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Efficacy and Safety of Nintedanib in Patients With Progressive Fibrosing Interstitial Lung Disease (PF-ILD) (INBUILD®)

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ClinicalTrials.gov Identifier: NCT02999178
Recruitment Status : Completed
First Posted : December 21, 2016
Results First Posted : May 5, 2020
Last Update Posted : May 5, 2020
Sponsor:
Information provided by (Responsible Party):
Boehringer Ingelheim

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double;   Primary Purpose: Treatment
Condition Lung Diseases, Interstitial
Interventions Drug: Nintedanib
Drug: Placebo
Enrollment 663
Recruitment Details Randomized (1:1 ratio), placebo-controlled, double-blind, parallel-group trial comparing nintedanib to placebo over a 52-week treatment period (Part A). Participants continued on blinded, randomized treatment beyond 52 weeks (Part B). Data base lock (DBL) one was on 6-June-2019, DBL two was on 11-September-2019. Overall Study Period=Part A and B.
Pre-assignment Details All subjects were screened for eligibility prior to participation in the trial. Subjects attended a specialist site which ensured that they (the subjects) strictly met all inclusion and none of the exclusion criteria. Subjects were not to be allocated to a treatment group if any of the entry criteria were violated.
Arm/Group Title 150 mg Nintedanib Placebo
Hide Arm/Group Description 150 milligram (mg) Nintedanib as soft gelatine capsule, administered orally, twice daily (bid), with optional dose reduction to 100 mg bid to manage adverse events (AEs). Continuous daily dosing over a 52-week treatment period (Part A). After completion of the 52-week treatment period, participants continued on blinded treatment until the end of the trial or until a reason for treatment withdrawal was met (Part B). 150 mg Nintedanib matching placebo, soft gelatine capsule, administered orally, bid, with optional dose reduction to 100 mg bid to manage AEs. Continuous daily dosing over a 52-week treatment period (Part A). After completion of the 52-week treatment period, participants continued on blinded treatment until the end of the trial or until a reason for treatment withdrawal was met (Part B).
Period Title: Overall Study
Started 332 331
Completed 218 [1] 231 [1]
Not Completed 114 100
Reason Not Completed
Adverse Event             85             62
Protocol Violation             1             2
Lost to Follow-up             0             2
Withdrawal by Subject             21             21
Other reason not defined above             7             13
[1]
On treatment at analysis cut-off date, 12-August-2019
Arm/Group Title 150 mg Nintedanib Placebo Total
Hide Arm/Group Description 150 milligram (mg) Nintedanib as soft gelatine capsule, administered orally, twice daily (bid), with optional dose reduction to 100 mg bid to manage adverse events (AEs). Continuous daily dosing over a 52-week treatment period (Part A). After completion of the 52-week treatment period, participants continued on blinded treatment until the end of the trial or until a reason for treatment withdrawal was met (Part B). 150 mg Nintedanib matching placebo, soft gelatine capsule, administered orally, bid, with optional dose reduction to 100 mg bid to manage AEs. Continuous daily dosing over a 52-week treatment period (Part A). After completion of the 52-week treatment period, participants continued on blinded treatment until the end of the trial or until a reason for treatment withdrawal was met (Part B). Total of all reporting groups
Overall Number of Baseline Participants 332 331 663
Hide Baseline Analysis Population Description
Treated set: This set included all randomized participants who received at least 1 dose of trial medication.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 332 participants 331 participants 663 participants
65.2  (9.7) 66.3  (9.8) 65.8  (9.8)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 332 participants 331 participants 663 participants
Female
153
  46.1%
154
  46.5%
307
  46.3%
Male
179
  53.9%
177
  53.5%
356
  53.7%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 332 participants 331 participants 663 participants
Hispanic or Latino
47
  14.2%
49
  14.8%
96
  14.5%
Not Hispanic or Latino
285
  85.8%
282
  85.2%
567
  85.5%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 332 participants 331 participants 663 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
Asian
83
  25.0%
80
  24.2%
163
  24.6%
Native Hawaiian or Other Pacific Islander
1
   0.3%
0
   0.0%
1
   0.2%
Black or African American
5
   1.5%
5
   1.5%
10
   1.5%
White
242
  72.9%
246
  74.3%
488
  73.6%
More than one race
1
   0.3%
0
   0.0%
1
   0.2%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
Baseline High Resolution Computed Tomography (HRCT) fibrotic pattern   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 332 participants 331 participants 663 participants
UIP-like fibrotic pattern only
206
  62.0%
206
  62.2%
412
  62.1%
Other fibrotic patterns
126
  38.0%
125
  37.8%
251
  37.9%
[1]
Measure Description: HRCT fibrotic pattern, i.e. imaging pattern of the lung disease on high-resolution computed tomography assessed by central review. HRCT fibrotic pattern had two categories: 'Usual Interstitial Pneumonia (UIP)-like fibrotic pattern only', 'Other fibrotic patterns'.
Baseline Forced Vital Capacity (FVC) - Overall Population   [1] 
Mean (Standard Deviation)
Unit of measure:  Milliliter (mL)
Number Analyzed 332 participants 331 participants 663 participants
2340.07  (740.19) 2321.15  (727.97) 2330.62  (733.62)
[1]
Measure Description: FVC is the volume of air (measured in milliliter) which can be forcibly exhaled from the lungs after taking the deepest breath possible.
Baseline FVC - Participants with HRCT fibrotic pattern=UIP-like fibrotic pattern only   [1] [2] 
Mean (Standard Deviation)
Unit of measure:  Milliliter (mL)
Number Analyzed 206 participants 206 participants 412 participants
2363.43  (762.89) 2373.59  (720.05) 2368.51  (740.89)
[1]
Measure Description: FVC is the volume of air (measured in milliliter) which can be forcibly exhaled from the lungs after taking the deepest breath possible.
[2]
Measure Analysis Population Description: All randomized participants with HRCT fibrotic pattern=UIP-like fibrotic pattern only who received at least 1 dose of trial medication.
1.Primary Outcome
Title Annual Rate of Decline in Forced Vital Capacity - Overall Population
Hide Description Forced Vital Capacity (FVC) is the volume of air (measured in milliliter) which can be forcibly exhaled from the lungs after taking the deepest breath possible. Overall population consists of all randomized participants with HRCT fibrotic pattern=UIP-like fibrotic pattern only or HRCT fibrotic pattern= Other fibrotic patterns. Annual rate of decline in Forced Vital Capacity in milliliter (mL) per year in the overall population is based on a random coefficient regression with fixed effects for treatment, HRCT fibrotic pattern, and baseline FVC [mL], and including treatment-by-time and baseline-by-time interactions. Within-participant errors are modelled by an unstructured variance-covariance matrix.
Time Frame Baseline, 2, 4, 6, 12, 24, 36, 52 weeks after first drug intake (planned post-baseline visits)
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants in the overall population who received at least 1 dose of trial medication.
Arm/Group Title 150 mg Nintedanib Placebo
Hide Arm/Group Description:
150 milligram (mg) Nintedanib as soft gelatine capsule, administered orally, twice daily (bid), with optional dose reduction to 100 mg bid to manage adverse events (AEs). Continuous daily dosing over a 52-week treatment period (Part A). After completion of the 52-week treatment period, participants continued on blinded treatment until the end of the trial or until a reason for treatment withdrawal was met (Part B).
150 mg Nintedanib matching placebo, soft gelatine capsule, administered orally, bid, with optional dose reduction to 100 mg bid to manage AEs. Continuous daily dosing over a 52-week treatment period (Part A). After completion of the 52-week treatment period, participants continued on blinded treatment until the end of the trial or until a reason for treatment withdrawal was met (Part B).
Overall Number of Participants Analyzed 332 331
Least Squares Mean (95% Confidence Interval)
Unit of Measure: Milliliter per year
-80.82
(-110.42 to -51.22)
-187.78
(-216.92 to -158.64)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 150 mg Nintedanib, Placebo
Comments The decrease in FVC was assumed to be linear within each participant over 52 weeks. The intercepts and slopes were assumed to be normally distributed with unstructured covariance matrix. The within participant error was assumed to be independent and normally distributed with mean 0 and a common variance. The Kenward-Roger approximation was used to estimate denominator degrees of freedom and adjust standard errors (SEs).
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <.0001
Comments Treatment comparison of slopes was assessed through the treatment-by-time interaction coefficient. P-value was not adjusted for multiple comparisons.
Method Mixed Models Analysis
Comments

Fixed effects: Treatment, HRCT fibrotic pattern, baseline FVC (mL), treatment-by-time, baseline-by-time interactions.

Random effects: time, intercept.

Method of Estimation Estimation Parameter Adjusted mean difference
Estimated Value 106.96
Confidence Interval (2-Sided) 95%
65.42 to 148.50
Parameter Dispersion
Type: Standard Error of the Mean
Value: 21.15
Estimation Comments Difference of adjusted annual rates of decline was calculated as Nintedanib - Placebo.
2.Primary Outcome
Title Annual Rate of Decline in Forced Vital Capacity - Participants With HRCT Fibrotic Pattern=UIP-like Fibrotic Pattern Only
Hide Description Forced Vital Capacity (FVC) is the volume of air (measured in milliliter) which can be forcibly exhaled from the lungs after taking the deepest breath possible. Annual rate of decline in Forced Vital Capacity in milliliter (mL) per year in participants with HRCT fibrotic pattern=UIP-like fibrotic pattern only is based on a random coefficient regression with fixed effects for treatment, baseline FVC [mL], and including treatment-by-time and baseline-by-time interactions. Within-participant errors are modelled by an unstructured variance-covariance matrix.
Time Frame Baseline, 2, 4, 6, 12, 24, 36, 52 weeks after first drug intake (planned post-baseline visits)
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants with HRCT fibrotic pattern=UIP-like fibrotic pattern only who received at least 1 dose of trial medication.
Arm/Group Title 150 mg Nintedanib Placebo
Hide Arm/Group Description:
150 milligram (mg) Nintedanib as soft gelatine capsule, administered orally, twice daily (bid), with optional dose reduction to 100 mg bid to manage adverse events (AEs). Continuous daily dosing over a 52-week treatment period (Part A). After completion of the 52-week treatment period, participants continued on blinded treatment until the end of the trial or until a reason for treatment withdrawal was met (Part B).
