Abstract
Background: A randomised, placebo-controlled, 14- or 28-day, dose-finding, Phase II trial evaluated the safety and pharmacokinetics of nintedanib alone and when added to ongoing pirfenidone therapy in Japanese patients with idiopathic pulmonary fibrosis (IPF). Patients who completed this trial and were still receiving pirfenidone could receive combination therapy with nintedanib and pirfenidone open-label in an extension study.
Aim: To investigate the long-term safety and tolerability of nintedanib in combination with pirfenidone in patients with IPF.
Methods: Patients received open-label nintedanib 150 mg twice daily (bid) and pirfenidone (400 or 600 mg three times daily) in the extension trial. Nintedanib treatment interruption and/or dose reduction to 100 mg bid were permitted.
Results: Twenty patients were treated in the extension trial. Mean (SD) duration of exposure in the extension was 27.0 (15.8) months. The most frequently reported adverse events in the extension were progression of IPF (which included disease worsening and acute exacerbations) (13 patients; 65%), diarrhoea (13 patients; 65%), nausea (12 patients; 60%), constipation (8 patients; 40%) and decreased appetite (8 patients; 40%). One patient discontinued treatment due to a gastrointestinal adverse event (diarrhoea).
Conclusion: In Japanese patients with IPF, treatment with nintedanib in combination with pirfenidone had an acceptable safety and tolerability profile, in line with the adverse event profiles for each drug. No new safety signals were identified. However, no definite conclusions on the safety and tolerability of combination treatment can be drawn based on the small number of patients in this study.
- Copyright ©the authors 2016
