Safety And Efficacy of BIBF 1120 in Idiopathic Pulmonary Fibrosis

Pulmonary Fibrosis Clinical Trial

Official title:

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.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00514683
• Other study ID #: 1199.30
• Status: Completed
• Phase: Phase 2
• First received: August 9, 2007
• Last updated: January 5, 2015
• Start date: August 2007

Study information

• Verified date: January 2015
• Source: Boehringer Ingelheim
• Contact: n/a
• Is FDA regulated: No
• Health authority: Argentina: A.N.M.A.T. (Administración Nacional de Medicamentos, Alimentos y Tecnologia Médica)Australia: Dept of Health and Ageing Therapeutic Goods AdminBelgium: Federal Agency for Medicines and Health Products, FAMHPBrazil: ANVISABulgaria: Bulgarian Drug Agency, BG-1504 SofiaCanada: Therapeutic Products DirectorateChile: Instituto de Salud Pública de ChileChina: Food and Drug AdministrationCzech Republic: State Institute for Drug Control (SUKL), CZ-100 41 Prague 10France: AGENCE FRANCAISE DE SECURITE SANITAIRE DES PRODUITS DE SANTEGermany: Bundesinstitut für Arzneimittel und Medizinprodukte, Fachregistratur Z 14.02.06, Kurt-Georg-Kiesinger-Allee 3, 53175 BonnGreat Britain: MHRAGreece: National Organization for Medicines (EOF) National Ethics CommitteeHungary: National Institute of Pharmacy, H-1051 BudapestIreland: Irish Medicines BoardItaly: Comitato Etico Provinciale di Modena - MODENAKorea, Republic of: Korea Food and Drug Administration (KFDA)Mexico: Federal Commission for Protection Against Health RisksNetherlands: The Central Committee on Research Involving Human Subjects (CCMO)Portugal: National Pharmacy and Medicines InstituteRussia: Ministry of Healthcare and Social Development of Russian Federation, MoscowSouth Africa: Medicines Control CouncilSpain: Spanish Agency for Medicines and Health ProductsTaiwan: Department of Health, Executive Yuan, TaiwanTurkey: Ministry of Health Central Ethics Committee
• Study type: Interventional

Clinical Trial 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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 432
• Est. primary completion date: June 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 40 Years and older

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double-Blind, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Fibrosis
• Idiopathic Interstitial Pneumonias
• Idiopathic Pulmonary Fibrosis
• Pulmonary Fibrosis

Intervention

Drug:
• low dose BIBF1120 once daily
low dose BIBF1120 once daily
• low dose BIBF 1120 twice daily
low dose BIBF 1120 twice daily
• intermediate dose BIBF 1120 twice daily
intermediate dose BIBF 1120 twice daily
• high dose BIBF 1120 twice daily
high dose BIBF 1120 twice daily
• placebo
placebo

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Boehringer Ingelheim

Countries where clinical trial is conducted

Argentina,  Australia,  Belgium,  Brazil,  Bulgaria,  Canada,  Chile,  China,  Czech Republic,  France,  Germany,  Greece,  Hungary,  Ireland,  Italy,  Korea, Republic of,  Mexico,  Netherlands,  Portugal,  Russian Federation,  South Africa,  Spain,  Taiwan,  Turkey,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	St George's Respiratory Questionnaire (SGRQ) Responder	St George's Respiratory Questionnaire (SGRQ) responder (<= -4 points change) (%) at 52 weeks-worst case	52 weeks	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	Occurrences of IPF Exacerbations Per Patient Per Year	Occurrences of Idiopathic Pulmonary Fibrosis (IPF) exacerbations per patient per year at 52 weeks	52 weeks	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No

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