Macitentan Use in an Idiopathic Pulmonary Fibrosis Clinical Study

NCT ID: NCT00903331

Last Updated: 2014-02-17

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 178 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-05-31
• Study Completion Date: 2011-08-31

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.

Conditions

Idiopathic Pulmonary Fibrosis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

ACT-064922

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

Group Type: EXPERIMENTAL

ACT-064992 (macitentan)

Intervention Type: DRUG

ACT-064992 (macitentan) tablet, 10 mg, once daily

Placebo

Matching placebo, once daily

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

matching placebo, once daily

Interventions

ACT-064992 (macitentan)

ACT-064992 (macitentan) tablet, 10 mg, once daily

Intervention Type: DRUG

Placebo

matching placebo, once daily

Intervention Type: DRUG

Other Intervention Names

macitentan

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Actelion

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Loic Perchenet, Ph.D.

Role: STUDY_CHAIR

Actelion

Locations

University of Alabama at Birmingham

Birmingham, Alabama, United States

Pulmonary Associates, P.A.

Phoenix, Arizona, United States

Mayo Clinic - Arizona

Scottsdale, Arizona, United States

U.C. Davis University of California

Sacramento, California, United States

UCSD Pulmonary Critical Care

San Diego, California, United States

University of California - San Francisco

San Francisco, California, United States

Stanford University Medical Center - Chest Clinic

Stanford, California, United States

National Jewish Medical & Research Center

Denver, Colorado, United States

Yale University School of Medicine

New Haven, Connecticut, United States

Wichita Clinic P.A

Wichita, Kansas, United States

St. Luke's Medical Group

Chesterfield, Missouri, United States

The Cleveland Clinic Foundation

Cleveland, Ohio, United States

Temple University Hospital - Lung Center

Philadelphia, Pennsylvania, United States

Baylor College of Medicine - Baylor Clinic

Houston, Texas, United States

University of Wisconsin - Madison

Madison, Wisconsin, United States

Prince Charles Hospital Lung Transplant

Chermside, , Australia

St. Vincent's Public Hospital

Darlinghurst, , Australia

The Alfred Hospital

Melbourne, , Australia

Royal Perth Hospital

Perth, , Australia

University of Alberta - Health Sciences Center

Edmonton, Alberta, Canada

Kelowna General Hospital

Kelowna, British Columbia, Canada

St. Paul's Hospital

Vancouver, British Columbia, Canada

St. Joseph's Healthcare

Hamilton, Ontario, Canada

Toronto General Hospital

Toronto, Ontario, Canada

Hospital Notre-Dame du CHUM

Montreal, Quebec, Canada

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

Universität zu Köln

Cologne, , Germany

Justus-Liebig-Universität Gießen

Giessen, , Germany

Fachklinik fur Lungenerkrankungen

Immenhausen, , Germany

Ludwig-Maximilian-Universität München

München, , 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 Litwinsky, , 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

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 (Türkiye)

Ege University School of Medicine

Izmir, , Turkey (Türkiye)

Countries

United States; Australia; Canada; France; Germany; Israel; Italy; Slovenia; South Africa; Spain; Sweden; Turkey (Türkiye)

References

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.

Reference Type: DERIVED

PMID: 23682110 (View on PubMed)

Other Identifiers

AC-055B201

Identifier Type: -

Identifier Source: org_study_id