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

Primary Purpose

Idiopathic Pulmonary Fibrosis

Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
ACT-064992 (macitentan)
Placebo
Sponsored by
Actelion
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Idiopathic Pulmonary Fibrosis focused on measuring idiopathic pulmonary fibrosis, MUSIC

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • University of Alabama at Birmingham
  • Pulmonary Associates, P.A.
  • Mayo Clinic - Arizona
  • U.C. Davis University of California
  • UCSD Pulmonary Critical Care
  • University of California - San Francisco
  • Stanford University Medical Center - Chest Clinic
  • National Jewish Medical & Research Center
  • Yale University School of Medicine
  • Wichita Clinic P.A
  • St. Luke's Medical Group
  • The Cleveland Clinic Foundation
  • Temple University Hospital - Lung Center
  • Baylor College of Medicine - Baylor Clinic
  • University of Wisconsin - Madison
  • Prince Charles Hospital Lung Transplant
  • St. Vincent's Public Hospital
  • The Alfred Hospital
  • Royal Perth Hospital
  • University of Alberta - Health Sciences Center
  • Kelowna General Hospital
  • St. Paul's Hospital
  • St. Joseph's Healthcare
  • Toronto General Hospital
  • Hospital Notre-Dame du CHUM
  • Hopital Avicenne
  • Hôpital Cardiologique et Pneumologique Louis Pradel
  • CHRU - Hopital Calmette Clinique des Maladies Respiratoires
  • Helios Klinikum Emil von Behring
  • Justus-Liebig-Universität Gießen
  • Fachklinik fur Lungenerkrankungen
  • Universität zu Köln
  • Ludwig-Maximilian-Universität München
  • Hadassah Ein Kerem Medical Center
  • Rabin Medical Center, Beilinson Hospital
  • Kaplan Medical Center
  • Tel-Aviv Sourasky Medical Center
  • The Chaim Sheba Medical Center
  • Ospedale San Giuseppe Milanocuore
  • Università degli Studi di Torino Clinica di Malattie dell'Apparato Respiratorio
  • A.O.U Policlinico Tor Vergata
  • Ospedale di Cattinara
  • Bolnišnica Golnik
  • Centre for Chest Diseases, Milpark Hospital
  • Pretoria East Hospital
  • Hospital Clinic I Provincial de Barcelona
  • Hospital General Vall d'Hebron
  • Fundación Hospital Alcorcón
  • Hospital Clinico San Carlos
  • Hospital Universitario Ramón y Cajal
  • Karolinska Universitetssjukhuset Lung Allergi kliniken
  • Ankara University School of Medicine
  • Ege University School of Medicine

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

ACT-064922

Placebo

Arm Description

ACT-064922 tablet (macitentan), 10 mg, once daily

Matching placebo, once daily

Outcomes

Primary Outcome Measures

Forced Vital Capacity (FVC) at Baseline and End of Period 1
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
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).

Full Information

First Posted
May 14, 2009
Last Updated
January 2, 2014
Sponsor
Actelion
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1. Study Identification

Unique Protocol Identification Number
NCT00903331
Brief Title
Macitentan Use in an Idiopathic Pulmonary Fibrosis Clinical Study
Acronym
MUSIC
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 Type
Interventional

2. Study Status

Record Verification Date
January 2014
Overall Recruitment Status
Completed
Study Start Date
May 2009 (undefined)
Primary Completion Date
June 2011 (Actual)
Study Completion Date
August 2011 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Actelion

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Idiopathic Pulmonary Fibrosis
Keywords
idiopathic pulmonary fibrosis, MUSIC

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
178 (Actual)

