Safety And Efficacy of BIBF 1120 in Idiopathic Pulmonary Fibrosis
Condition: Pulmonary Fibrosis
MeSH terms: Pulmonary Fibrosis; Idiopathic Pulmonary Fibrosis; Fibrosis
Intervention: low dose BIBF1120 once daily; low dose BIBF 1120 twice daily; intermediate dose BIBF 1120 twice daily; high dose BIBF 1120 twice daily; placebo
Intervention description: low dose BIBF1120 once daily; low dose BIBF 1120 twice daily; intermediate dose BIBF 1120 twice daily; high dose BIBF 1120 twice daily; placebo
Intervention MeSH terms: Nintedanib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double
Enrollment: 432.0
Sex: All
Minimum age: 40 Years
Healthy volunteers: No

Summary:

      The general purpose of this trial is to investigate the efficacy and safety of 4 dose
      strategies of BIBF 1120 treatment for 12 months, compared to placebo in patients with
      idiopathic pulmonary fibrosis.

      The primary objective of this study is to demonstrate whether at least one dose strategy is
      superior to placebo in patients with IPF, in modifying the rate of decline of Forced Vital
      Capacity (FVC).

      As a secondary objective, additional parameters will be assessed in order to differentiate
      between dose strategies on the basis of safety and efficacy
    

Eligibility criteria:

        Inclusion Criteria:

          1. Patient >40 years

          2. Written informed consent signed prior to entry into the study

          3. IPF diagnosed (according to ATS / ERS criteria) less than 5 years prior to screening
             visit.

          4. HRCT within 12 months of randomisation and biopsy (the latter if needed to fulfil
             ATS/ERS criteria) centrally reviewed and consistent with diagnosis.

          5. FVC>50 % of predicted value

             Predicted normal values will be calculated according to ESCS (R94-1408):

             Males :

             FVC predicted (L) = 5.76 x height (meters)- 0.026 x age (years) -4.34

             Females :

             FVC predicted (L) = 4.43 x height (meters)- 0.026 x age (years) -2.89

          6. Single breath DLCO (corrected for Hb) 30 - 79% inclusive of predicted .

             Different sites may use different prediction formulas, based on the method used to
             measure DLco. In any case, the method used must be in compliance with the ATS/ERS
             guideline on DLCO measurements (R06-2002), and the prediction formula appropriate for
             that method. Raw data (gas mixture, equation used for prediction of normal, further
             adjustments made if so) must be traced.

             Adjustment for haemoglobin (R06-2002):

             Males :

             DLCO predicted for Hb = DLCO predicted x (1.7Hb/[10.22+Hb])

             Females :

             DLCO predicted for Hb = DLCO predicted x (1.7Hb/[9.38+Hb]) where Hb is expressed in
             g/dL-1

          7. PaO2 >= 55 mmHg (sea level to 1500 m) or 50 mmHg (above 1500 m) room air

        Exclusion Criteria:

          1. AST, ALT > 1.5 x ULN ;

          2. Bilirubin > 1.5 x ULN

          3. Relevant airways obstruction

          4. Continuous oxygen supplementation at randomisation (defined as > 15 hours supplemental
             oxygen per day).

          5. Active infection at screening or randomisation.

          6. Neutrophils < 1500 / mm3

          7. International normalised ratio (INR) > 1.5 and/or Partial thromboplastin time (PTT) >
             1.5 x ULN ;

          8. Platelets < 100 000 /mL

          9. Haemoglobin < 9.0 g/dL

         10. In the opinion of the Investigator, patient is likely to have lung transplantation
             during study

         11. Life expectancy for disease other than IPF < 2.5 years (Investigator assessment).

         12. Other disease that may interfere with testing procedures or in judgement of
             Investigator may interfere with trial participation or may put the patient at risk
             when participating to this trial.

               -  Myocardial infarction during the previous 6 months

               -  Unstable angina during the previous month

         13. Other investigational therapy received within 8 weeks prior to screening visit.

         14. Pregnant women or women who are breast feeding or of child bearing potential not using
             a highly effective method of birth control for at least one month prior to enrolment.

         15. Sexually active males not committing to using condoms during the course of the study
             (except if their partner is not of childbearing potential).

         16. Known or suspected active alcohol or drug abuse.

         17. Bleeding risk : Known inherited predisposition to bleeding, patients who require
             full-dose anticoagulation, Patients who require full-dose antiplatelet therapy,
             History of hemorrhagic CNS event within 12 months prior to screening , Any of the
             following within 3 months prior to screening : Gross / frank haemoptysis or
             haematuria, Active gastro-intestinal bleeding or ulcers, Major injury or surgery

         18. Thrombotic risk

         19. Surgical procedures planned to occur during trial period.

         20. Coagulopathy

         21. Uncontrolled systemic arterial hypertension

         22. known hypersensitivity to lactose or any component of the study medication