150 mg Nintedanib matching placebo, soft gelatine capsule, administered orally, bid, with optional dose reduction to 100 mg bid to manage AEs. Continuous daily dosing over a 52-week treatment period (Part A). After completion of the 52-week treatment period, participants continued on blinded treatment until the end of the trial or until a reason for treatment withdrawal was met (Part B).
Overall Number of Participants Analyzed 206 206
Least Squares Mean (95% Confidence Interval)
Unit of Measure: Milliliter per year
-82.87
(-123.73 to -42.02)
-211.07
(-251.38 to -170.77)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 150 mg Nintedanib, Placebo
Comments The decrease in FVC was assumed to be linear within each participant over 52 weeks. The intercepts and slopes were assumed to be normally distributed with unstructured covariance matrix. The within participant error was assumed to be independent and normally distributed with mean 0 and a common variance. The Kenward-Roger approximation was used to estimate denominator degrees of freedom and adjust standard errors (SEs).
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <.0001
Comments Treatment comparison of slopes was assessed through the treatment-by-time interaction coefficient. P-value was not adjusted for multiple comparisons.
Method Mixed Models Analysis
Comments Fixed effects: Treatment, baseline FVC (mL), treatment-by-time, baseline-by-time interactions. Random effects: time, intercept.
Method of Estimation Estimation Parameter Adjusted mean difference
Estimated Value 128.20
Confidence Interval (2-Sided) 95%
70.81 to 185.59
Parameter Dispersion
Type: Standard Error of the Mean
Value: 29.17
Estimation Comments Difference of adjusted annual rates of decline was calculated as Nintedanib - Placebo.
3.Secondary Outcome
Title Absolute Change From Baseline in King's Brief Interstitial Lung Disease Questionnaire (K-BILD) Total Score at Week 52 - Overall Population
Hide Description King's Brief Interstitial Lung Disease questionnaire (K-BILD) consists of 15 items and 3 domains: breathlessness and activities, psychological, and chest symptoms. Possible score ranges from 0-100, score of 100 representing the best health status. If missing items were >50% per domain, the domain score was set to missing. If any of the domain scores were missing, the total score was set to missing. Absolute change from baseline in K-BILD Total score at week 52 in the overall population was based on a Mixed Model Repeated Measures (MMRM), with fixed effects for baseline K-BILD Total score, HRCT fibrotic pattern, visit, treatment-by-visit interaction, baseline-by-visit interactions and random effect for participant. Visit was the repeated measure. Within-participant errors were modelled by unstructured variance-covariance matrix.
Time Frame Baseline, 12, 24, 36, 52 weeks after first drug intake (planned post-baseline visits)
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants in the overall population who received at least 1 dose of trial medication and contributed to the model evaluation.
Arm/Group Title 150 mg Nintedanib Placebo
Hide Arm/Group Description:
150 milligram (mg) Nintedanib as soft gelatine capsule, administered orally, twice daily (bid), with optional dose reduction to 100 mg bid to manage adverse events (AEs). Continuous daily dosing over a 52-week treatment period (Part A). After completion of the 52-week treatment period, participants continued on blinded treatment until the end of the trial or until a reason for treatment withdrawal was met (Part B).
150 mg Nintedanib matching placebo, soft gelatine capsule, administered orally, bid, with optional dose reduction to 100 mg bid to manage AEs. Continuous daily dosing over a 52-week treatment period (Part A). After completion of the 52-week treatment period, participants continued on blinded treatment until the end of the trial or until a reason for treatment withdrawal was met (Part B).
Overall Number of Participants Analyzed 332 330
Least Squares Mean (95% Confidence Interval)
Unit of Measure: Unit on scale
0.55
(-0.62 to 1.72)
-0.79
(-1.94 to 0.37)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 150 mg Nintedanib, Placebo
Comments [Not Specified]
Type of Statistical Test Other
Comments No formal hypotheses were tested.
Statistical Test of Hypothesis P-Value 0.1115
Comments [Not Specified]
Method Mixed Model Repeated Measures (MMRM)
Comments Fixed effects: baseline K-BILD Total score, visit, treatment-by-visit and baseline-by-visit interactions, random effect: participant.
Method of Estimation Estimation Parameter Adjusted mean difference
Estimated Value 1.34
Confidence Interval (2-Sided) 95%
-0.31 to 2.98
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.84
Estimation Comments Adjusted mean difference was calculated as Nintedanib - Placebo.
4.Secondary Outcome
Title Absolute Change From Baseline in King's Brief Interstitial Lung Disease (K-BILD) Questionnaire Total Score at Week 52 - Participants With HRCT Fibrotic Pattern=UIP-like Fibrotic Pattern Only
Hide Description King's Brief Interstitial Lung Disease questionnaire (K-BILD) consists of 15 items and 3 domains: breathlessness and activities, psychological, and chest symptoms. Possible score ranges from 0-100, score of 100 representing the best health status. If missing items were >50% per domain, the domain score was set to missing. If any of the domain scores were missing, the total score was set to missing. Absolute change from baseline in K-BILD Total score at week 52 in participants with HRCT fibrotic pattern=UIP-like fibrotic pattern only was based on a Mixed Model Repeated Measures (MMRM), with fixed effects for baseline K-BILD Total score, HRCT fibrotic pattern, visit, treatment-by-visit interaction, baseline-by-visit interactions and random effect for participant. Visit was the repeated measure. Within-participant errors were modelled by unstructured variance-covariance matrix.
Time Frame Baseline, 12, 24, 36, 52 weeks after first drug intake (planned post-baseline visits)
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants with HRCT fibrotic pattern=UIP-like fibrotic pattern only who received at least 1 dose of trial medication and who contributed to the model evaluation.
Arm/Group Title 150 mg Nintedanib Placebo
Hide Arm/Group Description:
150 milligram (mg) Nintedanib as soft gelatine capsule, administered orally, twice daily (bid), with optional dose reduction to 100 mg bid to manage adverse events (AEs). Continuous daily dosing over a 52-week treatment period (Part A). After completion of the 52-week treatment period, participants continued on blinded treatment until the end of the trial or until a reason for treatment withdrawal was met (Part B).
150 mg Nintedanib matching placebo, soft gelatine capsule, administered orally, bid, with optional dose reduction to 100 mg bid to manage AEs. Continuous daily dosing over a 52-week treatment period (Part A). After completion of the 52-week treatment period, participants continued on blinded treatment until the end of the trial or until a reason for treatment withdrawal was met (Part B).
Overall Number of Participants Analyzed 206 205
Least Squares Mean (95% Confidence Interval)
Unit of Measure: Unit on scale
0.75
(-0.82 to 2.31)
-0.78
(-2.34 to 0.78)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 150 mg Nintedanib, Placebo
Comments [Not Specified]
Type of Statistical Test Other
Comments No formal hypotheses were tested.
Statistical Test of Hypothesis P-Value 0.1747
Comments [Not Specified]
Method Mixed Model Repeated Measures (MMRM)
Comments Fixed effects: baseline K-BILD Total score, visit, treatment-by-visit and baseline-by-visit interactions, random effect: participant.
Method of Estimation Estimation Parameter Adjusted mean difference
Estimated Value 1.53
Confidence Interval (2-Sided) 95%
-0.68 to 3.74
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.12
Estimation Comments Adjusted mean difference was calculated as Nintedanib - Placebo.
5.Secondary Outcome
Title Time to First Acute Interstitial Lung Disease (ILD) Exacerbation or Death Over 52 Weeks - Overall Population
Hide Description Time to first acute ILD exacerbation or death over 52 weeks was defined as time to first acute ILD exacerbation or death due to any cause within the first 52 weeks and was computed as earliest of date of first documented acute ILD exacerbation or death - date of first drug intake + 1. Participants alive who did not experience any ILD exacerbation event or with unknown status within the first 52 weeks were censored.
Time Frame From first drug intake until date of first acute ILD exacerbation or date of death or last contact date, up to 372 days
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants in the overall population who received at least 1 dose of trial medication.
Arm/Group Title 150 mg Nintedanib Placebo
Hide Arm/Group Description:
150 milligram (mg) Nintedanib as soft gelatine capsule, administered orally, twice daily (bid), with optional dose reduction to 100 mg bid to manage adverse events (AEs). Continuous daily dosing over a 52-week treatment period (Part A). After completion of the 52-week treatment period, participants continued on blinded treatment until the end of the trial or until a reason for treatment withdrawal was met (Part B).
150 mg Nintedanib matching placebo, soft gelatine capsule, administered orally, bid, with optional dose reduction to 100 mg bid to manage AEs. Continuous daily dosing over a 52-week treatment period (Part A). After completion of the 52-week treatment period, participants continued on blinded treatment until the end of the trial or until a reason for treatment withdrawal was met (Part B).
Overall Number of Participants Analyzed 332 331
Median (Inter-Quartile Range)
Unit of Measure: Days
NA [1] 
(NA to NA)
NA [1] 
(NA to NA)
[1]
Non-calculable because the 25 percentile was not reached.
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 150 mg Nintedanib, Placebo
Comments [Not Specified]
Type of Statistical Test Other
Comments No formal hypotheses were tested.
Statistical Test of Hypothesis P-Value 0.3948
Comments [Not Specified]
Method Log Rank
Comments Stratified by HRCT fibrotic pattern.
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.80
Confidence Interval (2-Sided) 95%
0.48 to 1.34
Estimation Comments A Cox proportional hazards model, stratified by HRCT fibrotic pattern, was used to estimate the hazard ratio calculated as Nintedanib divided by Placebo.
6.Secondary Outcome
Title Time to First Acute Interstitial Lung Disease (ILD) Exacerbation or Death Over 52 Weeks - Participants With HRCT Fibrotic Pattern=UIP-like Fibrotic Pattern Only
Hide Description Time to first acute ILD exacerbation or death over 52 weeks was defined as time to first acute ILD exacerbation or death due to any cause within the first 52 weeks and was computed as earliest of date of first documented acute ILD exacerbation or death - date of first drug intake + 1. Participants alive who did not experience any ILD exacerbation event or with unknown status within the first 52 weeks were censored.
Time Frame From first drug intake until date of first acute ILD exacerbation or date of death or last contact date, up to 372 days
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants with HRCT fibrotic pattern=UIP-like fibrotic pattern only who received at least 1 dose of trial medication.
Arm/Group Title 150 mg Nintedanib Placebo
Hide Arm/Group Description:
150 milligram (mg) Nintedanib as soft gelatine capsule, administered orally, twice daily (bid), with optional dose reduction to 100 mg bid to manage adverse events (AEs). Continuous daily dosing over a 52-week treatment period (Part A). After completion of the 52-week treatment period, participants continued on blinded treatment until the end of the trial or until a reason for treatment withdrawal was met (Part B).
150 mg Nintedanib matching placebo, soft gelatine capsule, administered orally, bid, with optional dose reduction to 100 mg bid to manage AEs. Continuous daily dosing over a 52-week treatment period (Part A). After completion of the 52-week treatment period, participants continued on blinded treatment until the end of the trial or until a reason for treatment withdrawal was met (Part B).
Overall Number of Participants Analyzed 206 206
Median (Inter-Quartile Range)
Unit of Measure: Days
NA [1] 
(NA to NA)
NA [1] 
(NA to NA)
[1]
Non-calculable because the 25 percentile was not reached.
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 150 mg Nintedanib, Placebo
Comments [Not Specified]
Type of Statistical Test Other
Comments No formal hypotheses were tested.
Statistical Test of Hypothesis P-Value 0.1985
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.67
Confidence Interval (2-Sided) 95%
0.36 to 1.24
Estimation Comments A Cox proportional hazards model was used to estimate the hazard ratio calculated as Nintedanib divided by Placebo.
7.Secondary Outcome
Title Time to Death Over 52 Weeks - Overall Population
Hide Description Time to death over 52 weeks defined as the time from date of first drug intake until date of death from any cause for participants with known date of death (from any cause) within the first 52 weeks. Participants with no event (death from any cause) or unknown status within the first 52 weeks were censored.
Time Frame From first drug intake until date of death or last contact date, up to 372 days
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants in the overall population who received at least 1 dose of trial medication.
Arm/Group Title 150 mg Nintedanib Placebo
Hide Arm/Group Description:
150 milligram (mg) Nintedanib as soft gelatine capsule, administered orally, twice daily (bid), with optional dose reduction to 100 mg bid to manage adverse events (AEs). Continuous daily dosing over a 52-week treatment period (Part A). After completion of the 52-week treatment period, participants continued on blinded treatment until the end of the trial or until a reason for treatment withdrawal was met (Part B).
150 mg Nintedanib matching placebo, soft gelatine capsule, administered orally, bid, with optional dose reduction to 100 mg bid to manage AEs. Continuous daily dosing over a 52-week treatment period (Part A). After completion of the 52-week treatment period, participants continued on blinded treatment until the end of the trial or until a reason for treatment withdrawal was met (Part B).
Overall Number of Participants Analyzed 332 331
Median (Inter-Quartile Range)
Unit of Measure: Days
NA [1] 
(NA to NA)
NA [1] 
(NA to NA)
[1]
Non-calculable because the 25 percentile was not reached.
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 150 mg Nintedanib, Placebo
Comments [Not Specified]
Type of Statistical Test Other
Comments No formal hypotheses were tested.
Statistical Test of Hypothesis P-Value 0.8544
Comments [Not Specified]
Method Log Rank
Comments Stratified by HRCT fibrotic pattern.
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.94
Confidence Interval (2-Sided) 95%
0.47 to 1.86
Estimation Comments A Cox proportional hazards model, stratified by HRCT fibrotic pattern, was used to estimate the hazard ratio calculated as Nintedanib divided by Placebo.
8.Secondary Outcome
Title Time to Death Over 52 Weeks - Participants With HRCT Fibrotic Pattern=UIP-like Fibrotic Pattern Only
Hide Description Time to death over 52 weeks defined as the time from date of first drug intake until date of death from any cause for participants with known date of death (from any cause) within the first 52 weeks. Participants with no event (death from any cause) or unknown status within the first 52 weeks were censored.
Time Frame From first drug intake until date of death or last contact date, up to 372 days
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants with HRCT fibrotic pattern=UIP-like fibrotic pattern only who received at least 1 dose of trial medication.
Arm/Group Title 150 mg Nintedanib Placebo
Hide Arm/Group Description:
150 milligram (mg) Nintedanib as soft gelatine capsule, administered orally, twice daily (bid), with optional dose reduction to 100 mg bid to manage adverse events (AEs). Continuous daily dosing over a 52-week treatment period (Part A). After completion of the 52-week treatment period, participants continued on blinded treatment until the end of the trial or until a reason for treatment withdrawal was met (Part B).
150 mg Nintedanib matching placebo, soft gelatine capsule, administered orally, bid, with optional dose reduction to 100 mg bid to manage AEs. Continuous daily dosing over a 52-week treatment period (Part A). After completion of the 52-week treatment period, participants continued on blinded treatment until the end of the trial or until a reason for treatment withdrawal was met (Part B).
Overall Number of Participants Analyzed 206 206
Median (Inter-Quartile Range)
Unit of Measure: Days
NA [1] 
(NA to NA)
NA [1] 
(NA to NA)
[1]
Non-calculable because the 25 percentile was not reached.
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 150 mg Nintedanib, Placebo
Comments [Not Specified]
Type of Statistical Test Other
Comments No formal hypotheses were tested.
Statistical Test of Hypothesis P-Value 0.3291
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.68
Confidence Interval (2-Sided) 95%
0.32 to 1.47
Estimation Comments A Cox proportional hazards model was used to estimate the hazard ratio calculated as Nintedanib divided by Placebo.
9.Secondary Outcome
Title Time to Death Due to Respiratory Cause Over 52 Weeks - Overall Population
Hide Description Time to death due to respiratory cause over 52 weeks is defined as the time from date of first drug intake until date of death attributed to respiratory causes (determined by an independent Adjudication Committee) for participants with known date of death (from respiratory causes) within the first 52 weeks. Participants with no event (death from respiratory causes) or unknown status within the first 52 weeks were censored. As less than 4.95% of the total of participants in the analysis population experienced an event, only descriptive statistics were performed, as pre-specified.
Time Frame From date of first trial drug intake up to date of death from respiratory causes or last contact date, up to 372 days
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants in the overall population who received at least 1 dose of trial medication.
Arm/Group Title 150 mg Nintedanib Placebo
Hide Arm/Group Description:
150 milligram (mg) Nintedanib as soft gelatine capsule, administered orally, twice daily (bid), with optional dose reduction to 100 mg bid to manage adverse events (AEs). Continuous daily dosing over a 52-week treatment period (Part A). After completion of the 52-week treatment period, participants continued on blinded treatment until the end of the trial or until a reason for treatment withdrawal was met (Part B).
150 mg Nintedanib matching placebo, soft gelatine capsule, administered orally, bid, with optional dose reduction to 100 mg bid to manage AEs. Continuous daily dosing over a 52-week treatment period (Part A). After completion of the 52-week treatment period, participants continued on blinded treatment until the end of the trial or until a reason for treatment withdrawal was met (Part B).
Overall Number of Participants Analyzed 332 331
Median (Inter-Quartile Range)
Unit of Measure: Days
NA [1] 
(NA to NA)
NA [1] 
(NA to NA)
[1]
Non-calculable because the 25 percentile was not reached.
10.Secondary Outcome
Title Time to Death Due to Respiratory Cause Over 52 Weeks - Participants With HRCT Fibrotic Pattern=UIP-like Fibrotic Pattern Only
Hide Description Time to death due to respiratory cause over 52 weeks is defined as the time from date of first drug intake until date of death attributed to respiratory causes (determined by an independent Adjudication Committee) for participants with known date of death (from respiratory causes) within the first 52 weeks. Participants with no event (death from respiratory causes) or unknown status within the first 52 weeks were censored. As less than 4.95% of the total of participants in the analysis population experienced an event, only descriptive statistics were performed, as pre-specified.
Time Frame From date of first trial drug intake up to date of death from respiratory causes or last contact date, up to 372 days
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants with HRCT fibrotic pattern=UIP-like fibrotic pattern only who received at least 1 dose of trial medication.
Arm/Group Title 150 mg Nintedanib Placebo
Hide Arm/Group Description:
150 milligram (mg) Nintedanib as soft gelatine capsule, administered orally, twice daily (bid), with optional dose reduction to 100 mg bid to manage adverse events (AEs). Continuous daily dosing over a 52-week treatment period (Part A). After completion of the 52-week treatment period, participants continued on blinded treatment until the end of the trial or until a reason for treatment withdrawal was met (Part B).
150 mg Nintedanib matching placebo, soft gelatine capsule, administered orally, bid, with optional dose reduction to 100 mg bid to manage AEs. Continuous daily dosing over a 52-week treatment period (Part A). After completion of the 52-week treatment period, participants continued on blinded treatment until the end of the trial or until a reason for treatment withdrawal was met (Part B).
Overall Number of Participants Analyzed 206 206
Median (Inter-Quartile Range)
Unit of Measure: Days
NA [1] 
(NA to NA)
NA [1] 
(NA to NA)
[1]
Non-calculable because the 25 percentile was not reached.
11.Secondary Outcome
Title Time to Progression or Death Over 52 Weeks - Overall Population
Hide Description Time to progression or death over 52 weeks is defined as the time from date of first drug intake to date of progression, or date of death (from any cause) if a participant died earlier. Participants with no event (progression or death from any cause) or unknown status were censored. Date of progression is defined as the date when ≥ 10% of absolute decline in FVC percent predicted compared to baseline occured for the first time. Forced Vital Capacity (FVC) is the volume of air (measured in milliliter) which can be forcibly exhaled from the lungs after taking the deepest breath possible. Predicted normal values of FVC were calculated according to the Global Lung Initiative. FVC percent predicted (FVC % pred) is the FVC divided by its predicted value in percent.
Time Frame From first drug intake until date of progression or date of death or last contact date, up to 372 days
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants in the overall population who received at least 1 dose of trial medication.
Arm/Group Title 150 mg Nintedanib Placebo
Hide Arm/Group Description:
150 milligram (mg) Nintedanib as soft gelatine capsule, administered orally, twice daily (bid), with optional dose reduction to 100 mg bid to manage adverse events (AEs). Continuous daily dosing over a 52-week treatment period (Part A). After completion of the 52-week treatment period, participants continued on blinded treatment until the end of the trial or until a reason for treatment withdrawal was met (Part B).
150 mg Nintedanib matching placebo, soft gelatine capsule, administered orally, bid, with optional dose reduction to 100 mg bid to manage AEs. Continuous daily dosing over a 52-week treatment period (Part A). After completion of the 52-week treatment period, participants continued on blinded treatment until the end of the trial or until a reason for treatment withdrawal was met (Part B).
Overall Number of Participants Analyzed 332 331
Median (Inter-Quartile Range)
Unit of Measure: Days
NA [1] 
(367 to NA)
NA [1] 
(269 to NA)
[1]
Non-calculable because the 50 percentile was not reached.
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 150 mg Nintedanib, Placebo
Comments [Not Specified]
Type of Statistical Test Other
Comments No formal hypotheses were tested.
Statistical Test of Hypothesis P-Value 0.0017
Comments [Not Specified]
Method Log Rank
Comments Stratified by HRCT fibrotic pattern.
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.65
Confidence Interval (2-Sided) 95%
0.49 to 0.85
Estimation Comments A Cox proportional hazards model, stratified by HRCT fibrotic pattern, was used to estimate the hazard ratio calculated as Nintedanib divided by Placebo.
12.Secondary Outcome
Title Time to Progression or Death Over 52 Weeks - Participants With HRCT Fibrotic Pattern=UIP-like Fibrotic Pattern Only
Hide Description Time to progression or death over 52 weeks is defined as the time from date of first drug intake to date of progression, or date of death (from any cause) if a participant died earlier. Participants with no event (progression or death from any cause) or unknown status were censored. Date of progression is defined as the date when ≥ 10% of absolute decline in FVC percent predicted compared to baseline occured for the first time. Forced Vital Capacity (FVC) is the volume of air (measured in milliliter) which can be forcibly exhaled from the lungs after taking the deepest breath possible. Predicted normal values of FVC were calculated according to the Global Lung Initiative. FVC percent predicted (FVC % pred) is the FVC divided by its predicted value in percent.
Time Frame From first drug intake until date of progression or date of death or last contact date, up to 372 days
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants with HRCT fibrotic pattern=UIP-like fibrotic pattern only who received at least 1 dose of trial medication.
Arm/Group Title 150 mg Nintedanib Placebo
Hide Arm/Group Description:
150 milligram (mg) Nintedanib as soft gelatine capsule, administered orally, twice daily (bid), with optional dose reduction to 100 mg bid to manage adverse events (AEs). Continuous daily dosing over a 52-week treatment period (Part A). After completion of the 52-week treatment period, participants continued on blinded treatment until the end of the trial or until a reason for treatment withdrawal was met (Part B).
150 mg Nintedanib matching placebo, soft gelatine capsule, administered orally, bid, with optional dose reduction to 100 mg bid to manage AEs. Continuous daily dosing over a 52-week treatment period (Part A). After completion of the 52-week treatment period, participants continued on blinded treatment until the end of the trial or until a reason for treatment withdrawal was met (Part B).
Overall Number of Participants Analyzed 206 206
Median (Inter-Quartile Range)
Unit of Measure: Days
NA [1] 
(365 to NA)
NA [1] 
(254 to NA)
[1]
Non-calculable because the 50 percentile was not reached.
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 150 mg Nintedanib, Placebo
Comments [Not Specified]
Type of Statistical Test Other
Comments No formal hypotheses were tested.
Statistical Test of Hypothesis P-Value 0.0081
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.64
Confidence Interval (2-Sided) 95%
0.45 to 0.89
Estimation Comments A Cox proportional hazards model was used to estimate the hazard ratio calculated as Nintedanib divided by Placebo.
13.Secondary Outcome
Title Percentage of Participants With a Relative Decline From Baseline in FVC Percent Predicted of More Than 10 Percent at Week 52 - Overall Population
Hide Description Forced Vital Capacity (FVC) is the volume of air (measured in milliliter) which can be forcibly exhaled from the lungs after taking the deepest breath possible. Predicted normal values of FVC were calculated according to the Global Lung Initiative. FVC percent predicted (FVC % pred) is the FVC divided by its predicted value in percent. Participants with relative decline from baseline in FVC % pred greater than 10% at week 52 were those participants with a negative relative change from baseline in FVC % pred at week 52 the absolute value of which being greater than 10% and those participants with missing data (worst case analysis).
Time Frame Baseline and up to 52 weeks after first drug intake
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants in the overall population who received at least 1 dose of trial medication.
Arm/Group Title 150 mg Nintedanib Placebo
Hide Arm/Group Description:
150 milligram (mg) Nintedanib as soft gelatine capsule, administered orally, twice daily (bid), with optional dose reduction to 100 mg bid to manage adverse events (AEs). Continuous daily dosing over a 52-week treatment period (Part A). After completion of the 52-week treatment period, participants continued on blinded treatment until the end of the trial or until a reason for treatment withdrawal was met (Part B).
150 mg Nintedanib matching placebo, soft gelatine capsule, administered orally, bid, with optional dose reduction to 100 mg bid to manage AEs. Continuous daily dosing over a 52-week treatment period (Part A). After completion of the 52-week treatment period, participants continued on blinded treatment until the end of the trial or until a reason for treatment withdrawal was met (Part B).
Overall Number of Participants Analyzed 332 331
Measure Type: Number
Unit of Measure: Percentage of participants
40.7 48.9
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 150 mg Nintedanib, Placebo
Comments [Not Specified]
Type of Statistical Test Other
Comments No formal hypotheses were tested.
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Regression, Logistic
Comments Logistic regression model with continuous covariate baseline FVC % pred and binary covariate HRCT fibrotic pattern.
Method of Estimation Estimation Parameter Adjusted Odds Ratio
Estimated Value 0.70
Confidence Interval (2-Sided) 95%
0.52 to 0.96
Estimation Comments Ratio calculated as Nintedanib divided by Placebo.
14.Secondary Outcome
Title Percentage of Participants With a Relative Decline From Baseline in FVC Percent Predicted of More Than 10 Percent at Week 52 - Participants With HRCT Fibrotic Pattern=UIP-like Fibrotic Pattern Only
Hide Description Forced Vital Capacity (FVC) is the volume of air (measured in milliliter) which can be forcibly exhaled from the lungs after taking the deepest breath possible. Predicted normal values of FVC were calculated according to the Global Lung Initiative. FVC percent predicted (FVC % pred) is the FVC divided by its predicted value in percent. Participants with relative decline from baseline in FVC % pred greater than 10% at week 52 were those participants with a negative relative change from baseline in FVC % pred at week 52 the absolute value of which being greater than 10% and those participants with missing data (worst case analysis).
Time Frame Baseline and up to 52 weeks after first drug intake
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants with HRCT fibrotic pattern=UIP-like fibrotic pattern only who received at least 1 dose of trial medication.
Arm/Group Title 150 mg Nintedanib Placebo
Hide Arm/Group Description:
150 milligram (mg) Nintedanib as soft gelatine capsule, administered orally, twice daily (bid), with optional dose reduction to 100 mg bid to manage adverse events (AEs). Continuous daily dosing over a 52-week treatment period (Part A). After completion of the 52-week treatment period, participants continued on blinded treatment until the end of the trial or until a reason for treatment withdrawal was met (Part B).
150 mg Nintedanib matching placebo, soft gelatine capsule, administered orally, bid, with optional dose reduction to 100 mg bid to manage AEs. Continuous daily dosing over a 52-week treatment period (Part A). After completion of the 52-week treatment period, participants continued on blinded treatment until the end of the trial or until a reason for treatment withdrawal was met (Part B).
Overall Number of Participants Analyzed 206 206
Measure Type: Number
Unit of Measure: Percentage of participants
41.3 52.4
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 150 mg Nintedanib, Placebo
Comments [Not Specified]
Type of Statistical Test Other
Comments No formal hypotheses were tested.
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Regression, Logistic
Comments Logistic regression model with continuous covariate baseline FVC % pred.
Method of Estimation Estimation Parameter Adjusted Odds Ratio
Estimated Value 0.63
Confidence Interval (2-Sided) 95%
0.43 to 0.94
Estimation Comments Ratio calculated as Nintedanib divided by Placebo.
15.Secondary Outcome
Title Percentage of Participants With a Relative Decline From Baseline in FVC Percent Predicted of More Than 5 Percent at Week 52 - Overall Population
Hide Description Forced Vital Capacity (FVC) is the volume of air (measured in milliliter) which can be forcibly exhaled from the lungs after taking the deepest breath possible. Predicted normal values of FVC were calculated according to the Global Lung Initiative. FVC percent predicted (FVC % pred) is the FVC divided by its predicted value in percent. Participants with relative decline from baseline in FVC % pred greater than 5% at week 52 were those participants with a negative relative change from baseline in FVC % pred at week 52 the absolute value of which being greater than 5% and those participants with missing data (worst case analysis).
Time Frame Baseline and up to 52 weeks after first drug intake
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants in the overall population who received at least 1 dose of trial medication.
Arm/Group Title 150 mg Nintedanib Placebo
Hide Arm/Group Description:
150 milligram (mg) Nintedanib as soft gelatine capsule, administered orally, twice daily (bid), with optional dose reduction to 100 mg bid to manage adverse events (AEs). Continuous daily dosing over a 52-week treatment period (Part A). After completion of the 52-week treatment period, participants continued on blinded treatment until the end of the trial or until a reason for treatment withdrawal was met (Part B).
150 mg Nintedanib matching placebo, soft gelatine capsule, administered orally, bid, with optional dose reduction to 100 mg bid to manage AEs. Continuous daily dosing over a 52-week treatment period (Part A). After completion of the 52-week treatment period, participants continued on blinded treatment until the end of the trial or until a reason for treatment withdrawal was met (Part B).
Overall Number of Participants Analyzed 332 331
Measure Type: Number
Unit of Measure: Percentage of participants
52.4 68.6
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 150 mg Nintedanib, Placebo
Comments [Not Specified]
Type of Statistical Test Other
Comments No formal hypotheses were tested.
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Regression, Logistic
Comments Logistic regression model with continuous covariate baseline FVC % pred and binary covariate HRCT fibrotic pattern.
Method of Estimation Estimation Parameter Adjusted Odds Ratio
Estimated Value 0.50
Confidence Interval (2-Sided) 95%
0.36 to 0.68
Estimation Comments Ratio calculated as Nintedanib divided by Placebo.
16.Secondary Outcome
Title Percentage of Participants With a Relative Decline From Baseline in FVC Percent Predicted of More Than 5 Percent at Week 52 - Participants With HRCT Fibrotic Pattern=UIP-like Fibrotic Pattern Only
Hide Description Forced Vital Capacity (FVC) is the volume of air (measured in milliliter) which can be forcibly exhaled from the lungs after taking the deepest breath possible. Predicted normal values of FVC were calculated according to the Global Lung Initiative. FVC percent predicted (FVC % pred) is the FVC divided by its predicted value in percent. Participants with relative decline from baseline in FVC % pred greater than 5% at week 52 were those participants with a negative relative change from baseline in FVC % pred at week 52 the absolute value of which being greater than 5% and those participants with missing data (worst case analysis).
Time Frame Baseline and up to 52 weeks after first drug intake
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants with HRCT fibrotic pattern=UIP-like fibrotic pattern only who received at least 1 dose of trial medication.
Arm/Group Title 150 mg Nintedanib Placebo
Hide Arm/Group Description:
150 milligram (mg) Nintedanib as soft gelatine capsule, administered orally, twice daily (bid), with optional dose reduction to 100 mg bid to manage adverse events (AEs). Continuous daily dosing over a 52-week treatment period (Part A). After completion of the 52-week treatment period, participants continued on blinded treatment until the end of the trial or until a reason for treatment withdrawal was met (Part B).
150 mg Nintedanib matching placebo, soft gelatine capsule, administered orally, bid, with optional dose reduction to 100 mg bid to manage AEs. Continuous daily dosing over a 52-week treatment period (Part A). After completion of the 52-week treatment period, participants continued on blinded treatment until the end of the trial or until a reason for treatment withdrawal was met (Part B).
Overall Number of Participants Analyzed 206 206
Measure Type: Number
Unit of Measure: Percentage of participants
52.4 70.4
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 150 mg Nintedanib, Placebo
Comments [Not Specified]
Type of Statistical Test Other
Comments No formal hypotheses were tested.
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Regression, Logistic
Comments Logistic regression model with continuous covariate baseline FVC % pred.
Method of Estimation Estimation Parameter Adjusted Odds Ratio
Estimated Value 0.46
Confidence Interval (2-Sided) 95%
0.31 to 0.69
Estimation Comments Ratio calculated as Nintedanib divided by Placebo.
17.Secondary Outcome
Title Absolute Change From Baseline in Living With Pulmonary Fibrosis (L-PF) Symptoms Dyspnea Domain Score at Week 52 - Overall Population
Hide Description Living with Pulmonary Fibrosis (L-PF) questionnaire is a 44 item questionnaire with two modules Symptoms (23 items) and Impacts (21 items) where the symptoms module yields three domain scores dyspnea, cough and fatigue as well as a total symptoms score (impacts module yields a single impacts score). L-PF Symptoms dyspnea domain score (dyspnea score) ranges from 0-100, the higher the score the greater the impairment. If missing items were ≥50 % within a score, then the corresponding score was set to missing. Absolute change from baseline in dyspnea score at week 52 is based on a Mixed Model Repeated Measures, with fixed effects for baseline dyspnea score, HRCT fibrotic pattern, visit, treatment-by-visit interaction, baseline dyspnea score-by-visit interaction and random effect for participant, visit as repeated measure. The Adjusted mean is based on all analysed participants in the model (not only participants with a baseline and measurement at week 52).
Time Frame Baseline, 12, 24, 36, 52 weeks after first drug intake (planned post-baseline visits)
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants in the overall population who received at least 1 dose of trial medication and contributed to the model evaluation.
Arm/Group Title 150 mg Nintedanib Placebo
Hide Arm/Group Description:
150 milligram (mg) Nintedanib as soft gelatine capsule, administered orally, twice daily (bid), with optional dose reduction to 100 mg bid to manage adverse events (AEs). Continuous daily dosing over a 52-week treatment period (Part A). After completion of the 52-week treatment period, participants continued on blinded treatment until the end of the trial or until a reason for treatment withdrawal was met (Part B).
150 mg Nintedanib matching placebo, soft gelatine capsule, administered orally, bid, with optional dose reduction to 100 mg bid to manage AEs. Continuous daily dosing over a 52-week treatment period (Part A). After completion of the 52-week treatment period, participants continued on blinded treatment until the end of the trial or until a reason for treatment withdrawal was met (Part B).
Overall Number of Participants Analyzed 329 323
Least Squares Mean (95% Confidence Interval)
Unit of Measure: Unit on scale
4.28
(2.43 to 6.14)
7.81
(5.97 to 9.66)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 150 mg Nintedanib, Placebo
Comments [Not Specified]
Type of Statistical Test Other
Comments No formal hypotheses were tested.
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Mixed Model Repeated Measures
Comments Fixed effects: baseline, HRCT fibrotic pattern, visit, treatment-by-visit interaction, baseline-by-visit interaction, random effect: participant.
Method of Estimation Estimation Parameter Adjusted mean difference
Estimated Value -3.53
Confidence Interval (2-Sided) 95%
-6.14 to -0.92
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.33
Estimation Comments Adjusted mean difference was calculated as Nintedanib - Placebo.
18.Secondary Outcome
Title Absolute Change From Baseline in L-PF Symptoms Dyspnea Domain Score at Week 52 - Participants With HRCT Fibrotic Pattern=UIP-like Fibrotic Pattern Only
Hide Description Living with Pulmonary Fibrosis (L-PF) questionnaire is a 44 item questionnaire with two modules Symptoms (23 items) and Impacts (21 items) where the symptoms module yields three domain scores dyspnea, cough and fatigue as well as a total symptoms score (impacts module yields a single impacts score). L-PF Symptoms dyspnea domain score (dyspnea score) ranges from 0-100, the higher the score the greater the impairment. If missing items were ≥50 % within a score, then the corresponding score was set to missing. Absolute change from baseline in dyspnea score at week 52 is based on a Mixed Model Repeated Measures, with fixed effects for baseline dyspnea score, visit, treatment-by-visit interaction, baseline dyspnea score-by-visit interaction and random effect for participant, visit as repeated measure. The Adjusted mean is based on all analysed participants in the model (not only participants with a baseline and measurement at week 52).
Time Frame Baseline, 12, 24, 36, 52 weeks after first drug intake (planned post-baseline visits)
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants with HRCT fibrotic pattern=UIP-like fibrotic pattern only who received at least 1 dose of trial medication and contributed to the model evaluation.
Arm/Group Title 150 mg Nintedanib Placebo
Hide Arm/Group Description:
150 milligram (mg) Nintedanib as soft gelatine capsule, administered orally, twice daily (bid), with optional dose reduction to 100 mg bid to manage adverse events (AEs). Continuous daily dosing over a 52-week treatment period (Part A). After completion of the 52-week treatment period, participants continued on blinded treatment until the end of the trial or until a reason for treatment withdrawal was met (Part B).
150 mg Nintedanib matching placebo, soft gelatine capsule, administered orally, bid, with optional dose reduction to 100 mg bid to manage AEs. Continuous daily dosing over a 52-week treatment period (Part A). After completion of the 52-week treatment period, participants continued on blinded treatment until the end of the trial or until a reason for treatment withdrawal was met (Part B).
Overall Number of Participants Analyzed 204 201
Least Squares Mean (95% Confidence Interval)
Unit of Measure: Unit on scale
4.14
(1.81 to 6.47)
8.32
(5.99 to 10.66)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 150 mg Nintedanib, Placebo
Comments [Not Specified]
Type of Statistical Test Other
Comments No formal hypotheses were tested.
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Mixed Model Repeated Measures
Comments Fixed effects: baseline, visit, treatment-by-visit interaction, baseline-by-visit interaction, random effect: participant.
Method of Estimation Estimation Parameter Adjusted mean difference
Estimated Value -4.18
Confidence Interval (2-Sided) 95%
-7.48 to -0.88
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.68
Estimation Comments Adjusted mean difference was calculated as Nintedanib - Placebo.
19.Secondary Outcome
Title Absolute Change From Baseline in L-PF Symptoms Cough Domain Score at Week 52 - Overall Population
Hide Description Living with Pulmonary Fibrosis (L-PF) questionnaire is a 44 item questionnaire with two modules Symptoms (23 items) and Impacts (21 items) where the symptoms module yields three domain scores dyspnea, cough and fatigue as well as a total symptoms score (impacts module yields a single impacts score). L-PF Symptoms cough domain score (cough score) ranges from 0-100, the higher the score the greater the impairment. If missing items were ≥50 % within a score, then the corresponding score was set to missing. Absolute change from baseline in cough score at week 52 is based on a Mixed Model Repeated Measures, with fixed effects for baseline cough score, HRCT fibrotic pattern, visit, treatment-by-visit interaction, baseline cough score-by-visit interaction and random effect for participant, visit as repeated measure. The Adjusted mean is based on all analysed participants in the model (not only participants with a baseline and measurement at week 52).
Time Frame Baseline, 12, 24, 36, 52 weeks after first drug intake (planned post-baseline visits)
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants in the overall population who received at least 1 dose of trial medication and contributed to the model evaluation.
