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.