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

Inclusion criteria

• Written informed consent consistent with International Conference on Harmonisation Good Clinical Practice and local laws, signed prior to participation in the trial including any study related procedures being performed;
• Male or female patients aged >=40 years at Visit 1;
• A clinical diagnosis of Idiopathic pulmonary fibrosis (IPF) within the last 3 years from visit 0, based upon the American Thoracic Society/ European Respiratory Society /Japanese Respiratory Society/ Latin American Thoracic Association 2011 guideline;
• Chest high resolution computed tomography (HRCT) scan performed within 18 months of Visit 0;
• Combination of HRCT pattern, and surgical lung biopsy pattern (the latter if available) as assessed by central review are consistent with the diagnosis of Idiopathic pulmonary fibrosis;
• Forced vital capacity (FVC) >=80% of predicted normal at Visit 1.

Exclusion criteria

• 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;
• Further exclusion criteria apply.