A twelve week, open-label, randomised, parallel-group study evaluating safety, tolerability and pharmacokinetics (PK) of oral nintedanib in combination with oral pirfenidone, compared to treatment with nintedanib alone, in patients with idiopathic pulmonary fibrosis (IPF)

Recruitment & Eligibility

Status: Completed

Sex: Not specified

Target Recruitment: 15

Inclusion Criteria

-Written informed consent consistent with ICH-GCP 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/ERS/JRS/ALAT 2011 guideline and confirmed by the investigator based on chest high resolution computed tomography (HRCT) scan performed within 12 months of visit 1
-FVC greater than or equal to 50% of predicted normal at visit 1

Exclusion Criteria

-ALT, AST >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/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),
Prothrombin time and partial thromboplastin time (PTT) > 150%
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 Cockroft-Gault formula at visit 1) or end stage renal disease requiering dialysis
-Treatment with NAC, 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 AEs 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 correctly for 28 days prior to and 3 months after nintedanib administration;-Patients not able to understand and follow study procedures including completion of selfadministered 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 impairment)

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>The primary endpoint is the percentage of patients with on-treatment<br /><br>gastrointestinal (GI) AEs from baseline to week 12.</p><br>

Secondary Outcome Measures

Name	Time	Method
<p>Pre-dose plasma concentrations at steady state of nintedanib<br /><br>at baseline, weeks 2 and 4.<br /><br>Pre-dose plasma concentrations at steady state of<br /><br>pirfenidone at weeks 2 and 4.</p><br>