Safety and pharmacokinetics of nintedanib and pirfenidone in idiopathic pulmonary fibrosis.

Abstract

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.

• Authors: Takashi Ogura, Hiroyuki Taniguchi, Arata Azuma, Yoshikazu Inoue, Yasuhiro Kondoh, Yoshinori Hasegawa, Masashi Bando, Shinji Abe, Yoshiro Mochizuki, Kingo Chida, Matthias Klüglich, Tsuyoshi Fujimoto, Kotaro Okazaki, Yusuke Tadayasu, Wataru Sakamoto, Yukihiko Sugiyama
• Journal: The European respiratory journal (Eur Respir J) Vol. 45 Issue 5 Pg. 1382-92 (May 2015) ISSN: 1399-3003 [Electronic] England
• PMID: 25504994 (Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: Copyright ©ERS 2015.

Chemical References

• Anti-Inflammatory Agents, Non-Steroidal
• Enzyme Inhibitors
• Indoles
• Pyridones
• pirfenidone
• nintedanib

Topics

• Aged
• Anti-Inflammatory Agents, Non-Steroidal (administration & dosage, adverse effects, pharmacokinetics)
• Dose-Response Relationship, Drug
• Double-Blind Method
• Enzyme Inhibitors (administration & dosage, adverse effects, pharmacokinetics)
• Female
• Humans
• Idiopathic Pulmonary Fibrosis (drug therapy)
• Indoles (administration & dosage, adverse effects, pharmacokinetics)
• Japan
• Male
• Middle Aged
• Patient Safety
• Pyridones (administration & dosage, adverse effects, pharmacokinetics)
• Treatment Outcome
• Vital Capacity