Pulmonary FibrosisPhase 2NCT00514683
Safety And Efficacy of BIBF 1120 in Idiopathic Pulmonary Fibrosis
A Phase 2 study testing low dose BIBF1120 once daily, low dose BIBF 1120 twice daily and intermediate dose BIBF 1120 twice daily in people with Pulmonary Fibrosis, run by Boehringer Ingelheim at 92 sites in 25 countries.
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. Read more about this study
- Who is it for?
- Ages 40 years and older
- Conditions the study is for
- Pulmonary Fibrosis
- What is being tested?
- low dose BIBF1120 once daily, low dose BIBF 1120 twice daily and intermediate dose BIBF 1120 twice daily
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 432 participants
- Where
- 92 sitesin 25 countries
- Study dates
- Aug 2007to Jun 2010
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 40 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patient >40 years
- Written informed consent signed prior to entry into the study
- IPF diagnosed (according to ATS / ERS criteria) less than 5 years prior to screening visit.
- HRCT within 12 months of randomisation and biopsy (the latter if needed to fulfil ATS/ERS criteria) centrally reviewed and consistent with diagnosis.
- FVC>50 % of predicted value
- Predicted normal values will be calculated according to ESCS (R94-1408):
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- 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
- 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
- PaO2 >= 55 mmHg (sea level to 1500 m) or 50 mmHg (above 1500 m) room air
Who cannot join
- AST, ALT > 1.5 x ULN ;
- Bilirubin > 1.5 x ULN
- Relevant airways obstruction
- Continuous oxygen supplementation at randomisation (defined as > 15 hours supplemental oxygen per day).
- Active infection at screening or randomisation.
- Neutrophils < 1500 / mm3
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- International normalised ratio (INR) > 1.5 and/or Partial thromboplastin time (PTT) > 1.5 x ULN ;
- Platelets < 100 000 /mL
- Haemoglobin < 9.0 g/dL
- In the opinion of the Investigator, patient is likely to have lung transplantation during study
- Life expectancy for disease other than IPF < 2.5 years (Investigator assessment).
- 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
- Other investigational therapy received within 8 weeks prior to screening visit.
- 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.
- Sexually active males not committing to using condoms during the course of the study (except if their partner is not of childbearing potential).
- Known or suspected active alcohol or drug abuse.
- 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
- Thrombotic risk
- Surgical procedures planned to occur during trial period.
- Coagulopathy
- Uncontrolled systemic arterial hypertension
- known hypersensitivity to lactose or any component of the study medication
Trial locations and contacts
92 sites in 25 countries.
92 sites in 25 countries
Italy10 sites
1199.30.39008 Boehringer Ingelheim Investigational Site
Ascoli Piceno
1199.30.39013 Boehringer Ingelheim Investigational Site
Busto Arsizio (va)
1199.30.39007 Boehringer Ingelheim Investigational Site
Milan
1199.30.39001 Boehringer Ingelheim Investigational Site
Modena
1199.30.39012 Boehringer Ingelheim Investigational Site
Naples
1199.30.39009 Boehringer Ingelheim Investigational Site
Pavia
1199.30.39011 Boehringer Ingelheim Investigational Site
Roma
1199.30.39010 Boehringer Ingelheim Investigational Site
Siena
1199.30.39003 Boehringer Ingelheim Investigational Site
Terni
