Safety And Efficacy of BIBF 1120 in Idiopathic Pulmonary Fibrosis

A 12 Month, Double Blind, Randomized, Placebo-controlled Trial Evaluating the Effect of BIBF 1120 Administered at Oral Doses of 50 mg qd, 50 mg Bid, 100 mg Bid and 150 mg Bid on Forced Vital Capacity Decline During One Year, in Patients With Idiopathic Pulmonary Fibrosis, With Optional Active Treatment Extension Until Last Patient Out.

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

Study Overview

• Status: Completed
• Conditions: Pulmonary Fibrosis
• Intervention / Treatment: Drug: placebo; Drug: low dose BIBF1120 once daily; Drug: low dose BIBF 1120 twice daily; Drug: intermediate dose BIBF 1120 twice daily; Drug: high dose BIBF 1120 twice daily

• Study Type: Interventional
• Enrollment (Actual): 432
• Phase: Phase 2

Contacts and Locations

Study Locations

• Argentina
  • Mendoza, Argentina
    • 1199.30.54002 Boehringer Ingelheim Investigational Site
• Australia
  • Queensland
    • South Brisbane, Queensland, Australia
      • 1199.30.61005 Boehringer Ingelheim Investigational Site
  • South Australia
    • Toorak Gardens, South Australia, Australia
      • 1199.30.61003 Boehringer Ingelheim Investigational Site
    • Woodville, South Australia, Australia
      • 1199.30.61004 Boehringer Ingelheim Investigational Site
  • Western Australia
    • Perth, Western Australia, Australia
      • 1199.30.61001 Royal Perth Hospital
• Belgium
  • Bruxelles, Belgium
    • 1199.30.32004 Boehringer Ingelheim Investigational Site
  • Leuven, Belgium
    • 1199.30.32001 Boehringer Ingelheim Investigational Site
  • Yvoir, Belgium
    • 1199.30.32002 Boehringer Ingelheim Investigational Site
• Brazil
  • Porto Alegre, Brazil
    • 1199.30.55002 Boehringer Ingelheim Investigational Site
  • Vila Clementino, Brazil
    • 1199.30.55001 Boehringer Ingelheim Investigational Site
• Bulgaria
  • Sofia, Bulgaria
    • 1199.30.06004 Boehringer Ingelheim Investigational Site
  • Sofia, Bulgaria
    • 1199.30.06005 Boehringer Ingelheim Investigational Site
• Canada
  • Nova Scotia
    • Halifax, Nova Scotia, Canada
      • 1199.30.01003 Division of Respirology
  • Ontario
    • Hamilton, Ontario, Canada
      • 1199.30.01002 St. Joseph's Healthcare
• Chile
  • Providencia, Chile
    • 1199.30.56001 Boehringer Ingelheim Investigational Site
• China
  • Beijing, China
    • 1199.30.86001 Boehringer Ingelheim Investigational Site
  • Beijing, China
    • 1199.30.86002 Boehringer Ingelheim Investigational Site
  • Nanjing, China
    • 1199.30.86005 Boehringer Ingelheim Investigational Site
  • Shanghai, China
    • 1199.30.86003 Boehringer Ingelheim Investigational Site
  • Shenyang, China
    • 1199.30.86004 Boehringer Ingelheim Investigational Site
• Czech Republic
  • Prague 8, Czech Republic
    • 1199.30.42002 Boehringer Ingelheim Investigational Site
  • Usti nad Labem, Czech Republic
    • 1199.30.42001 Boehringer Ingelheim Investigational Site
• France
  • Bobigny, France
    • 1199.30.3302A Boehringer Ingelheim Investigational Site
  • Dijon, France
    • 1199.30.3306A Boehringer Ingelheim Investigational Site
  • Grenoble, France
    • 1199.30.3303A Boehringer Ingelheim Investigational Site
  • Lille Cedex, France
    • 1199.30.3305A Boehringer Ingelheim Investigational Site
  • Lille Cedex, France
    • 1199.30.3305B Boehringer Ingelheim Investigational Site
  • Lille Cedex, France
    • 1199.30.3305C Boehringer Ingelheim Investigational Site
  • Montpellier, France
    • 1199.30.3304C Boehringer Ingelheim Investigational Site
  • Nice Cedex 1, France
    • 1199.30.3307A Boehringer Ingelheim Investigational Site
  • Paris Cedex 18, France
    • 1199.30.3301A Boehringer Ingelheim Investigational Site
• Germany
  • Bad Berka, Germany
    • 1199.30.49008 Boehringer Ingelheim Investigational Site
  • Berlin, Germany
    • 1199.30.49007 Boehringer Ingelheim Investigational Site
  • Donaustauf, Germany
    • 1199.30.49006 Boehringer Ingelheim Investigational Site
  • Essen, Germany
    • 1199.30.49001 Boehringer Ingelheim Investigational Site
  • Freiburg/Breisgau, Germany
    • 1199.30.49002 Boehringer Ingelheim Investigational Site
  • Großhansdorf, Germany
    • 1199.30.49003 Boehringer Ingelheim Investigational Site
  • Leipzig, Germany
    • 1199.30.49009 Boehringer Ingelheim Investigational Site
  • Mainz, Germany
    • 1199.30.49004 Boehringer Ingelheim Investigational Site
  • München, Germany
    • 1199.30.49005 Boehringer Ingelheim Investigational Site
• Greece
  • Alexandroupolis, Greece
    • 1199.30.30004 Boehringer Ingelheim Investigational Site
  • Heraklion, Greece
    • 1199.30.30001 Boehringer Ingelheim Investigational Site
  • Larisa, Greece
    • 1199.30.30002 Boehringer Ingelheim Investigational Site
• Hungary
  • Budapest, Hungary
    • 1199.30.36002 Boehringer Ingelheim Investigational Site
  • Budapest, Hungary
    • 1199.30.36003 Boehringer Ingelheim Investigational Site
  • Deszk, Hungary
    • 1199.30.36004 Boehringer Ingelheim Investigational Site
  • Pecs, Hungary
    • 1199.30.36001 Boehringer Ingelheim Investigational Site
  • Szekesfehervar, Hungary
    • 1199.30.36005 Boehringer Ingelheim Investigational Site
• Ireland
  • Dublin 7, Ireland
    • 1199.30.35301 Mater Misericordiae Hospital
• Italy
  • Ascoli Piceno, Italy
    • 1199.30.39008 Boehringer Ingelheim Investigational Site
  • Busto Arsizio (va), Italy
    • 1199.30.39013 Boehringer Ingelheim Investigational Site
  • Milano, Italy
    • 1199.30.39007 Boehringer Ingelheim Investigational Site
  • Modena, Italy
    • 1199.30.39001 Boehringer Ingelheim Investigational Site
  • Napoli, Italy
    • 1199.30.39012 Boehringer Ingelheim Investigational Site
  • Pavia, Italy
    • 1199.30.39009 Boehringer Ingelheim Investigational Site
  • Roma, Italy
    • 1199.30.39011 Boehringer Ingelheim Investigational Site
  • Siena, Italy
    • 1199.30.39010 Boehringer Ingelheim Investigational Site
  • Terni, Italy
    • 1199.30.39003 Boehringer Ingelheim Investigational Site
  • Trieste, Italy
    • 1199.30.39004 Boehringer Ingelheim Investigational Site
• Korea, Republic of
  • Gyunggido, Korea, Republic of
    • 1199.30.82002 Boehringer Ingelheim Investigational Site
  • Incheon, Korea, Republic of
    • 1199.30.82004 Boehringer Ingelheim Investigational Site
  • Seoul, Korea, Republic of
    • 1199.30.82001 Boehringer Ingelheim Investigational Site
  • Seoul, Korea, Republic of
    • 1199.30.82003 Boehringer Ingelheim Investigational Site
  • Seoul, Korea, Republic of
    • 1199.30.82005 Boehringer Ingelheim Investigational Site
• Mexico
  • Distrito Federal, Mexico
    • 1199.30.52001 Boehringer Ingelheim Investigational Site
• Netherlands
  • Nieuwegein, Netherlands
    • 1199.30.31002 Boehringer Ingelheim Investigational Site
• Portugal
  • Coimbra, Portugal
    • 1199.30.35105 Boehringer Ingelheim Investigational Site
  • Coimbra, Portugal
    • 1199.30.35106 Boehringer Ingelheim Investigational Site
  • Lisboa, Portugal
    • 1199.30.35107 Boehringer Ingelheim Investigational Site
  • Lisboa, Portugal
    • 1199.30.35108 Boehringer Ingelheim Investigational Site
  • Lisboa, Portugal
    • 1199.30.35109 Boehringer Ingelheim Investigational Site
  • Porto, Portugal
    • 1199.30.35101 Boehringer Ingelheim Investigational Site
• Russian Federation
  • Moscow, Russian Federation
    • 1199.30.07001 Boehringer Ingelheim Investigational Site
  • Moscow, Russian Federation
    • 1199.30.07002 Boehringer Ingelheim Investigational Site
  • St. Petersburg, Russian Federation
    • 1199.30.07003 Boehringer Ingelheim Investigational Site
• South Africa
  • Bellville, South Africa
    • 1199.30.27001 Boehringer Ingelheim Investigational Site
  • Cape Town, South Africa
    • 1199.30.27003 Boehringer Ingelheim Investigational Site
  • Tygerberg, South Africa
    • 1199.30.27002 Boehringer Ingelheim Investigational Site
• Spain
  • Barcelona, Spain
    • 1199.30.34001 Boehringer Ingelheim Investigational Site
  • Valencia, Spain
    • 1199.30.34002 Boehringer Ingelheim Investigational Site
• Taiwan
  • Taichung, Taiwan
    • 1199.30.88605 Boehringer Ingelheim Investigational Site
  • Taipei, Taiwan
    • 1199.30.88601 National Taiwan University
  • Taipei, Taiwan
    • 1199.30.88603 Tri-service General Hospital
  • Taipei, Taiwan
    • 1199.30.88606 Boehringer Ingelheim Investigational Site
  • Taoyuan, Taiwan
    • 1199.30.88604 Chang Gung Memorial Hosp-Linkou
• Turkey
  • Ankara, Turkey
    • 1199.30.90001 Boehringer Ingelheim Investigational Site
  • Istanbul, Turkey
    • 1199.30.90002 Boehringer Ingelheim Investigational Site
• United Kingdom
  • Aberdeen, United Kingdom
    • 1199.30.44006 Boehringer Ingelheim Investigational Site
  • Birmingham, United Kingdom
    • 1199.30.44003 Boehringer Ingelheim Investigational Site
  • Birmingham, United Kingdom
    • 1199.30.44005 Boehringer Ingelheim Investigational Site
  • Manchester, United Kingdom
    • 1199.30.44007 Boehringer Ingelheim Investigational Site
  • Westbury on Trym, United Kingdom
    • 1199.30.44001 Boehringer Ingelheim Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: placebo	Drug: placebo; placebo
Experimental: dose 1; low dose BIBF1120 once daily	Drug: low dose BIBF1120 once daily; low dose BIBF1120 once daily
Experimental: dose 2; low dose BIBF 1120 twice daily	Drug: low dose BIBF 1120 twice daily; low dose BIBF 1120 twice daily
Experimental: dose 3; intermediate dose BIBF 1120 twice daily	Drug: intermediate dose BIBF 1120 twice daily; intermediate dose BIBF 1120 twice daily
Experimental: dose 4; high dose BIBF 1120 twice daily	Drug: high dose BIBF 1120 twice daily; high dose BIBF 1120 twice daily

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of Decline in FVC	Rate of decline in Forced Vital Capacity (FVC) evaluated from baseline until 52 weeks of treatment. The means presents actually the adjusted rate based on a MMRM with fixed terms for treatment*time, gender*height, gender*age and random terms for patient effect, patient*time.	Baseline until 52 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Absolute Change From Baseline in FVC%Pred	Change from baseline in percentage of predicted Forced Vital Capacity (FVC%pred) at 52 weeks. Means were adjusted based on an ANCOVA with fixed terms for treatment, baseline and region.	Baseline and 52 weeks
Absolute Change From Baseline in FVC	Change from baseline in percentage of absolute Forced Vital Capacity (FVC) at 52 weeks. Means were adjusted based on an ANCOVA with fixed terms for treatment, baseline and region.	Baseline and 52 weeks
Relative Change From Baseline in FVC%Pred	Percent change from baseline in percentage of predicted Forced Vital Capacity (FVC%pred) at 52 weeks. Means were adjusted based on an ANCOVA with fixed terms for treatment, baseline and region.	Baseline and 52 weeks
Relative Change From Baseline in FVC	Percent change from baseline in absolute Forced Vital Capacity (FVC) at 52 weeks. Means were adjusted based on an ANCOVA with fixed terms for treatment, baseline and region	Baseline and 52 weeks
Number of Participants With Change From Baseline in FVC by Categories	Change from baseline in percentage of Forced Vital Capacity (FVC) at 52 weeks in below mentioned categories: Decrease > 10% or 200mL; Change within <= 10% or <=200 mL; Increase > 10% or 200mL	Baseline and 52 weeks
Survival (All Causes of Death and Lung-transplant Free)	Survival (all causes of death and lung-transplant free) at 52 weeks, based on overall mortality and on-treatment survival. Failure means participants with event and Censored means participants with no event.	52 weeks
Absolute Change From Baseline in SpO2 at Rest	Absolute change from baseline in oxygen saturation (SpO2) at rest. Means were adjusted based on an ANCOVA with fixed terms for treatment, baseline, region.	Baseline and 52 weeks
Absolute Change From Baseline in SpO2 at Rest by Categories	Absolute change from baseline in oxygen saturation (SpO2) at rest by below mentioned categories: SpO2 (non-invasive) at 52 weeks: Decrease > 4% SpO2; Change within +/- 4% SpO2; Increase > 4% SpO2	Baseline and 52 weeks
Absolute Change From Baseline in PaO2	Absolute change from baseline in Arterial oxygen partial pressure (PaO2) at week 52. Means were adjusted based on an ANCOVA with fixed terms for treatment, baseline, region.	Baseline and 52 weeks
Absolute Change From Baseline in P(A-a)O2	Absolute change from baseline in Alveolo-arterial oxygen gradient (P(A-a)O2) at week 52. Means were adjusted based on an ANCOVA with fixed terms for treatment, baseline, region.	Baseline and 52 weeks
Absolute Change From Baseline in PaCO2	Absolute change from baseline in Arterial carbon dioxyde partial pressure (PaCO2) at week 52. Means were adjusted based on an ANCOVA with fixed terms for treatment, baseline, region.	Baseline and 52 weeks
Absolute Change From Baseline in PaO2 by Categories	Absolute change from baseline in Arterial oxygen partial pressure (PaO2) by below mentioned categories: Decrease > 4 mmHg; Change within +/- 4 mmHg; Increase > 4 mmHg	Baseline and 52 weeks
Absolute Change From Baseline in P(A-a) O2 by Categories	Absolute change from baseline in Alveolo-arterial oxygen gradient (P(A-a) O2) by below mentioned categories: Decrease > 4 mmHg; Change within +/- 4 mmHg; Increase > 4 mmHg	Baseline and 52 weeks
Absolute Change From Baseline in DLCO	Absolute change from Baseline in Diffusing capacity of the lung for carbon monoxide (DLCO) at 52 weeks. Means were adjusted based on an ANCOVA with fixed terms for treatment, baseline, region.	Baseline and 52 weeks
Absolute Change From Baseline in DLCO by Categories	Absolute change from baseline in Diffusing capacity of the lung for carbon monoxide (DLCO) by below mentioned categories: Decrease > 15% or > 1; Change <= 15% or <= 1; Increase > 15% or > 1	Baseline and 52 weeks
Absolute Change From Baseline in Distance Walk (6-MWT)	Absolute change from baseline in distance walk (6-MWT) at 52 weeks. The 6-Minutes Walk Test (6-MWT) was conducted according to the American Thoracic Society (ATS) Criteria. Means were adjusted based on an ANCOVA with fixed terms for treatment, baseline, region.	Baseline and 52 weeks
Absolute Change From Baseline in Dyspnoea Rating on Borg Scale Before Exercise (6-MWT)	Absolute change from baseline in Dyspnoea rating before exercise (6-MWT) at 52 weeks based on Borg scale as mentioned below : 0: Nothing at all, 0.5: Very, very slight (just noticable), 1: Very slight, 2: Slight (light), 3: Moderate, 4: Somewhat severe, 5: Severe (heavy), 6, 7:Very severe, 8, 9, 10: Very, very severe (Maximal). The 6-Minutes Walk Test (6-MWT) was conducted according to the ATS Criteria. Means were adjusted based on an ANCOVA with fixed terms for treatment, baseline, region.	Baseline and 52 weeks
