Pulmonary Fibrosis
Conditions
Brief summary
The general purpose of this trial is to investigate the efficacy and safety of 4 dose strategies of BIBF 1120 treatment for 12 months, compared to placebo in patients with idiopathic pulmonary fibrosis. The primary objective of this study is to demonstrate whether at least one dose strategy is superior to placebo in patients with IPF, in modifying the rate of decline of Forced Vital Capacity (FVC). As a secondary objective, additional parameters will be assessed in order to differentiate between dose strategies on the basis of safety and efficacy
Interventions
DRUGlow dose BIBF1120 once daily
low dose BIBF1120 once daily
DRUGlow dose BIBF 1120 twice daily
low dose BIBF 1120 twice daily
DRUGintermediate dose BIBF 1120 twice daily
intermediate dose BIBF 1120 twice daily
DRUGhigh dose BIBF 1120 twice daily
high dose BIBF 1120 twice daily
DRUGplacebo
placebo
Sponsors
Boehringer Ingelheim
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE
Eligibility
Sex/Gender
ALL
Age
40 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Patient \>40 years 2. Written informed consent signed prior to entry into the study 3. IPF diagnosed (according to ATS / ERS criteria) less than 5 years prior to screening visit. 4. HRCT within 12 months of randomisation and biopsy (the latter if needed to fulfil ATS/ERS criteria) centrally reviewed and consistent with diagnosis. 5. FVC\>50 % of predicted value Predicted normal values will be calculated according to ESCS (R94-1408): Males : FVC predicted (L) = 5.76 x height (meters)- 0.026 x age (years) -4.34 Females : FVC predicted (L) = 4.43 x height (meters)- 0.026 x age (years) -2.89 6. Single breath DLCO (corrected for Hb) 30 - 79% inclusive of predicted . Different sites may use different prediction formulas, based on the method used to measure DLco. In any case, the method used must be in compliance with the ATS/ERS guideline on DLCO measurements (R06-2002), and the prediction formula appropriate for that method. Raw data (gas mixture, equation used for prediction of normal, further adjustments made if so) must be traced. Adjustment for haemoglobin (R06-2002): Males : DLCO predicted for Hb = DLCO predicted x (1.7Hb/\[10.22+Hb\]) Females : DLCO predicted for Hb = DLCO predicted x (1.7Hb/\[9.38+Hb\]) where Hb is expressed in g/dL-1 7. PaO2 \>= 55 mmHg (sea level to 1500 m) or 50 mmHg (above 1500 m) room air
Exclusion criteria
1. AST, ALT \> 1.5 x ULN ; 2. Bilirubin \> 1.5 x ULN 3. Relevant airways obstruction 4. Continuous oxygen supplementation at randomisation (defined as \> 15 hours supplemental oxygen per day). 5. Active infection at screening or randomisation. 6. Neutrophils \< 1500 / mm3 7. International normalised ratio (INR) \> 1.5 and/or Partial thromboplastin time (PTT) \> 1.5 x ULN ; 8. Platelets \< 100 000 /mL 9. Haemoglobin \< 9.0 g/dL 10. In the opinion of the Investigator, patient is likely to have lung transplantation during study 11. Life expectancy for disease other than IPF \< 2.5 years (Investigator assessment). 12. Other disease that may interfere with testing procedures or in judgement of Investigator may interfere with trial participation or may put the patient at risk when participating to this trial. * Myocardial infarction during the previous 6 months * Unstable angina during the previous month 13. Other investigational therapy received within 8 weeks prior to screening visit. 14. Pregnant women or women who are breast feeding or of child bearing potential not using a highly effective method of birth control for at least one month prior to enrolment. 15. Sexually active males not committing to using condoms during the course of the study (except if their partner is not of childbearing potential). 16. Known or suspected active alcohol or drug abuse. 17. Bleeding risk : Known inherited predisposition to bleeding, patients who require full-dose anticoagulation, Patients who require full-dose antiplatelet therapy, History of hemorrhagic CNS event within 12 months prior to screening , Any of the following within 3 months prior to screening : Gross / frank haemoptysis or haematuria, Active gastro-intestinal bleeding or ulcers, Major injury or surgery 18. Thrombotic risk 19. Surgical procedures planned to occur during trial period. 20. Coagulopathy 21. Uncontrolled systemic arterial hypertension 22. known hypersensitivity to lactose or any component of the study medication
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Rate of Decline in FVC | Baseline until 52 weeks | Rate of decline in Forced Vital Capacity (FVC) evaluated from baseline until 52 weeks of treatment. The means presents actually the adjusted rate based on a MMRM with fixed terms for treatment\*time, gender\*height, gender\*age and random terms for patient effect, patient\*time. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Absolute Change From Baseline in FVC | Baseline and 52 weeks | Change from baseline in percentage of absolute Forced Vital Capacity (FVC) at 52 weeks. Means were adjusted based on an ANCOVA with fixed terms for treatment, baseline and region. |
| Relative Change From Baseline in FVC%Pred | Baseline and 52 weeks | Percent change from baseline in percentage of predicted Forced Vital Capacity (FVC%pred) at 52 weeks. Means were adjusted based on an ANCOVA with fixed terms for treatment, baseline and region. |
| Relative Change From Baseline in FVC | Baseline and 52 weeks | Percent change from baseline in absolute Forced Vital Capacity (FVC) at 52 weeks. Means were adjusted based on an ANCOVA with fixed terms for treatment, baseline and region |
| Number of Participants With Change From Baseline in FVC by Categories | Baseline and 52 weeks | Change from baseline in percentage of Forced Vital Capacity (FVC) at 52 weeks in below mentioned categories: 1. Decrease \> 10% or 200mL 2. Change within \<= 10% or \<=200 mL 3. Increase \> 10% or 200mL |
| Survival (All Causes of Death and Lung-transplant Free) | 52 weeks | Survival (all causes of death and lung-transplant free) at 52 weeks, based on overall mortality and on-treatment survival. Failure means participants with event and Censored means participants with no event. |
| Absolute Change From Baseline in SpO2 at Rest | Baseline and 52 weeks | Absolute change from baseline in oxygen saturation (SpO2) at rest. Means were adjusted based on an ANCOVA with fixed terms for treatment, baseline, region. |
| Absolute Change From Baseline in SpO2 at Rest by Categories | Baseline and 52 weeks | Absolute change from baseline in oxygen saturation (SpO2) at rest by below mentioned categories: SpO2 (non-invasive) at 52 weeks: 1. Decrease \> 4% SpO2 2. Change within +/- 4% SpO2 3. Increase \> 4% SpO2 |
