Pharmacokinetics (PK) of nintedanib with add-on pirfenidone in patients with idiopathic pulmonary fibrosis (IPF): results from INJOURNEY

Introduction: In a small phase II trial in Japanese patients with IPF, there was a trend towards lower nintedanib exposure when nintedanib 150 mg bid was added to pirfenidone than when given alone. Aim: To explore the PK of nintedanib with add-on pirfenidone. Methods: After a 4 – 5 week run-in with nintedanib 150 mg bid, patients with IPF were randomised to open-label nintedanib 150 mg bid with add-on pirfenidone or nintedanib 150 mg bid alone for 12 weeks. In the combination group, patients received pirfenidone 267 mg tid from randomisation to week 1, 534 mg tid from week 1 to week 2, 801 mg tid from week 2. Pre-dose plasma trough concentrations were measured at baseline (for nintedanib) and at weeks 2 and 4 (for nintedanib and pirfenidone). Results: Pre-dose pirfenidone gMean (gCV%) concentrations were 1120 (122) and 1220 (91) ng/mL at weeks 2 and 4, respectively. Pre-dose plasma trough concentrations of nintedanib were similar at each time point, irrespective of whether nintedanib 150 mg bid was administered alone or with add-on pirfenidone 534 mg or 801 mg tid (table). Moderate to high variability was observed in both groups. Nintedanib 150 mg bid alone Nintedanib 150 mg bid with add-on pirfenidone 534 mg or 801 mg tid* † N gMean (gCV%) N gMean (gCV%) Pre-dose concentration of nintedanib (ng/mL) Baseline* 46 7.08 (56.0) 46 7.65 (72.5) Week 2 41 7.25 (52.7) 35 8.17 (69.8) Week 4 44 5.92 (73.5) 30 7.13 (63.9) *Nintedanib 150 mg bid alone at baseline. † Pirfenidone dose titration: 267 mg tid from randomisation to week 1, 534 mg tid from week 1 to week 2. 801 mg tid from week 2. gCV, geometric coefficient of variation; gMean, geometric mean. Conclusion: In patients with IPF, nintedanib plasma trough concentrations were similar when nintedanib was administered alone or with add-on pirfenidone; however, data from a dedicated drug-drug interaction study are needed to draw robust conclusions.