Nintedanib Twice Daily vs Placebo in Patients Diagnosed With Idiopathic Pulmonary Fibrosis (IPF)
Condition: Idiopathic Pulmonary Fibrosis
MeSH terms: Pulmonary Fibrosis; Idiopathic Pulmonary Fibrosis; Fibrosis
Intervention: Matching Placebo; Nintedanib
Intervention description: twice daily dosing; gelating capsule
Intervention MeSH terms: Nintedanib
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double
Enrollment: 113.0
Sex: All
Minimum age: 40 Years
Healthy volunteers: No

Summary:

      This is an 6 month multi-centre, prospective, randomized, placebo controlled, double blind
      clinical trial followed by conversion of each arm to active nintedanib for an additional 6
      months comparing the effect of nintedanib 150mg bis in die (BID twice daily) on the
      progression of IPF measured by using High Resolution Computerized Tomography(HRCT), lung
      function, functional component (6MWT), biomarkers, and PRO component (PROs) with continued
      treatment and assessments for up to 18 months.
    

Eligibility criteria:

        Inclusion criteria:

          1. Written Informed Consent consistent with International Conference on Harmonisation
             Good Clinical Practice (ICH-GCP) and local laws signed prior to entry into the study

          2. Patient aged >= 40 years at Visit 1.

          3. IPF diagnosed, according to the 2011 American Thoracic Society (ATS) / European
             Respiratory Society (ERS) / Japanese Respiratory Society(JRS)/ Latin American Thoracic
             Association (ALAT)/ Latin American Thoracic Association/ Idiopathic Pulmonary Fibrosis
             (IPF) guidelines for diagnosis and management, within 5 years and reaffirmed applying
             2011 Guidelines (P11-07084) if diagnosed >2 years and up to 5 year from Visit 1,.
             Diagnosis must be confirmed by chest High Resolution Computerized Tomography (HRCT)
             taken within 24 months of Visit 1. All HRCT results reported to be possible or
             inconsistent usual interstitial pneumonia (UIP) must have confirmatory pathology.

          4. Carbon monoxide Diffusing capacity or Transfer factor of the lung for carbon monoxide
             (DLCO) (corrected for Hb): 30%-79% predicted of normal

          5. Forced Vital Capacity (FVC) >= 50% predicted of normal at Visit 1 and Visit 2

        Exclusion criteria:

          1. AST, ALT > 1.5 fold ULN

          2. Bilirubin > 1.5 fold ULN

          3. Bleeding risk:

               1. Patients who require fibrinolysis, full-dose therapeutic anticoagulation (e.g.
                  vitamin K antagonists, dabigatran, heparin, hirudin), or high dose antiplatelet
                  therapy. Exceptions: prophylactic low dose heparin or heparin flush as needed for
                  maintenance of an indwelling intravenous device (e.g. enoxaparin 4000 IU s.c. per
                  day) and prophylactic use of antiplatelet therapy (e.g. acetyl salicylic acid up
                  to 325 mg/d, or clopidogrel at 75 mg/d, or equivalent doses of other antiplatelet
                  therapy)

               2. History of hemorrhagic Central Nervous System (CNS) event within 12 months

               3. Any of the following within 3 months:

                    -  Haemoptysis or haematuria.

                    -  Active gastro-intestinal bleeding or ulcers.

                    -  Major injury or surgery.

               4. Coagulation parameters: International normalised ratio (INR) > 2, prothrombin
                  time (PT) and partial thromboplastin time (PTT) > 150% of institutional ULN.

          4. Planned major surgery within the next 3 months, including lung transplantation, major
             abdominal or major intestinal surgery.

          5. Thrombotic risk

               1. Known inherited predisposition to thrombosis.

               2. History of thrombotic event (including stroke and transient ischemic attacks)
                  within 12 months

          6. Current or planned usage of any investigational drug during the course of this trial

          7. Previous treatment with nintedanib within a clinical trial in the previous 3 months
             and discontinuation of nintedanib study treatment due to an adverse event

          8. Known hypersensitivity to the trial drug or its component

          9. A disease or condition which in the opinion of investigator may put the patient at
             risk because of participation in this trial or limit the patient's ability to
             participate in this trial. Patients will be excluded if they require greater than
             12L/min oxygen, are not ambulatory or require use of a walker or cane during the 6
             Minute Titration Walk Test. Patients who cannot complete the 6 Minute Titration Walk
             Test are excluded from participation.

         10. Alcohol or drug abuse which in the opinion of the investigator would interfere with
             trial participation.

         11. Pregnant women or women who are breast feeding or of child bearing potential not using
             two effective methods of birth control (one barrier and one highly effective
             non-barrier) for at least 1 month prior to trial and/or not committing to using it
             until 3 months after end of treatment.