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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT00903331




Registration number
NCT00903331
Ethics application status
Date submitted
14/05/2009
Date registered
15/05/2009
Date last updated
2/01/2014

Titles & IDs
Public title
Macitentan Use in an Idiopathic Pulmonary Fibrosis Clinical Study
Scientific 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
Secondary ID [1] 0 0
AC-055B201
Universal Trial Number (UTN)
Trial acronym
MUSIC
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Idiopathic Pulmonary Fibrosis 0 0
Idiopathic Pulmonary Fibrosis 0 0
Condition category
Condition code
Inflammatory and Immune System 0 0 0 0
Connective tissue diseases
Inflammatory and Immune System 0 0 0 0
Other inflammatory or immune system disorders
Respiratory 0 0 0 0
Other respiratory disorders / diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - ACT-064992 (macitentan)
Treatment: Drugs - Placebo
Treatment: Drugs - ACT-064992 (macitentan)
Treatment: Drugs - Placebo

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

Placebo Comparator: Placebo - Matching placebo, once daily

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

Placebo Comparator: Placebo - Matching placebo, once daily


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

Treatment: Drugs: Placebo
matching placebo, once daily

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

Treatment: Drugs: Placebo
matching placebo, once daily

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
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.
Timepoint [1] 0 0
12 months
Primary outcome [2] 0 0
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.
Timepoint [2] 0 0
12 months
Secondary outcome [1] 0 0
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).
Timepoint [1] 0 0
Up to end of study (Up to 24 months)
Secondary outcome [2] 0 0
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).
Timepoint [2] 0 0
Up to end of study (Up to 24 months)

Eligibility
Key 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.
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key 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
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Prince Charles Hospital Lung Transplant - Chermside
Recruitment hospital [2] 0 0
St. Vincent's Public Hospital - Darlinghurst
Recruitment hospital [3] 0 0
The Alfred Hospital - Melbourne
Recruitment hospital [4] 0 0
Royal Perth Hospital - Perth
Recruitment postcode(s) [1] 0 0
- Chermside
Recruitment postcode(s) [2] 0 0
- Darlinghurst
Recruitment postcode(s) [3] 0 0
- Melbourne
Recruitment postcode(s) [4] 0 0
- Perth
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
Arizona
Country [3] 0 0
United States of America
State/province [3] 0 0
California
Country [4] 0 0
United States of America
State/province [4] 0 0
Colorado
Country [5] 0 0
United States of America
State/province [5] 0 0
Connecticut
Country [6] 0 0
United States of America
State/province [6] 0 0
Kansas
Country [7] 0 0
United States of America
State/province [7] 0 0
Missouri
Country [8] 0 0
United States of America
State/province [8] 0 0
Ohio
Country [9] 0 0
United States of America
State/province [9] 0 0
Pennsylvania
Country [10] 0 0
United States of America
State/province [10] 0 0
Texas
Country [11] 0 0
United States of America
State/province [11] 0 0
Wisconsin
Country [12] 0 0
Canada
State/province [12] 0 0
Alberta
Country [13] 0 0
Canada
State/province [13] 0 0
British Columbia
Country [14] 0 0
Canada
State/province [14] 0 0
Ontario
Country [15] 0 0
Canada
State/province [15] 0 0
Quebec
Country [16] 0 0
France
State/province [16] 0 0
Bobigny
Country [17] 0 0
France
State/province [17] 0 0
Bron
Country [18] 0 0
France
State/province [18] 0 0
Lille
Country [19] 0 0
Germany
State/province [19] 0 0
Berlin
Country [20] 0 0
Germany
State/province [20] 0 0
Giessen
Country [21] 0 0
Germany
State/province [21] 0 0
Immenhausen
Country [22] 0 0
Germany
State/province [22] 0 0
Koln
Country [23] 0 0
Germany
State/province [23] 0 0
Munchen
Country [24] 0 0
Israel
State/province [24] 0 0
Jerusalem
Country [25] 0 0
Israel
State/province [25] 0 0
Petach Tikvah
Country [26] 0 0
Israel
State/province [26] 0 0
Rehovot
Country [27] 0 0
Israel
State/province [27] 0 0
Tel Aviv
Country [28] 0 0
Israel
State/province [28] 0 0
Tel Hashomer
Country [29] 0 0
Italy
State/province [29] 0 0
Milan
Country [30] 0 0
Italy
State/province [30] 0 0
Orbassano
Country [31] 0 0
Italy
State/province [31] 0 0
Roma
Country [32] 0 0
Italy
State/province [32] 0 0
Trieste
Country [33] 0 0
Slovenia
State/province [33] 0 0
Golnik
Country [34] 0 0
South Africa
State/province [34] 0 0
Johannesburg
Country [35] 0 0
South Africa
State/province [35] 0 0
Pretoria
Country [36] 0 0
Spain
State/province [36] 0 0
Barcelona
Country [37] 0 0
Spain
State/province [37] 0 0
Madrid
Country [38] 0 0
Sweden
State/province [38] 0 0
Stockholm
Country [39] 0 0
Turkey
State/province [39] 0 0
Ankara
Country [40] 0 0
Turkey
State/province [40] 0 0
Izmir

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Actelion
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/show/NCT00903331
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Loic Perchenet, Ph.D.
Address 0 0
Actelion
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications