A Study to Compare the Amount of Nintedanib and Pirfenidone in the Blood When Nintedanib and Pirfenidone Are Given Separately or in Combination
Condition: Idiopathic Pulmonary Fibrosis
MeSH terms: Pulmonary Fibrosis; Idiopathic Pulmonary Fibrosis
Intervention: nintedanib; pirfenidone
Intervention MeSH terms: Pirfenidone; Nintedanib
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 37.0
Sex: All
Minimum age: 40 Years
Healthy volunteers: No

Summary:

      The primary objective of this study is to investigate the effect of steady state pirfenidone
      on the pharmacokinetics of nintedanib and its metabolites following oral administration of
      2403 mg/day pirfenidone and to investigate the effect of steady state nintedanib on the
      pharmacokinetics of pirfenidone at steady state following oral administration of 150 mg bid
      nintedanib. There will be two cohorts of patients; the first one will consist of patients not
      treated with pirfenidone or nintedanib, while the second one will consist of patients on
      pirfenidone treatment.
    

Eligibility criteria:

        Inclusion criteria:

        Any patients diagnosed with IPF and who comply with eligibility requirements may qualify
        for participation in the trial.

          -  Written informed consent consistent with International Conference on Harmonisation -
             Good Clinical Practice (ICH-GCP) and local laws, signed prior to any study procedures
             being performed (including any required washout).

          -  Male or female patients aged >=40 years at Visit 1

          -  IPF diagnosis, based upon the American Thoracic Society (ATS)/European Respiratory
             Society(ERS)/Japanese Respiratory Society (JRS)/Latin American Thoracic Association
             (ALAT) 2011 guideline and chest high-resolution computed tomography (HRCT) scan.

          -  Force Vital Capacity (FVC) >=50% of predicted normal at Visit 1

          -  Diffusing capacity of the Lung for Carbon monoxide (DLCO) (corrected for Hb [visit
             1]): 30%-79% predicted of normal at visit 2. (test can be performed at visits 1 or 2,
             or during the screening period)

          -  Currently treated with pirfenidone at full dose (this is only for patients going into
             Group 2).

        Exclusion criteria:

          -  Alanine transaminase (ALT), Aspartate aminotransferase (AST) >1.5 fold upper limit of
             normal (ULN) at visit 1.

          -  Total bilirubin >1.5 fold ULN at visit 1.

          -  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 (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 (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 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 n-acetylcysteine, prednisone >15 mg daily or >30 mg every 2 days OR
             equivalent dose of other oral corticosteroids 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 in the past three months prior to Visit 2 (Group 1
             only).

          -  Previous treatment with nintedanib in the past 14 days prior to Visit 2.

          -  Permanent discontinuation of nintedanib or pirfenidone in the past due to adverse
             events considered drug-related.

          -  Known hypersensitivity to nintedanib, pirfenidone or their excipients; or to peanut or
             soya.

          -  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 using highly effective methods of birth control
             per ICH M3, note 3, highly effective methods of birth control are defined as those,
             alone or in combination, that result in a low failure rate of less than 1% per year
             when used consistently and correctly such as implants, injectables, combined oral
             contraceptives, some intrauterine devices (IUDs), sexual abstinence or vasectomised
             partner. Barrier contraceptives (e.g. male condom or diaphragm) are acceptable if used
             in combination with spermicides (e.g. foam, gel). Contraception must be used for 28
             days prior to and 3 months after nintedanib and pirfenidone administration.

          -  Patients not able to understand and follow study procedures including completion of
             diaries without help.

          -  Current smoker (vaping and e-cigarettes are acceptable)