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Safety And Efficacy of BIBF 1120 in Idiopathic Pulmonary Fibrosis

Primary Purpose

Pulmonary Fibrosis

Status

Completed

Phase

Phase 2

Locations

International

Study Type

Interventional

Intervention

low dose BIBF1120 once daily

low dose BIBF 1120 twice daily

intermediate dose BIBF 1120 twice daily

high dose BIBF 1120 twice daily

placebo

About this trial

This is an interventional treatment trial for Pulmonary Fibrosis

Eligibility Criteria

40 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm Type

Experimental

Placebo Comparator

Arm Label

dose 1

dose 2

dose 3

dose 4

placebo

Arm Description

low dose BIBF1120 once daily

low dose BIBF 1120 twice daily

intermediate dose BIBF 1120 twice daily

high dose BIBF 1120 twice daily

placebo

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.

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.

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.

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

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

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.

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.

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

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.

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.

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.

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

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

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.

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

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.

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.

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.

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

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.

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.

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.

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.

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.

St George's Respiratory Questionnaire (SGRQ) Responder

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

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.

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.

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.

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.

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.

Number of Patients With at Least One IPF Exacerbation

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

Occurrences of IPF Exacerbations Per Patient Per Year

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

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.

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.

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.

Full Information

NCT ID

NCT00514683

First Posted

August 9, 2007

Last Updated

January 5, 2015

Sponsor

Boehringer Ingelheim

1. Study Identification

Unique Protocol Identification Number

NCT00514683

Brief Title

Safety And Efficacy of BIBF 1120 in Idiopathic Pulmonary Fibrosis

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.

Study Type

Interventional

2. Study Status

Record Verification Date

January 2015

Overall Recruitment Status

Completed

Study Start Date

August 2007 (undefined)

Primary Completion Date

June 2010 (Actual)

Study Completion Date

undefined (undefined)

3. Sponsor/Collaborators

Name of the Sponsor

Boehringer Ingelheim

4. Oversight

5. Study Description

Brief 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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Pulmonary Fibrosis

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

Double

Allocation

Randomized

Enrollment

432 (Actual)

8. Arms, Groups, and Interventions

Arm Title

dose 1

Arm Type

Experimental

Arm Description

low dose BIBF1120 once daily

Arm Title

dose 2

Arm Type

Experimental

Arm Description

low dose BIBF 1120 twice daily

Arm Title

dose 3

Arm Type

Experimental

Arm Description

intermediate dose BIBF 1120 twice daily

Arm Title

dose 4

Arm Type

Experimental

Arm Description

high dose BIBF 1120 twice daily

Arm Title

placebo

Arm Type

Placebo Comparator

Arm Description

placebo

Intervention Type

Drug

Intervention Name(s)

low dose BIBF1120 once daily

Intervention Description

low dose BIBF1120 once daily

Intervention Type

Drug

Intervention Name(s)

low dose BIBF 1120 twice daily

Intervention Description

low dose BIBF 1120 twice daily

Intervention Type

Drug

Intervention Name(s)

intermediate dose BIBF 1120 twice daily

Intervention Description

intermediate dose BIBF 1120 twice daily

Intervention Type

Drug

Intervention Name(s)

high dose BIBF 1120 twice daily

Intervention Description

high dose BIBF 1120 twice daily

Intervention Type

Drug

Intervention Name(s)

placebo

Intervention Description

placebo

Primary Outcome Measure Information:

Title

Rate of Decline in FVC

Description

Time Frame

Baseline until 52 weeks

Secondary Outcome Measure Information:

Title

Absolute Change From Baseline in FVC%Pred

Description

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.

Time Frame

Baseline and 52 weeks

Title

Absolute Change From Baseline in FVC

Description

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.

Time Frame

Baseline and 52 weeks

Title

Relative Change From Baseline in FVC%Pred

Description

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.

Time Frame

Baseline and 52 weeks

Title

Relative Change From Baseline in FVC

Description

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

Time Frame

Baseline and 52 weeks

Title

Number of Participants With Change From Baseline in FVC by Categories

Description

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

Time Frame

Baseline and 52 weeks

Title

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

Description

Time Frame

52 weeks

Title

Absolute Change From Baseline in SpO2 at Rest

Description

Absolute change from baseline in oxygen saturation (SpO2) at rest. Means were adjusted based on an ANCOVA with fixed terms for treatment, baseline, region.

Time Frame

Baseline and 52 weeks

Title

Absolute Change From Baseline in SpO2 at Rest by Categories

Description

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

Time Frame

Baseline and 52 weeks

Title

Absolute Change From Baseline in PaO2

Description

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.

Time Frame

Baseline and 52 weeks

Title

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

Description

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.

Time Frame

Baseline and 52 weeks

Title

Absolute Change From Baseline in PaCO2

Description

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.

Time Frame

Baseline and 52 weeks

Title

Absolute Change From Baseline in PaO2 by Categories

Description

Absolute change from baseline in Arterial oxygen partial pressure (PaO2) by below mentioned categories: Decrease > 4 mmHg Change within +/- 4 mmHg Increase > 4 mmHg

Time Frame

Baseline and 52 weeks

Title

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

Description

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

Time Frame

Baseline and 52 weeks

Title

Absolute Change From Baseline in DLCO

Description

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.

Time Frame

Baseline and 52 weeks

Title

Absolute Change From Baseline in DLCO by Categories

Description

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

Time Frame

Baseline and 52 weeks

Title

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

Description

Time Frame

Baseline and 52 weeks

Title

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

Description

Time Frame

Baseline and 52 weeks

Title

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

Description

Time Frame

Baseline and 52 weeks

Title

Absolute Change From Baseline in MRC Dyspnea Scale by Categories

Description

Absolute change from baseline in Medical Research Council (MRC) dyspnea scale by below mentioned categories: Decrease No Change Increase

Time Frame

Baseline and 52 weeks

Title

Absolute Change From Baseline in FEV1/FVC

Description

Time Frame

Baseline and 52 weeks

Title

Change From Baseline in SGRQ Total Score

Description

Time Frame

Baseline and 52 weeks

Title

Change From Baseline in SGRQ Domain Score Symptoms

Description

Time Frame

Baseline and 52 weeks

Title

Change From Baseline in SGRQ Domain Score Impacts

Description

Time Frame

Baseline and 52 weeks

Title

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

Description

Time Frame

Baseline and 52 weeks

Title

St George's Respiratory Questionnaire (SGRQ) Responder

Description

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

Time Frame

52 weeks

Title

Change From Baseline in TLC

Description

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.

Time Frame

Baseline and 52 weeks

Title

Change From Baseline in RV

Description

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

Time Frame

Baseline and 52 weeks

Title

Change From Baseline in TGV

Description

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.

Time Frame

Baseline and 52 weeks

Title

Change From Baseline in VC

Description

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

Time Frame

Baseline and 52 weeks

Title

Change From Baseline in IC

Description

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

Time Frame

Baseline and 52 weeks

Title

Number of Patients With at Least One IPF Exacerbation

Description

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

Time Frame

52 weeks

Title

Occurrences of IPF Exacerbations Per Patient Per Year

Description

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

Time Frame

52 weeks

Title

Time to First Occurrence of IPF Exacerbation

Description

Time Frame

52 weeks

Title

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

Description

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 Frame

52 weeks

Title

Time to Progression

Description

Time Frame

52 weeks

Title

Pre-dose Plasma Concentration of Nintedanib in Plasma at Steady State on Day 365 (Cpre,ss,365) and Day 729 (Cpre,ss,729).

Description

Time Frame

day 365 and day 729

10. Eligibility

Sex

All

Minimum Age & Unit of Time

40 Years

Accepts Healthy Volunteers

Eligibility Criteria

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Boehringer Ingelheim

Organizational Affiliation

Boehringer Ingelheim

Official's Role

Study Chair

Facility Information:

Facility Name

1199.30.54002 Boehringer Ingelheim Investigational Site

City

Mendoza

Country

Argentina

Facility Name

1199.30.61005 Boehringer Ingelheim Investigational Site

City

South Brisbane

State/Province

Queensland

Country

Australia

Facility Name

1199.30.61003 Boehringer Ingelheim Investigational Site

City

Toorak Gardens

State/Province

South Australia

Country

Australia

Facility Name

1199.30.61004 Boehringer Ingelheim Investigational Site

City

Woodville

State/Province

South Australia

Country

Australia

Facility Name

1199.30.61001 Royal Perth Hospital

City

Perth

State/Province

Western Australia

Country

Australia

Facility Name

1199.30.32004 Boehringer Ingelheim Investigational Site

City

Bruxelles

Country

Belgium

Facility Name

1199.30.32001 Boehringer Ingelheim Investigational Site

City

Leuven

Country

Belgium

Facility Name

1199.30.32002 Boehringer Ingelheim Investigational Site

City

Yvoir

Country

Belgium

Facility Name

1199.30.55002 Boehringer Ingelheim Investigational Site

City

Porto Alegre

Country

Brazil

Facility Name

1199.30.55001 Boehringer Ingelheim Investigational Site

City

Vila Clementino

Country

Brazil

Facility Name

1199.30.06004 Boehringer Ingelheim Investigational Site

City

Sofia

Country

Bulgaria

Facility Name

1199.30.06005 Boehringer Ingelheim Investigational Site

City

Sofia

Country

Bulgaria

Facility Name

1199.30.01003 Division of Respirology

City

Halifax

State/Province

Nova Scotia

Country

Canada

Facility Name

1199.30.01002 St. Joseph's Healthcare

City

Hamilton

State/Province

Ontario

Country

Canada

Facility Name

1199.30.56001 Boehringer Ingelheim Investigational Site

City

Providencia

Country

Chile

Facility Name

1199.30.86001 Boehringer Ingelheim Investigational Site

City

Beijing

Country

China

Facility Name

1199.30.86002 Boehringer Ingelheim Investigational Site

City

Beijing

Country

China

Facility Name

1199.30.86005 Boehringer Ingelheim Investigational Site

City

Nanjing

Country

China

Facility Name

1199.30.86003 Boehringer Ingelheim Investigational Site

City

Shanghai

Country

China

Facility Name

1199.30.86004 Boehringer Ingelheim Investigational Site

City

Shenyang

Country

China

Facility Name

1199.30.42002 Boehringer Ingelheim Investigational Site

City

Prague 8

Country

Czech Republic

Facility Name

1199.30.42001 Boehringer Ingelheim Investigational Site

City

Usti nad Labem

Country

Czech Republic

Facility Name

1199.30.3302A Boehringer Ingelheim Investigational Site

City

Bobigny

Country

France

Facility Name

1199.30.3306A Boehringer Ingelheim Investigational Site

City

Dijon

Country

France

Facility Name

1199.30.3303A Boehringer Ingelheim Investigational Site

City

Grenoble

Country

France

Facility Name

1199.30.3305A Boehringer Ingelheim Investigational Site

City

Lille Cedex

Country

France

Facility Name

1199.30.3305B Boehringer Ingelheim Investigational Site

City

Lille Cedex

Country

France

Facility Name

1199.30.3305C Boehringer Ingelheim Investigational Site

City

Lille Cedex

Country

France

Facility Name

1199.30.3304C Boehringer Ingelheim Investigational Site

City

Montpellier

Country

France

Facility Name

1199.30.3307A Boehringer Ingelheim Investigational Site

City

Nice Cedex 1

Country

France

Facility Name

1199.30.3301A Boehringer Ingelheim Investigational Site

City

Paris Cedex 18

Country

France

Facility Name

1199.30.49008 Boehringer Ingelheim Investigational Site

City

Bad Berka

Country

Germany

Facility Name

1199.30.49007 Boehringer Ingelheim Investigational Site

City

Berlin

Country

Germany

Facility Name

1199.30.49006 Boehringer Ingelheim Investigational Site

City

Donaustauf

Country

Germany

Facility Name

1199.30.49001 Boehringer Ingelheim Investigational Site

City

Essen

Country

Germany

Facility Name

1199.30.49002 Boehringer Ingelheim Investigational Site

City

Freiburg/Breisgau

Country

Germany

Facility Name

1199.30.49003 Boehringer Ingelheim Investigational Site

City

Großhansdorf

Country

Germany

Facility Name

1199.30.49009 Boehringer Ingelheim Investigational Site

City

Leipzig

Country

Germany

Facility Name

1199.30.49004 Boehringer Ingelheim Investigational Site

City

Mainz

Country

Germany

Facility Name

1199.30.49005 Boehringer Ingelheim Investigational Site

City

München

Country

Germany

Facility Name

1199.30.30004 Boehringer Ingelheim Investigational Site

City

Alexandroupolis

Country

Greece

Facility Name

1199.30.30001 Boehringer Ingelheim Investigational Site

City

Heraklion

Country

Greece

Facility Name

1199.30.30002 Boehringer Ingelheim Investigational Site

City

Larisa

Country

Greece

Facility Name

1199.30.36002 Boehringer Ingelheim Investigational Site

City

Budapest

Country

Hungary

Facility Name

1199.30.36003 Boehringer Ingelheim Investigational Site

City

Budapest

Country

Hungary

Facility Name

1199.30.36004 Boehringer Ingelheim Investigational Site

City

Deszk

Country

Hungary

Facility Name

1199.30.36001 Boehringer Ingelheim Investigational Site

City

Pecs

Country

Hungary

Facility Name

1199.30.36005 Boehringer Ingelheim Investigational Site

City

Szekesfehervar

Country

Hungary

Facility Name

1199.30.35301 Mater Misericordiae Hospital

City

Dublin 7

Country

Ireland

Facility Name

1199.30.39008 Boehringer Ingelheim Investigational Site

City

Ascoli Piceno

Country

Italy

Facility Name

1199.30.39013 Boehringer Ingelheim Investigational Site

City

Busto Arsizio (va)

Country

Italy

Facility Name

1199.30.39007 Boehringer Ingelheim Investigational Site

City

Milano

Country

Italy

Facility Name

1199.30.39001 Boehringer Ingelheim Investigational Site

City

Modena

Country

Italy

Facility Name

1199.30.39012 Boehringer Ingelheim Investigational Site

City

Napoli

Country

Italy

Facility Name

1199.30.39009 Boehringer Ingelheim Investigational Site

City

Pavia

Country

Italy

Facility Name

1199.30.39011 Boehringer Ingelheim Investigational Site

City

Roma

Country

Italy

Facility Name

1199.30.39010 Boehringer Ingelheim Investigational Site

City

Siena

Country

Italy

Facility Name

1199.30.39003 Boehringer Ingelheim Investigational Site

City

Terni

Country

Italy

Facility Name

1199.30.39004 Boehringer Ingelheim Investigational Site

City

Trieste

Country

Italy

Facility Name

1199.30.82002 Boehringer Ingelheim Investigational Site

City

Gyunggido

Country

Korea, Republic of

Facility Name

1199.30.82004 Boehringer Ingelheim Investigational Site

City

Incheon

Country

Korea, Republic of

Facility Name

1199.30.82001 Boehringer Ingelheim Investigational Site

City

Seoul

Country

Korea, Republic of

Facility Name

1199.30.82003 Boehringer Ingelheim Investigational Site

City

Seoul

Country

Korea, Republic of

Facility Name

1199.30.82005 Boehringer Ingelheim Investigational Site

City

Seoul

Country

Korea, Republic of

Facility Name

1199.30.52001 Boehringer Ingelheim Investigational Site

City

Distrito Federal

Country

Mexico

Facility Name

1199.30.31002 Boehringer Ingelheim Investigational Site

City

Nieuwegein

Country

Netherlands

Facility Name

1199.30.35105 Boehringer Ingelheim Investigational Site

City

Coimbra

Country

Portugal

Facility Name

1199.30.35106 Boehringer Ingelheim Investigational Site

City

Coimbra

Country

Portugal

Facility Name

1199.30.35107 Boehringer Ingelheim Investigational Site

City

Lisboa

Country

Portugal

Facility Name

1199.30.35108 Boehringer Ingelheim Investigational Site

City

Lisboa

Country

Portugal

Facility Name

1199.30.35109 Boehringer Ingelheim Investigational Site

City

Lisboa

Country

Portugal

Facility Name

1199.30.35101 Boehringer Ingelheim Investigational Site

City

Porto

Country

Portugal

Facility Name

1199.30.07001 Boehringer Ingelheim Investigational Site

City

Moscow

Country

Russian Federation

Facility Name

1199.30.07002 Boehringer Ingelheim Investigational Site

City

Moscow

Country

Russian Federation

Facility Name

1199.30.07003 Boehringer Ingelheim Investigational Site

City

St. Petersburg

Country

Russian Federation

Facility Name

1199.30.27001 Boehringer Ingelheim Investigational Site

City

Bellville

Country

South Africa

Facility Name

1199.30.27003 Boehringer Ingelheim Investigational Site

City

Cape Town

Country

South Africa

Facility Name

1199.30.27002 Boehringer Ingelheim Investigational Site

City

Tygerberg

Country

South Africa

Facility Name

1199.30.34001 Boehringer Ingelheim Investigational Site

City

Barcelona

Country

Spain

Facility Name

1199.30.34002 Boehringer Ingelheim Investigational Site

City

Valencia

Country

Spain

Facility Name

1199.30.88605 Boehringer Ingelheim Investigational Site

City

Taichung

Country

Taiwan

Facility Name

1199.30.88601 National Taiwan University

City

Taipei

Country

Taiwan

Facility Name

1199.30.88603 Tri-service General Hospital

City

Taipei

Country

Taiwan

Facility Name

1199.30.88606 Boehringer Ingelheim Investigational Site

City

Taipei

Country

Taiwan

Facility Name

1199.30.88604 Chang Gung Memorial Hosp-Linkou

City

Taoyuan

Country

Taiwan

Facility Name

1199.30.90001 Boehringer Ingelheim Investigational Site

City

Ankara

Country

Turkey

Facility Name

1199.30.90002 Boehringer Ingelheim Investigational Site

City

Istanbul

Country

Turkey

Facility Name

1199.30.44006 Boehringer Ingelheim Investigational Site

City

Aberdeen

Country

United Kingdom

Facility Name

1199.30.44003 Boehringer Ingelheim Investigational Site

City

Birmingham

Country

United Kingdom

Facility Name

1199.30.44005 Boehringer Ingelheim Investigational Site

City

Birmingham

Country

United Kingdom

Facility Name

1199.30.44007 Boehringer Ingelheim Investigational Site

City

Manchester

Country

United Kingdom

Facility Name

1199.30.44001 Boehringer Ingelheim Investigational Site

City

Westbury on Trym

Country

United Kingdom

12. IPD Sharing Statement

Citations:

PubMed Identifier

33902584

Citation

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.

Results Reference

derived

PubMed Identifier

28993537

Citation

Richeldi L, Kreuter M, Selman M, Crestani B, Kirsten AM, Wuyts WA, Xu Z, Bernois K, Stowasser S, Quaresma M, Costabel U. Long-term treatment of patients with idiopathic pulmonary fibrosis with nintedanib: results from the TOMORROW trial and its open-label extension. Thorax. 2018 Jun;73(6):581-583. doi: 10.1136/thoraxjnl-2016-209701. Epub 2017 Oct 9.

Results Reference

derived

PubMed Identifier

28388260

Citation

Paterniti MO, Bi Y, Rekic D, Wang Y, Karimi-Shah BA, Chowdhury BA. Acute Exacerbation and Decline in Forced Vital Capacity Are Associated with Increased Mortality in Idiopathic Pulmonary Fibrosis. Ann Am Thorac Soc. 2017 Sep;14(9):1395-1402. doi: 10.1513/AnnalsATS.201606-458OC.

Results Reference

derived

PubMed Identifier

21992121

Citation

Richeldi L, Costabel U, Selman M, Kim DS, Hansell DM, Nicholson AG, Brown KK, Flaherty KR, Noble PW, Raghu G, Brun M, Gupta A, Juhel N, Kluglich M, du Bois RM. Efficacy of a tyrosine kinase inhibitor in idiopathic pulmonary fibrosis. N Engl J Med. 2011 Sep 22;365(12):1079-87. doi: 10.1056/NEJMoa1103690.

Results Reference

derived

Links:

URL

http://trials.boehringer-ingelheim.com

Description

Related Info

Learn more about this trial

Safety And Efficacy of BIBF 1120 in Idiopathic Pulmonary Fibrosis

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Safety And Efficacy of BIBF 1120 in Idiopathic Pulmonary Fibrosis

Pulmonary Fibrosis

About this trial

Eligibility Criteria

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

1. Study Identification

2. Study Status

3. Sponsor/Collaborators

4. Oversight

5. Study Description

6. Conditions and Keywords

7. Study Design

8. Arms, Groups, and Interventions

10. Eligibility

12. IPD Sharing Statement

Learn more about this trial