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

January 2, 2014 updated by: Actelion

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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

Enrollment (Actual)

178

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

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

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: QUADRUPLE

Arms and Interventions

Participant Group / 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 Names:
  • macitentan
PLACEBO_COMPARATOR: Placebo
Matching placebo, once daily
Drug: Placebo
matching placebo, once daily

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
12 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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).
Up to end of study (Up to 24 months)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Actelion

Investigators

  • Study Chair: Loic Perchenet, Ph.D., Actelion

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

May 1, 2009

Primary Completion (ACTUAL)

June 1, 2011

Study Completion (ACTUAL)

August 1, 2011

Study Registration Dates

First Submitted

May 14, 2009

First Submitted That Met QC Criteria

May 15, 2009

First Posted (ESTIMATE)

May 18, 2009

Study Record Updates

Last Update Posted (ESTIMATE)

February 17, 2014

Last Update Submitted That Met QC Criteria

January 2, 2014

Last Verified

January 1, 2014

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • AC-055B201

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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