Macitentan for the treatment of idiopathic pulmonary fibrosis: The randomised controlled MUSIC trial

Ganesh Raghu, Rachel Million-Rousseau, Adele Morganti, Loïc Perchenet, Juergen Behr, N. Goh, A. Glanville, M. Musk, P. Hopkins, D. C. Lien, C. Chan, J. D. Rolf, P. Wilcox, P. G. Cox, H. Manganas, V. Cottin, D. Valeyre, B. Walleart, S. Andreas, C. NeurohrA. Guenther, N. Schönfeld, A. Koch, M. Kramer, R. Breuer, I. Ben-Dov, G. Fink, Y. Schwarz, C. Albera, M. Confalonieri, C. Saltini, S. Harari, M. Flezar, M. Greenblatt, G. J. Ras, F. Morell, J. L. Alvarez-Sala, A. Xaubet, A. Sueiro, M. J. Linares, M. Sköld, O. Kayacan, N. Mogulkoc, A. Chan, J. Chapman, J. Parambil, N. Ettinger, J. Golden, K. C. Meyer, J. J. Swigris, G. L. Yung, D. Antin-Ozerkis, P. K. Mohabir, L. J. Wesselius, J. De Andrade, F. Cordova, Z. Safdar, M. Wencel

Research output: Contribution to journalArticle

147 Citations (Scopus)

Abstract

Idiopathic pulmonary fibrosis is a progressive, fatal disease. This prospective, randomised, double-blind, multicentre, parallel-group, placebo-controlled phase II trial (NCT00903331) investigated the efficacy and safety of the endothelin receptor antagonist macitentan in idiopathic pulmonary fibrosis. Eligible subjects were adults with idiopathic pulmonary fibrosis of <3 years duration and a histological pattern of usual interstitial pneumonia on surgical lung biopsy. The primary objective was to demonstrate that macitentan (10 mg once daily) positively affected forced vital capacity versus placebo. Using a centralised system, 178 subjects were randomised (2:1) to macitentan (n=119) or placebo (n=59). The median change from baseline up to month 12 in forced vital capacity was -0.20 L in the macitentan arm and -0.20 L in the placebo arm. Overall, no differences between treatments were observed in pulmonary function tests or time to disease worsening or death. Median exposures to macitentan and placebo were 14.5 months and 15.0 months, respectively. Alanine and/or aspartate aminotransferase elevations over three times upper limit of normal arose in 3.4% of macitentan-treated subjects and 5.1% of placebo recipients. In conclusion, the primary objective was not met. Long-term exposure to macitentan was well tolerated with a similar, low incidence of elevated hepatic aminotransferases in each treatment group.

Original languageEnglish (US)
Pages (from-to)1622-1632
Number of pages11
JournalEuropean Respiratory Journal
Volume42
Issue number6
DOIs
StatePublished - Dec 1 2013

Fingerprint

Idiopathic Pulmonary Fibrosis
Randomized Controlled Trials
Placebos
Vital Capacity
Therapeutics
Respiratory Function Tests
Aspartate Aminotransferases
Transaminases
macitentan
Alanine Transaminase
Biopsy
Safety
Lung
Liver
Incidence

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine

Cite this

Raghu, G., Million-Rousseau, R., Morganti, A., Perchenet, L., Behr, J., Goh, N., ... Wencel, M. (2013). Macitentan for the treatment of idiopathic pulmonary fibrosis: The randomised controlled MUSIC trial. European Respiratory Journal, 42(6), 1622-1632. https://doi.org/10.1183/09031936.00104612

Macitentan for the treatment of idiopathic pulmonary fibrosis : The randomised controlled MUSIC trial. / Raghu, Ganesh; Million-Rousseau, Rachel; Morganti, Adele; Perchenet, Loïc; Behr, Juergen; Goh, N.; Glanville, A.; Musk, M.; Hopkins, P.; Lien, D. C.; Chan, C.; Rolf, J. D.; Wilcox, P.; Cox, P. G.; Manganas, H.; Cottin, V.; Valeyre, D.; Walleart, B.; Andreas, S.; Neurohr, C.; Guenther, A.; Schönfeld, N.; Koch, A.; Kramer, M.; Breuer, R.; Ben-Dov, I.; Fink, G.; Schwarz, Y.; Albera, C.; Confalonieri, M.; Saltini, C.; Harari, S.; Flezar, M.; Greenblatt, M.; Ras, G. J.; Morell, F.; Alvarez-Sala, J. L.; Xaubet, A.; Sueiro, A.; Linares, M. J.; Sköld, M.; Kayacan, O.; Mogulkoc, N.; Chan, A.; Chapman, J.; Parambil, J.; Ettinger, N.; Golden, J.; Meyer, K. C.; Swigris, J. J.; Yung, G. L.; Antin-Ozerkis, D.; Mohabir, P. K.; Wesselius, L. J.; De Andrade, J.; Cordova, F.; Safdar, Z.; Wencel, M.

In: European Respiratory Journal, Vol. 42, No. 6, 01.12.2013, p. 1622-1632.

Research output: Contribution to journalArticle

Raghu, G, Million-Rousseau, R, Morganti, A, Perchenet, L, Behr, J, Goh, N, Glanville, A, Musk, M, Hopkins, P, Lien, DC, Chan, C, Rolf, JD, Wilcox, P, Cox, PG, Manganas, H, Cottin, V, Valeyre, D, Walleart, B, Andreas, S, Neurohr, C, Guenther, A, Schönfeld, N, Koch, A, Kramer, M, Breuer, R, Ben-Dov, I, Fink, G, Schwarz, Y, Albera, C, Confalonieri, M, Saltini, C, Harari, S, Flezar, M, Greenblatt, M, Ras, GJ, Morell, F, Alvarez-Sala, JL, Xaubet, A, Sueiro, A, Linares, MJ, Sköld, M, Kayacan, O, Mogulkoc, N, Chan, A, Chapman, J, Parambil, J, Ettinger, N, Golden, J, Meyer, KC, Swigris, JJ, Yung, GL, Antin-Ozerkis, D, Mohabir, PK, Wesselius, LJ, De Andrade, J, Cordova, F, Safdar, Z & Wencel, M 2013, 'Macitentan for the treatment of idiopathic pulmonary fibrosis: The randomised controlled MUSIC trial', European Respiratory Journal, vol. 42, no. 6, pp. 1622-1632. https://doi.org/10.1183/09031936.00104612
Raghu, Ganesh ; Million-Rousseau, Rachel ; Morganti, Adele ; Perchenet, Loïc ; Behr, Juergen ; Goh, N. ; Glanville, A. ; Musk, M. ; Hopkins, P. ; Lien, D. C. ; Chan, C. ; Rolf, J. D. ; Wilcox, P. ; Cox, P. G. ; Manganas, H. ; Cottin, V. ; Valeyre, D. ; Walleart, B. ; Andreas, S. ; Neurohr, C. ; Guenther, A. ; Schönfeld, N. ; Koch, A. ; Kramer, M. ; Breuer, R. ; Ben-Dov, I. ; Fink, G. ; Schwarz, Y. ; Albera, C. ; Confalonieri, M. ; Saltini, C. ; Harari, S. ; Flezar, M. ; Greenblatt, M. ; Ras, G. J. ; Morell, F. ; Alvarez-Sala, J. L. ; Xaubet, A. ; Sueiro, A. ; Linares, M. J. ; Sköld, M. ; Kayacan, O. ; Mogulkoc, N. ; Chan, A. ; Chapman, J. ; Parambil, J. ; Ettinger, N. ; Golden, J. ; Meyer, K. C. ; Swigris, J. J. ; Yung, G. L. ; Antin-Ozerkis, D. ; Mohabir, P. K. ; Wesselius, L. J. ; De Andrade, J. ; Cordova, F. ; Safdar, Z. ; Wencel, M. / Macitentan for the treatment of idiopathic pulmonary fibrosis : The randomised controlled MUSIC trial. In: European Respiratory Journal. 2013 ; Vol. 42, No. 6. pp. 1622-1632.
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abstract = "Idiopathic pulmonary fibrosis is a progressive, fatal disease. This prospective, randomised, double-blind, multicentre, parallel-group, placebo-controlled phase II trial (NCT00903331) investigated the efficacy and safety of the endothelin receptor antagonist macitentan in idiopathic pulmonary fibrosis. Eligible subjects were adults with idiopathic pulmonary fibrosis of <3 years duration and a histological pattern of usual interstitial pneumonia on surgical lung biopsy. The primary objective was to demonstrate that macitentan (10 mg once daily) positively affected forced vital capacity versus placebo. Using a centralised system, 178 subjects were randomised (2:1) to macitentan (n=119) or placebo (n=59). The median change from baseline up to month 12 in forced vital capacity was -0.20 L in the macitentan arm and -0.20 L in the placebo arm. Overall, no differences between treatments were observed in pulmonary function tests or time to disease worsening or death. Median exposures to macitentan and placebo were 14.5 months and 15.0 months, respectively. Alanine and/or aspartate aminotransferase elevations over three times upper limit of normal arose in 3.4{\%} of macitentan-treated subjects and 5.1{\%} of placebo recipients. In conclusion, the primary objective was not met. Long-term exposure to macitentan was well tolerated with a similar, low incidence of elevated hepatic aminotransferases in each treatment group.",
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T1 - Macitentan for the treatment of idiopathic pulmonary fibrosis

T2 - The randomised controlled MUSIC trial

AU - Raghu, Ganesh

AU - Million-Rousseau, Rachel

AU - Morganti, Adele

AU - Perchenet, Loïc

AU - Behr, Juergen

AU - Goh, N.

AU - Glanville, A.

AU - Musk, M.

AU - Hopkins, P.

AU - Lien, D. C.

AU - Chan, C.

AU - Rolf, J. D.

AU - Wilcox, P.

AU - Cox, P. G.

AU - Manganas, H.

AU - Cottin, V.

AU - Valeyre, D.

AU - Walleart, B.

AU - Andreas, S.

AU - Neurohr, C.

AU - Guenther, A.

AU - Schönfeld, N.

AU - Koch, A.

AU - Kramer, M.

AU - Breuer, R.

AU - Ben-Dov, I.

AU - Fink, G.

AU - Schwarz, Y.

AU - Albera, C.

AU - Confalonieri, M.

AU - Saltini, C.

AU - Harari, S.

AU - Flezar, M.

AU - Greenblatt, M.

AU - Ras, G. J.

AU - Morell, F.

AU - Alvarez-Sala, J. L.

AU - Xaubet, A.

AU - Sueiro, A.

AU - Linares, M. J.

AU - Sköld, M.

AU - Kayacan, O.

AU - Mogulkoc, N.

AU - Chan, A.

AU - Chapman, J.

AU - Parambil, J.

AU - Ettinger, N.

AU - Golden, J.

AU - Meyer, K. C.

AU - Swigris, J. J.

AU - Yung, G. L.

AU - Antin-Ozerkis, D.

AU - Mohabir, P. K.

AU - Wesselius, L. J.

AU - De Andrade, J.

AU - Cordova, F.

AU - Safdar, Z.

AU - Wencel, M.

PY - 2013/12/1

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