Safety, Tolerability and PK of Nintedanib in Combination With Pirfenidone in IPF

Inclusion criteria:

- Written informed consent consistent with ICH-GCP(The International Conference on
Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human
Use- Good clinical practice) and local laws, signed prior to any study procedures
being performed (including any required washout)

- Male or female patients aged greater than or equal to 40 years at visit 1

- Idiopathic Pulmonary Fibrosis (IPF) diagnosis, based upon the ATS (American Thoracic
Society)/ERS (European Respiratory Society)/JRS (Japanese Respiratory Society)/ALAT
(Latin American Thoracic Association) 2011 guideline and confirmed by the investigator
based on chest high resolution computed tomography (HRCT) scan performed within 12
months of visit 1

- FVC (Forced vital capacity) greater than or equal to 50% of predicted normal at visit
1

Exclusion criteria:

- ALT (Alanine transaminase), AST (Aspartate aminotransferase)> 1.5 fold upper limit of
normal (ULN) at visit 1

- Total bilirubin > 1.5 fold ULN at visit 1

- Relevant airways obstruction (i.e. pre-bronchodilator FEV1 (Forced Expiratory Volume
in one second)/FVC <0.7) at visit 1

- 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 (e.g. vitamin K antagonists,
dabigatran, heparin, hirudin etc) or high dose antiplatelet therapy, History of
haemorrhagic central nervous system 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 and partial thromboplastin time (PTT) > 150% of
institutional 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

- Severe renal impairment (Creatinine clearance <30 mL/min calculated by Cockcroft-Gault
formula at visit 1) or end-stage renal disease requiring dialysis

- Treatment with NAC (n-acetylcysteine), prednisone >15 mg daily or >30 mg every 2 days
OR equivalent dose of other oral corticosteroids and/or fluvoxamine within 2 weeks of
visit 2

- Treatment with azathioprine, cyclophosphamide, cyclosporine as well as any other
investigational drug within 8 weeks of visit 2

- Previous treatment with pirfenidone

- Permanent discontinuation of nintedanib in the past due to Adverse Events considered
drug-related

- Known hypersensitivity to nintedanib, pirfenidone, peanut or soya or to any of the
excipients

- 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 treatment

- Women who are pregnant, nursing, or who plan to become pregnant while in the trial

- Women of childbearing potential not willing or able to use highly effective methods of
birth control per ICH M3 (R2) that result in a low failure rate of less than 1% per
year when used consistently and correctly5 for 28 days prior to and 3 months after
nintedanib administration

- Patients not able to understand and follow study procedures including completion of
self administered questionnaires without help

- Patients who require dose reduction and/or temporary interruption during the run-in
period with nintedanib 150 mg bid

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