Comment Period Extended to 3/23/2015 for Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

Safety And Efficacy of BIBF 1120 in Idiopathic Pulmonary Fibrosis

This study has been completed.
Sponsor:
Information provided by:
Boehringer Ingelheim
ClinicalTrials.gov Identifier:
NCT00514683
First received: August 9, 2007
Last updated: January 5, 2015
Last verified: January 2015

August 9, 2007
January 5, 2015
August 2007
June 2010   (final data collection date for primary outcome measure)
Rate of Decline in FVC [ Time Frame: Baseline until 52 weeks ] [ Designated as safety issue: No ]

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.

The primary endpoint is the rate of decline in FVC (expressed in mL per year), evaluated from baseline until 12 month of treatment, compared to placebo.
Complete list of historical versions of study NCT00514683 on ClinicalTrials.gov Archive Site
  • Absolute Change From Baseline in FVC%Pred [ Time Frame: Baseline and 52 weeks ] [ Designated as safety issue: No ]

    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.

  • Absolute Change From Baseline in FVC [ Time Frame: Baseline and 52 weeks ] [ Designated as safety issue: No ]

    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.

  • Relative Change From Baseline in FVC%Pred [ Time Frame: Baseline and 52 weeks ] [ Designated as safety issue: No ]

    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.

  • Relative Change From Baseline in FVC [ Time Frame: Baseline and 52 weeks ] [ Designated as safety issue: No ]

    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

  • Number of Participants With Change From Baseline in FVC by Categories [ Time Frame: Baseline and 52 weeks ] [ Designated as safety issue: No ]

    Change from baseline in percentage of Forced Vital Capacity (FVC) at 52 weeks in below mentioned categories:

    1. Decrease > 10% or 200mL
    2. Change within <= 10% or <=200 mL
    3. Increase > 10% or 200mL
  • Survival (All Causes of Death and Lung-transplant Free) [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]

    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.

  • Absolute Change From Baseline in SpO2 at Rest [ Time Frame: Baseline and 52 weeks ] [ Designated as safety issue: No ]

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

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

  • Absolute Change From Baseline in SpO2 at Rest by Categories [ Time Frame: Baseline and 52 weeks ] [ Designated as safety issue: No ]

    Absolute change from baseline in oxygen saturation (SpO2) at rest by below mentioned categories:

    SpO2 (non-invasive) at 52 weeks:

    1. Decrease > 4% SpO2
    2. Change within +/- 4% SpO2
    3. Increase > 4% SpO2
  • Absolute Change From Baseline in PaO2 [ Time Frame: Baseline and 52 weeks ] [ Designated as safety issue: No ]
    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.
  • Absolute Change From Baseline in P(A-a)O2 [ Time Frame: Baseline and 52 weeks ] [ Designated as safety issue: No ]
    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.
  • Absolute Change From Baseline in PaCO2 [ Time Frame: Baseline and 52 weeks ] [ Designated as safety issue: No ]
    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.
  • Absolute Change From Baseline in PaO2 by Categories [ Time Frame: Baseline and 52 weeks ] [ Designated as safety issue: No ]

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

    1. Decrease > 4 mmHg
    2. Change within +/- 4 mmHg
    3. Increase > 4 mmHg
  • Absolute Change From Baseline in P(A-a) O2 by Categories [ Time Frame: Baseline and 52 weeks ] [ Designated as safety issue: No ]

    Absolute change from baseline in Alveolo-arterial oxygen gradient (P(A-a) O2) by below mentioned categories:

    1. Decrease > 4 mmHg
    2. Change within +/- 4 mmHg
    3. Increase > 4 mmHg
  • Absolute Change From Baseline in DLCO [ Time Frame: Baseline and 52 weeks ] [ Designated as safety issue: No ]

    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.

  • Absolute Change From Baseline in DLCO by Categories [ Time Frame: Baseline and 52 weeks ] [ Designated as safety issue: No ]

    Absolute change from baseline in Diffusing capacity of the lung for carbon monoxide (DLCO) by below mentioned categories:

    1. Decrease > 15% or > 1
    2. Change <= 15% or <= 1
    3. Increase > 15% or > 1
  • Absolute Change From Baseline in Distance Walk (6-MWT) [ Time Frame: Baseline and 52 weeks ] [ Designated as safety issue: No ]
    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.
  • Absolute Change From Baseline in Dyspnoea Rating on Borg Scale Before Exercise (6-MWT) [ Time Frame: Baseline and 52 weeks ] [ Designated as safety issue: No ]

    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.

  • Change From Baseline in Dyspnoea Rating on Borg Scale After Exercise (6-MWT) [ Time Frame: Baseline and 52 weeks ] [ Designated as safety issue: No ]

    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.