Change From Baseline in Dyspnoea Rating on Borg Scale After Exercise (6-MWT)	Change from baseline in Dyspnoea rating after exercise (6-MWT) at 52 weeks based on Borg scale as mentioned below : 0: Nothing at all, 0.5: Very, very slight (just noticable), 1: Very slight, 2: Slight (light), 3: Moderate, 4: Somewhat severe, 5: Severe (heavy), 6, 7:Very severe, 8, 9, 10: Very, very severe (Maximal). The 6-Minutes Walk Test (6-MWT) was conducted according to the ATS Criteria. Means were adjusted based on an ANCOVA with fixed terms for treatment, baseline, region.	Baseline and 52 weeks
Absolute Change From Baseline in MRC Dyspnea Scale by Categories	Absolute change from baseline in Medical Research Council (MRC) dyspnea scale by below mentioned categories: Decrease; No Change; Increase	Baseline and 52 weeks
Absolute Change From Baseline in FEV1/FVC	Change from baseline of percentage of FVC expelled in the first second of a forced expiration (FEV1/FVC) at 52 weeks. Means were adjusted based on an ANCOVA with fixed terms for treatment, baseline, region.	Baseline and 52 weeks
Change From Baseline in SGRQ Total Score	Change from baseline in Saint George's Respiratory Questionnaire (SGRQ) total score. Total score is defined as sum of the three domain scores symptoms, activities and impacts. Scores range from 0 to 100, with higher scores indicating worst possible health status. Means were adjusted based on an ANCOVA with fixed terms for treatment, baseline, region.	Baseline and 52 weeks
Change From Baseline in SGRQ Domain Score Symptoms	Change from baseline in Saint George's Respiratory Questionnaire (SGRQ) domain score symptoms. Scores range from 0 to 100, with higher scores indicating more limitations. Means were adjusted based on an ANCOVA with fixed terms for treatment, baseline, region.	Baseline and 52 weeks
Change From Baseline in SGRQ Domain Score Impacts	Change from baseline in Saint George's Respiratory Questionnaire (SGRQ) domain score impacts. Scores range from 0 to 100, with higher scores indicating worst possible health status. Means were adjusted based on an ANCOVA with fixed terms for treatment, baseline, region.	Baseline and 52 weeks
Change From Baseline in St George's Respiratory Questionnaire (SGRQ) Domain Score Activities	Change from baseline in Saint George's Respiratory Questionnaire (SGRQ) domain score activities. Scores range from 0 to 100, with higher scores indicating worst possible health status. Means were adjusted based on an ANCOVA with fixed terms for treatment, baseline, region.	Baseline and 52 weeks
St George's Respiratory Questionnaire (SGRQ) Responder	St George's Respiratory Questionnaire (SGRQ) responder (<= -4 points change) (%) at 52 weeks-worst case	52 weeks
Change From Baseline in TLC	Change from Baseline in Total Lung Capacity (TLC) at 52 weeks. Means were adjusted based on an ANCOVA with fixed terms for treatment, baseline, region.	Baseline and 52 weeks
Change From Baseline in RV	Change from Baseline in Residual volume (RV) at 52 weeks. Means were adjusted based on an ANCOVA with fixed terms for treatment, baseline, region.	Baseline and 52 weeks
Change From Baseline in TGV	Change from Baseline in Thoracic gas volume (TGV) at 52 weeks. Means were adjusted based on an ANCOVA with fixed terms for treatment, baseline, region.	Baseline and 52 weeks
Change From Baseline in VC	Change from baseline in Vital capacity (VC) at 52 weeks. Means were adjusted based on an ANCOVA with fixed terms for treatment, baseline, region.	Baseline and 52 weeks
Change From Baseline in IC	Change from Baseline in Inspiratory Capacity (IC) at 52 weeks. Means were adjusted based on an ANCOVA with fixed terms for treatment, baseline, region.	Baseline and 52 weeks
Number of Patients With at Least One IPF Exacerbation	Number of patients with at least one Idiopathic Pulmonary Fibrosis (IPF) exacerbation at 52 weeks	52 weeks
Occurrences of IPF Exacerbations Per Patient Per Year	Occurrences of Idiopathic Pulmonary Fibrosis (IPF) exacerbations per patient per year at 52 weeks	52 weeks
Time to First Occurrence of IPF Exacerbation	This endpoint is called time to first occurrence of IPF exacerbation however it was actually analysed as the proportion of patients having occurrence of Idiopathic Pulmonary Fibrosis (IPF) exacerbation at 52 weeks. Failure means participants with event and Censored means participants with no event.	52 weeks
Survival (Death Due to Respiratory Cause, and Lung-transplant Free)	Survival (death due to respiratory cause, and lung-transplant free) at 52 weeks. Failure means participants with event and Censored means participants with no event.	52 weeks
Time to Progression	Time to progression. Progression was defined as at least one of the following: 5mmHg increase in the alveolo-arterial pressure difference in oxygen (P(A-a)O2), 10% decrease in FVC (FVC(baseline)-FVC(progression) >= 10%) or Death. Failure means participants with event and Censored means participants with no event.	52 weeks
Pre-dose Plasma Concentration of Nintedanib in Plasma at Steady State on Day 365 (Cpre,ss,365) and Day 729 (Cpre,ss,729).	Cpre,ss,729 represents the pre-dose plasma concentration of nintedanib in plasma at steady state on Day 729 and Cpre,ss,365 represents the pre-dose plasma concentration of nintedanib in plasma at steady state on Day 365. At day 365, values only for Nintedanib 50 qd group are presented as no values reported for other groups and at day 729, values are presented for all group except for Nintedanib 50 qd group as no values reported for it.	day 365 and day 729

Collaborators and Investigators

• Sponsor: Boehringer Ingelheim

Publications and helpful links

General Publications

• Paterniti MO, Bi Y, Rekic D, Wang Y, Karimi-Shah BA, Chowdhury BA. Acute Exacerbation and Decline in Forced Vital Capacity Are Associated with Increased Mortality in Idiopathic Pulmonary Fibrosis. Ann Am Thorac Soc. 2017 Sep;14(9):1395-1402. doi: 10.1513/AnnalsATS.201606-458OC.
• Glaspole I, Bonella F, Bargagli E, Glassberg MK, Caro F, Stansen W, Quaresma M, Orsatti L, Bendstrup E. Efficacy and safety of nintedanib in patients with idiopathic pulmonary fibrosis who are elderly or have comorbidities. Respir Res. 2021 Apr 26;22(1):125. doi: 10.1186/s12931-021-01695-y.
• Richeldi L, Kreuter M, Selman M, Crestani B, Kirsten AM, Wuyts WA, Xu Z, Bernois K, Stowasser S, Quaresma M, Costabel U. Long-term treatment of patients with idiopathic pulmonary fibrosis with nintedanib: results from the TOMORROW trial and its open-label extension. Thorax. 2018 Jun;73(6):581-583. doi: 10.1136/thoraxjnl-2016-209701. Epub 2017 Oct 9.
• Richeldi L, Costabel U, Selman M, Kim DS, Hansell DM, Nicholson AG, Brown KK, Flaherty KR, Noble PW, Raghu G, Brun M, Gupta A, Juhel N, Kluglich M, du Bois RM. Efficacy of a tyrosine kinase inhibitor in idiopathic pulmonary fibrosis. N Engl J Med. 2011 Sep 22;365(12):1079-87. doi: 10.1056/NEJMoa1103690.

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start: August 1, 2007
• Primary Completion (Actual): June 1, 2010

Study Registration Dates

• First Submitted: August 9, 2007
• First Submitted That Met QC Criteria: August 9, 2007
• First Posted (Estimate): August 10, 2007

Study Record Updates

• Last Update Posted (Estimate): January 6, 2015
• Last Update Submitted That Met QC Criteria: January 5, 2015
• Last Verified: January 1, 2015

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Respiratory Tract Diseases; Lung Diseases; Fibrosis; Pulmonary Fibrosis; Idiopathic Pulmonary Fibrosis; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Nintedanib
• Other Study ID Numbers: 1199.30