PT - JOURNAL ARTICLE AU - Takashi Ogura AU - Hiroyuki Taniguchi AU - Arata Azuma AU - Yoshikazu Inoue AU - Yasuhiro Kondoh AU - Yoshinori Hasegawa AU - Masashi Bando AU - Shinji Abe AU - Yoshiro Mochizuki AU - Kingo Chida AU - Matthias Klüglich AU - Tsuyoshi Fujimoto AU - Kotaro Okazaki AU - Yusuke Tadayasu AU - Wataru Sakamoto AU - Yukihiko Sugiyama TI - Safety and pharmacokinetics of nintedanib and pirfenidone in idiopathic pulmonary fibrosis AID - 10.1183/09031936.00198013 DP - 2014 Dec 10 TA - European Respiratory Journal PG - ERJ-01980-2013 4099 - http://erj.ersjournals.com/content/early/2014/12/16/09031936.00198013.short 4100 - http://erj.ersjournals.com/content/early/2014/12/16/09031936.00198013.full AB - A randomised, double-blind, phase II, dose escalation trial was conducted to assess the safety, tolerability and pharmacokinetics of the tyrosine kinase inhibitor nintedanib, alone and when added to ongoing pirfenidone therapy, in Japanese patients with idiopathic pulmonary fibrosis. 50 Japanese patients were randomised to receive nintedanib or placebo in one of three cohorts (nintedanib 50 mg twice daily or 100 mg twice daily for 14 days, or 150 mg twice daily for 28 days). Patients receiving pirfenidone at inclusion were stratified to every nintedanib dose group and placebo. Adverse events were reported in nine out of 17 patients receiving nintedanib alone and 10 out of 21 patients receiving nintedanib added to pirfenidone. All adverse events were mild or moderate in intensity. Gastrointestinal disorders were the most common adverse event. Maximum plasma concentration and area under the curve at steady state for nintedanib and its metabolites tended to be lower when nintedanib was added to pirfenidone. Nintedanib had no effect on the pharmacokinetics of pirfenidone. In conclusion, further study is needed to evaluate the safety and tolerability profile of nintedanib when added to pirfenidone in patients with idiopathic pulmonary fibrosis. There was a trend toward lower exposure of nintedanib when it was added to pirfenidone. Nintedanib had acceptable safety and tolerability in Japanese patients with IPF http://ow.ly/DNG4k