Effect of Nintedanib on Biomarkers of Extracellular Matrix Turnover in Patients With Idiopathic Pulmonary Fibrosis and Limited Forced Vital Capacity Impairment

Alanine transaminase, Aspartate aminotransferase \> 1.5 fold upper limit of normal (ULN) at Visit 1;

Total bilirubin \> 1.5 fold ULN at Visit 1;

Patients with underlying chronic liver disease (Child Pugh A, B or C hepatic impairment);

Relevant airways obstruction, i.e. pre-bronchodilator Forced expiratory volume in 1 second / Forced vital capacity \< 0.70;

History of myocardial infarction within 6 months of visit 1 or unstable angina within 1 month of Visit 1;

Bleeding Risk:

* Known genetic predisposition to bleeding;

* Patients who require fibrinolysis, full-dose therapeutic anticoagulation or high dose antiplatelet therapy;

* History of haemorrhagic central nervous system (CNS) event within 12 months prior to Visit 1;

* History of haemoptysis or haematuria, active gastro-intestinal bleeding or ulcers and/or major injury or surgery within 3 months prior to Visit 1;

* International normalised ratio (INR) \> 2 at Visit 1;

* Prothrombin time (PT) and partial thromboplastin time (PTT) \> 150% of ULN at Visit 1;

Planned major surgery during the trial participation, including lung transplantation, major abdominal or major intestinal surgery;

History of thrombotic event (including stroke and transient ischemic attack) within 12 months of Visit 1;

Creatinine clearance \< 30 mL/min calculated by Cockcroft-Gault formula at Visit 1;

Treatment with nintedanib, pirfenidone, azathioprine, cyclophosphamide, cyclosporine, any other investigational drug, n-acetylcysteine, prednisone/prednisolone \>15 mg daily or \>30 mg every 2 days OR use of other systemic corticosteroids as well as any investigational drugs within 4 weeks of Visit 2;

Known hypersensitivity to nintedanib, peanut, soya or to any other components of the study medication;

Prior discontinuation of nintedanib treatment due to intolerability/ adverse events considered drug related;

A disease or condition which in the opinion of the investigator may interfere with testing procedures or put the patient at risk when participating in this trial;

Alcohol or drug abuse which in the opinion of the treating physician would interfere with the treatment and would affect patient's ability to participate in this trial;

Patients not able to understand and follow any study procedures such as but not limited to home spirometry, including completion of self-administered questionnaires without help;

Women who are pregnant, nursing, who plan to become pregnant while in the trial or female patients with positive pregnancy (ß-HCG) test at Visit 1 and/or Visit 2;

Women of childbearing potential4 not willing or able to use highly effective methods of birth control per International Conference on Harmonisation (ICH) M3 (R2) that result in a low failure rate of less than 1% per year when used consistently and correctly.

Patients with acute IPF exacerbation or any respiratory tract infection in the four weeks prior to Visit 1 or during the screening period;

Patients who are or have been participating in another trial with investigational drug/s within one month prior to Visit 1 and patients who have previously been enrolled in this trial;

What this study is about