8. Arms, Groups, and Interventions

Arm Title
ACT-064922
Arm Type
Experimental
Arm Description
ACT-064922 tablet (macitentan), 10 mg, once daily
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Matching placebo, once daily
Intervention Type
Drug
Intervention Name(s)
ACT-064992 (macitentan)
Other Intervention Name(s)
macitentan
Intervention Description
ACT-064992 (macitentan) tablet, 10 mg, once daily
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
matching placebo, once daily
Primary Outcome Measure Information:
Title
Forced Vital Capacity (FVC) at Baseline and End of Period 1
Description
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.
Time Frame
12 months
Secondary Outcome Measure Information:
Title
Number of Patients at Risk of Event of Disease Worsening or Death up to the End of Study
Description
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).
Time Frame
Up to end of study (Up to 24 months)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Signed informed consent. Male or female patients of at least 18 years of age (females of child-bearing potential must use a reliable method of contraception). 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: Interstitial lung disease due to conditions other than IPF. Presence of extensive honeycombing on Baseline high-resolution computed tomography (HRCT) scan performed within 3 months prior to randomization. Severe concomitant illness limiting life expectancy (< 1 year). Severe restrictive lung disease: forced vital capacity (FVC) < 50% predicted, or FVC < 1.2 liter. Diffusing capacity of the lung for carbon monoxide (DLCO) < 30% predicted. Residual volume ≥ 120% predicted. Obstructive lung disease: forced expiratory volume in 1 second (FEV1)/FVC) < 0.70. Documented sustained improvement of the patient's IPF condition up to 12 months prior to randomization with or without IPF-specific therapy. Recent pulmonary or upper respiratory tract infection (up to 4 weeks prior to randomization). Acute or chronic impairment (other than dyspnea) limiting the ability to comply with study requirements (e.g., pulmonary function tests). Chronic heart failure with New York Heart Association class III/IV or known left ventricular ejection fraction < 25%. Moderate to severe hepatic impairment, i.e., Child-Pugh Class B or C. Estimated creatinine clearance < 30 mL/min. Aspartate aminotransferase (AST) and/or alanine aminotransferase > 1.5 x upper limit of normal. Hemoglobin < 75% of the lower limit of the normal range. Systolic blood pressure < 100 mmHg. Pregnant or breast-feeding. Current drug or alcohol dependence. 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. Treatment with endothelin receptor antagonists within 4 weeks prior to randomization. Systemic treatment within 4 weeks prior to randomization with cyclosporine A or tacrolimus, everolimus, sirolimus (calcineurin or mammalian target of rapamycin (mTOR) inhibitors). Treatment with Cytochrome P450 3A inducers within 4 weeks prior to randomization. Known hypersensitivity to drugs of the same class as the study drug, or any of their excipients. Planned treatment, or treatment with another investigational drug within 4 weeks prior to randomization.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Loic Perchenet, Ph.D.
Organizational Affiliation
Actelion
Official's Role
Study Chair
Facility Information:
Facility Name
University of Alabama at Birmingham
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35294
Country
United States
Facility Name
Pulmonary Associates, P.A.
City
Phoenix
State/Province
Arizona
ZIP/Postal Code
85006
Country
United States
Facility Name
Mayo Clinic - Arizona
City
Scottsdale
State/Province
Arizona
ZIP/Postal Code
85259
Country
United States
Facility Name
U.C. Davis University of California
City
Sacramento
State/Province
California
ZIP/Postal Code
95817
Country
United States
Facility Name
UCSD Pulmonary Critical Care
City
San Diego
State/Province
California
ZIP/Postal Code
92103
Country
United States
Facility Name
University of California - San Francisco
City
San Francisco
State/Province
California
ZIP/Postal Code
94143
Country
United States
Facility Name
Stanford University Medical Center - Chest Clinic
City
Stanford
State/Province
California
ZIP/Postal Code
94305
Country
United States
Facility Name
National Jewish Medical & Research Center
City
Denver
State/Province
Colorado
ZIP/Postal Code
80206
Country
United States
Facility Name
Yale University School of Medicine
City
New Haven
State/Province
Connecticut
ZIP/Postal Code
06520
Country
United States
Facility Name
Wichita Clinic P.A
City
Wichita
State/Province
Kansas
ZIP/Postal Code
67208
Country
United States
Facility Name
St. Luke's Medical Group
City
Chesterfield
State/Province
Missouri
ZIP/Postal Code
63017
Country
United States
Facility Name
The Cleveland Clinic Foundation
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44195
Country
United States
Facility Name
Temple University Hospital - Lung Center
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19140
Country
United States
Facility Name
Baylor College of Medicine - Baylor Clinic
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
University of Wisconsin - Madison
City
Madison
State/Province
Wisconsin
ZIP/Postal Code
53792
Country
United States
Facility Name
Prince Charles Hospital Lung Transplant
City
Chermside
Country
Australia
Facility Name
St. Vincent's Public Hospital
City
Darlinghurst
Country
Australia
Facility Name
The Alfred Hospital
City
Melbourne
Country
Australia
Facility Name
Royal Perth Hospital
City
Perth
Country
Australia
Facility Name
University of Alberta - Health Sciences Center
City
Edmonton
State/Province
Alberta
ZIP/Postal Code
T6G2B7
Country
Canada
Facility Name
Kelowna General Hospital
City
Kelowna
State/Province
British Columbia
ZIP/Postal Code
V1W3T1
Country
Canada
Facility Name
St. Paul's Hospital
City
Vancouver
State/Province
British Columbia
ZIP/Postal Code
V6Z1Y6
Country
Canada
Facility Name
St. Joseph's Healthcare
City
Hamilton
State/Province
Ontario
ZIP/Postal Code
L8N4A6
Country
Canada
Facility Name
Toronto General Hospital
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5G2N2
Country
Canada
Facility Name
Hospital Notre-Dame du CHUM
City
Montreal
State/Province
Quebec
ZIP/Postal Code
H2L4M1
Country
Canada
Facility Name
Hopital Avicenne
City
Bobigny
Country
France
Facility Name
Hôpital Cardiologique et Pneumologique Louis Pradel
City
Bron
Country
France
Facility Name
CHRU - Hopital Calmette Clinique des Maladies Respiratoires
City
Lille
Country
France
Facility Name
Helios Klinikum Emil von Behring
City
Berlin
Country
Germany
Facility Name
Justus-Liebig-Universität Gießen
City
Giessen
Country
Germany
Facility Name
Fachklinik fur Lungenerkrankungen
City
Immenhausen
Country
Germany
Facility Name
Universität zu Köln
City
Koln
Country
Germany
Facility Name
Ludwig-Maximilian-Universität München
City
Munchen
Country
Germany
Facility Name
Hadassah Ein Kerem Medical Center
City
Jerusalem
Country
Israel
Facility Name
Rabin Medical Center, Beilinson Hospital
City
Petach Tikvah
Country
Israel
Facility Name
Kaplan Medical Center
City
Rehovot
Country
Israel
Facility Name
Tel-Aviv Sourasky Medical Center
City
Tel Aviv
Country
Israel
Facility Name
The Chaim Sheba Medical Center
City
Tel Hashomer
Country
Israel
Facility Name
Ospedale San Giuseppe Milanocuore
City
Milan
Country
Italy
Facility Name
Università degli Studi di Torino Clinica di Malattie dell'Apparato Respiratorio
City
Orbassano
Country
Italy
Facility Name
A.O.U Policlinico Tor Vergata
City
Roma
Country
Italy
Facility Name
Ospedale di Cattinara
City
Trieste
Country
Italy
Facility Name
Bolnišnica Golnik
City
Golnik
Country
Slovenia
Facility Name
Centre for Chest Diseases, Milpark Hospital
City
Johannesburg
Country
South Africa
Facility Name
Pretoria East Hospital
City
Pretoria
Country
South Africa
Facility Name
Hospital Clinic I Provincial de Barcelona
City
Barcelona
Country
Spain
Facility Name
Hospital General Vall d'Hebron
City
Barcelona
Country
Spain
Facility Name
Fundación Hospital Alcorcón
City
Madrid
Country
Spain
Facility Name
Hospital Clinico San Carlos
City
Madrid
Country
Spain
Facility Name
Hospital Universitario Ramón y Cajal
City
Madrid
Country
Spain
Facility Name
Karolinska Universitetssjukhuset Lung Allergi kliniken
City
Stockholm
Country
Sweden
Facility Name
Ankara University School of Medicine
City
Ankara
Country
Turkey
Facility Name
Ege University School of Medicine
City
Izmir
Country
Turkey

12. IPD Sharing Statement

Citations:
PubMed Identifier
23682110
Citation
Raghu G, Million-Rousseau R, Morganti A, Perchenet L, Behr J; MUSIC Study Group. Macitentan for the treatment of idiopathic pulmonary fibrosis: the randomised controlled MUSIC trial. Eur Respir J. 2013 Dec;42(6):1622-32. doi: 10.1183/09031936.00104612. Epub 2013 May 16.
Results Reference
derived

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Macitentan Use in an Idiopathic Pulmonary Fibrosis Clinical Study

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