| Absolute Change From Baseline in PaO2 | Baseline and 52 weeks | Absolute change from baseline in Arterial oxygen partial pressure (PaO2) at week 52. Means were adjusted based on an ANCOVA with fixed terms for treatment, baseline, region. |
| Absolute Change From Baseline in P(A-a)O2 | Baseline and 52 weeks | Absolute change from baseline in Alveolo-arterial oxygen gradient (P(A-a)O2) at week 52. Means were adjusted based on an ANCOVA with fixed terms for treatment, baseline, region. |
| Absolute Change From Baseline in PaCO2 | Baseline and 52 weeks | Absolute change from baseline in Arterial carbon dioxyde partial pressure (PaCO2) at week 52. Means were adjusted based on an ANCOVA with fixed terms for treatment, baseline, region. |
| Absolute Change From Baseline in PaO2 by Categories | Baseline and 52 weeks | Absolute change from baseline in Arterial oxygen partial pressure (PaO2) by below mentioned categories: 1. Decrease \> 4 mmHg 2. Change within +/- 4 mmHg 3. Increase \> 4 mmHg |
| Absolute Change From Baseline in P(A-a) O2 by Categories | Baseline and 52 weeks | Absolute change from baseline in Alveolo-arterial oxygen gradient (P(A-a) O2) by below mentioned categories: 1. Decrease \> 4 mmHg 2. Change within +/- 4 mmHg 3. Increase \> 4 mmHg |
| Absolute Change From Baseline in DLCO | Baseline and 52 weeks | Absolute change from Baseline in Diffusing capacity of the lung for carbon monoxide (DLCO) at 52 weeks. Means were adjusted based on an ANCOVA with fixed terms for treatment, baseline, region. |
| Absolute Change From Baseline in DLCO by Categories | Baseline and 52 weeks | Absolute change from baseline in Diffusing capacity of the lung for carbon monoxide (DLCO) by below mentioned categories: 1. Decrease \> 15% or \> 1 2. Change \<= 15% or \<= 1 3. Increase \> 15% or \> 1 |
| Absolute Change From Baseline in Distance Walk (6-MWT) | Baseline and 52 weeks | Absolute change from baseline in distance walk (6-MWT) at 52 weeks. The 6-Minutes Walk Test (6-MWT) was conducted according to the American Thoracic Society (ATS) Criteria. Means were adjusted based on an ANCOVA with fixed terms for treatment, baseline, region. |
| Absolute Change From Baseline in Dyspnoea Rating on Borg Scale Before Exercise (6-MWT) | Baseline and 52 weeks | Absolute change from baseline in Dyspnoea rating before exercise (6-MWT) at 52 weeks based on Borg scale as mentioned below : 0: Nothing at all, 0.5: Very, very slight (just noticable), 1: Very slight, 2: Slight (light), 3: Moderate, 4: Somewhat severe, 5: Severe (heavy), 6, 7:Very severe, 8, 9, 10: Very, very severe (Maximal). The 6-Minutes Walk Test (6-MWT) was conducted according to the ATS Criteria. Means were adjusted based on an ANCOVA with fixed terms for treatment, baseline, region. |
| Change From Baseline in Dyspnoea Rating on Borg Scale After Exercise (6-MWT) | Baseline and 52 weeks | Change from baseline in Dyspnoea rating after exercise (6-MWT) at 52 weeks based on Borg scale as mentioned below : 0: Nothing at all, 0.5: Very, very slight (just noticable), 1: Very slight, 2: Slight (light), 3: Moderate, 4: Somewhat severe, 5: Severe (heavy), 6, 7:Very severe, 8, 9, 10: Very, very severe (Maximal). The 6-Minutes Walk Test (6-MWT) was conducted according to the ATS Criteria. Means were adjusted based on an ANCOVA with fixed terms for treatment, baseline, region. |
| Absolute Change From Baseline in FVC%Pred | Baseline and 52 weeks | Change from baseline in percentage of predicted Forced Vital Capacity (FVC%pred) at 52 weeks. Means were adjusted based on an ANCOVA with fixed terms for treatment, baseline and region. |
| Absolute Change From Baseline in FEV1/FVC | Baseline and 52 weeks | Change from baseline of percentage of FVC expelled in the first second of a forced expiration (FEV1/FVC) at 52 weeks. Means were adjusted based on an ANCOVA with fixed terms for treatment, baseline, region. |
| Change From Baseline in SGRQ Total Score | Baseline and 52 weeks | Change from baseline in Saint George's Respiratory Questionnaire (SGRQ) total score. Total score is defined as sum of the three domain scores symptoms, activities and impacts. Scores range from 0 to 100, with higher scores indicating worst possible health status. Means were adjusted based on an ANCOVA with fixed terms for treatment, baseline, region. |
| Change From Baseline in SGRQ Domain Score Symptoms | Baseline and 52 weeks | Change from baseline in Saint George's Respiratory Questionnaire (SGRQ) domain score symptoms. Scores range from 0 to 100, with higher scores indicating more limitations. Means were adjusted based on an ANCOVA with fixed terms for treatment, baseline, region. |
| Change From Baseline in SGRQ Domain Score Impacts | Baseline and 52 weeks | Change from baseline in Saint George's Respiratory Questionnaire (SGRQ) domain score impacts. Scores range from 0 to 100, with higher scores indicating worst possible health status. Means were adjusted based on an ANCOVA with fixed terms for treatment, baseline, region. |
| Change From Baseline in St George's Respiratory Questionnaire (SGRQ) Domain Score Activities | Baseline and 52 weeks | Change from baseline in Saint George's Respiratory Questionnaire (SGRQ) domain score activities. Scores range from 0 to 100, with higher scores indicating worst possible health status. Means were adjusted based on an ANCOVA with fixed terms for treatment, baseline, region. |
| St George's Respiratory Questionnaire (SGRQ) Responder | 52 weeks | St George's Respiratory Questionnaire (SGRQ) responder (\<= -4 points change) (%) at 52 weeks-worst case |
| Change From Baseline in TLC | Baseline and 52 weeks | Change from Baseline in Total Lung Capacity (TLC) at 52 weeks. Means were adjusted based on an ANCOVA with fixed terms for treatment, baseline, region. |
| Change From Baseline in RV | Baseline and 52 weeks | Change from Baseline in Residual volume (RV) at 52 weeks. Means were adjusted based on an ANCOVA with fixed terms for treatment, baseline, region. |
| Change From Baseline in TGV | Baseline and 52 weeks | Change from Baseline in Thoracic gas volume (TGV) at 52 weeks. Means were adjusted based on an ANCOVA with fixed terms for treatment, baseline, region. |
| Change From Baseline in VC | Baseline and 52 weeks | Change from baseline in Vital capacity (VC) at 52 weeks. Means were adjusted based on an ANCOVA with fixed terms for treatment, baseline, region. |
| Change From Baseline in IC | Baseline and 52 weeks | Change from Baseline in Inspiratory Capacity (IC) at 52 weeks. Means were adjusted based on an ANCOVA with fixed terms for treatment, baseline, region. |
| Number of Patients With at Least One IPF Exacerbation | 52 weeks | Number of patients with at least one Idiopathic Pulmonary Fibrosis (IPF) exacerbation at 52 weeks |
| Occurrences of IPF Exacerbations Per Patient Per Year | 52 weeks | Occurrences of Idiopathic Pulmonary Fibrosis (IPF) exacerbations per patient per year at 52 weeks |
| Time to First Occurrence of IPF Exacerbation | 52 weeks | This endpoint is called time to first occurrence of IPF exacerbation however it was actually analysed as the proportion of patients having occurrence of Idiopathic Pulmonary Fibrosis (IPF) exacerbation at 52 weeks. Failure means participants with event and Censored means participants with no event. |
| Survival (Death Due to Respiratory Cause, and Lung-transplant Free) | 52 weeks | Survival (death due to respiratory cause, and lung-transplant free) at 52 weeks. Failure means participants with event and Censored means participants with no event. |
| Time to Progression | 52 weeks | Time to progression. Progression was defined as at least one of the following: 5mmHg increase in the alveolo-arterial pressure difference in oxygen (P(A-a)O2), 10% decrease in FVC (FVC(baseline)-FVC(progression) \>= 10%) or Death. Failure means participants with event and Censored means participants with no event. |
| Pre-dose Plasma Concentration of Nintedanib in Plasma at Steady State on Day 365 (Cpre,ss,365) and Day 729 (Cpre,ss,729). | day 365 and day 729 | Cpre,ss,729 represents the pre-dose plasma concentration of nintedanib in plasma at steady state on Day 729 and Cpre,ss,365 represents the pre-dose plasma concentration of nintedanib in plasma at steady state on Day 365. At day 365, values only for Nintedanib 50 qd group are presented as no values reported for other groups and at day 729, values are presented for all group except for Nintedanib 50 qd group as no values reported for it. |
| Absolute Change From Baseline in MRC Dyspnea Scale by Categories | Baseline and 52 weeks | Absolute change from baseline in Medical Research Council (MRC) dyspnea scale by below mentioned categories: 1. Decrease 2. No Change 3. Increase |
Countries
Argentina, Australia, Belgium, Brazil, Bulgaria, Canada, Chile, China, Czechia, France, Germany, Greece, Hungary, Ireland, Italy, Mexico, Netherlands, Portugal, Russia, South Africa, South Korea, Spain, Taiwan, Turkey (Türkiye), United Kingdom
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo Patients were treated with matching Placebo. | 85 |
| Nintedanib 50 qd Patients were treated with 50mg nintedanib once daily | 86 |
| Nintedanib 50 Bid Patients were treated with 50mg nintedanib twice daily | 86 |
| Nintedanib 100 Bid Patients were treated with 100mg nintedanib twice daily | 86 |
| Nintedanib 150 Bid Patients were treated with 150mg nintedanib twice daily | 85 |
| Total | 428 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 21 | 20 | 15 | 13 | 27 |
| Overall Study | Not treated | 2 | 1 | 0 | 0 | 1 |
| Overall Study | Protocol Violation | 1 | 1 | 0 | 1 | 0 |
| Overall Study | Reason other than listed above | 0 | 1 | 2 | 0 | 1 |
| Overall Study | Withdrawal by Subject | 2 | 2 | 1 | 0 | 4 |
Baseline characteristics
| Characteristic | Placebo | Nintedanib 50 qd | Nintedanib 50 Bid | Nintedanib 100 Bid | Nintedanib 150 Bid | Total |
|---|---|---|---|---|---|---|
| Age, Continuous | 64.8 years STANDARD_DEVIATION 8.57 | 65.3 years STANDARD_DEVIATION 9.42 | 64.9 years STANDARD_DEVIATION 8.48 | 65.1 years STANDARD_DEVIATION 8.63 | 65.4 years STANDARD_DEVIATION 7.82 | 65.1 years STANDARD_DEVIATION 8.56 |
| Sex: Female, Male Female | 22 Participants | 21 Participants | 24 Participants | 21 Participants | 20 Participants | 108 Participants |
| Sex: Female, Male Male | 63 Participants | 65 Participants | 62 Participants | 65 Participants | 65 Participants | 320 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 51 / 85 | 52 / 86 | 55 / 86 | 64 / 86 | 57 / 85 |
| serious Total, serious adverse events | 26 / 85 | 26 / 86 | 23 / 86 | 18 / 86 | 23 / 85 |
Outcome results
Primary
Rate of Decline in FVC
Rate of decline in Forced Vital Capacity (FVC) evaluated from baseline until 52 weeks of treatment. The means presents actually the adjusted rate based on a MMRM with fixed terms for treatment\*time, gender\*height, gender\*age and random terms for patient effect, patient\*time.
Time frame: Baseline until 52 weeks
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Rate of Decline in FVC | -0.190 Liters/year | Standard Error 0.036 |
| Nintedanib 50 qd | Rate of Decline in FVC | -0.174 Liters/year | Standard Error 0.037 |
| Nintedanib 50 Bid | Rate of Decline in FVC | -0.210 Liters/year | Standard Error 0.035 |
| Nintedanib 100 Bid | Rate of Decline in FVC | -0.162 Liters/year | Standard Error 0.035 |
| Nintedanib 150 Bid | Rate of Decline in FVC | -0.060 Liters/year | Standard Error 0.039 |
p-value: 0.85395% CI: [-0.086, 0.118]Mixed Models Analysis
p-value: 0.7558Mixed Models Analysis
p-value: 0.79295% CI: [-0.119, 0.08]Mixed Models Analysis
p-value: 0.6991Mixed Models Analysis
p-value: 0.85395% CI: [-0.071, 0.128]Mixed Models Analysis
p-value: 0.5736Mixed Models Analysis
p-value: 0.063995% CI: [0.027, 0.235]Mixed Models Analysis
p-value: 0.0136Mixed Models Analysis
Secondary
Absolute Change From Baseline in Distance Walk (6-MWT)
Absolute change from baseline in distance walk (6-MWT) at 52 weeks. The 6-Minutes Walk Test (6-MWT) was conducted according to the American Thoracic Society (ATS) Criteria. Means were adjusted based on an ANCOVA with fixed terms for treatment, baseline, region.
Time frame: Baseline and 52 weeks
Population: LOCF-Randomised set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Absolute Change From Baseline in Distance Walk (6-MWT) | -35.67 Meter | Standard Error 12.732 |
| Nintedanib 50 qd | Absolute Change From Baseline in Distance Walk (6-MWT) | -46.91 Meter | Standard Error 13.652 |
| Nintedanib 50 Bid | Absolute Change From Baseline in Distance Walk (6-MWT) | -48.84 Meter | Standard Error 11.974 |
| Nintedanib 100 Bid | Absolute Change From Baseline in Distance Walk (6-MWT) | -36.80 Meter | Standard Error 12.131 |
| Nintedanib 150 Bid | Absolute Change From Baseline in Distance Walk (6-MWT) | -29.35 Meter | Standard Error 12.957 |
p-value: 0.417695% CI: [-45.11, 18.76]ANCOVA
p-value: 0.511195% CI: [-44.86, 22.37]ANCOVA
p-value: 0.945495% CI: [-33.6, 31.34]ANCOVA
p-value: 0.710195% CI: [-27.08, 39.72]ANCOVA
Secondary
Absolute Change From Baseline in DLCO
Absolute change from Baseline in Diffusing capacity of the lung for carbon monoxide (DLCO) at 52 weeks. Means were adjusted based on an ANCOVA with fixed terms for treatment, baseline, region.
Time frame: Baseline and 52 weeks
Population: LOCF-Randomised set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Absolute Change From Baseline in DLCO | -0.455 mmol.min^-1.kPa^-1 | Standard Error 0.1098 |
| Nintedanib 50 qd | Absolute Change From Baseline in DLCO | -0.357 mmol.min^-1.kPa^-1 | Standard Error 0.1163 |
| Nintedanib 50 Bid | Absolute Change From Baseline in DLCO | -0.610 mmol.min^-1.kPa^-1 | Standard Error 0.1038 |
| Nintedanib 100 Bid | Absolute Change From Baseline in DLCO | -0.535 mmol.min^-1.kPa^-1 | Standard Error 0.1035 |
| Nintedanib 150 Bid | Absolute Change From Baseline in DLCO | -0.576 mmol.min^-1.kPa^-1 | Standard Error 0.1111 |
p-value: 0.499895% CI: [-0.188, 0.385]ANCOVA
p-value: 0.267995% CI: [-0.43, 0.12]ANCOVA
p-value: 0.567895% CI: [-0.355, 0.195]ANCOVA
p-value: 0.405395% CI: [-0.406, 0.164]ANCOVA
Secondary
Absolute Change From Baseline in DLCO by Categories
Absolute change from baseline in Diffusing capacity of the lung for carbon monoxide (DLCO) by below mentioned categories: 1. Decrease \> 15% or \> 1 2. Change \<= 15% or \<= 1 3. Increase \> 15% or \> 1
Time frame: Baseline and 52 weeks
Population: LOCF Randomized set
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Absolute Change From Baseline in DLCO by Categories | Increase > 15% or > 1 | 4.0 percentage of patients |
| Placebo | Absolute Change From Baseline in DLCO by Categories | Decrease > 15% or > 1 | 37.3 percentage of patients |
| Placebo | Absolute Change From Baseline in DLCO by Categories | Change <= 15% or <= 1 | 58.7 percentage of patients |
| Nintedanib 50 qd | Absolute Change From Baseline in DLCO by Categories | Change <= 15% or <= 1 | 51.5 percentage of patients |
| Nintedanib 50 qd | Absolute Change From Baseline in DLCO by Categories | Increase > 15% or > 1 | 10.3 percentage of patients |
| Nintedanib 50 qd | Absolute Change From Baseline in DLCO by Categories | Decrease > 15% or > 1 | 38.2 percentage of patients |
| Nintedanib 50 Bid | Absolute Change From Baseline in DLCO by Categories | Decrease > 15% or > 1 | 43.8 percentage of patients |
| Nintedanib 50 Bid | Absolute Change From Baseline in DLCO by Categories | Change <= 15% or <= 1 | 51.3 percentage of patients |
| Nintedanib 50 Bid | Absolute Change From Baseline in DLCO by Categories | Increase > 15% or > 1 | 5.0 percentage of patients |
| Nintedanib 100 Bid | Absolute Change From Baseline in DLCO by Categories | Decrease > 15% or > 1 | 35.8 percentage of patients |
| Nintedanib 100 Bid | Absolute Change From Baseline in DLCO by Categories | Increase > 15% or > 1 | 7.4 percentage of patients |
| Nintedanib 100 Bid | Absolute Change From Baseline in DLCO by Categories | Change <= 15% or <= 1 | 56.8 percentage of patients |
| Nintedanib 150 Bid | Absolute Change From Baseline in DLCO by Categories | Change <= 15% or <= 1 | 44.9 percentage of patients |
| Nintedanib 150 Bid | Absolute Change From Baseline in DLCO by Categories | Decrease > 15% or > 1 | 50.7 percentage of patients |
| Nintedanib 150 Bid | Absolute Change From Baseline in DLCO by Categories | Increase > 15% or > 1 | 4.3 percentage of patients |
p-value: 0.730795% CI: [0.465, 1.71]Regression, Logistic
p-value: 0.386995% CI: [0.706, 2.458]Regression, Logistic
p-value: 0.823795% CI: [0.498, 1.741]Regression, Logistic
p-value: 0.117795% CI: [0.878, 3.202]Regression, Logistic
Secondary
Absolute Change From Baseline in Dyspnoea Rating on Borg Scale Before Exercise (6-MWT)
Absolute change from baseline in Dyspnoea rating before exercise (6-MWT) at 52 weeks based on Borg scale as mentioned below : 0: Nothing at all, 0.5: Very, very slight (just noticable), 1: Very slight, 2: Slight (light), 3: Moderate, 4: Somewhat severe, 5: Severe (heavy), 6, 7:Very severe, 8, 9, 10: Very, very severe (Maximal). The 6-Minutes Walk Test (6-MWT) was conducted according to the ATS Criteria. Means were adjusted based on an ANCOVA with fixed terms for treatment, baseline, region.
Time frame: Baseline and 52 weeks
Population: LOCF-Randomised set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Absolute Change From Baseline in Dyspnoea Rating on Borg Scale Before Exercise (6-MWT) | 0.227 Units on a scale | Standard Error 0.1695 |
| Nintedanib 50 qd | Absolute Change From Baseline in Dyspnoea Rating on Borg Scale Before Exercise (6-MWT) | 0.282 Units on a scale | Standard Error 0.1817 |
| Nintedanib 50 Bid | Absolute Change From Baseline in Dyspnoea Rating on Borg Scale Before Exercise (6-MWT) | 0.045 Units on a scale | Standard Error 0.1594 |
| Nintedanib 100 Bid | Absolute Change From Baseline in Dyspnoea Rating on Borg Scale Before Exercise (6-MWT) | 0.260 Units on a scale | Standard Error 0.1612 |
| Nintedanib 150 Bid | Absolute Change From Baseline in Dyspnoea Rating on Borg Scale Before Exercise (6-MWT) | 0.086 Units on a scale | Standard Error 0.1736 |
p-value: 0.80995% CI: [-0.392, 0.502]ANCOVA
p-value: 0.399595% CI: [-0.606, 0.242]ANCOVA
p-value: 0.882295% CI: [-0.399, 0.464]ANCOVA
p-value: 0.533895% CI: [-0.584, 0.303]ANCOVA
Secondary
Absolute Change From Baseline in FEV1/FVC
Change from baseline of percentage of FVC expelled in the first second of a forced expiration (FEV1/FVC) at 52 weeks. Means were adjusted based on an ANCOVA with fixed terms for treatment, baseline, region.
Time frame: Baseline and 52 weeks
Population: LOCF-Randomised set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Absolute Change From Baseline in FEV1/FVC | 1.25 percentage of FVC | Standard Error 0.529 |
| Nintedanib 50 qd | Absolute Change From Baseline in FEV1/FVC | -0.10 percentage of FVC | Standard Error 0.533 |
| Nintedanib 50 Bid | Absolute Change From Baseline in FEV1/FVC | 0.00 percentage of FVC | Standard Error 0.511 |
| Nintedanib 100 Bid | Absolute Change From Baseline in FEV1/FVC | -0.53 percentage of FVC | Standard Error 0.516 |
| Nintedanib 150 Bid | Absolute Change From Baseline in FEV1/FVC | -0.42 percentage of FVC | Standard Error 0.513 |
p-value: 0.047995% CI: [-2.69, -0.01]ANCOVA
p-value: 0.068595% CI: [-2.58, 0.09]ANCOVA
p-value: 0.009995% CI: [-3.12, -0.43]ANCOVA
p-value: 0.015295% CI: [-3.01, -0.32]ANCOVA
Secondary
Absolute Change From Baseline in FVC
Change from baseline in percentage of absolute Forced Vital Capacity (FVC) at 52 weeks. Means were adjusted based on an ANCOVA with fixed terms for treatment, baseline and region.
