjukhuset Lung Allergi kliniken
Stockholm, Sweden
Turkey
Ankara University School of Medicine
Ankara, Turkey
Ege University School of Medicine
Izmir, Turkey
Sponsors and Collaborators
Actelion
Investigators
Study Chair: Loic Perchenet, Ph.D. Actelion
  More Information

No publications provided by Actelion

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Actelion
ClinicalTrials.gov Identifier: NCT00903331     History of Changes
Other Study ID Numbers: AC-055B201
Study First Received: May 14, 2009
Results First Received: October 29, 2013
Last Updated: January 2, 2014
Health Authority: Canada: Ethics Review Committee
Canada: Health Canada
United States: Food and Drug Administration
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
France: Committee of Protection of Individuals SUD-EST IV (Lyon)
Slovenia: Agency for Medicinal Products - Ministry of Health
Slovenia: Ethics Committee
Australia: Department of Health and Ageing Therapeutic Goods Administration
Australia: Human Research Ethics Committee
Australia: District Research Governance
Germany: Ethics Commission
Germany: Federal Institute for Drugs and Medical Devices
South Africa: Human Research Ethics Committee
South Africa: Medicines Control Council
Turkey: Ethics Committee
Turkey: Ministry of Health
Israel: Ethics Commission
Israel: Israeli Health Ministry Pharmaceutical Administration
Italy: Ethics Committee
Spain: Comité Ético de Investigación Clínica
Spain: Spanish Agency of Medicines
Sweden: Medical Products Agency
Sweden: Regional Ethical Review Board

Keywords provided by Actelion:
idiopathic pulmonary fibrosis
MUSIC

Additional relevant MeSH terms:
Fibrosis
Pulmonary Fibrosis
Idiopathic Pulmonary Fibrosis
Pathologic Processes
Lung Diseases
Respiratory Tract Diseases
Idiopathic Interstitial Pneumonias
Lung Diseases, Interstitial

ClinicalTrials.gov processed this record on September 18, 2014