Arm/Group Title 150 mg Nintedanib Placebo
Hide Arm/Group Description:
150 milligram (mg) Nintedanib as soft gelatine capsule, administered orally, twice daily (bid), with optional dose reduction to 100 mg bid to manage adverse events (AEs). Continuous daily dosing over a 52-week treatment period (Part A). After completion of the 52-week treatment period, participants continued on blinded treatment until the end of the trial or until a reason for treatment withdrawal was met (Part B).
150 mg Nintedanib matching placebo, soft gelatine capsule, administered orally, bid, with optional dose reduction to 100 mg bid to manage AEs. Continuous daily dosing over a 52-week treatment period (Part A). After completion of the 52-week treatment period, participants continued on blinded treatment until the end of the trial or until a reason for treatment withdrawal was met (Part B).
Overall Number of Participants Analyzed 327 320
Least Squares Mean (95% Confidence Interval)
Unit of Measure: Unit on scale
-1.84
(-4.36 to 0.69)
4.25
(1.74 to 6.76)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 150 mg Nintedanib, Placebo
Comments [Not Specified]
Type of Statistical Test Other
Comments No formal hypotheses were tested.
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Mixed Model Repeated Measures
Comments Fixed effects: baseline, HRCT fibrotic pattern, visit, treatment-by-visit interaction, baseline-by-visit interaction, random effect: participant.
Method of Estimation Estimation Parameter Adjusted mean difference
Estimated Value -6.09
Confidence Interval (2-Sided) 95%
-9.65 to -2.53
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.81
Estimation Comments Adjusted mean difference was calculated as Nintedanib - Placebo.
20.Secondary Outcome
Title Absolute Change From Baseline in Living With Pulmonary Fibrosis (L-PF) Symptoms Cough Domain Score at Week 52 - Participants With HRCT Fibrotic Pattern=UIP-like Fibrotic Pattern Only
Hide Description Living with Pulmonary Fibrosis (L-PF) questionnaire is a 44 item questionnaire with two modules Symptoms (23 items) and Impacts (21 items) where the symptoms module yields three domain scores dyspnea, cough and fatigue as well as a total symptoms score (impacts module yields a single impacts score). L-PF Symptoms cough domain score (cough score) ranges from 0-100, the higher the score the greater the impairment. If missing items were ≥50 % within a score, then the corresponding score was set to missing. Absolute change from baseline in cough score at week 52 is based on a Mixed Model Repeated Measures, with fixed effects for baseline cough score, visit, treatment-by-visit interaction, baseline cough score-by-visit interaction and random effect for participant, visit as repeated measure. The Adjusted mean is based on all analysed participants in the model (not only participants with a baseline and measurement at week 52).
Time Frame Baseline, 12, 24, 36, 52 weeks after first drug intake (planned post-baseline visits)
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants with HRCT fibrotic pattern=UIP-like fibrotic pattern only who received at least 1 dose of trial medication and contributed to the model evaluation.
Arm/Group Title 150 mg Nintedanib Placebo
Hide Arm/Group Description:
150 milligram (mg) Nintedanib as soft gelatine capsule, administered orally, twice daily (bid), with optional dose reduction to 100 mg bid to manage adverse events (AEs). Continuous daily dosing over a 52-week treatment period (Part A). After completion of the 52-week treatment period, participants continued on blinded treatment until the end of the trial or until a reason for treatment withdrawal was met (Part B).
150 mg Nintedanib matching placebo, soft gelatine capsule, administered orally, bid, with optional dose reduction to 100 mg bid to manage AEs. Continuous daily dosing over a 52-week treatment period (Part A). After completion of the 52-week treatment period, participants continued on blinded treatment until the end of the trial or until a reason for treatment withdrawal was met (Part B).
Overall Number of Participants Analyzed 203 199
Least Squares Mean (95% Confidence Interval)
Unit of Measure: Unit on scale
-3.20
(-6.43 to 0.04)
4.09
(0.85 to 7.32)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 150 mg Nintedanib, Placebo
Comments [Not Specified]
Type of Statistical Test Other
Comments No formal hypotheses were tested.
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Mixed Model Repeated Measures
Comments Fixed effects: baseline, visit, treatment-by-visit interaction, baseline-by-visit interaction, random effect: participant.
Method of Estimation Estimation Parameter Adjusted mean difference
Estimated Value -7.28
Confidence Interval (2-Sided) 95%
-11.86 to -2.71
Parameter Dispersion
Type: Standard Error of the Mean
Value: 2.33
Estimation Comments Adjusted mean difference was calculated as Nintedanib - Placebo.
Time Frame Treatment period plus 28 days (residual effect period), up to 836 days. Time frame for All-Cause-Mortality: Treatment period plus Follow-up, up to 900 days.
Adverse Event Reporting Description All participants who signed the informed consent.
 
Arm/Group Title Nintedanib Placebo
Hide Arm/Group Description 150 milligram (mg) Nintedanib as soft gelatine capsule, administered orally, twice daily (bid), with optional dose reduction to 100 mg bid to manage adverse events (AEs). Continuous daily dosing over a 52-week treatment period (Part A). After completion of the 52-week treatment period, participants continued on blinded treatment until the end of the trial or until a reason for treatment withdrawal was met (Part B). 150 mg Nintedanib matching placebo, soft gelatine capsule, administered orally, bid, with optional dose reduction to 100 mg bid to manage AEs. Continuous daily dosing over a 52-week treatment period (Part A). After completion of the 52-week treatment period, participants continued on blinded treatment until the end of the trial or until a reason for treatment withdrawal was met (Part B).
All-Cause Mortality
Nintedanib Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   36/332 (10.84%)   45/331 (13.60%) 
Hide Serious Adverse Events
Nintedanib Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   147/332 (44.28%)   164/331 (49.55%) 
Blood and lymphatic system disorders     
Blood loss anaemia  1  1/332 (0.30%)  0/331 (0.00%) 
Disseminated intravascular coagulation  1  0/332 (0.00%)  1/331 (0.30%) 
Leukocytosis  1  0/332 (0.00%)  1/331 (0.30%) 
Pancytopenia  1  0/332 (0.00%)  1/331 (0.30%) 
Cardiac disorders     
Acute coronary syndrome  1  0/332 (0.00%)  1/331 (0.30%) 
Acute myocardial infarction  1  3/332 (0.90%)  1/331 (0.30%) 
Angina pectoris  1  2/332 (0.60%)  3/331 (0.91%) 
Angina unstable  1  0/332 (0.00%)  1/331 (0.30%) 
Arteriosclerosis coronary artery  1  1/332 (0.30%)  0/331 (0.00%) 
Atrial fibrillation  1  5/332 (1.51%)  1/331 (0.30%) 
Atrial flutter  1  1/332 (0.30%)  2/331 (0.60%) 
Atrial thrombosis  1  0/332 (0.00%)  1/331 (0.30%) 
Bradycardia  1  1/332 (0.30%)  0/331 (0.00%) 
Bundle branch block left  1  0/332 (0.00%)  1/331 (0.30%) 
Cardiac arrest  1  1/332 (0.30%)  0/331 (0.00%) 
Cardiac failure  1  3/332 (0.90%)  2/331 (0.60%) 
Cardiac failure chronic  1  1/332 (0.30%)  0/331 (0.00%) 
Cardiac failure congestive  1  1/332 (0.30%)  2/331 (0.60%) 
Chronic right ventricular failure  1  0/332 (0.00%)  1/331 (0.30%) 
Cor pulmonale acute  1  0/332 (0.00%)  1/331 (0.30%) 
Coronary artery disease  1  1/332 (0.30%)  3/331 (0.91%) 