Time frame: Baseline and 52 weeks
Population: LOCF-Randomised set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Absolute Change From Baseline in FVC | -0.23 Liters | Standard Error 0.036 |
| Nintedanib 50 qd | Absolute Change From Baseline in FVC | -0.18 Liters | Standard Error 0.036 |
| Nintedanib 50 Bid | Absolute Change From Baseline in FVC | -0.19 Liters | Standard Error 0.035 |
| Nintedanib 100 Bid | Absolute Change From Baseline in FVC | -0.13 Liters | Standard Error 0.035 |
| Nintedanib 150 Bid | Absolute Change From Baseline in FVC | -0.06 Liters | Standard Error 0.035 |
p-value: 0.364495% CI: [-0.05, 0.13]ANCOVA
p-value: 0.452595% CI: [-0.06, 0.13]ANCOVA
p-value: 0.047195% CI: [0, 0.18]ANCOVA
p-value: 0.000495% CI: [0.08, 0.26]ANCOVA
Secondary
Absolute Change From Baseline in FVC%Pred
Change from baseline in percentage of predicted Forced Vital Capacity (FVC%pred) at 52 weeks. Means were adjusted based on an ANCOVA with fixed terms for treatment, baseline and region.
Time frame: Baseline and 52 weeks
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Absolute Change From Baseline in FVC%Pred | -6.00 percentage of predicted FVC | Standard Error 1.019 |
| Nintedanib 50 qd | Absolute Change From Baseline in FVC%Pred | -4.58 percentage of predicted FVC | Standard Error 1.029 |
| Nintedanib 50 Bid | Absolute Change From Baseline in FVC%Pred | -4.90 percentage of predicted FVC | Standard Error 0.984 |
| Nintedanib 100 Bid | Absolute Change From Baseline in FVC%Pred | -3.15 percentage of predicted FVC | Standard Error 1.004 |
| Nintedanib 150 Bid | Absolute Change From Baseline in FVC%Pred | -1.04 percentage of predicted FVC | Standard Error 0.99 |
p-value: 0.277495% CI: [-1.15, 4.01]ANCOVA
p-value: 0.401495% CI: [-1.48, 3.68]ANCOVA
p-value: 0.031495% CI: [0.26, 5.46]ANCOVA
p-value: 0.000295% CI: [2.37, 7.56]ANCOVA
Secondary
Absolute Change From Baseline in MRC Dyspnea Scale by Categories
Absolute change from baseline in Medical Research Council (MRC) dyspnea scale by below mentioned categories: 1. Decrease 2. No Change 3. Increase
Time frame: Baseline and 52 weeks
Population: LOCF- Randomised
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Absolute Change From Baseline in MRC Dyspnea Scale by Categories | Decrease | 7.8 percentage of participants |
| Placebo | Absolute Change From Baseline in MRC Dyspnea Scale by Categories | Increase | 40.3 percentage of participants |
| Placebo | Absolute Change From Baseline in MRC Dyspnea Scale by Categories | No Change | 51.9 percentage of participants |
| Nintedanib 50 qd | Absolute Change From Baseline in MRC Dyspnea Scale by Categories | No Change | 45.3 percentage of participants |
| Nintedanib 50 qd | Absolute Change From Baseline in MRC Dyspnea Scale by Categories | Decrease | 13.3 percentage of participants |
| Nintedanib 50 qd | Absolute Change From Baseline in MRC Dyspnea Scale by Categories | Increase | 41.3 percentage of participants |
| Nintedanib 50 Bid | Absolute Change From Baseline in MRC Dyspnea Scale by Categories | No Change | 53.1 percentage of participants |
| Nintedanib 50 Bid | Absolute Change From Baseline in MRC Dyspnea Scale by Categories | Decrease | 8.6 percentage of participants |
| Nintedanib 50 Bid | Absolute Change From Baseline in MRC Dyspnea Scale by Categories | Increase | 38.3 percentage of participants |
| Nintedanib 100 Bid | Absolute Change From Baseline in MRC Dyspnea Scale by Categories | Decrease | 14.6 percentage of participants |
| Nintedanib 100 Bid | Absolute Change From Baseline in MRC Dyspnea Scale by Categories | Increase | 40.2 percentage of participants |
| Nintedanib 100 Bid | Absolute Change From Baseline in MRC Dyspnea Scale by Categories | No Change | 45.1 percentage of participants |
| Nintedanib 150 Bid | Absolute Change From Baseline in MRC Dyspnea Scale by Categories | No Change | 53.9 percentage of participants |
| Nintedanib 150 Bid | Absolute Change From Baseline in MRC Dyspnea Scale by Categories | Decrease | 11.8 percentage of participants |
| Nintedanib 150 Bid | Absolute Change From Baseline in MRC Dyspnea Scale by Categories | Increase | 34.2 percentage of participants |
p-value: 0.964695% CI: [0.54, 1.906]Regression, Logistic
p-value: 0.98595% CI: [0.536, 1.844]Regression, Logistic
p-value: 0.713695% CI: [0.604, 2.089]Regression, Logistic
p-value: 0.170595% CI: [0.828, 2.906]Regression, Logistic
Secondary
Absolute Change From Baseline in P(A-a)O2
Absolute change from baseline in Alveolo-arterial oxygen gradient (P(A-a)O2) at week 52. Means were adjusted based on an ANCOVA with fixed terms for treatment, baseline, region.
