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Completed

NCT Number: NCT00514683

Safety And Efficacy of BIBF 1120 in Idiopathic Pulmonary Fibrosis

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

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Key information

Conditions

Pulmonary Fibrosis Fibrosis Lung Diseases Lung Diseases, Interstitial Pathologic Processes Pathological Conditions, Signs and Symptoms Respiratory Tract Diseases

Age range

40 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

1199.30.54002 Boehringer Ingelheim Investigational Site, Mendoza, Argentina

Loading trial locations.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • 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):

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

Exclusion criteria

  • 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
  • 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

Treatment and study plan

low dose BIBF1120 once daily

Drug

low dose BIBF1120 once daily

low dose BIBF 1120 twice daily

Drug

low dose BIBF 1120 twice daily

intermediate dose BIBF 1120 twice daily

Drug

intermediate dose BIBF 1120 twice daily

high dose BIBF 1120 twice daily

Drug

high dose BIBF 1120 twice daily

Placebo

Drug

placebo

Primary outcomes

  1. 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.

Secondary outcomes

  1. Absolute Change From Baseline in FVC%Pred

    Time frame: Baseline and 52 weeks

    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.

  2. Absolute Change From Baseline in FVC

    Time frame: Baseline and 52 weeks

    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.

  3. Relative Change From Baseline in FVC%Pred

    Time frame: Baseline and 52 weeks

    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.

  4. Relative Change From Baseline in FVC

    Time frame: Baseline and 52 weeks

    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

  5. Number of Participants With Change From Baseline in FVC by Categories

    Time frame: Baseline and 52 weeks

    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

  6. Survival (All Causes of Death and Lung-transplant Free)

    Time frame: 52 weeks

    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.

  7. Absolute Change From Baseline in SpO2 at Rest

    Time frame: Baseline and 52 weeks

    Absolute change from baseline in oxygen saturation (SpO2) at rest.

    Means were adjusted based on an ANCOVA with fixed terms for treatment, baseline, region.

  8. Absolute Change From Baseline in SpO2 at Rest by Categories

    Time frame: Baseline and 52 weeks

    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

  9. Absolute Change From Baseline in PaO2

    Time frame: Baseline and 52 weeks

    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.

  10. Absolute Change From Baseline in P(A-a)O2

    Time frame: Baseline and 52 weeks

    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.

  11. Absolute Change From Baseline in PaCO2

    Time frame: Baseline and 52 weeks

    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.

  12. Absolute Change From Baseline in PaO2 by Categories

    Time frame: Baseline and 52 weeks

    Absolute change from baseline in Arterial oxygen partial pressure (PaO2) by below mentioned categories:

    • Decrease > 4 mmHg
    • Change within +/- 4 mmHg
    • Increase > 4 mmHg

  13. Absolute Change From Baseline in P(A-a) O2 by Categories

    Time frame: Baseline and 52 weeks

    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

  14. Absolute Change From Baseline in DLCO

    Time frame: Baseline and 52 weeks

    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.

  15. Absolute Change From Baseline in DLCO by Categories

    Time frame: Baseline and 52 weeks

    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

  16. Absolute Change From Baseline in Distance Walk (6-MWT)

    Time frame: Baseline and 52 weeks

    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.

  17. Absolute Change From Baseline in Dyspnoea Rating on Borg Scale Before Exercise (6-MWT)

    Time frame: Baseline and 52 weeks

    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.

  18. Change From Baseline in Dyspnoea Rating on Borg Scale After Exercise (6-MWT)

    Time frame: Baseline and 52 weeks

    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.

  19. Absolute Change From Baseline in MRC Dyspnea Scale by Categories

    Time frame: Baseline and 52 weeks

    Absolute change from baseline in Medical Research Council (MRC) dyspnea scale by below mentioned categories:

    • Decrease
    • No Change
    • Increase

  20. Absolute Change From Baseline in FEV1/FVC

    Time frame: Baseline and 52 weeks

    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.

  21. Change From Baseline in SGRQ Total Score

    Time frame: Baseline and 52 weeks

    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.

  22. Change From Baseline in SGRQ Domain Score Symptoms

    Time frame: Baseline and 52 weeks

    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.

  23. Change From Baseline in SGRQ Domain Score Impacts

    Time frame: Baseline and 52 weeks

    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.

  24. Change From Baseline in St George's Respiratory Questionnaire (SGRQ) Domain Score Activities

    Time frame: Baseline and 52 weeks

    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.

  25. St George's Respiratory Questionnaire (SGRQ) Responder

    Time frame: 52 weeks

    St George's Respiratory Questionnaire (SGRQ) responder (<= -4 points change) (%) at 52 weeks-worst case

  26. Change From Baseline in TLC

    Time frame: Baseline and 52 weeks

    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.

  27. Change From Baseline in RV

    Time frame: Baseline and 52 weeks

    Change from Baseline in Residual volume (RV) at 52 weeks. Means were adjusted based on an ANCOVA with fixed terms for treatment, baseline, region.

  28. Change From Baseline in TGV

    Time frame: Baseline and 52 weeks

    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.

  29. Change From Baseline in VC

    Time frame: Baseline and 52 weeks

    Change from baseline in Vital capacity (VC) at 52 weeks. Means were adjusted based on an ANCOVA with fixed terms for treatment, baseline, region.

  30. Change From Baseline in IC

    Time frame: Baseline and 52 weeks

    Change from Baseline in Inspiratory Capacity (IC) at 52 weeks. Means were adjusted based on an ANCOVA with fixed terms for treatment, baseline, region.

  31. Number of Patients With at Least One IPF Exacerbation

    Time frame: 52 weeks

    Number of patients with at least one Idiopathic Pulmonary Fibrosis (IPF) exacerbation at 52 weeks

  32. Occurrences of IPF Exacerbations Per Patient Per Year

    Time frame: 52 weeks

    Occurrences of Idiopathic Pulmonary Fibrosis (IPF) exacerbations per patient per year at 52 weeks

  33. Time to First Occurrence of IPF Exacerbation

    Time frame: 52 weeks

    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.

  34. Survival (Death Due to Respiratory Cause, and Lung-transplant Free)

    Time frame: 52 weeks

    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.

  35. Time to Progression

    Time frame: 52 weeks

    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.

  36. 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

    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.

Sponsors and collaborators

Lead sponsor

Boehringer Ingelheim

Industry

Registry information

Official study 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.

Important dates

Study start
2007
Primary completion
2010
First posted
Aug 10, 2007
Registry last updated
Jan 6, 2015

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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