1199.30.39004 Boehringer Ingelheim Investigational Site
Trieste
France9 sites
1199.30.3302A Boehringer Ingelheim Investigational Site
Bobigny
1199.30.3306A Boehringer Ingelheim Investigational Site
Dijon
1199.30.3303A Boehringer Ingelheim Investigational Site
Grenoble
1199.30.3305A Boehringer Ingelheim Investigational Site
Lille
1199.30.3305B Boehringer Ingelheim Investigational Site
Lille
1199.30.3305C Boehringer Ingelheim Investigational Site
Lille
1199.30.3304C Boehringer Ingelheim Investigational Site
Montpellier
1199.30.3307A Boehringer Ingelheim Investigational Site
Nice
1199.30.3301A Boehringer Ingelheim Investigational Site
Paris
Germany9 sites
1199.30.49008 Boehringer Ingelheim Investigational Site
Bad Berka
1199.30.49007 Boehringer Ingelheim Investigational Site
Berlin
1199.30.49006 Boehringer Ingelheim Investigational Site
Donaustauf
1199.30.49001 Boehringer Ingelheim Investigational Site
Essen
1199.30.49002 Boehringer Ingelheim Investigational Site
Freiburg/Breisgau
1199.30.49003 Boehringer Ingelheim Investigational Site
Großhansdorf
1199.30.49009 Boehringer Ingelheim Investigational Site
Leipzig
1199.30.49004 Boehringer Ingelheim Investigational Site
Mainz
1199.30.49005 Boehringer Ingelheim Investigational Site
München
Portugal6 sites
1199.30.35105 Boehringer Ingelheim Investigational Site
Coimbra
1199.30.35106 Boehringer Ingelheim Investigational Site
Coimbra
1199.30.35107 Boehringer Ingelheim Investigational Site
Lisbon
1199.30.35108 Boehringer Ingelheim Investigational Site
Lisbon
1199.30.35109 Boehringer Ingelheim Investigational Site
Lisbon
1199.30.35101 Boehringer Ingelheim Investigational Site
Porto
China5 sites
1199.30.86001 Boehringer Ingelheim Investigational Site
Beijing
1199.30.86002 Boehringer Ingelheim Investigational Site
Beijing
1199.30.86005 Boehringer Ingelheim Investigational Site
Nanjing
1199.30.86003 Boehringer Ingelheim Investigational Site
Shanghai
1199.30.86004 Boehringer Ingelheim Investigational Site
Shenyang
Hungary5 sites
1199.30.36002 Boehringer Ingelheim Investigational Site
Budapest
1199.30.36003 Boehringer Ingelheim Investigational Site
Budapest
1199.30.36004 Boehringer Ingelheim Investigational Site
Deszk
1199.30.36001 Boehringer Ingelheim Investigational Site
Pécs
1199.30.36005 Boehringer Ingelheim Investigational Site
Székesfehérvár
South Korea5 sites
1199.30.82002 Boehringer Ingelheim Investigational Site
Gyunggido
1199.30.82004 Boehringer Ingelheim Investigational Site
Incheon
1199.30.82001 Boehringer Ingelheim Investigational Site
Seoul
1199.30.82003 Boehringer Ingelheim Investigational Site
Seoul
1199.30.82005 Boehringer Ingelheim Investigational Site
Seoul
Taiwan5 sites
1199.30.88605 Boehringer Ingelheim Investigational Site
Taichung
1199.30.88601 National Taiwan University
Taipei
1199.30.88603 Tri-service General Hospital
Taipei
1199.30.88606 Boehringer Ingelheim Investigational Site
Taipei
1199.30.88604 Chang Gung Memorial Hosp-Linkou
Taoyuan
United Kingdom5 sites
1199.30.44006 Boehringer Ingelheim Investigational Site
Aberdeen
1199.30.44003 Boehringer Ingelheim Investigational Site
Birmingham
1199.30.44005 Boehringer Ingelheim Investigational Site
Birmingham
1199.30.44007 Boehringer Ingelheim Investigational Site
Manchester
1199.30.44001 Boehringer Ingelheim Investigational Site
Westbury on Trym
Australia4 sites
1199.30.61001 Royal Perth Hospital
Perth, Western Australia
1199.30.61005 Boehringer Ingelheim Investigational Site
South Brisbane, Queensland
1199.30.61003 Boehringer Ingelheim Investigational Site
Toorak Gardens, South Australia
1199.30.61004 Boehringer Ingelheim Investigational Site