Time frame: Baseline and 52 weeks
Population: OC-Randomised set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Absolute Change From Baseline in P(A-a)O2 | 1.21 mmHg | Standard Error 1.898 |
| Nintedanib 50 qd | Absolute Change From Baseline in P(A-a)O2 | 1.27 mmHg | Standard Error 1.984 |
| Nintedanib 50 Bid | Absolute Change From Baseline in P(A-a)O2 | 2.22 mmHg | Standard Error 1.773 |
| Nintedanib 100 Bid | Absolute Change From Baseline in P(A-a)O2 | 1.62 mmHg | Standard Error 1.723 |
| Nintedanib 150 Bid | Absolute Change From Baseline in P(A-a)O2 | 2.56 mmHg | Standard Error 1.944 |
p-value: 0.981195% CI: [-4.84, 4.96]ANCOVA
p-value: 0.677295% CI: [-3.74, 5.75]ANCOVA
p-value: 0.863195% CI: [-4.27, 5.09]ANCOVA
p-value: 0.594295% CI: [-3.62, 6.31]ANCOVA
Secondary
Absolute Change From Baseline in P(A-a) O2 by Categories
Absolute change from baseline in Alveolo-arterial oxygen gradient (P(A-a) O2) by below mentioned categories: 1. Decrease \> 4 mmHg 2. Change within +/- 4 mmHg 3. Increase \> 4 mmHg
Time frame: Baseline and 52 weeks
Population: OC - Randomised set
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Absolute Change From Baseline in P(A-a) O2 by Categories | Decrease > 4 mmHg | 25.0 percentage of participants |
| Placebo | Absolute Change From Baseline in P(A-a) O2 by Categories | Increase > 4 mmHg | 41.1 percentage of participants |
| Placebo | Absolute Change From Baseline in P(A-a) O2 by Categories | Change within +/- 4 mmHg | 33.9 percentage of participants |
| Nintedanib 50 qd | Absolute Change From Baseline in P(A-a) O2 by Categories | Change within +/- 4 mmHg | 14.8 percentage of participants |
| Nintedanib 50 qd | Absolute Change From Baseline in P(A-a) O2 by Categories | Decrease > 4 mmHg | 37.0 percentage of participants |
| Nintedanib 50 qd | Absolute Change From Baseline in P(A-a) O2 by Categories | Increase > 4 mmHg | 48.1 percentage of participants |
| Nintedanib 50 Bid | Absolute Change From Baseline in P(A-a) O2 by Categories | Decrease > 4 mmHg | 31.3 percentage of participants |
| Nintedanib 50 Bid | Absolute Change From Baseline in P(A-a) O2 by Categories | Change within +/- 4 mmHg | 25.0 percentage of participants |
| Nintedanib 50 Bid | Absolute Change From Baseline in P(A-a) O2 by Categories | Increase > 4 mmHg | 43.0 percentage of participants |
| Nintedanib 100 Bid | Absolute Change From Baseline in P(A-a) O2 by Categories | Decrease > 4 mmHg | 25.4 percentage of participants |
| Nintedanib 100 Bid | Absolute Change From Baseline in P(A-a) O2 by Categories | Increase > 4 mmHg | 46.3 percentage of participants |
| Nintedanib 100 Bid | Absolute Change From Baseline in P(A-a) O2 by Categories | Change within +/- 4 mmHg | 28.4 percentage of participants |
| Nintedanib 150 Bid | Absolute Change From Baseline in P(A-a) O2 by Categories | Change within +/- 4 mmHg | 45.1 percentage of participants |
| Nintedanib 150 Bid | Absolute Change From Baseline in P(A-a) O2 by Categories | Decrease > 4 mmHg | 17.6 percentage of participants |
| Nintedanib 150 Bid | Absolute Change From Baseline in P(A-a) O2 by Categories | Increase > 4 mmHg | 37.3 percentage of participants |
p-value: 0.982995% CI: [0.506, 1.949]Regression, Logistic
p-value: 0.888795% CI: [0.521, 2.122]Regression, Logistic
p-value: 0.575895% CI: [0.613, 2.41]Regression, Logistic
p-value: 0.937595% CI: [0.476, 1.985]Regression, Logistic
Secondary
Absolute Change From Baseline in PaCO2
Absolute change from baseline in Arterial carbon dioxyde partial pressure (PaCO2) at week 52. Means were adjusted based on an ANCOVA with fixed terms for treatment, baseline, region.
Time frame: Baseline and 52 weeks
Population: OC-Randomised set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Absolute Change From Baseline in PaCO2 | -0.63 mmHg | Standard Error 0.549 |
| Nintedanib 50 qd | Absolute Change From Baseline in PaCO2 | 0.16 mmHg | Standard Error 0.573 |
| Nintedanib 50 Bid | Absolute Change From Baseline in PaCO2 | -0.44 mmHg | Standard Error 0.517 |
| Nintedanib 100 Bid | Absolute Change From Baseline in PaCO2 | -0.74 mmHg | Standard Error 0.5 |
| Nintedanib 150 Bid | Absolute Change From Baseline in PaCO2 | -0.77 mmHg | Standard Error 0.569 |
p-value: 0.271695% CI: [-0.62, 2.19]ANCOVA
p-value: 0.787195% CI: [-1.18, 1.56]ANCOVA
p-value: 0.872195% CI: [-1.46, 1.24]ANCOVA
p-value: 0.852395% CI: [-1.58, 1.31]ANCOVA
Secondary
Absolute Change From Baseline in PaO2
Absolute change from baseline in Arterial oxygen partial pressure (PaO2) at week 52. Means were adjusted based on an ANCOVA with fixed terms for treatment, baseline, region.
Time frame: Baseline and 52 weeks
Population: OC-Randomised set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Absolute Change From Baseline in PaO2 | -1.69 mmHg | Standard Error 1.79 |
| Nintedanib 50 qd | Absolute Change From Baseline in PaO2 | -2.77 mmHg | Standard Error 1.865 |
| Nintedanib 50 Bid | Absolute Change From Baseline in PaO2 | -3.00 mmHg | Standard Error 1.686 |
| Nintedanib 100 Bid | Absolute Change From Baseline in PaO2 | -1.46 mmHg | Standard Error 1.632 |
| Nintedanib 150 Bid | Absolute Change From Baseline in PaO2 | -0.76 mmHg | Standard Error 1.854 |
p-value: 0.644395% CI: [-5.66, 3.51]ANCOVA
p-value: 0.565695% CI: [-5.8, 3.18]ANCOVA
p-value: 0.918195% CI: [-4.18, 4.64]ANCOVA
p-value: 0.69795% CI: [-3.77, 5.63]ANCOVA
Secondary
Absolute Change From Baseline in PaO2 by Categories
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
Population: OC - Randomised set
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Absolute Change From Baseline in PaO2 by Categories | Decrease > 4 mmHg | 34.5 percentage of participants |
| Placebo | Absolute Change From Baseline in PaO2 by Categories | Change within +/- 4 mmHg | 50.0 percentage of participants |
| Placebo | Absolute Change From Baseline in PaO2 by Categories | Increase > 4 mmHg | 15.5 percentage of participants |
| Nintedanib 50 qd | Absolute Change From Baseline in PaO2 by Categories | Increase > 4 mmHg | 28.6 percentage of participants |
| Nintedanib 50 qd | Absolute Change From Baseline in PaO2 by Categories | Change within +/- 4 mmHg | 21.4 percentage of participants |
| Nintedanib 50 qd | Absolute Change From Baseline in PaO2 by Categories | Decrease > 4 mmHg | 50.0 percentage of participants |
| Nintedanib 50 Bid | Absolute Change From Baseline in PaO2 by Categories | Change within +/- 4 mmHg | 32.8 percentage of participants |
| Nintedanib 50 Bid | Absolute Change From Baseline in PaO2 by Categories | Increase > 4 mmHg | 25.0 percentage of participants |
| Nintedanib 50 Bid | Absolute Change From Baseline in PaO2 by Categories | Decrease > 4 mmHg | 42.2 percentage of participants |
| Nintedanib 100 Bid | Absolute Change From Baseline in PaO2 by Categories | Decrease > 4 mmHg | 39.7 percentage of participants |
| Nintedanib 100 Bid | Absolute Change From Baseline in PaO2 by Categories | Increase > 4 mmHg | 29.4 percentage of participants |
| Nintedanib 100 Bid | Absolute Change From Baseline in PaO2 by Categories | Change within +/- 4 mmHg | 30.9 percentage of participants |
| Nintedanib 150 Bid | Absolute Change From Baseline in PaO2 by Categories | Increase > 4 mmHg | 27.5 percentage of participants |
| Nintedanib 150 Bid | Absolute Change From Baseline in PaO2 by Categories | Change within +/- 4 mmHg | 43.1 percentage of participants |
| Nintedanib 150 Bid | Absolute Change From Baseline in PaO2 by Categories | Decrease > 4 mmHg | 29.4 percentage of participants |
p-value: 0.799795% CI: [0.549, 2.175]Regression, Logistic
p-value: 0.798995% CI: [0.467, 1.797]Regression, Logistic
p-value: 0.459695% CI: [0.403, 1.508]Regression, Logistic
p-value: 0.254895% CI: [0.33, 1.341]Regression, Logistic
Secondary
Absolute Change From Baseline in SpO2 at Rest
Absolute change from baseline in oxygen saturation (SpO2) at rest. Means were adjusted based on an ANCOVA with fixed terms for treatment, baseline, region.
