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

This is an interventional treatment trial for Idiopathic Pulmonary Fibrosis Read More

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)