  • Absolute Change From Baseline in MRC Dyspnea Scale by Categories [ Time Frame: Baseline and 52 weeks ] [ Designated as safety issue: No ]

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

    1. Decrease
    2. No Change
    3. Increase
  • Absolute Change From Baseline in FEV1/FVC [ Time Frame: Baseline and 52 weeks ] [ Designated as safety issue: No ]

    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.

  • Change From Baseline in SGRQ Total Score [ Time Frame: Baseline and 52 weeks ] [ Designated as safety issue: No ]

    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.

  • Change From Baseline in SGRQ Domain Score Symptoms [ Time Frame: Baseline and 52 weeks ] [ Designated as safety issue: No ]

    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.

  • Change From Baseline in SGRQ Domain Score Impacts [ Time Frame: Baseline and 52 weeks ] [ Designated as safety issue: No ]

    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.

  • Change From Baseline in St George's Respiratory Questionnaire (SGRQ) Domain Score Activities [ Time Frame: Baseline and 52 weeks ] [ Designated as safety issue: No ]

    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.

  • St George's Respiratory Questionnaire (SGRQ) Responder [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]
    St George's Respiratory Questionnaire (SGRQ) responder (<= -4 points change) (%) at 52 weeks-worst case
  • Change From Baseline in TLC [ Time Frame: Baseline and 52 weeks ] [ Designated as safety issue: No ]
    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.
  • Change From Baseline in RV [ Time Frame: Baseline and 52 weeks ] [ Designated as safety issue: No ]
    Change from Baseline in Residual volume (RV) at 52 weeks. Means were adjusted based on an ANCOVA with fixed terms for treatment, baseline, region.
  • Change From Baseline in TGV [ Time Frame: Baseline and 52 weeks ] [ Designated as safety issue: No ]
    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.
  • Change From Baseline in VC [ Time Frame: Baseline and 52 weeks ] [ Designated as safety issue: No ]
    Change from baseline in Vital capacity (VC) at 52 weeks. Means were adjusted based on an ANCOVA with fixed terms for treatment, baseline, region.
  • Change From Baseline in IC [ Time Frame: Baseline and 52 weeks ] [ Designated as safety issue: No ]
    Change from Baseline in Inspiratory Capacity (IC) at 52 weeks. Means were adjusted based on an ANCOVA with fixed terms for treatment, baseline, region.
  • Number of Patients With at Least One IPF Exacerbation [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]
    Number of patients with at least one Idiopathic Pulmonary Fibrosis (IPF) exacerbation at 52 weeks
  • Occurrences of IPF Exacerbations Per Patient Per Year [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]
    Occurrences of Idiopathic Pulmonary Fibrosis (IPF) exacerbations per patient per year at 52 weeks
  • Time to First Occurrence of IPF Exacerbation [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]

    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.

  • Survival (Death Due to Respiratory Cause, and Lung-transplant Free) [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]

    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.

  • Time to Progression [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]

    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.

  • 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 ] [ Designated as safety issue: No ]
    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.
Not Provided
Not Provided
Not Provided
 
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

Not Provided
Interventional
Phase 2
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double-Blind
Primary Purpose: Treatment
Pulmonary Fibrosis
  • Drug: low dose BIBF1120 once daily
    low dose BIBF1120 once daily
  • Drug: low dose BIBF 1120 twice daily
    low dose BIBF 1120 twice daily
  • Drug: intermediate dose BIBF 1120 twice daily
    intermediate dose BIBF 1120 twice daily
  • Drug: high dose BIBF 1120 twice daily
    high dose BIBF 1120 twice daily
  • Drug: placebo
    placebo
  • Experimental: dose 1
    low dose BIBF1120 once daily
    Intervention: Drug: low dose BIBF1120 once daily
  • Experimental: dose 2
    low dose BIBF 1120 twice daily
    Intervention: Drug: low dose BIBF 1120 twice daily
  • Experimental: dose 3
    intermediate dose BIBF 1120 twice daily
    Intervention: Drug: intermediate dose BIBF 1120 twice daily
  • Experimental: dose 4
    high dose BIBF 1120 twice daily
    Intervention: Drug: high dose BIBF 1120 twice daily
  • Placebo Comparator: placebo
    placebo
    Intervention: Drug: placebo
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, Klüglich 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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
432
Not Provided
June 2010   (final data collection date for primary outcome measure)

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
Both
40 Years and older
No
Contact information is only displayed when the study is recruiting subjects
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
El Salvador
 
NCT00514683
1199.30
Not Provided
Boehringer Ingelheim, Study Chair, Boehringer Ingelheim
Boehringer Ingelheim
Not Provided
Study Chair: Boehringer Ingelheim Boehringer Ingelheim
Boehringer Ingelheim
January 2015

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP