Macitentan Use in an Idiopathic Pulmonary Fibrosis Clinical Study

Idiopathic Pulmonary Fibrosis Clinical Trial

— 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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00903331
• Other study ID #: AC-055B201
• Status: Completed
• Phase: Phase 2
• First received: May 14, 2009
• Last updated: January 2, 2014
• Start date: May 2009
• Est. completion date: August 2011

Study information

• Verified date: January 2014
• Source: Actelion
• Contact: n/a
• Is FDA regulated: No
• Health authority: Canada: Ethics Review CommitteeCanada: Health CanadaUnited States: Food and Drug AdministrationFrance: 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 HealthSlovenia: Ethics CommitteeAustralia: Department of Health and Ageing Therapeutic Goods AdministrationAustralia: Human Research Ethics CommitteeAustralia: District Research GovernanceGermany: Ethics CommissionGermany: Federal Institute for Drugs and Medical DevicesSouth Africa: Human Research Ethics CommitteeSouth Africa: Medicines Control CouncilTurkey: Ethics CommitteeTurkey: Ministry of HealthIsrael: Ethics CommissionIsrael: Israeli Health Ministry Pharmaceutical AdministrationItaly: Ethics CommitteeSpain: Comité Ético de Investigación ClínicaSpain: Spanish Agency of MedicinesSweden: Medical Products AgencySweden: Regional Ethical Review Board
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 178
• Est. completion date: August 2011
• Est. primary completion date: June 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 a blockers, imatinib and interferon ?,

• 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 Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Fibrosis
• Idiopathic Interstitial Pneumonias
• Idiopathic Pulmonary Fibrosis
• Pulmonary Fibrosis

Intervention

Drug:
• ACT-064992 (macitentan)
ACT-064992 (macitentan) tablet, 10 mg, once daily
• Placebo
matching placebo, once daily

Locations

Country	Name	City	State
Australia	Prince Charles Hospital Lung Transplant	Chermside
Australia	St. Vincent's Public Hospital	Darlinghurst
Australia	The Alfred Hospital	Melbourne
Australia	Royal Perth Hospital	Perth
Canada	University of Alberta - Health Sciences Center	Edmonton	Alberta
Canada	St. Joseph's Healthcare	Hamilton	Ontario
Canada	Kelowna General Hospital	Kelowna	British Columbia
Canada	Hospital Notre-Dame du CHUM	Montreal	Quebec
Canada	Toronto General Hospital	Toronto	Ontario
Canada	St. Paul's Hospital	Vancouver	British Columbia
France	Hopital Avicenne	Bobigny
France	Hôpital Cardiologique et Pneumologique Louis Pradel	Bron
France	CHRU - Hopital Calmette Clinique des Maladies Respiratoires	Lille
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
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
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
Slovenia	Bolnišnica Golnik	Golnik
South Africa	Centre for Chest Diseases, Milpark Hospital	Johannesburg
South Africa	Pretoria East Hospital	Pretoria
Spain	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
Sweden	Karolinska Universitetssjukhuset Lung Allergi kliniken	Stockholm
Turkey	Ankara University School of Medicine	Ankara
Turkey	Ege University School of Medicine	Izmir
United States	University of Alabama at Birmingham	Birmingham	Alabama
United States	St. Luke's Medical Group	Chesterfield	Missouri
United States	The Cleveland Clinic Foundation	Cleveland	Ohio
United States	National Jewish Medical & Research Center	Denver	Colorado
United States	Baylor College of Medicine - Baylor Clinic	Houston	Texas
United States	University of Wisconsin - Madison	Madison	Wisconsin
United States	Yale University School of Medicine	New Haven	Connecticut
United States	Temple University Hospital - Lung Center	Philadelphia	Pennsylvania
United States	Pulmonary Associates, P.A.	Phoenix	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	Mayo Clinic - Arizona	Scottsdale	Arizona
United States	Stanford University Medical Center - Chest Clinic	Stanford	California
United States	Wichita Clinic P.A	Wichita	Kansas

Sponsors (1)

Lead Sponsor	Collaborator
Actelion

Countries where clinical trial is conducted

United States,  Australia,  Canada,  France,  Germany,  Israel,  Italy,  Slovenia,  South Africa,  Spain,  Sweden,  Turkey, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	12 months	No
Secondary	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).	Up to end of study (Up to 24 months)	No