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Safety And Efficacy of BIBF 1120 in Idiopathic Pulmonary Fibrosis

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00514683
Recruitment Status : Completed
First Posted : August 10, 2007
Results First Posted : January 6, 2015
Last Update Posted : January 6, 2015
Sponsor:
Information provided by:
Boehringer Ingelheim

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double;   Primary Purpose: Treatment
Condition Pulmonary Fibrosis
Interventions Drug: low dose BIBF1120 once daily
Drug: low dose BIBF 1120 twice daily
Drug: intermediate dose BIBF 1120 twice daily
Drug: high dose BIBF 1120 twice daily
Drug: placebo
Enrollment 432
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Placebo Nintedanib 50 qd Nintedanib 50 Bid Nintedanib 100 Bid Nintedanib 150 Bid
Hide Arm/Group Description Patients were treated with matching Placebo. Patients were treated with 50mg nintedanib once daily Patients were treated with 50mg nintedanib twice daily Patients were treated with 100mg nintedanib twice daily Patients were treated with 150mg nintedanib twice daily
Period Title: Overall Study
Started 87 [1] 87 [1] 86 [1] 86 [1] 86 [1]
Completed 61 62 68 72 53
Not Completed 26 25 18 14 33
Reason Not Completed
Not treated             2             1             0             0             1
Adverse Event             21             20             15             13             27
Protocol Violation             1             1             0             1             0
Withdrawal by Subject             2             2             1             0             4
Reason other than listed above             0             1             2             0             1
[1]
Randomised
Arm/Group Title Placebo Nintedanib 50 qd Nintedanib 50 Bid Nintedanib 100 Bid Nintedanib 150 Bid Total
Hide Arm/Group Description Patients were treated with matching Placebo. Patients were treated with 50mg nintedanib once daily Patients were treated with 50mg nintedanib twice daily Patients were treated with 100mg nintedanib twice daily Patients were treated with 150mg nintedanib twice daily Total of all reporting groups
Overall Number of Baseline Participants 85 86 86 86 85 428
Hide Baseline Analysis Population Description
Treated Set: This patient set includes all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 85 participants 86 participants 86 participants 86 participants 85 participants 428 participants
64.8  (8.57) 65.3  (9.42) 64.9  (8.48) 65.1  (8.63) 65.4  (7.82) 65.1  (8.56)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 85 participants 86 participants 86 participants 86 participants 85 participants 428 participants
Female
22
  25.9%
21
  24.4%
24
  27.9%
21
  24.4%
20
  23.5%
108
  25.2%
Male
63
  74.1%
65
  75.6%
62
  72.1%
65
  75.6%
65
  76.5%
320
  74.8%
1.Primary Outcome
Title Rate of Decline in FVC
Hide Description

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.

Time Frame Baseline until 52 weeks
Hide Outcome Measure Data
Hide Analysis Population Description

Observed Case (OC): This method was used for the replacement of missing values.

Randomised set: This patient set includes all randomised patients whether treated or not.

Arm/Group Title Placebo Nintedanib 50 qd Nintedanib 50 Bid Nintedanib 100 Bid Nintedanib 150 Bid
Hide Arm/Group Description:
Patients were treated with matching Placebo.
Patients were treated with 50mg nintedanib once daily
Patients were treated with 50mg nintedanib twice daily
Patients were treated with 100mg nintedanib twice daily
Patients were treated with 150mg nintedanib twice daily
Overall Number of Participants Analyzed 83 85 86 85 84
Mean (Standard Error)
Unit of Measure: Liters/year
-0.190  (0.036) -0.174  (0.037) -0.210  (0.035) -0.162  (0.035) -0.060  (0.039)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Nintedanib 50 qd
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.8530
Comments The p-value presented is computed in the course of the closing testing procedure.
Method Mixed Models Analysis
Comments MMRM with fixed terms for treatment*time, gender*height, gender*age and random terms for patient effect, patient*time.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.016
Confidence Interval (2-Sided) 95%
-0.086 to 0.118
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.052
Estimation Comments Mean difference to placebo is calculated. Negative change indicates worsening.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Nintedanib 50 qd
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7558
Comments The p-value from the hierarchical testing procedure was calculated as a sensitivity analysis
Method Mixed Models Analysis
Comments MMRM with fixed terms for treatment*time, gender*height, gender*age and random terms for patient effect, patient*time.
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, Nintedanib 50 Bid
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7920
Comments The p-value presented is computed in the course of the closing testing procedure.
Method Mixed Models Analysis
Comments MMRM with fixed terms for treatment*time, gender*height, gender*age and random terms for patient effect, patient*time.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.020
Confidence Interval (2-Sided) 95%
-0.119 to 0.080
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.051
Estimation Comments Mean difference to placebo is calculated. Negative change indicates worsening.
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo, Nintedanib 50 Bid
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.6991
Comments The p-value from the hierarchical testing procedure was calculated as a sensitivity analysis
Method Mixed Models Analysis
Comments MMRM with fixed terms for treatment*time, gender*height, gender*age and random terms for patient effect, patient*time.
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Placebo, Nintedanib 100 Bid
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.8530
Comments The p-value presented is computed in the course of the closing testing procedure.
Method Mixed Models Analysis
Comments MMRM with fixed terms for treatment*time, gender*height, gender*age and random terms for patient effect, patient*time.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.028
Confidence Interval (2-Sided) 95%
-0.071 to 0.128
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.051
Estimation Comments Mean difference to placebo is calculated. Negative change indicates worsening.
Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Placebo, Nintedanib 100 Bid
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5736
Comments Additionally the p-value from the hierarchical testing procedure was calculated as a sensitivity analysis
Method Mixed Models Analysis
Comments MMRM with fixed terms for treatment*time, gender*height, gender*age and random terms for patient effect, patient*time.
Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Placebo, Nintedanib 150 Bid
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0639
Comments The p-value presented is computed in the course of the closing testing procedure.
Method Mixed Models Analysis
Comments MMRM with fixed terms for treatment*time, gender*height, gender*age and random terms for patient effect, patient*time.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.131
Confidence Interval (2-Sided) 95%
0.027 to 0.235
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.053
Estimation Comments Mean difference to placebo is calculated. Negative change indicates worsening.
Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Placebo, Nintedanib 150 Bid
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0136
Comments Additionally the p-value from the hierarchical testing procedure was calculated as a sensitivity analysis
Method Mixed Models Analysis
Comments MMRM with fixed terms for treatment*time, gender*height, gender*age and random terms for patient effect, patient*time.
2.Secondary Outcome
Title Absolute Change From Baseline in FVC%Pred
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description

Last Observation Carried Forward (LOCF): This method was used for the replacement of missing values.

Randomised set: This patient set includes all randomised patients whether treated or not.

Arm/Group Title Placebo Nintedanib 50 qd Nintedanib 50 Bid Nintedanib 100 Bid Nintedanib 150 Bid
Hide Arm/Group Description:
Patients were treated with matching Placebo.
Patients were treated with 50mg nintedanib once daily
Patients were treated with 50mg nintedanib twice daily
Patients were treated with 100mg nintedanib twice daily
Patients were treated with 150mg nintedanib twice daily
Overall Number of Participants Analyzed 84 85 86 85 84
Mean (Standard Error)
Unit of Measure: percentage of predicted FVC
-6.00  (1.019) -4.58  (1.029) -4.90  (0.984) -3.15  (1.004) -1.04  (0.990)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Nintedanib 50 qd
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2774
Comments [Not Specified]
Method ANCOVA
Comments ANCOVA with fixed terms for treatment, baseline, region.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 1.43
Confidence Interval (2-Sided) 95%
-1.15 to 4.01
Parameter Dispersion
Type: Standard Error of the mean
Value: 1.312
Estimation Comments Mean difference to placebo is calculated. Negative change indicates worsening.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Nintedanib 50 Bid
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4014
Comments [Not Specified]
Method ANCOVA
Comments ANCOVA with fixed terms for treatment, baseline, region.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 1.10
Confidence Interval (2-Sided) 95%
-1.48 to 3.68
Parameter Dispersion
Type: Standard Error of the mean
Value: 1.312
Estimation Comments Mean difference to placebo is calculated. Negative change indicates worsening.
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, Nintedanib 100 Bid
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0314
Comments [Not Specified]
Method ANCOVA
Comments ANCOVA with fixed terms for treatment, baseline, region.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 2.86
Confidence Interval (2-Sided) 95%
0.26 to 5.46
Parameter Dispersion
Type: Standard Error of the mean
Value: 1.324
Estimation Comments Mean difference to placebo is calculated. Negative change indicates worsening.
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo, Nintedanib 150 Bid
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0002
Comments [Not Specified]
Method ANCOVA
Comments ANCOVA with fixed terms for treatment, baseline, region.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 4.97
Confidence Interval (2-Sided) 95%
2.37 to 7.56
Parameter Dispersion
Type: Standard Error of the mean
Value: 1.319
Estimation Comments Mean difference to placebo is calculated. Negative change indicates worsening.
3.Secondary Outcome
Title Absolute Change From Baseline in FVC
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
LOCF-Randomised set
Arm/Group Title Placebo Nintedanib 50 qd Nintedanib 50 Bid Nintedanib 100 Bid Nintedanib 150 Bid
Hide Arm/Group Description:
Patients were treated with matching Placebo.
Patients were treated with 50mg nintedanib once daily
Patients were treated with 50mg nintedanib twice daily
Patients were treated with 100mg nintedanib twice daily
Patients were treated with 150mg nintedanib twice daily
Overall Number of Participants Analyzed 84 85 86 85 84
Mean (Standard Error)
Unit of Measure: Liters
-0.23  (0.036) -0.18  (0.036) -0.19  (0.035) -0.13  (0.035) -0.06  (0.035)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Nintedanib 50 qd
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3644
Comments [Not Specified]
Method ANCOVA
Comments ANCOVA with fixed terms for treatment, baseline, region.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.04
Confidence Interval (2-Sided) 95%
-0.05 to 0.13
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.046
Estimation Comments Mean difference to placebo is calculated. Negative change indicates worsening.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Nintedanib 50 Bid
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4525
Comments [Not Specified]
Method ANCOVA
Comments ANCOVA with fixed terms for treatment, baseline, region.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.03
Confidence Interval (2-Sided) 95%
-0.06 to 0.13
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.046
Estimation Comments Mean difference to placebo is calculated. Negative change indicates worsening.
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, Nintedanib 100 Bid
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0471
Comments [Not Specified]
Method ANCOVA
Comments ANCOVA with fixed terms for treatment, baseline, region.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.09
Confidence Interval (2-Sided) 95%
0.00 to 0.18
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.046
Estimation Comments Mean difference to placebo is calculated. Negative change indicates worsening.
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo, Nintedanib 150 Bid
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0004
Comments [Not Specified]
Method ANCOVA
Comments ANCOVA with fixed terms for treatment, baseline, region.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.17
Confidence Interval (2-Sided) 95%
0.08 to 0.26
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.046
Estimation Comments Mean difference to placebo is calculated. Negative change indicates worsening.
4.Secondary Outcome
Title Relative Change From Baseline in FVC%Pred
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
LOCF-Randomised set
Arm/Group Title Placebo Nintedanib 50 qd Nintedanib 50 Bid Nintedanib 100 Bid Nintedanib 150 Bid
Hide Arm/Group Description:
Patients were treated with matching Placebo.
Patients were treated with 50mg nintedanib once daily
Patients were treated with 50mg nintedanib twice daily
Patients were treated with 100mg nintedanib twice daily
Patients were treated with 150mg nintedanib twice daily
Overall Number of Participants Analyzed 84 85 86 85 84
Mean (Standard Error)
Unit of Measure: percentage of change
-7.28  (1.321) -6.37  (1.334) -6.42  (1.277) -3.47  (1.302) -1.81  (1.283)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Nintedanib 50 qd
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5920
Comments [Not Specified]
Method ANCOVA
Comments ANCOVA with fixed terms for treatment, baseline, region.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.91
Confidence Interval (2-Sided) 95%
-2.43 to 4.26
Parameter Dispersion
Type: Standard Error of the mean
Value: 1.702
Estimation Comments Mean difference to placebo is calculated. Negative change indicates worsening.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Nintedanib 50 Bid
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.6155
Comments [Not Specified]
Method ANCOVA
Comments ANCOVA with fixed terms for treatment, baseline, region.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.86
Confidence Interval (2-Sided) 95%
-2.49 to 4.20
Parameter Dispersion
Type: Standard Error of the mean
Value: 1.702
Estimation Comments Mean difference to placebo is calculated. Negative change indicates worsening.
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, Nintedanib 100 Bid
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0271
Comments [Not Specified]
Method ANCOVA
Comments ANCOVA with fixed terms for treatment, baseline, region.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 3.81
Confidence Interval (2-Sided) 95%
0.43 to 7.18
Parameter Dispersion
Type: Standard Error of the mean
Value: 1.716
Estimation Comments Mean difference to placebo is calculated. Negative change indicates worsening.
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo, Nintedanib 150 Bid
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0015
Comments [Not Specified]
Method ANCOVA
Comments ANCOVA with fixed terms for treatment, baseline, region.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 5.47
Confidence Interval (2-Sided) 95%
2.11 to 8.83
Parameter Dispersion
Type: Standard Error of the mean
Value: 1.710
Estimation Comments Mean difference to placebo is calculated. Negative change indicates worsening.
5.Secondary Outcome
Title Relative Change From Baseline in FVC
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
LOCF-Randomised set
Arm/Group Title Placebo Nintedanib 50 qd Nintedanib 50 Bid Nintedanib 100 Bid Nintedanib 150 Bid
Hide Arm/Group Description:
Patients were treated with matching Placebo.
Patients were treated with 50mg nintedanib once daily
Patients were treated with 50mg nintedanib twice daily
Patients were treated with 100mg nintedanib twice daily
Patients were treated with 150mg nintedanib twice daily
Overall Number of Participants Analyzed 84 85 86 85 84
Mean (Standard Error)
Unit of Measure: percentage change
-7.96  (1.314) -6.98  (1.327) -7.16  (1.272) -4.13  (1.285) -2.52  (1.277)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Nintedanib 50 qd
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5601
Comments ANCOVA with fixed terms for treatment, baseline, region.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.99
Confidence Interval (2-Sided) 95%
-2.34 to 4.31
Parameter Dispersion
Type: Standard Error of the mean
Value: 1.692
Estimation Comments Mean difference to placebo is calculated. Negative change indicates worsening.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Nintedanib 50 Bid
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.6366
Comments [Not Specified]
Method ANCOVA
Comments ANCOVA with fixed terms for treatment, baseline, region.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.80
Confidence Interval (2-Sided) 95%
-2.53 to 4.13
Parameter Dispersion
Type: Standard Error of the mean
Value: 1.694
Estimation Comments Mean difference to placebo is calculated. Negative change indicates worsening.
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, Nintedanib 100 Bid
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0246
Comments [Not Specified]
Method ANCOVA
Comments ANCOVA with fixed terms for treatment, baseline, region.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 3.84
Confidence Interval (2-Sided) 95%
0.49 to 7.18
Parameter Dispersion
Type: Standard Error of the mean
Value: 1.702
Estimation Comments Mean difference to placebo is calculated. Negative change indicates worsening.
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo, Nintedanib 150 Bid
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0015
Comments [Not Specified]
Method ANCOVA
Comments ANCOVA with fixed terms for treatment, baseline, region.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 5.44
Confidence Interval (2-Sided) 95%
2.10 to 8.78
Parameter Dispersion
Type: Standard Error of the mean
Value: 1.700
Estimation Comments Mean difference to placebo is calculated. Negative change indicates worsening.
6.Secondary Outcome
Title Number of Participants With Change From Baseline in FVC by Categories
Hide Description

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
Time Frame Baseline and 52 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
LOCF-Randomised set
Arm/Group Title Placebo Nintedanib 50 qd Nintedanib 50 Bid Nintedanib 100 Bid Nintedanib 150 Bid
Hide Arm/Group Description:
Patients were treated with matching Placebo.
Patients were treated with 50mg nintedanib once daily
Patients were treated with 50mg nintedanib twice daily
Patients were treated with 100mg nintedanib twice daily
Patients were treated with 150mg nintedanib twice daily
Overall Number of Participants Analyzed 84 85 86 85 84
Measure Type: Number
Unit of Measure: participants
Decrease > 10% or 200mL 37 35 41 30 20
Change within <= 10% or <=200mL 41 44 39 46 52
Increase > 10% or 200mL 6 6 6 9 12
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Nintedanib 50 qd
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7543
Comments [Not Specified]
Method Regression, Logistic
Comments Logistic regression model with fixed terms for treatment, baseline of corresponding continuous value, region.
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.911
Confidence Interval (2-Sided) 95%
0.506 to 1.637
Estimation Comments Odds ratio lower than 1 favours the treatment group over placebo.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Nintedanib 50 Bid
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.6704
Comments [Not Specified]
Method Regression, Logistic
Comments Logistic regression model with fixed terms for treatment, baseline of corresponding continuous value, region.
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.136
Confidence Interval (2-Sided) 95%
0.631 to 2.045
Estimation Comments Odds ratio lower than 1 favours the treatment group over placebo.
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, Nintedanib 100 Bid
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1649
Comments [Not Specified]
Method Regression, Logistic
Comments Logistic regression model with fixed terms for treatment, baseline of corresponding continuous value, region.
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.657
Confidence Interval (2-Sided) 95%
0.363 to 1.189
Estimation Comments Odds ratio lower than 1 favours the treatment group over placebo.
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo, Nintedanib 150 Bid
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0041
Comments [Not Specified]
Method Regression, Logistic
Comments Logistic regression model with fixed terms for treatment, baseline of corresponding continuous value, region.
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.415
Confidence Interval (2-Sided) 95%
0.227 to 0.757
Estimation Comments Odds ratio lower than 1 favours the treatment group over placebo.
7.Secondary Outcome
Title Survival (All Causes of Death and Lung-transplant Free)
Hide Description

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.

Time Frame 52 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
OC-Randomised set
Arm/Group Title Placebo Nintedanib 50 qd Nintedanib 50 Bid Nintedanib 100 Bid Nintedanib 150 Bid
Hide Arm/Group Description:
Patients were treated with matching Placebo.
Patients were treated with 50mg nintedanib once daily
Patients were treated with 50mg nintedanib twice daily
Patients were treated with 100mg nintedanib twice daily
Patients were treated with 150mg nintedanib twice daily
Overall Number of Participants Analyzed 87 87 86 86 86
Measure Type: Number
Unit of Measure: participants
Failure 9 11 3 4 7
Censored 78 76 83 82 79
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Nintedanib 50 qd
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5882
Comments [Not Specified]
Method Regression, Cox
Comments Cox regression model with fixed terms for treatment, gender, age, height, region.
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.278
Confidence Interval (2-Sided) 95%
0.526 to 3.102
Estimation Comments Hazard ratio lower than 1 favours the treatment group over placebo.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Nintedanib 50 Bid
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0653
Comments [Not Specified]
Method Regression, Cox
Comments Cox regression model with fixed terms for treatment, gender, age, height, region.
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.290
Confidence Interval (2-Sided) 95%
0.078 to 1.081
Estimation Comments Hazard ratio lower than 1 favours the treatment group over placebo.
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, Nintedanib 100 Bid
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0847
Comments [Not Specified]
Method Regression, Cox
Comments Cox regression model with fixed terms for treatment, gender, age, height, region.
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.350
Confidence Interval (2-Sided) 95%
0.106 to 1.154
Estimation Comments Hazard ratio lower than 1 favours the treatment group over placebo.
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo, Nintedanib 150 Bid
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5383
Comments [Not Specified]
Method Regression, Cox
Comments Cox regression model with fixed terms for treatment, gender, age, height, region.
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.732
Confidence Interval (2-Sided) 95%
0.271 to 1.977
Estimation Comments Hazard ratio lower than 1 favours the treatment group over placebo.
8.Secondary Outcome
Title Absolute Change From Baseline in SpO2 at Rest
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
LOCF-Randomised set
Arm/Group Title Placebo Nintedanib 50 qd Nintedanib 50 Bid Nintedanib 100 Bid Nintedanib 150 Bid
Hide Arm/Group Description:
Patients were treated with matching Placebo.
Patients were treated with 50mg nintedanib once daily
Patients were treated with 50mg nintedanib twice daily
Patients were treated with 100mg nintedanib twice daily
Patients were treated with 150mg nintedanib twice daily
Overall Number of Participants Analyzed 82 82 86 84 83
Mean (Standard Error)
Unit of Measure: Percentage of SpO2
-1.29  (0.373) -0.86  (0.380) -0.97  (0.357) 0.06  (0.363) -0.18  (0.360)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Nintedanib 50 qd
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3658
Comments [Not Specified]
Method ANCOVA
Comments ANCOVA with fixed terms for treatment, baseline, region.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.44
Confidence Interval (2-Sided) 95%
-0.51 to 1.39
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.483
Estimation Comments Mean difference to placebo is calculated. Negative change indicates worsening.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Nintedanib 50 Bid
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4956
Comments [Not Specified]
Method ANCOVA
Comments ANCOVA with fixed terms for treatment, baseline, region.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.33
Confidence Interval (2-Sided) 95%
-0.61 to 1.27
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.478
Estimation Comments Mean difference to placebo is calculated. Negative change indicates worsening.
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, Nintedanib 100 Bid
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0051
Comments [Not Specified]
Method ANCOVA
Comments ANCOVA with fixed terms for treatment, baseline, region.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 1.36
Confidence Interval (2-Sided) 95%
0.41 to 2.31
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.482
Estimation Comments Mean difference to placebo is calculated. Negative change indicates worsening.
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo, Nintedanib 150 Bid
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0211
Comments [Not Specified]
Method ANCOVA
Comments ANCOVA with fixed terms for treatment, baseline, region.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 1.12
Confidence Interval (2-Sided) 95%
0.17 to 2.07
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.483
Estimation Comments Mean difference to placebo is calculated. Negative change indicates worsening.
9.Secondary Outcome
Title Absolute Change From Baseline in SpO2 at Rest by Categories
Hide Description

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
Time Frame Baseline and 52 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
LOCF-Randomised set
Arm/Group Title Placebo Nintedanib 50 qd Nintedanib 50 Bid Nintedanib 100 Bid Nintedanib 150 Bid
Hide Arm/Group Description:
Patients were treated with matching Placebo.
Patients were treated with 50mg nintedanib once daily
Patients were treated with 50mg nintedanib twice daily
Patients were treated with 100mg nintedanib twice daily
Patients were treated with 150mg nintedanib twice daily
Overall Number of Participants Analyzed 82 82 86 84 83
Measure Type: Number
Unit of Measure: percentage of participants
Decrease > 4% 11.0 4.9 8.1 6.0 3.6
Change within +/- 4% 87.8 90.2 89.5 89.3 92.8
Increase > 4% 1.2 4.9 2.3 4.8 3.6
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Nintedanib 50 qd
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1021
Comments [Not Specified]
Method Regression, Logistic
Comments Logistic regression model with fixed terms for treatment, baseline of corresponding continuous value, region.
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.428
Confidence Interval (2-Sided) 95%
0.155 to 1.184
Estimation Comments Odds ratio lower than 1 favours the treatment group over placebo.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Nintedanib 50 Bid
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4318
Comments [Not Specified]
Method Regression, Logistic
Comments Logistic regression model with fixed terms for treatment, baseline of corresponding continuous value, region.
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.682
Confidence Interval (2-Sided) 95%
0.262 to 1.773
Estimation Comments Odds ratio lower than 1 favours the treatment group over placebo.
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, Nintedanib 100 Bid
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0934
Comments [Not Specified]
Method Regression, Logistic
Comments Logistic regression model with fixed terms for treatment, baseline of corresponding continuous value, region.
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.412
Confidence Interval (2-Sided) 95%
0.146 to 1.161
Estimation Comments Odds ratio lower than 1 favours the treatment group over placebo.
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo, Nintedanib 150 Bid
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0317
Comments [Not Specified]
Method Regression, Logistic
Comments Logistic regression model with fixed terms for treatment, baseline of corresponding continuous value, region.
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.313
Confidence Interval (2-Sided) 95%
0.108 to 0.903
Estimation Comments Odds ratio lower than 1 favours the treatment group over placebo.
10.Secondary Outcome
Title Absolute Change From Baseline in PaO2
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
OC-Randomised set
Arm/Group Title Placebo Nintedanib 50 qd Nintedanib 50 Bid Nintedanib 100 Bid Nintedanib 150 Bid
Hide Arm/Group Description:
Patients were treated with matching Placebo.
Patients were treated with 50mg nintedanib once daily
Patients were treated with 50mg nintedanib twice daily
Patients were treated with 100mg nintedanib twice daily
Patients were treated with 150mg nintedanib twice daily
Overall Number of Participants Analyzed 58 56 64 68 51
Mean (Standard Error)
Unit of Measure: mmHg
-1.69  (1.790) -2.77  (1.865) -3.00  (1.686) -1.46  (1.632) -0.76  (1.854)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Nintedanib 50 qd
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.6443
Comments [Not Specified]
Method ANCOVA
Comments ANCOVA with fixed terms for treatment, baseline, region.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -1.08
Confidence Interval (2-Sided) 95%
-5.66 to 3.51
Parameter Dispersion
Type: Standard Error of the mean
Value: 2.330
Estimation Comments Mean difference to placebo is calculated. Negative change indicates worsening.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Nintedanib 50 Bid
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5656
Comments [Not Specified]
Method ANCOVA
Comments ANCOVA with fixed terms for treatment, baseline, region.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -1.31
Confidence Interval (2-Sided) 95%
-5.80 to 3.18
Parameter Dispersion
Type: Standard Error of the mean
Value: 2.280
Estimation Comments Mean difference to placebo is calculated. Negative change indicates worsening.
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, Nintedanib 100 Bid
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9181
Comments [Not Specified]
Method ANCOVA
Comments ANCOVA with fixed terms for treatment, baseline, region.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.23
Confidence Interval (2-Sided) 95%
-4.18 to 4.64
Parameter Dispersion
Type: Standard Error of the mean
Value: 2.240
Estimation Comments Mean difference to placebo is calculated. Negative change indicates worsening.
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo, Nintedanib 150 Bid
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.6970
Comments [Not Specified]
Method ANCOVA
Comments ANCOVA with fixed terms for treatment, baseline, region.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.93
Confidence Interval (2-Sided) 95%
-3.77 to 5.63
Parameter Dispersion
Type: Standard Error of the mean
Value: 2.387
Estimation Comments Mean difference to placebo is calculated. Negative change indicates worsening.
11.Secondary Outcome
Title Absolute Change From Baseline in P(A-a)O2
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
OC-Randomised set
Arm/Group Title Placebo Nintedanib 50 qd Nintedanib 50 Bid Nintedanib 100 Bid Nintedanib 150 Bid
Hide Arm/Group Description:
Patients were treated with matching Placebo.
Patients were treated with 50mg nintedanib once daily
Patients were treated with 50mg nintedanib twice daily
Patients were treated with 100mg nintedanib twice daily
Patients were treated with 150mg nintedanib twice daily
Overall Number of Participants Analyzed 56 54 64 67 51
Mean (Standard Error)
Unit of Measure: mmHg
1.21  (1.898) 1.27  (1.984) 2.22  (1.773) 1.62  (1.723) 2.56  (1.944)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Nintedanib 50 qd
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9811
Comments [Not Specified]
Method ANCOVA
Comments ANCOVA with fixed terms for treatment, baseline, region.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.06
Confidence Interval (2-Sided) 95%
-4.84 to 4.96
Parameter Dispersion
Type: Standard Error of the mean
Value: 2.490
Estimation Comments Mean difference to placebo is calculated. Negative change indicates worsening.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Nintedanib 50 Bid
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.6772
Comments [Not Specified]
Method ANCOVA
Comments ANCOVA with fixed terms for treatment, baseline, region.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 1.01
Confidence Interval (2-Sided) 95%
-3.74 to 5.75
Parameter Dispersion
Type: Standard Error of the mean
Value: 2.412
Estimation Comments Mean difference to placebo is calculated. Negative change indicates worsening.
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, Nintedanib 100 Bid
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.8631
Comments [Not Specified]
Method ANCOVA
Comments ANCOVA with fixed terms for treatment, baseline, region.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.41
Confidence Interval (2-Sided) 95%
-4.27 to 5.09
Parameter Dispersion
Type: Standard Error of the mean
Value: 2.379
Estimation Comments Mean difference to placebo is calculated. Negative change indicates worsening.
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo, Nintedanib 150 Bid
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5942
Comments [Not Specified]
Method ANCOVA
Comments ANCOVA with fixed terms for treatment, baseline, region.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 1.35
Confidence Interval (2-Sided) 95%
-3.62 to 6.31
Parameter Dispersion
Type: Standard Error of the mean
Value: 2.523
Estimation Comments Mean difference to placebo is calculated. Negative change indicates worsening.
12.Secondary Outcome
Title Absolute Change From Baseline in PaCO2
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
OC-Randomised set
Arm/Group Title Placebo Nintedanib 50 qd Nintedanib 50 Bid Nintedanib 100 Bid Nintedanib 150 Bid
Hide Arm/Group Description:
Patients were treated with matching Placebo.
Patients were treated with 50mg nintedanib once daily
Patients were treated with 50mg nintedanib twice daily
Patients were treated with 100mg nintedanib twice daily
Patients were treated with 150mg nintedanib twice daily
Overall Number of Participants Analyzed 58 56 64 68 51
Mean (Standard Error)
Unit of Measure: mmHg
-0.63  (0.549) 0.16  (0.573) -0.44  (0.517) -0.74  (0.500) -0.77  (0.569)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Nintedanib 50 qd
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2716
Comments [Not Specified]
Method ANCOVA
Comments ANCOVA with fixed terms for treatment, baseline, region.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.79
Confidence Interval (2-Sided) 95%
-0.62 to 2.19
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.715
Estimation Comments Mean difference to placebo is calculated. Negative change indicates worsening.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Nintedanib 50 Bid
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7871
Comments [Not Specified]
Method ANCOVA
Comments ANCOVA with fixed terms for treatment, baseline, region.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.19
Confidence Interval (2-Sided) 95%
-1.18 to 1.56
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.696
Estimation Comments Mean difference to placebo is calculated. Negative change indicates worsening.
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, Nintedanib 100 Bid
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.8721
Comments [Not Specified]
Method ANCOVA
Comments ANCOVA with fixed terms for treatment, baseline, region.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.11
Confidence Interval (2-Sided) 95%
-1.46 to 1.24
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.685
Estimation Comments Mean difference to placebo is calculated. Negative change indicates worsening.
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo, Nintedanib 150 Bid
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.8523
Comments [Not Specified]
Method ANCOVA
Comments ANCOVA with fixed terms for treatment, baseline, region.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.14
Confidence Interval (2-Sided) 95%
-1.58 to 1.31
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.734
Estimation Comments Mean difference to placebo is calculated. Negative change indicates worsening.
13.Secondary Outcome
Title Absolute Change From Baseline in PaO2 by Categories
Hide Description

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
Time Frame Baseline and 52 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
OC - Randomised set
Arm/Group Title Placebo Nintedanib 50 qd Nintedanib 50 Bid Nintedanib 100 Bid Nintedanib 150 Bid
Hide Arm/Group Description:
Patients were treated with matching Placebo.
Patients were treated with 50mg nintedanib once daily
Patients were treated with 50mg nintedanib twice daily
Patients were treated with 100mg nintedanib twice daily
Patients were treated with 150mg nintedanib twice daily
Overall Number of Participants Analyzed 58 56 64 68 51
Measure Type: Number
Unit of Measure: percentage of participants
Decrease > 4 mmHg 34.5 50.0 42.2 39.7 29.4
Change within +/- 4 mmHg 50.0 21.4 32.8 30.9 43.1
Increase > 4 mmHg 15.5 28.6 25.0 29.4 27.5
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Nintedanib 50 qd
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7997
Comments [Not Specified]
Method Regression, Logistic
Comments Logistic regression model with fixed terms for treatment, baseline of corresponding continuous value, region.
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.093
Confidence Interval (2-Sided) 95%
0.549 to 2.175
Estimation Comments Odds ratio lower than 1 favours the treatment group over placebo.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Nintedanib 50 Bid
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7989
Comments [Not Specified]
Method Regression, Logistic
Comments Logistic regression model with fixed terms for treatment, baseline of corresponding continuous value, region.
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.916
Confidence Interval (2-Sided) 95%
0.467 to 1.797
Estimation Comments Odds ratio lower than 1 favours the treatment group over placebo.
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, Nintedanib 100 Bid
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4596
Comments [Not Specified]
Method Regression, Logistic
Comments Logistic regression model with fixed terms for treatment, baseline of corresponding continuous value, region.
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.780
Confidence Interval (2-Sided) 95%
0.403 to 1.508
Estimation Comments Odds ratio lower than 1 favours the treatment group over placebo.
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo, Nintedanib 150 Bid
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2548
Comments [Not Specified]
Method Regression, Logistic
Comments Logistic regression model with fixed terms for treatment, baseline of corresponding continuous value, region.
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.665
Confidence Interval (2-Sided) 95%
0.330 to 1.341
Estimation Comments Odds ratio lower than 1 favours the treatment group over placebo.
14.Secondary Outcome
Title Absolute Change From Baseline in P(A-a) O2 by Categories
Hide Description

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
Time Frame Baseline and 52 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
OC - Randomised set
Arm/Group Title Placebo Nintedanib 50 qd Nintedanib 50 Bid Nintedanib 100 Bid Nintedanib 150 Bid
Hide Arm/Group Description:
Patients were treated with matching Placebo.
Patients were treated with 50mg nintedanib once daily
Patients were treated with 50mg nintedanib twice daily
Patients were treated with 100mg nintedanib twice daily
Patients were treated with 150mg nintedanib twice daily
Overall Number of Participants Analyzed 56 54 64 67 51
Measure Type: Number
Unit of Measure: percentage of participants
Decrease > 4 mmHg 25.0 37.0 31.3 25.4 17.6
Change within +/- 4 mmHg 33.9 14.8 25.0 28.4 45.1
Increase > 4 mmHg 41.1 48.1 43.0 46.3 37.3
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Nintedanib 50 qd
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.8887
Comments [Not Specified]
Method Regression, Logistic
Comments Logistic regression model with fixed terms for treatment, baseline of corresponding continuous value, region.
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.051
Confidence Interval (2-Sided) 95%
0.521 to 2.122
Estimation Comments Odds ratio lower than 1 favours the treatment group over placebo.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Nintedanib 50 Bid
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5758
Comments [Not Specified]
Method Regression, Logistic
Comments Logistic regression model with fixed terms for treatment, baseline of corresponding continuous value, region.
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.216
Confidence Interval (2-Sided) 95%
0.613 to 2.410
Estimation Comments Odds ratio lower than 1 favours the treatment group over placebo.
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, Nintedanib 100 Bid
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9829
Comments [Not Specified]
Method Regression, Logistic
Comments Logistic regression model with fixed terms for treatment, baseline of corresponding continuous value, region.
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.993
Confidence Interval (2-Sided) 95%
0.506 to 1.949
Estimation Comments Odds ratio lower than 1 favours the treatment group over placebo.
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo, Nintedanib 150 Bid
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9375
Comments [Not Specified]
Method Regression, Logistic
Comments Logistic regression model with fixed terms for treatment, baseline of corresponding continuous value, region.
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.972
Confidence Interval (2-Sided) 95%
0.476 to 1.985
Estimation Comments Odds ratio lower than 1 favours the treatment group over placebo.
15.Secondary Outcome
Title Absolute Change From Baseline in DLCO
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
LOCF-Randomised set
Arm/Group Title Placebo Nintedanib 50 qd Nintedanib 50 Bid Nintedanib 100 Bid Nintedanib 150 Bid
Hide Arm/Group Description:
Patients were treated with matching Placebo.
Patients were treated with 50mg nintedanib once daily
Patients were treated with 50mg nintedanib twice daily
Patients were treated with 100mg nintedanib twice daily
Patients were treated with 150mg nintedanib twice daily
Overall Number of Participants Analyzed 75 68 80 81 69
Mean (Standard Error)
Unit of Measure: mmol.min^-1.kPa^-1
-0.455  (0.1098) -0.357  (0.1163) -0.610  (0.1038) -0.535  (0.1035) -0.576  (0.1111)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Nintedanib 50 qd
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4998
Comments [Not Specified]
Method ANCOVA
Comments ANCOVA with fixed terms for treatment, baseline, region.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.098
Confidence Interval (2-Sided) 95%
-0.188 to 0.385
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.1456
Estimation Comments Mean difference to placebo is calculated. Negative change indicates worsening.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Nintedanib 50 Bid
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2679
Comments [Not Specified]
Method ANCOVA
Comments ANCOVA with fixed terms for treatment, baseline, region.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.155
Confidence Interval (2-Sided) 95%
-0.430 to 0.120
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.1399
Estimation Comments Mean difference to placebo is calculated. Negative change indicates worsening.
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, Nintedanib 100 Bid
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5678
Comments [Not Specified]
Method ANCOVA
Comments ANCOVA with fixed terms for treatment, baseline, region.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.080
Confidence Interval (2-Sided) 95%
-0.355 to 0.195
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.1400
Estimation Comments Mean difference to placebo is calculated. Negative change indicates worsening.
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo, Nintedanib 150 Bid
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4053
Comments [Not Specified]
Method ANCOVA
Comments ANCOVA with fixed terms for treatment, baseline, region.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.121
Confidence Interval (2-Sided) 95%
-0.406 to 0.164
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.1448
Estimation Comments Mean difference to placebo is calculated. Negative change indicates worsening.
16.Secondary Outcome
Title Absolute Change From Baseline in DLCO by Categories
Hide Description

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
Time Frame Baseline and 52 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
LOCF Randomized set
Arm/Group Title Placebo Nintedanib 50 qd Nintedanib 50 Bid Nintedanib 100 Bid Nintedanib 150 Bid
Hide Arm/Group Description:
Patients were treated with matching Placebo.
Patients were treated with 50mg nintedanib once daily
Patients were treated with 50mg nintedanib twice daily
Patients were treated with 100mg nintedanib twice daily
Patients were treated with 150mg nintedanib twice daily
Overall Number of Participants Analyzed 75 68 80 81 69
Measure Type: Number
Unit of Measure: percentage of patients
Decrease > 15% or > 1 37.3 38.2 43.8 35.8 50.7
Change <= 15% or <= 1 58.7 51.5 51.3 56.8 44.9
Increase > 15% or > 1 4.0 10.3 5.0 7.4 4.3
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Nintedanib 50 qd
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7307
Comments [Not Specified]
Method Regression, Logistic
Comments An ordinal logistic regression model with fixed terms for treatment, baseline of corresponding continuous value, region.
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.892
Confidence Interval (2-Sided) 95%
0.465 to 1.710
Estimation Comments Odds ratio lower than 1 favours the treatment group over placebo.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Nintedanib 50 Bid
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3869
Comments [Not Specified]
Method Regression, Logistic
Comments An ordinal logistic regression model with fixed terms for treatment, baseline of corresponding continuous value, region.
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.317
Confidence Interval (2-Sided) 95%
0.706 to 2.458
Estimation Comments Odds ratio lower than 1 favours the treatment group over placebo.
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, Nintedanib 100 Bid
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.8237
Comments [Not Specified]
Method Regression, Logistic
Comments An ordinal logistic regression model with fixed terms for treatment, baseline of corresponding continuous value, region.
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.931
Confidence Interval (2-Sided) 95%
0.498 to 1.741
Estimation Comments Odds ratio lower than 1 favours the treatment group over placebo.
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo, Nintedanib 150 Bid
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1177
Comments [Not Specified]
Method Regression, Logistic
Comments An ordinal logistic regression model with fixed terms for treatment, baseline of corresponding continuous value, region.
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.676
Confidence Interval (2-Sided) 95%
0.878 to 3.202
Estimation Comments Odds ratio lower than 1 favours the treatment group over placebo.
17.Secondary Outcome
Title Absolute Change From Baseline in Distance Walk (6-MWT)
Hide Description 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.
Time Frame Baseline and 52 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
LOCF-Randomised set
Arm/Group Title Placebo Nintedanib 50 qd Nintedanib 50 Bid Nintedanib 100 Bid Nintedanib 150 Bid
Hide Arm/Group Description:
Patients were treated with matching Placebo.
Patients were treated with 50mg nintedanib once daily
Patients were treated with 50mg nintedanib twice daily
Patients were treated with 100mg nintedanib twice daily
Patients were treated with 150mg nintedanib twice daily
Overall Number of Participants Analyzed 69 61 75 72 63
Mean (Standard Error)
Unit of Measure: Meter
-35.67  (12.732) -46.91  (13.652) -48.84  (11.974) -36.80  (12.131) -29.35  (12.957)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Nintedanib 50 qd
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5111
Comments [Not Specified]
Method ANCOVA
Comments ANCOVA with fixed terms for treatment, baseline, region.
Method of Estimation Estimation Parameter Median Difference (Final Values)
Estimated Value -11.24
Confidence Interval (2-Sided) 95%
-44.86 to 22.37
Parameter Dispersion
Type: Standard Error of the mean
Value: 17.089
Estimation Comments Mean difference to placebo is calculated. Negative change indicates worsening.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Nintedanib 50 Bid
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4176
Comments [Not Specified]
Method ANCOVA
Comments ANCOVA with fixed terms for treatment, baseline, region.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -13.17
Confidence Interval (2-Sided) 95%
-45.11 to 18.76
Parameter Dispersion
Type: Standard Error of the mean
Value: 16.234
Estimation Comments Mean difference to placebo is calculated. Negative change indicates worsening.
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, Nintedanib 100 Bid
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9454
Comments [Not Specified]
Method ANCOVA
Comments ANCOVA with fixed terms for treatment, baseline, region.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -1.13
Confidence Interval (2-Sided) 95%
-33.60 to 31.34
Parameter Dispersion
Type: Standard Error of the mean
Value: 16.506
Estimation Comments Mean difference to placebo is calculated. Negative change indicates worsening.
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo, Nintedanib 150 Bid
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7101
Comments [Not Specified]
Method ANCOVA
Comments ANCOVA with fixed terms for treatment, baseline, region.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 6.32
Confidence Interval (2-Sided) 95%
-27.08 to 39.72
Parameter Dispersion
Type: Standard Error of the mean
Value: 16.980
Estimation Comments Mean difference to placebo is calculated. Negative change indicates worsening.
18.Secondary Outcome
Title Absolute Change From Baseline in Dyspnoea Rating on Borg Scale Before Exercise (6-MWT)
Hide Description

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.

Time Frame Baseline and 52 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
LOCF-Randomised set
Arm/Group Title Placebo Nintedanib 50 qd Nintedanib 50 Bid Nintedanib 100 Bid Nintedanib 150 Bid
Hide Arm/Group Description:
Patients were treated with matching Placebo.
Patients were treated with 50mg nintedanib once daily
Patients were treated with 50mg nintedanib twice daily
Patients were treated with 100mg nintedanib twice daily
Patients were treated with 150mg nintedanib twice daily
Overall Number of Participants Analyzed 69 61 75 72 63
Mean (Standard Error)
Unit of Measure: Units on a scale
0.227  (0.1695) 0.282  (0.1817) 0.045  (0.1594) 0.260  (0.1612) 0.086  (0.1736)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Nintedanib 50 qd
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.8090
Comments [Not Specified]
Method ANCOVA
Comments ANCOVA with fixed terms for treatment, baseline, region.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.055
Confidence Interval (2-Sided) 95%
-0.392 to 0.502
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.2271
Estimation Comments Mean difference to placebo is calculated. Positive change indicates worsening.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Nintedanib 50 Bid
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3995
Comments [Not Specified]
Method ANCOVA
Comments ANCOVA with fixed terms for treatment, baseline, region.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.182
Confidence Interval (2-Sided) 95%
-0.606 to 0.242
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.2158
Estimation Comments Mean difference to placebo is calculated. Positive change indicates worsening.
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, Nintedanib 100 Bid
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.8822
Comments [Not Specified]
Method ANCOVA
Comments ANCOVA with fixed terms for treatment, baseline, region.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.033
Confidence Interval (2-Sided) 95%
-0.399 to 0.464
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.2193
Estimation Comments Mean difference to placebo is calculated. Positive change indicates worsening.
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo, Nintedanib 150 Bid
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5338
Comments [Not Specified]
Method ANCOVA
Comments ANCOVA with fixed terms for treatment, baseline, region.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.141
Confidence Interval (2-Sided) 95%
-0.584 to 0.303
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.2257
Estimation Comments Mean difference to placebo is calculated. Positive change indicates worsening.
19.Secondary Outcome
Title Change From Baseline in Dyspnoea Rating on Borg Scale After Exercise (6-MWT)
Hide Description

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.

Time Frame Baseline and 52 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
LOCF-Randomised set
Arm/Group Title Placebo Nintedanib 50 qd Nintedanib 50 Bid Nintedanib 100 Bid Nintedanib 150 Bid
Hide Arm/Group Description:
Patients were treated with matching Placebo.
Patients were treated with 50mg nintedanib once daily
Patients were treated with 50mg nintedanib twice daily
Patients were treated with 100mg nintedanib twice daily
Patients were treated with 150mg nintedanib twice daily
Overall Number of Participants Analyzed 69 61 75 72 63
Mean (Standard Error)
Unit of Measure: Units on a scale
0.527  (0.2439) 0.639  (0.2616) 0.449  (0.2295) 0.377  (0.2321) 0.194  (0.2492)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Nintedanib 50 qd
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7329
Comments [Not Specified]
Method ANCOVA
Comments ANCOVA with fixed terms for treatment, baseline, region.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.112
Confidence Interval (2-Sided) 95%
-0.532 to 0.755
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.3272
Estimation Comments Mean difference to placebo is calculated. Positive change indicates worsening.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Nintedanib 50 Bid
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.8009
Comments [Not Specified]
Method ANCOVA
Comments ANCOVA with fixed terms for treatment, baseline, region.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.078
Confidence Interval (2-Sided) 95%
-0.690 to 0.533
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.3109
Estimation Comments Mean difference to placebo is calculated. Positive change indicates worsening.
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, Nintedanib 100 Bid
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.6358
Comments [Not Specified]
Method ANCOVA
Comments ANCOVA with fixed terms for treatment, baseline, region.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.150
Confidence Interval (2-Sided) 95%
-0.771 to 0.472
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.3159
Estimation Comments Mean difference to placebo is calculated. Positive change indicates worsening.
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo, Nintedanib 150 Bid
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3064
Comments [Not Specified]
Method ANCOVA
Comments ANCOVA with fixed terms for treatment, baseline, region.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.333
Confidence Interval (2-Sided) 95%
-0.973 to 0.307
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.3252
Estimation Comments Mean difference to placebo is calculated. Positive change indicates worsening.
20.Secondary Outcome
Title Absolute Change From Baseline in MRC Dyspnea Scale by Categories
Hide Description

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

  1. Decrease
  2. No Change
  3. Increase
Time Frame Baseline and 52 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
LOCF- Randomised
Arm/Group Title Placebo Nintedanib 50 qd Nintedanib 50 Bid Nintedanib 100 Bid Nintedanib 150 Bid
Hide Arm/Group Description:
Patients were treated with matching Placebo.
Patients were treated with 50mg nintedanib once daily
Patients were treated with 50mg nintedanib twice daily
Patients were treated with 100mg nintedanib twice daily
Patients were treated with 150mg nintedanib twice daily
Overall Number of Participants Analyzed 77 75 81 82 76
Measure Type: Number
Unit of Measure: percentage of participants
Decrease 7.8 13.3 8.6 14.6 11.8
No Change 51.9 45.3 53.1 45.1 53.9
Increase 40.3 41.3 38.3 40.2 34.2
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Nintedanib 50 qd
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9646
Comments [Not Specified]
Method Regression, Logistic
Comments An ordinal logistic regression model with fixed terms for treatment, baseline of corresponding continuous value, region.
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.014
Confidence Interval (2-Sided) 95%
0.540 to 1.906
Estimation Comments Odds ratio lower than 1 favours the treatment group over placebo. Negative change indicates worsening.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Nintedanib 50 Bid
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9850
Comments [Not Specified]
Method Regression, Logistic
Comments An ordinal logistic regression model with fixed terms for treatment, baseline of corresponding continuous value, region.
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.994
Confidence Interval (2-Sided) 95%
0.536 to 1.844
Estimation Comments Odds ratio lower than 1 favours the treatment group over placebo. Negative change indicates worsening.
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, Nintedanib 100 Bid
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7136
Comments [Not Specified]
Method Regression, Logistic
Comments An ordinal logistic regression model with fixed terms for treatment, baseline of corresponding continuous value, region.
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.123
Confidence Interval (2-Sided) 95%
0.604 to 2.089
Estimation Comments Odds ratio lower than 1 favours the treatment group over placebo. Negative change indicates worsening.
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo, Nintedanib 150 Bid
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1705
Comments [Not Specified]
Method Regression, Logistic
Comments An ordinal logistic regression model with fixed terms for treatment, baseline of corresponding continuous value, region.
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.551
Confidence Interval (2-Sided) 95%
0.828 to 2.906
Estimation Comments Odds ratio lower than 1 favours the treatment group over placebo. Negative change indicates worsening.
21.Secondary Outcome
Title Absolute Change From Baseline in FEV1/FVC
Hide Description

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.

Time Frame Baseline and 52 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
LOCF-Randomised set
Arm/Group Title Placebo Nintedanib 50 qd Nintedanib 50 Bid Nintedanib 100 Bid Nintedanib 150 Bid
Hide Arm/Group Description:
Patients were treated with matching Placebo.
Patients were treated with 50mg nintedanib once daily
Patients were treated with 50mg nintedanib twice daily
Patients were treated with 100mg nintedanib twice daily
Patients were treated with 150mg nintedanib twice daily
Overall Number of Participants Analyzed 84 85 86 85 84
Mean (Standard Error)
Unit of Measure: percentage of FVC
1.25  (0.529) -0.10  (0.533) 0.00  (0.511) -0.53  (0.516) -0.42  (0.513)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Nintedanib 50 qd
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0479
Comments [Not Specified]
Method ANCOVA
Comments ANCOVA with fixed terms for treatment, baseline, region.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -1.35
Confidence Interval (2-Sided) 95%
-2.69 to -0.01
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.680
Estimation Comments Mean difference to placebo is calculated.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Nintedanib 50 Bid
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0685
Comments [Not Specified]
Method ANCOVA
Comments ANCOVA with fixed terms for treatment, baseline, region.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -1.24
Confidence Interval (2-Sided) 95%
-2.58 to 0.09
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.680
Estimation Comments Mean difference to placebo is calculated.
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, Nintedanib 100 Bid
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0099
Comments [Not Specified]
Method ANCOVA
Comments ANCOVA with fixed terms for treatment, baseline, region.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -1.77
Confidence Interval (2-Sided) 95%
-3.12 to -0.43
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.684
Estimation Comments Mean difference to placebo is calculated.
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo, Nintedanib 150 Bid
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0152
Comments [Not Specified]
Method ANCOVA
Comments ANCOVA with fixed terms for treatment, baseline, region.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -1.67
Confidence Interval (2-Sided) 95%
-3.01 to -0.32
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.683
Estimation Comments Mean difference to placebo is calculated.
22.Secondary Outcome
Title Change From Baseline in SGRQ Total Score
Hide Description

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.

Time Frame Baseline and 52 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
LOCF-Randomised set
Arm/Group Title Placebo Nintedanib 50 qd Nintedanib 50 Bid Nintedanib 100 Bid Nintedanib 150 Bid
Hide Arm/Group Description:
Patients were treated with matching Placebo.
Patients were treated with 50mg nintedanib once daily
Patients were treated with 50mg nintedanib twice daily
Patients were treated with 100mg nintedanib twice daily
Patients were treated with 150mg nintedanib twice daily
Overall Number of Participants Analyzed 79 76 82 82 75
Mean (Standard Error)
Unit of Measure: units on a scale
5.46  (1.731) 4.67  (1.779) 2.18  (1.654) 1.48  (1.660) -0.66  (1.712)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Nintedanib 50 qd
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7250
Comments [Not Specified]
Method ANCOVA
Comments ANCOVA with fixed terms for treatment, baseline, region.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.79
Confidence Interval (2-Sided) 95%
-5.22 to 3.64
Parameter Dispersion
Type: Standard Error of the mean
Value: 2.253
Estimation Comments Mean difference to placebo is calculated. Positive change indicates worsening.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Nintedanib 50 Bid
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1389
Comments [Not Specified]
Method ANCOVA
Comments ANCOVA with fixed terms for treatment, baseline, region.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -3.28
Confidence Interval (2-Sided) 95%
-7.63 to 1.07
Parameter Dispersion
Type: Standard Error of the mean
Value: 2.213
Estimation Comments Mean difference to placebo is calculated. Positive change indicates worsening.
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, Nintedanib 100 Bid
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0741
Comments [Not Specified]
Method ANCOVA
Comments ANCOVA with fixed terms for treatment, baseline, region.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -3.98
Confidence Interval (2-Sided) 95%
-8.35 to 0.39
Parameter Dispersion
Type: Standard Error of the mean
Value: 2.221
Estimation Comments Mean difference to placebo is calculated. Positive change indicates worsening.
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo, Nintedanib 150 Bid
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0071
Comments [Not Specified]
Method ANCOVA
Comments ANCOVA with fixed terms for treatment, baseline, region.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -6.12
Confidence Interval (2-Sided) 95%
-10.57 to -1.67
Parameter Dispersion
Type: Standard Error of the mean
Value: 2.262
Estimation Comments Mean difference to placebo is calculated. Positive change indicates worsening.
23.Secondary Outcome
Title Change From Baseline in SGRQ Domain Score Symptoms
Hide Description

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.

Time Frame Baseline and 52 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
LOCF-Randomised set
Arm/Group Title Placebo Nintedanib 50 qd Nintedanib 50 Bid Nintedanib 100 Bid Nintedanib 150 Bid
Hide Arm/Group Description:
Patients were treated with matching Placebo.
Patients were treated with 50mg nintedanib once daily
Patients were treated with 50mg nintedanib twice daily
Patients were treated with 100mg nintedanib twice daily
Patients were treated with 150mg nintedanib twice daily
Overall Number of Participants Analyzed 79 76 82 82 76
Mean (Standard Error)
Unit of Measure: units on a scale
6.45  (2.446) 3.39  (2.514) 2.11  (2.338) 2.33  (2.346) -3.14  (2.403)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Nintedanib 50 qd
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3370
Comments [Not Specified]
Method ANCOVA
Comments ANCOVA with fixed terms for treatment, baseline, region.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -3.06
Confidence Interval (2-Sided) 95%
-9.32 to 3.20
Parameter Dispersion
Type: Standard Error of the mean
Value: 3.183
Estimation Comments Mean difference to placebo is calculated. Positive change indicates worsening.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Nintedanib 50 Bid
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1659
Comments [Not Specified]
Method ANCOVA
Comments ANCOVA with fixed terms for treatment, baseline, region.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -4.34
Confidence Interval (2-Sided) 95%
-10.49 to 1.81
Parameter Dispersion
Type: Standard Error of the mean
Value: 3.126
Estimation Comments Mean difference to placebo is calculated. Positive change indicates worsening.
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, Nintedanib 100 Bid
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1897
Comments [Not Specified]
Method ANCOVA
Comments ANCOVA with fixed terms for treatment, baseline, region.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -4.12
Confidence Interval (2-Sided) 95%
-10.29 to 2.05
Parameter Dispersion
Type: Standard Error of the mean
Value: 3.138
Estimation Comments Mean difference to placebo is calculated. Positive change indicates worsening.
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo, Nintedanib 150 Bid
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0028
Comments [Not Specified]
Method ANCOVA
Comments ANCOVA with fixed terms for treatment, baseline, region.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -9.60
Confidence Interval (2-Sided) 95%
-15.86 to -3.34
Parameter Dispersion
Type: Standard Error of the mean
Value: 3.184
Estimation Comments Mean difference to placebo is calculated. Positive change indicates worsening.
24.Secondary Outcome
Title Change From Baseline in SGRQ Domain Score Impacts
Hide Description

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.

Time Frame Baseline and 52 weeks
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Hide Analysis Population Description
LOCF - Randomised set
Arm/Group Title Placebo Nintedanib 50 qd Nintedanib 50 Bid Nintedanib 100 Bid Nintedanib 150 Bid
Hide Arm/Group Description:
Patients were treated with matching Placebo.
Patients were treated with 50mg nintedanib once daily
Patients were treated with 50mg nintedanib twice daily
Patients were treated with 100mg nintedanib twice daily
Patients were treated with 150mg nintedanib twice daily
Overall Number of Participants Analyzed 79 76 82 82 75
Mean (Standard Error)
Unit of Measure: units on a scale
4.21  (1.986) 3.71  (2.040) 1.73  (1.897) 0.79  (1.906) -0.14  (1.965)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Nintedanib 50 qd
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.8458
Comments [Not Specified]
Method ANCOVA
Comments ANCOVA with fixed terms for treatment, baseline, region.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.50
Confidence Interval (2-Sided) 95%
-5.59 to 4.58
Parameter Dispersion
Type: Standard Error of the mean
Value: 2.586
Estimation Comments Mean difference to placebo is calculated. Positive change indicates worsening.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Nintedanib 50 Bid
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3286
Comments [Not Specified]
Method ANCOVA
Comments ANCOVA with fixed terms for treatment, baseline, region.
Method of Estimation Estimation Parameter