Coronary artery occlusion  1  1/332 (0.30%)  0/331 (0.00%) 
Ischaemic cardiomyopathy  1  0/332 (0.00%)  1/331 (0.30%) 
Long QT syndrome  1  0/332 (0.00%)  1/331 (0.30%) 
Myocardial infarction  1  2/332 (0.60%)  2/331 (0.60%) 
Myocardial ischaemia  1  1/332 (0.30%)  1/331 (0.30%) 
Prinzmetal angina  1  0/332 (0.00%)  1/331 (0.30%) 
Right ventricular failure  1  1/332 (0.30%)  1/331 (0.30%) 
Supraventricular tachycardia  1  1/332 (0.30%)  0/331 (0.00%) 
Systolic anterior motion of mitral valve  1  0/332 (0.00%)  1/331 (0.30%) 
Ear and labyrinth disorders     
Deafness unilateral  1  0/332 (0.00%)  1/331 (0.30%) 
Mixed deafness  1  1/332 (0.30%)  0/331 (0.00%) 
Vertigo  1  0/332 (0.00%)  1/331 (0.30%) 
Endocrine disorders     
Inappropriate antidiuretic hormone secretion  1  0/332 (0.00%)  1/331 (0.30%) 
Eye disorders     
Amaurosis fugax  1  0/332 (0.00%)  1/331 (0.30%) 
Cataract  1  1/332 (0.30%)  2/331 (0.60%) 
Glaucoma  1  1/332 (0.30%)  1/331 (0.30%) 
Retinal artery occlusion  1  0/332 (0.00%)  1/331 (0.30%) 
Retinal vascular thrombosis  1  1/332 (0.30%)  0/331 (0.00%) 
Gastrointestinal disorders     
Abdominal pain  1  1/332 (0.30%)  1/331 (0.30%) 
Abdominal pain upper  1  0/332 (0.00%)  1/331 (0.30%) 
Colitis ischaemic  1  1/332 (0.30%)  0/331 (0.00%) 
Constipation  1  1/332 (0.30%)  0/331 (0.00%) 
Diarrhoea  1  3/332 (0.90%)  0/331 (0.00%) 
Dyspepsia  1  1/332 (0.30%)  0/331 (0.00%) 
Enterocolitis haemorrhagic  1  0/332 (0.00%)  1/331 (0.30%) 
Gastrointestinal haemorrhage  1  3/332 (0.90%)  0/331 (0.00%) 
Gastrooesophageal reflux disease  1  1/332 (0.30%)  0/331 (0.00%) 
Haematemesis  1  1/332 (0.30%)  0/331 (0.00%) 
Haemorrhoids  1  1/332 (0.30%)  0/331 (0.00%) 
Ileus  1  0/332 (0.00%)  3/331 (0.91%) 
Pancreatitis  1  1/332 (0.30%)  0/331 (0.00%) 
Pancreatitis acute  1  1/332 (0.30%)  0/331 (0.00%) 
Rectal prolapse  1  1/332 (0.30%)  0/331 (0.00%) 
General disorders     
Asthenia  1  1/332 (0.30%)  0/331 (0.00%) 
Cardiac death  1  0/332 (0.00%)  1/331 (0.30%) 
Chest pain  1  0/332 (0.00%)  1/331 (0.30%) 
Condition aggravated  1  2/332 (0.60%)  1/331 (0.30%) 
Death  1  1/332 (0.30%)  0/331 (0.00%) 
Discomfort  1  0/332 (0.00%)  1/331 (0.30%) 
Disease progression  1  0/332 (0.00%)  2/331 (0.60%) 
General physical health deterioration  1  0/332 (0.00%)  1/331 (0.30%) 
Pyrexia  1  0/332 (0.00%)  1/331 (0.30%) 
Sudden cardiac death  1  0/332 (0.00%)  1/331 (0.30%) 
Sudden death  1  0/332 (0.00%)  1/331 (0.30%) 
Hepatobiliary disorders     
Cholecystitis acute  1  1/332 (0.30%)  0/331 (0.00%) 
Cholelithiasis  1  1/332 (0.30%)  1/331 (0.30%) 
Drug-induced liver injury  1  6/332 (1.81%)  0/331 (0.00%) 
Hepatic cirrhosis  1  1/332 (0.30%)  1/331 (0.30%) 
Liver injury  1  3/332 (0.90%)  2/331 (0.60%) 
Infections and infestations     
Adenovirus infection  1  0/332 (0.00%)  1/331 (0.30%) 
Appendicitis  1  2/332 (0.60%)  0/331 (0.00%) 
Atypical pneumonia  1  1/332 (0.30%)  0/331 (0.00%) 
Bacterial sepsis  1  1/332 (0.30%)  0/331 (0.00%) 
Bronchitis  1  4/332 (1.20%)  5/331 (1.51%) 
Bronchopulmonary aspergillosis  1  2/332 (0.60%)  2/331 (0.60%) 
Cellulitis  1  1/332 (0.30%)  1/331 (0.30%) 
Clostridium difficile colitis  1  1/332 (0.30%)  0/331 (0.00%) 
Diverticulitis  1  2/332 (0.60%)  0/331 (0.00%) 
Encephalitis  1  0/332 (0.00%)  1/331 (0.30%) 
Febrile infection  1  0/332 (0.00%)  1/331 (0.30%) 
Gastroenteritis norovirus  1  1/332 (0.30%)  0/331 (0.00%) 
Herpes zoster  1  1/332 (0.30%)  2/331 (0.60%) 
Herpes zoster oticus  1  1/332 (0.30%)  0/331 (0.00%) 
Infectious pleural effusion  1  0/332 (0.00%)  1/331 (0.30%) 
Influenza  1  4/332 (1.20%)  4/331 (1.21%) 
Leishmaniasis  1  0/332 (0.00%)  1/331 (0.30%) 
Localised infection  1  1/332 (0.30%)  0/331 (0.00%) 
Lower respiratory tract infection  1  1/332 (0.30%)  3/331 (0.91%) 
Lung infection  1  3/332 (0.90%)  3/331 (0.91%) 
Meningitis aseptic  1  1/332 (0.30%)  0/331 (0.00%) 
Metapneumovirus infection  1  0/332 (0.00%)  1/331 (0.30%) 
Orchitis  1  1/332 (0.30%)  0/331 (0.00%) 
Pneumococcal infection  1  0/332 (0.00%)  1/331 (0.30%) 
Pneumonia  1  24/332 (7.23%)  16/331 (4.83%) 
Pneumonia bacterial  1  1/332 (0.30%)  3/331 (0.91%) 
Pneumonia legionella  1  1/332 (0.30%)  0/331 (0.00%) 
Pneumonia pneumococcal  1  0/332 (0.00%)  3/331 (0.91%) 
Pneumonia viral  1  0/332 (0.00%)  2/331 (0.60%) 
Pseudomembranous colitis  1  1/332 (0.30%)  0/331 (0.00%) 
Pulmonary sepsis  1  1/332 (0.30%)  0/331 (0.00%) 
Pyelonephritis acute  1  1/332 (0.30%)  0/331 (0.00%) 
Respiratory syncytial virus infection  1  0/332 (0.00%)  1/331 (0.30%) 
Respiratory tract infection  1  3/332 (0.90%)  3/331 (0.91%) 
Sepsis  1  1/332 (0.30%)  2/331 (0.60%) 
Septic shock  1  2/332 (0.60%)  0/331 (0.00%) 
Sinusitis  1  0/332 (0.00%)  1/331 (0.30%) 
Skin infection  1  1/332 (0.30%)  0/331 (0.00%) 
Staphylococcal sepsis  1  1/332 (0.30%)  0/331 (0.00%) 
Urinary tract infection  1  2/332 (0.60%)  1/331 (0.30%) 
Urosepsis  1  0/332 (0.00%)  1/331 (0.30%) 
Viral infection  1  1/332 (0.30%)  0/331 (0.00%) 
Viral upper respiratory tract infection  1  1/332 (0.30%)  0/331 (0.00%) 
Injury, poisoning and procedural complications     
Anastomotic stenosis  1  0/332 (0.00%)  1/331 (0.30%) 
Coronary artery restenosis  1  1/332 (0.30%)  0/331 (0.00%) 
Fall  1  3/332 (0.90%)  4/331 (1.21%) 
Humerus fracture  1  1/332 (0.30%)  1/331 (0.30%) 
Lower limb fracture  1  0/332 (0.00%)  1/331 (0.30%) 
Rib fracture  1  0/332 (0.00%)  1/331 (0.30%) 
Spinal compression fracture  1  1/332 (0.30%)  2/331 (0.60%) 
Spinal fracture  1  2/332 (0.60%)  1/331 (0.30%) 
Subdural haematoma  1  0/332 (0.00%)  1/331 (0.30%) 
Thoracic vertebral fracture  1  1/332 (0.30%)  0/331 (0.00%) 
Wrist fracture  1  1/332 (0.30%)  1/331 (0.30%) 
Investigations     
Alanine aminotransferase increased  1  2/332 (0.60%)  1/331 (0.30%) 
Aspartate aminotransferase increased  1  2/332 (0.60%)  1/331 (0.30%) 
Blood lactate dehydrogenase increased  1  0/332 (0.00%)  1/331 (0.30%) 
Electrocardiogram Q wave abnormal  1  0/332 (0.00%)  1/331 (0.30%) 
Gamma-glutamyltransferase increased  1  0/332 (0.00%)  1/331 (0.30%) 
Hepatic enzyme increased  1  1/332 (0.30%)  1/331 (0.30%) 
Rotavirus test positive  1  1/332 (0.30%)  0/331 (0.00%) 
Transaminases increased  1  1/332 (0.30%)  0/331 (0.00%) 
Metabolism and nutrition disorders     
Decreased appetite  1  0/332 (0.00%)  1/331 (0.30%) 
Diabetes mellitus  1  0/332 (0.00%)  1/331 (0.30%) 
Fluid overload  1  0/332 (0.00%)  1/331 (0.30%) 
Hyperglycaemia  1  0/332 (0.00%)  1/331 (0.30%) 
Hypervolaemia  1  0/332 (0.00%)  1/331 (0.30%) 
Hypokalaemia  1  1/332 (0.30%)  0/331 (0.00%) 
Malnutrition  1  0/332 (0.00%)  1/331 (0.30%) 
Musculoskeletal and connective tissue disorders     
Arthralgia  1  1/332 (0.30%)  1/331 (0.30%) 
Back pain  1  0/332 (0.00%)  2/331 (0.60%) 
Connective tissue disorder  1  0/332 (0.00%)  1/331 (0.30%) 
Groin pain  1  0/332 (0.00%)  1/331 (0.30%) 
Intervertebral disc protrusion  1  1/332 (0.30%)  1/331 (0.30%) 
Lumbar spinal stenosis  1  0/332 (0.00%)  1/331 (0.30%) 
Myositis  1  0/332 (0.00%)  1/331 (0.30%) 
Osteoarthritis  1  2/332 (0.60%)  0/331 (0.00%) 
Osteonecrosis  1  0/332 (0.00%)  1/331 (0.30%) 
Osteoporosis  1  0/332 (0.00%)  1/331 (0.30%) 
Polymyositis  1  1/332 (0.30%)  0/331 (0.00%) 
Rotator cuff syndrome  1  0/332 (0.00%)  1/331 (0.30%) 
Scleroderma  1  1/332 (0.30%)  1/331 (0.30%) 
Sjogren's syndrome  1  1/332 (0.30%)  1/331 (0.30%) 
Spinal pain  1  1/332 (0.30%)  0/331 (0.00%) 
Spinal stenosis  1  0/332 (0.00%)  1/331 (0.30%) 
Systemic lupus erythematosus  1  0/332 (0.00%)  2/331 (0.60%) 
Systemic scleroderma  1  1/332 (0.30%)  0/331 (0.00%) 
Winged scapula  1  0/332 (0.00%)  1/331 (0.30%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Basal cell carcinoma  1  2/332 (0.60%)  4/331 (1.21%) 
Bladder cancer  1  1/332 (0.30%)  0/331 (0.00%) 
Bowen's disease  1  0/332 (0.00%)  1/331 (0.30%) 
Bronchial carcinoma  1  1/332 (0.30%)  0/331 (0.00%) 
Cancer pain  1  0/332 (0.00%)  1/331 (0.30%) 
Colon cancer  1  1/332 (0.30%)  0/331 (0.00%) 
Gallbladder adenocarcinoma  1  0/332 (0.00%)  1/331 (0.30%) 
Hepatic cancer  1  1/332 (0.30%)  0/331 (0.00%) 
Hepatocellular carcinoma  1  1/332 (0.30%)  0/331 (0.00%) 
Lung neoplasm malignant  1  1/332 (0.30%)  1/331 (0.30%) 
Lung squamous cell carcinoma metastatic  1  0/332 (0.00%)  1/331 (0.30%) 
Lymphangiosis carcinomatosa  1  0/332 (0.00%)  1/331 (0.30%) 
Neoplasm malignant  1  0/332 (0.00%)  2/331 (0.60%) 
Salivary gland adenoma  1  0/332 (0.00%)  1/331 (0.30%) 
Skin cancer  1  0/332 (0.00%)  1/331 (0.30%) 
Small cell lung cancer  1  2/332 (0.60%)  0/331 (0.00%) 
Squamous cell carcinoma  1  0/332 (0.00%)  1/331 (0.30%) 
Squamous cell carcinoma of lung  1  0/332 (0.00%)  1/331 (0.30%) 
Transitional cell carcinoma  1  1/332 (0.30%)  0/331 (0.00%) 
Nervous system disorders     
Cerebellar infarction  1  1/332 (0.30%)  0/331 (0.00%) 
Cerebral haemorrhage  1  0/332 (0.00%)  1/331 (0.30%) 
Cerebral infarction  1  1/332 (0.30%)  0/331 (0.00%) 
Cerebrovascular accident  1  1/332 (0.30%)  0/331 (0.00%) 
Dementia  1  1/332 (0.30%)  0/331 (0.00%) 
Hypokinesia  1  0/332 (0.00%)  1/331 (0.30%) 
Loss of consciousness  1  1/332 (0.30%)  1/331 (0.30%) 
Neuropathy peripheral  1  1/332 (0.30%)  0/331 (0.00%) 
Sciatica  1  1/332 (0.30%)  0/331 (0.00%) 
Syncope  1  1/332 (0.30%)  0/331 (0.00%) 
Transient ischaemic attack  1  0/332 (0.00%)  3/331 (0.91%) 
Psychiatric disorders     
Anxiety disorder  1  1/332 (0.30%)  0/331 (0.00%) 
Drug abuse  1  0/332 (0.00%)  1/331 (0.30%) 
Suicide attempt  1  0/332 (0.00%)  1/331 (0.30%) 
Renal and urinary disorders     
Acute kidney injury  1  3/332 (0.90%)  0/331 (0.00%) 
Calculus bladder  1  0/332 (0.00%)  1/331 (0.30%) 
Glomerulonephritis  1  1/332 (0.30%)  0/331 (0.00%) 
Haematuria  1  1/332 (0.30%)  0/331 (0.00%) 
Nephrolithiasis  1  0/332 (0.00%)  1/331 (0.30%) 
Renal failure  1  1/332 (0.30%)  0/331 (0.00%) 
Ureterolithiasis  1  0/332 (0.00%)  1/331 (0.30%) 
Urinary tract obstruction  1  0/332 (0.00%)  1/331 (0.30%) 
Reproductive system and breast disorders     
Prostatitis  1  1/332 (0.30%)  0/331 (0.00%) 
Respiratory, thoracic and mediastinal disorders     
Acute respiratory failure  1  16/332 (4.82%)  7/331 (2.11%) 
Asthma  1  0/332 (0.00%)  1/331 (0.30%) 
Chronic respiratory failure  1  1/332 (0.30%)  6/331 (1.81%) 
Cough  1  0/332 (0.00%)  1/331 (0.30%) 
Dyspnoea  1  6/332 (1.81%)  13/331 (3.93%) 
Eosinophilic pneumonia chronic  1  1/332 (0.30%)  0/331 (0.00%) 
Haemoptysis  1  0/332 (0.00%)  1/331 (0.30%) 
Hypersensitivity pneumonitis  1  2/332 (0.60%)  4/331 (1.21%) 
Hypoxia  1  3/332 (0.90%)  0/331 (0.00%) 
Idiopathic interstitial pneumonia  1  2/332 (0.60%)  1/331 (0.30%) 
Interstitial lung disease  1  19/332 (5.72%)  45/331 (13.60%) 
Lung disorder  1  0/332 (0.00%)  1/331 (0.30%) 
Organising pneumonia  1  2/332 (0.60%)  0/331 (0.00%) 
Pleuritic pain  1  1/332 (0.30%)  0/331 (0.00%) 
Pneumomediastinum  1  2/332 (0.60%)  1/331 (0.30%) 
Pneumonia aspiration  1  0/332 (0.00%)  2/331 (0.60%) 
Pneumonitis  1  1/332 (0.30%)  0/331 (0.00%) 
Pneumothorax  1  6/332 (1.81%)  6/331 (1.81%) 
Pneumothorax spontaneous  1  0/332 (0.00%)  1/331 (0.30%) 
Pulmonary arterial hypertension  1  0/332 (0.00%)  2/331 (0.60%) 
Pulmonary embolism  1  1/332 (0.30%)  5/331 (1.51%) 
Pulmonary fibrosis  1  7/332 (2.11%)  5/331 (1.51%) 
Pulmonary hypertension  1  5/332 (1.51%)  9/331 (2.72%) 
Pulmonary oedema  1  0/332 (0.00%)  1/331 (0.30%) 
Respiratory arrest  1  1/332 (0.30%)  0/331 (0.00%) 
Respiratory disorder  1  0/332 (0.00%)  1/331 (0.30%) 
Respiratory distress  1  0/332 (0.00%)  3/331 (0.91%) 
Respiratory failure  1  11/332 (3.31%)  10/331 (3.02%) 
Skin and subcutaneous tissue disorders     
Henoch-Schonlein purpura  1  0/332 (0.00%)  1/331 (0.30%) 
Pyoderma gangrenosum  1  0/332 (0.00%)  1/331 (0.30%) 
Vascular disorders     
Aortic aneurysm  1  1/332 (0.30%)  1/331 (0.30%) 
Aortic aneurysm rupture  1  0/332 (0.00%)  1/331 (0.30%) 
Arteritis  1  0/332 (0.00%)  1/331 (0.30%) 
Circulatory collapse  1  0/332 (0.00%)  1/331 (0.30%) 
Deep vein thrombosis  1  2/332 (0.60%)  2/331 (0.60%) 
Diabetic vascular disorder  1  0/332 (0.00%)  1/331 (0.30%) 
Hypertensive crisis  1  2/332 (0.60%)  1/331 (0.30%) 
Peripheral artery stenosis  1  0/332 (0.00%)  1/331 (0.30%) 
Shock haemorrhagic  1  0/332 (0.00%)  1/331 (0.30%) 
Vasculitis  1  2/332 (0.60%)  0/331 (0.00%) 
1
Term from vocabulary, MedDRA 22.0
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Nintedanib Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   308/332 (92.77%)   266/331 (80.36%) 
Gastrointestinal disorders     
Abdominal pain  1  34/332 (10.24%)  9/331 (2.72%) 
Abdominal pain upper  1  33/332 (9.94%)  6/331 (1.81%) 
Constipation  1  25/332 (7.53%)  32/331 (9.67%) 
Diarrhoea  1  239/332 (71.99%)  85/331 (25.68%) 
Nausea  1  100/332 (30.12%)  33/331 (9.97%) 
Vomiting  1  64/332 (19.28%)  16/331 (4.83%) 
General disorders     
Asthenia  1  18/332 (5.42%)  14/331 (4.23%) 
Chest pain  1  17/332 (5.12%)  14/331 (4.23%) 
Fatigue  1  34/332 (10.24%)  21/331 (6.34%) 
Oedema peripheral  1  18/332 (5.42%)  22/331 (6.65%) 
Pyrexia  1  17/332 (5.12%)  18/331 (5.44%) 
Hepatobiliary disorders     
Hepatic function abnormal  1  19/332 (5.72%)  3/331 (0.91%) 
Infections and infestations     
Bronchitis  1  44/332 (13.25%)  62/331 (18.73%) 
Nasopharyngitis  1  54/332 (16.27%)  48/331 (14.50%) 
Respiratory tract infection  1  18/332 (5.42%)  12/331 (3.63%) 
Upper respiratory tract infection  1  26/332 (7.83%)  25/331 (7.55%) 
Urinary tract infection  1  22/332 (6.63%)  20/331 (6.04%) 
Investigations     
Alanine aminotransferase increased  1  47/332 (14.16%)  12/331 (3.63%) 
Aspartate aminotransferase increased  1  41/332 (12.35%)  12/331 (3.63%) 
Gamma-glutamyltransferase increased  1  22/332 (6.63%)  6/331 (1.81%) 
Weight decreased  1  49/332 (14.76%)  18/331 (5.44%) 
Metabolism and nutrition disorders     
Decreased appetite  1  54/332 (16.27%)  22/331 (6.65%) 
Musculoskeletal and connective tissue disorders     
Arthralgia  1  12/332 (3.61%)  23/331 (6.95%) 
Back pain  1  28/332 (8.43%)  26/331 (7.85%) 
Nervous system disorders     
Dizziness  1  19/332 (5.72%)  15/331 (4.53%) 
Headache  1  37/332 (11.14%)  27/331 (8.16%) 
Psychiatric disorders     
Insomnia  1  18/332 (5.42%)  18/331 (5.44%) 
Respiratory, thoracic and mediastinal disorders     
Cough  1  40/332 (12.05%)  50/331 (15.11%) 
Dyspnoea  1  49/332 (14.76%)  46/331 (13.90%) 
Skin and subcutaneous tissue disorders     
Pruritus  1  12/332 (3.61%)  18/331 (5.44%) 
1
Term from vocabulary, MedDRA 22.0
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Boehringer Ingelheim Call Center
Organization: Boehringer Ingelheim
Phone: 1-800-243-0127
EMail: clintriage.rdg@boehringer-ingelheim.com
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
Responsible Party: Boehringer Ingelheim
ClinicalTrials.gov Identifier: NCT02999178    
Other Study ID Numbers: 1199.247
2015-003360-37 ( EudraCT Number )
First Submitted: December 19, 2016
First Posted: December 21, 2016
Results First Submitted: April 22, 2020
Results First Posted: May 5, 2020
Last Update Posted: May 5, 2020