Woodville, South Australia
Belgium3 sites
1199.30.32004 Boehringer Ingelheim Investigational Site
Brussels
1199.30.32001 Boehringer Ingelheim Investigational Site
Leuven
1199.30.32002 Boehringer Ingelheim Investigational Site
Yvoir
Greece3 sites
1199.30.30004 Boehringer Ingelheim Investigational Site
Alexandroupoli
1199.30.30001 Boehringer Ingelheim Investigational Site
Heraklion
1199.30.30002 Boehringer Ingelheim Investigational Site
Larissa
Russia3 sites
1199.30.07001 Boehringer Ingelheim Investigational Site
Moscow
1199.30.07002 Boehringer Ingelheim Investigational Site
Moscow
1199.30.07003 Boehringer Ingelheim Investigational Site
Saint Petersburg
South Africa3 sites
1199.30.27001 Boehringer Ingelheim Investigational Site
Bellville
1199.30.27003 Boehringer Ingelheim Investigational Site
Cape Town
1199.30.27002 Boehringer Ingelheim Investigational Site
Tygerberg
Brazil2 sites
1199.30.55002 Boehringer Ingelheim Investigational Site
Porto Alegre
1199.30.55001 Boehringer Ingelheim Investigational Site
Vila Clementino
Bulgaria2 sites
1199.30.06004 Boehringer Ingelheim Investigational Site
Sofia
1199.30.06005 Boehringer Ingelheim Investigational Site
Sofia
Canada2 sites
1199.30.01003 Division of Respirology
Halifax, Nova Scotia
1199.30.01002 St. Joseph's Healthcare
Hamilton, Ontario
Czechia2 sites
1199.30.42002 Boehringer Ingelheim Investigational Site
Prague
1199.30.42001 Boehringer Ingelheim Investigational Site
Ústí nad Labem
Spain2 sites
1199.30.34001 Boehringer Ingelheim Investigational Site
Barcelona
1199.30.34002 Boehringer Ingelheim Investigational Site
Valencia
Turkey (Türkiye)2 sites
1199.30.90001 Boehringer Ingelheim Investigational Site
Ankara
1199.30.90002 Boehringer Ingelheim Investigational Site
Istanbul
Argentina1 site
1199.30.54002 Boehringer Ingelheim Investigational Site
Mendoza
Mexico1 site
1199.30.52001 Boehringer Ingelheim Investigational Site
Distrito Federal
Netherlands1 site
1199.30.31002 Boehringer Ingelheim Investigational Site
Nieuwegein
About this study
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.
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
- Conditions
- Pulmonary Fibrosis
- Being tested
- low dose BIBF1120 once daily, low dose BIBF 1120 twice daily, intermediate dose BIBF 1120 twice daily, high dose BIBF 1120 twice daily, placebo
- Medical subject headings
- Pulmonary Fibrosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
low dose BIBF1120 once dailyDrug
low dose BIBF1120 once daily
low dose BIBF 1120 twice dailyDrug
low dose BIBF 1120 twice daily
intermediate dose BIBF 1120 twice dailyDrug
intermediate dose BIBF 1120 twice daily
high dose BIBF 1120 twice dailyDrug
high dose BIBF 1120 twice daily
placeboDrug
placebo
| Study group | Role | What they receive |
|---|---|---|
| dose 1 | Experimental | low dose BIBF1120 once daily Receives: Drug: low dose BIBF1120 once daily |
| dose 2 | Experimental | low dose BIBF 1120 twice daily Receives: Drug: low dose BIBF 1120 twice daily |
| dose 3 | Experimental | intermediate dose BIBF 1120 twice daily Receives: Drug: intermediate dose BIBF 1120 twice daily |
| dose 4 | Experimental | high dose BIBF 1120 twice daily Receives: Drug: high dose BIBF 1120 twice daily |
| placebo | Placebo comparator | placebo Receives: Drug: placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Baseline until 52 weeks
Secondary outcomes (36)
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.
Measured: 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.
Measured: 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.
