Clinical trial NCT00903331: Macitentan Use in an Idiopathic Pulmonary Fibrosis Clinical Study
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
Overall status: COMPLETED
Phase: PHASE2
Conditions: Idiopathic Pulmonary Fibrosis
Keywords: idiopathic pulmonary fibrosis
MUSIC
Lead sponsor: Actelion
Sponsor class: INDUSTRY
First posted: 2009-05-18
Enrollment: 178
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility 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.

Primary outcomes:
measure: Forced Vital Capacity (FVC) at Baseline and End of Period 1
timeFrame: 12 months
Secondary outcomes:
measure: Number of Patients at Risk of Event of Disease Worsening or Death up to the End of Study
timeFrame: Up to end of study (Up to 24 months)
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Phoenix
country: United States
facility: Pulmonary Associates, P.A.
state: Arizona
city: Scottsdale
country: United States
facility: Mayo Clinic - Arizona
state: Arizona
city: Sacramento
country: United States
facility: U.C. Davis University of California
state: California
city: San Diego
country: United States
facility: UCSD Pulmonary Critical Care
state: California
city: San Francisco
country: United States
facility: University of California - San Francisco
state: California
city: Stanford
country: United States
facility: Stanford University Medical Center - Chest Clinic
state: California
city: Denver
country: United States
facility: National Jewish Medical & Research Center
state: Colorado
city: New Haven
country: United States
facility: Yale University School of Medicine
state: Connecticut
city: Wichita
country: United States
facility: Wichita Clinic P.A
state: Kansas
city: Chesterfield
country: United States
facility: St. Luke's Medical Group
state: Missouri
city: Cleveland
country: United States
facility: The Cleveland Clinic Foundation
state: Ohio
city: Philadelphia
country: United States
facility: Temple University Hospital - Lung Center
state: Pennsylvania
city: Houston
country: United States
facility: Baylor College of Medicine - Baylor Clinic
state: Texas
city: Madison
country: United States
facility: University of Wisconsin - Madison
state: Wisconsin
city: Chermside
country: Australia
facility: Prince Charles Hospital Lung Transplant
city: Darlinghurst
country: Australia
facility: St. Vincent's Public Hospital
city: Melbourne
country: Australia
facility: The Alfred Hospital
city: Perth
country: Australia
facility: Royal Perth Hospital
city: Edmonton
country: Canada
facility: University of Alberta - Health Sciences Center
state: Alberta
city: Kelowna
country: Canada
facility: Kelowna General Hospital
state: British Columbia
city: Vancouver
country: Canada
facility: St. Paul's Hospital
state: British Columbia
city: Hamilton
country: Canada
facility: St. Joseph's Healthcare
state: Ontario
city: Toronto
country: Canada
facility: Toronto General Hospital
state: Ontario
city: Montreal
country: Canada
facility: Hospital Notre-Dame du CHUM
state: Quebec
city: Bobigny
country: France
facility: Hopital Avicenne
city: Bron
country: France
facility: Hôpital Cardiologique et Pneumologique Louis Pradel
city: Lille
country: France
facility: CHRU - Hopital Calmette Clinique des Maladies Respiratoires
city: Berlin
country: Germany
facility: Helios Klinikum Emil von Behring
city: Giessen
country: Germany
facility: Justus-Liebig-Universität Gießen
city: Immenhausen
country: Germany
facility: Fachklinik fur Lungenerkrankungen
city: Koln
country: Germany
facility: Universität zu Köln
city: Munchen
country: Germany
facility: Ludwig-Maximilian-Universität München
city: Jerusalem
country: Israel
facility: Hadassah Ein Kerem Medical Center
city: Petach Tikvah
country: Israel
facility: Rabin Medical Center, Beilinson Hospital
city: Rehovot
country: Israel
facility: Kaplan Medical Center
city: Tel Aviv
country: Israel
facility: Tel-Aviv Sourasky Medical Center
city: Tel Hashomer
country: Israel
facility: The Chaim Sheba Medical Center
city: Milan
country: Italy
facility: Ospedale San Giuseppe Milanocuore
city: Orbassano
country: Italy
facility: Università degli Studi di Torino Clinica di Malattie dell'Apparato Respiratorio
city: Roma
country: Italy
facility: A.O.U Policlinico Tor Vergata
city: Trieste
country: Italy
facility: Ospedale di Cattinara
city: Golnik
country: Slovenia
facility: Bolnišnica Golnik
city: Johannesburg
country: South Africa
facility: Centre for Chest Diseases, Milpark Hospital
city: Pretoria
country: South Africa
facility: Pretoria East Hospital
city: Barcelona
country: Spain
facility: Hospital Clinic I Provincial de Barcelona
city: Barcelona
country: Spain
facility: Hospital General Vall d'Hebron
city: Madrid
country: Spain
facility: Fundación Hospital Alcorcón
city: Madrid
country: Spain
facility: Hospital Clinico San Carlos
city: Madrid
country: Spain
facility: Hospital Universitario Ramón y Cajal
city: Stockholm
country: Sweden
facility: Karolinska Universitetssjukhuset Lung Allergi kliniken
city: Ankara
country: Turkey
facility: Ankara University School of Medicine
city: Izmir
country: Turkey
facility: Ege University School of Medicine
Study officials:
affiliation: Actelion
name: Loic Perchenet, Ph.D.
role: STUDY_CHAIR
References:
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.