Measured: 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
Measured: 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
Measured: 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.
Measured: 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.
Measured: 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
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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
Measured: 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
Measured: 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.
Measured: 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
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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
Measured: 52 weeks
Occurrences of IPF Exacerbations Per Patient Per Year
Occurrences of Idiopathic Pulmonary Fibrosis (IPF) exacerbations per patient per year at 52 weeks
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: day 365 and day 729
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Aug 2007 (estimated)
- Study startAug 2007
- Primary completionJun 2010
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Pulmonary FibrosisStudies of the same condition, open and under way.
- More trials run by Boehringer IngelheimThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Enrolment
- 432 participants (actual)
Sponsor and investigators
- Lead sponsor
- Boehringer Ingelheim
- Sponsor type
- Industry (pharma, biotech, devices)
- Investigators
- Boehringer Ingelheim, Study chair, Boehringer Ingelheim
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00514683
- Sponsor's protocol ID
- 1199.30
- Status last verified
- Jan 2015
- First submitted
- 9 Aug 2007
- Last updated
- 6 Jan 2015
- Results posted
- Yes, on ClinicalTrials.gov
Publications
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.
PubMed 33902584Richeldi 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.
PubMed 28993537Paterniti 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.
PubMed 28388260Richeldi 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.
PubMed 21992121
Study at a glance
From the registry record, last updated by the sponsor on 6 Jan 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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.
- ClinicalTrials.gov ID
- NCT00514683
- Acronym / sponsor ID
- 1199.30
- Conditions
- Pulmonary Fibrosis
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 432 participants (actual)
- Lead sponsor
- Boehringer IngelheimIndustry (pharma, biotech, devices)
- Study start
- Aug 2007
- Primary completion
- Jun 2010 (actual)
- First posted
- 10 Aug 2007 (estimated)
- Results
- Posted 6 Jan 2015
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| dose 1 | Experimental | Drug: low dose BIBF1120 once dailylow dose BIBF1120 once daily |
| dose 2 | Experimental | Drug: low dose BIBF 1120 twice dailylow dose BIBF 1120 twice daily |
| dose 3 | Experimental | Drug: intermediate dose BIBF 1120 twice dailyintermediate dose BIBF 1120 twice daily |
| dose 4 | Experimental | Drug: high dose BIBF 1120 twice dailyhigh dose BIBF 1120 twice daily |
| placebo | Placebo comparator | Drug: placeboplacebo |
Who may qualify
- Ages
- 40 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (18 listed)
- Patient >40 years
- Written informed consent signed prior to entry into the study
- IPF diagnosed (according to ATS / ERS criteria) less than 5 years prior to screening visit.
- HRCT within 12 months of randomisation and biopsy (the latter if needed to fulfil ATS/ERS criteria) centrally reviewed and consistent with diagnosis.
- FVC>50 % of predicted value
Key exclusion criteria (24 listed)
- AST, ALT > 1.5 x ULN ;
- Bilirubin > 1.5 x ULN
- Relevant airways obstruction
- Continuous oxygen supplementation at randomisation (defined as > 15 hours supplemental oxygen per day).
- Active infection at screening or randomisation.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| low dose BIBF1120 once dailylow dose BIBF1120 once daily | Drug | dose 1 |
| low dose BIBF 1120 twice dailylow dose BIBF 1120 twice daily | Drug | dose 2 |
| intermediate dose BIBF 1120 twice dailyintermediate dose BIBF 1120 twice daily | Drug | dose 3 |
| high dose BIBF 1120 twice dailyhigh dose BIBF 1120 twice daily | Drug | dose 4 |
| placeboplacebo | Drug | placebo |
Primary outcome
Rate of Decline in FVC
Time frame: Baseline until 52 weeks
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.
36 secondary outcomes
Absolute Change From Baseline in FVC%Pred
Time frame: Baseline and 52 weeks
Absolute Change From Baseline in FVC
Time frame: Baseline and 52 weeks
Relative Change From Baseline in FVC%Pred
Time frame: Baseline and 52 weeks
Relative Change From Baseline in FVC
Time frame: Baseline and 52 weeks
Number of Participants With Change From Baseline in FVC by Categories
Time frame: Baseline and 52 weeks
Survival (All Causes of Death and Lung-transplant Free)
Time frame: 52 weeks
Absolute Change From Baseline in SpO2 at Rest
Time frame: Baseline and 52 weeks
Absolute Change From Baseline in SpO2 at Rest by Categories
Time frame: Baseline and 52 weeks
Absolute Change From Baseline in PaO2
Time frame: Baseline and 52 weeks
Absolute Change From Baseline in P(A-a)O2
Time frame: Baseline and 52 weeks
Absolute Change From Baseline in PaCO2
Time frame: Baseline and 52 weeks
Absolute Change From Baseline in PaO2 by Categories
Time frame: Baseline and 52 weeks
Absolute Change From Baseline in P(A-a) O2 by Categories
Time frame: Baseline and 52 weeks
Absolute Change From Baseline in DLCO
Time frame: Baseline and 52 weeks
Absolute Change From Baseline in DLCO by Categories
Time frame: Baseline and 52 weeks
Absolute Change From Baseline in Distance Walk (6-MWT)
Time frame: Baseline and 52 weeks
Absolute Change From Baseline in Dyspnoea Rating on Borg Scale Before Exercise (6-MWT)
Time frame: Baseline and 52 weeks
Change From Baseline in Dyspnoea Rating on Borg Scale After Exercise (6-MWT)
Time frame: Baseline and 52 weeks
Absolute Change From Baseline in MRC Dyspnea Scale by Categories
Time frame: Baseline and 52 weeks
Absolute Change From Baseline in FEV1/FVC
Time frame: Baseline and 52 weeks
Change From Baseline in SGRQ Total Score
Time frame: Baseline and 52 weeks
Change From Baseline in SGRQ Domain Score Symptoms
Time frame: Baseline and 52 weeks
Change From Baseline in SGRQ Domain Score Impacts
Time frame: Baseline and 52 weeks
Change From Baseline in St George's Respiratory Questionnaire (SGRQ) Domain Score Activities
Time frame: Baseline and 52 weeks
St George's Respiratory Questionnaire (SGRQ) Responder
Time frame: 52 weeks
Change From Baseline in TLC
Time frame: Baseline and 52 weeks
Change From Baseline in RV
Time frame: Baseline and 52 weeks
Change From Baseline in TGV
Time frame: Baseline and 52 weeks
Change From Baseline in VC
Time frame: Baseline and 52 weeks
Change From Baseline in IC
Time frame: Baseline and 52 weeks
Number of Patients With at Least One IPF Exacerbation
Time frame: 52 weeks
Occurrences of IPF Exacerbations Per Patient Per Year
Time frame: 52 weeks
Time to First Occurrence of IPF Exacerbation
Time frame: 52 weeks
Survival (Death Due to Respiratory Cause, and Lung-transplant Free)
Time frame: 52 weeks
Time to Progression
Time frame: 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).
Time frame: day 365 and day 729
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Jan 2015.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 33902584Glaspole 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.
- Derived from this study: PubMed 28993537Richeldi 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.
- Derived from this study: PubMed 28388260Paterniti 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.
- Derived from this study: PubMed 21992121Richeldi 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Boehringer Ingelheim study chair
Boehringer Ingelheim
92 sites in 25 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing low dose BIBF1120 once daily, low dose BIBF 1120 twice daily and intermediate dose BIBF 1120 twice daily in people with Pulmonary Fibrosis, run by Boehringer Ingelheim at 92 sites in 25 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 18 inclusion and 24 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 6 Jan 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 92 sites in Italy, France, Germany, Portugal, China and 20 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 6 Jan 2015). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Rate of Decline in FVC (time frame: Baseline until 52 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00514683, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Jan 2015.