Time frame: Baseline and 52 weeks
Population: LOCF-Randomised set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Absolute Change From Baseline in SpO2 at Rest | -1.29 Percentage of SpO2 | Standard Error 0.373 |
| Nintedanib 50 qd | Absolute Change From Baseline in SpO2 at Rest | -0.86 Percentage of SpO2 | Standard Error 0.38 |
| Nintedanib 50 Bid | Absolute Change From Baseline in SpO2 at Rest | -0.97 Percentage of SpO2 | Standard Error 0.357 |
| Nintedanib 100 Bid | Absolute Change From Baseline in SpO2 at Rest | 0.06 Percentage of SpO2 | Standard Error 0.363 |
| Nintedanib 150 Bid | Absolute Change From Baseline in SpO2 at Rest | -0.18 Percentage of SpO2 | Standard Error 0.36 |
p-value: 0.365895% CI: [-0.51, 1.39]ANCOVA
p-value: 0.495695% CI: [-0.61, 1.27]ANCOVA
p-value: 0.005195% CI: [0.41, 2.31]ANCOVA
p-value: 0.021195% CI: [0.17, 2.07]ANCOVA
Secondary
Absolute Change From Baseline in SpO2 at Rest by Categories
Absolute change from baseline in oxygen saturation (SpO2) at rest by below mentioned categories: SpO2 (non-invasive) at 52 weeks: 1. Decrease \> 4% SpO2 2. Change within +/- 4% SpO2 3. Increase \> 4% SpO2
Time frame: Baseline and 52 weeks
Population: LOCF-Randomised set
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Absolute Change From Baseline in SpO2 at Rest by Categories | Decrease > 4% | 11.0 percentage of participants |
| Placebo | Absolute Change From Baseline in SpO2 at Rest by Categories | Increase > 4% | 1.2 percentage of participants |
| Placebo | Absolute Change From Baseline in SpO2 at Rest by Categories | Change within +/- 4% | 87.8 percentage of participants |
| Nintedanib 50 qd | Absolute Change From Baseline in SpO2 at Rest by Categories | Change within +/- 4% | 90.2 percentage of participants |
| Nintedanib 50 qd | Absolute Change From Baseline in SpO2 at Rest by Categories | Decrease > 4% | 4.9 percentage of participants |
| Nintedanib 50 qd | Absolute Change From Baseline in SpO2 at Rest by Categories | Increase > 4% | 4.9 percentage of participants |
| Nintedanib 50 Bid | Absolute Change From Baseline in SpO2 at Rest by Categories | Change within +/- 4% | 89.5 percentage of participants |
| Nintedanib 50 Bid | Absolute Change From Baseline in SpO2 at Rest by Categories | Decrease > 4% | 8.1 percentage of participants |
| Nintedanib 50 Bid | Absolute Change From Baseline in SpO2 at Rest by Categories | Increase > 4% | 2.3 percentage of participants |
| Nintedanib 100 Bid | Absolute Change From Baseline in SpO2 at Rest by Categories | Decrease > 4% | 6.0 percentage of participants |
| Nintedanib 100 Bid | Absolute Change From Baseline in SpO2 at Rest by Categories | Increase > 4% | 4.8 percentage of participants |
| Nintedanib 100 Bid | Absolute Change From Baseline in SpO2 at Rest by Categories | Change within +/- 4% | 89.3 percentage of participants |
| Nintedanib 150 Bid | Absolute Change From Baseline in SpO2 at Rest by Categories | Change within +/- 4% | 92.8 percentage of participants |
| Nintedanib 150 Bid | Absolute Change From Baseline in SpO2 at Rest by Categories | Decrease > 4% | 3.6 percentage of participants |
| Nintedanib 150 Bid | Absolute Change From Baseline in SpO2 at Rest by Categories | Increase > 4% | 3.6 percentage of participants |
p-value: 0.102195% CI: [0.155, 1.184]Regression, Logistic
p-value: 0.431895% CI: [0.262, 1.773]Regression, Logistic
p-value: 0.093495% CI: [0.146, 1.161]Regression, Logistic
p-value: 0.031795% CI: [0.108, 0.903]Regression, Logistic
Secondary
Change From Baseline in Dyspnoea Rating on Borg Scale After Exercise (6-MWT)
Change from baseline in Dyspnoea rating after exercise (6-MWT) at 52 weeks based on Borg scale as mentioned below : 0: Nothing at all, 0.5: Very, very slight (just noticable), 1: Very slight, 2: Slight (light), 3: Moderate, 4: Somewhat severe, 5: Severe (heavy), 6, 7:Very severe, 8, 9, 10: Very, very severe (Maximal). The 6-Minutes Walk Test (6-MWT) was conducted according to the ATS Criteria. Means were adjusted based on an ANCOVA with fixed terms for treatment, baseline, region.
Time frame: Baseline and 52 weeks
Population: LOCF-Randomised set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Dyspnoea Rating on Borg Scale After Exercise (6-MWT) | 0.527 Units on a scale | Standard Error 0.2439 |
| Nintedanib 50 qd | Change From Baseline in Dyspnoea Rating on Borg Scale After Exercise (6-MWT) | 0.639 Units on a scale | Standard Error 0.2616 |
| Nintedanib 50 Bid | Change From Baseline in Dyspnoea Rating on Borg Scale After Exercise (6-MWT) | 0.449 Units on a scale | Standard Error 0.2295 |
| Nintedanib 100 Bid | Change From Baseline in Dyspnoea Rating on Borg Scale After Exercise (6-MWT) | 0.377 Units on a scale | Standard Error 0.2321 |
| Nintedanib 150 Bid | Change From Baseline in Dyspnoea Rating on Borg Scale After Exercise (6-MWT) | 0.194 Units on a scale | Standard Error 0.2492 |
p-value: 0.732995% CI: [-0.532, 0.755]ANCOVA
p-value: 0.800995% CI: [-0.69, 0.533]ANCOVA
p-value: 0.635895% CI: [-0.771, 0.472]ANCOVA
p-value: 0.306495% CI: [-0.973, 0.307]ANCOVA
Secondary
Change From Baseline in IC
Change from Baseline in Inspiratory Capacity (IC) at 52 weeks. Means were adjusted based on an ANCOVA with fixed terms for treatment, baseline, region.
Time frame: Baseline and 52 weeks
Population: LOCF-Randomised set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in IC | -0.031 Liters | Standard Error 0.0509 |
| Nintedanib 50 qd | Change From Baseline in IC | -0.064 Liters | Standard Error 0.0539 |
| Nintedanib 50 Bid | Change From Baseline in IC | -0.053 Liters | Standard Error 0.0483 |
| Nintedanib 100 Bid | Change From Baseline in IC | -0.038 Liters | Standard Error 0.0479 |
| Nintedanib 150 Bid | Change From Baseline in IC | -0.012 Liters | Standard Error 0.0515 |
p-value: 0.630695% CI: [-0.165, 0.1]ANCOVA
p-value: 0.742695% CI: [-0.149, 0.106]ANCOVA
p-value: 0.920995% CI: [-0.134, 0.121]ANCOVA
p-value: 0.770195% CI: [-0.112, 0.152]ANCOVA
Secondary
Change From Baseline in RV
Change from Baseline in Residual volume (RV) at 52 weeks. Means were adjusted based on an ANCOVA with fixed terms for treatment, baseline, region.
Time frame: Baseline and 52 weeks
Population: LOCF-Randomised set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in RV | -0.036 Liters | Standard Error 0.0512 |
| Nintedanib 50 qd | Change From Baseline in RV | -0.056 Liters | Standard Error 0.0543 |
| Nintedanib 50 Bid | Change From Baseline in RV | 0.029 Liters | Standard Error 0.0484 |
| Nintedanib 100 Bid | Change From Baseline in RV | -0.012 Liters | Standard Error 0.0484 |
| Nintedanib 150 Bid | Change From Baseline in RV | 0.086 Liters | Standard Error 0.0518 |
p-value: 0.778995% CI: [-0.153, 0.115]ANCOVA
p-value: 0.314995% CI: [-0.063, 0.194]ANCOVA
p-value: 0.706295% CI: [-0.104, 0.153]ANCOVA
p-value: 0.070395% CI: [-0.01, 0.255]ANCOVA
Secondary
Change From Baseline in SGRQ Domain Score Impacts
Change from baseline in Saint George's Respiratory Questionnaire (SGRQ) domain score impacts. Scores range from 0 to 100, with higher scores indicating worst possible health status. Means were adjusted based on an ANCOVA with fixed terms for treatment, baseline, region.
Time frame: Baseline and 52 weeks
Population: LOCF - Randomised set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in SGRQ Domain Score Impacts | 4.21 units on a scale | Standard Error 1.986 |
| Nintedanib 50 qd | Change From Baseline in SGRQ Domain Score Impacts | 3.71 units on a scale | Standard Error 2.04 |
| Nintedanib 50 Bid | Change From Baseline in SGRQ Domain Score Impacts | 1.73 units on a scale | Standard Error 1.897 |
| Nintedanib 100 Bid | Change From Baseline in SGRQ Domain Score Impacts | 0.79 units on a scale | Standard Error 1.906 |
| Nintedanib 150 Bid | Change From Baseline in SGRQ Domain Score Impacts | -0.14 units on a scale | Standard Error 1.965 |
p-value: 0.845895% CI: [-5.59, 4.58]ANCOVA
p-value: 0.328695% CI: [-7.48, 2.51]ANCOVA
p-value: 0.179995% CI: [-8.43, 1.59]ANCOVA
p-value: 0.094895% CI: [-9.46, 0.76]ANCOVA
Secondary
Change From Baseline in SGRQ Domain Score Symptoms
Change from baseline in Saint George's Respiratory Questionnaire (SGRQ) domain score symptoms. Scores range from 0 to 100, with higher scores indicating more limitations. Means were adjusted based on an ANCOVA with fixed terms for treatment, baseline, region.
Time frame: Baseline and 52 weeks
Population: LOCF-Randomised set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in SGRQ Domain Score Symptoms | 6.45 units on a scale | Standard Error 2.446 |
| Nintedanib 50 qd | Change From Baseline in SGRQ Domain Score Symptoms | 3.39 units on a scale | Standard Error 2.514 |
| Nintedanib 50 Bid | Change From Baseline in SGRQ Domain Score Symptoms | 2.11 units on a scale | Standard Error 2.338 |
| Nintedanib 100 Bid | Change From Baseline in SGRQ Domain Score Symptoms | 2.33 units on a scale | Standard Error 2.346 |
| Nintedanib 150 Bid | Change From Baseline in SGRQ Domain Score Symptoms | -3.14 units on a scale | Standard Error 2.403 |
p-value: 0.33795% CI: [-9.32, 3.2]ANCOVA
p-value: 0.165995% CI: [-10.49, 1.81]ANCOVA
p-value: 0.189795% CI: [-10.29, 2.05]ANCOVA
p-value: 0.002895% CI: [-15.86, -3.34]ANCOVA
Secondary
Change From Baseline in SGRQ Total Score
Change from baseline in Saint George's Respiratory Questionnaire (SGRQ) total score. Total score is defined as sum of the three domain scores symptoms, activities and impacts. Scores range from 0 to 100, with higher scores indicating worst possible health status. Means were adjusted based on an ANCOVA with fixed terms for treatment, baseline, region.
Time frame: Baseline and 52 weeks
Population: LOCF-Randomised set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in SGRQ Total Score | 5.46 units on a scale | Standard Error 1.731 |
| Nintedanib 50 qd | Change From Baseline in SGRQ Total Score | 4.67 units on a scale | Standard Error 1.779 |
| Nintedanib 50 Bid | Change From Baseline in SGRQ Total Score | 2.18 units on a scale | Standard Error 1.654 |
| Nintedanib 100 Bid | Change From Baseline in SGRQ Total Score | 1.48 units on a scale | Standard Error 1.66 |
| Nintedanib 150 Bid | Change From Baseline in SGRQ Total Score | -0.66 units on a scale | Standard Error 1.712 |
p-value: 0.72595% CI: [-5.22, 3.64]ANCOVA
p-value: 0.138995% CI: [-7.63, 1.07]ANCOVA
p-value: 0.074195% CI: [-8.35, 0.39]ANCOVA
p-value: 0.007195% CI: [-10.57, -1.67]ANCOVA
Secondary
Change From Baseline in St George's Respiratory Questionnaire (SGRQ) Domain Score Activities
Change from baseline in Saint George's Respiratory Questionnaire (SGRQ) domain score activities. Scores range from 0 to 100, with higher scores indicating worst possible health status. Means were adjusted based on an ANCOVA with fixed terms for treatment, baseline, region.
Time frame: Baseline and 52 weeks
Population: LOCF-Randomised set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in St George's Respiratory Questionnaire (SGRQ) Domain Score Activities | 7.48 units on a scale | Standard Error 1.91 |
| Nintedanib 50 qd | Change From Baseline in St George's Respiratory Questionnaire (SGRQ) Domain Score Activities | 7.39 units on a scale | Standard Error 1.962 |
| Nintedanib 50 Bid | Change From Baseline in St George's Respiratory Questionnaire (SGRQ) Domain Score Activities | 3.54 units on a scale | Standard Error 1.824 |
| Nintedanib 100 Bid | Change From Baseline in St George's Respiratory Questionnaire (SGRQ) Domain Score Activities | 3.00 units on a scale | Standard Error 1.832 |
| Nintedanib 150 Bid | Change From Baseline in St George's Respiratory Questionnaire (SGRQ) Domain Score Activities | 0.32 units on a scale | Standard Error 1.887 |
p-value: 0.004395% CI: [-12.06, -2.26]ANCOVA
p-value: 0.970895% CI: [-4.98, 4.79]ANCOVA
p-value: 0.106995% CI: [-8.74, 0.85]ANCOVA
p-value: 0.068295% CI: [-9.31, 0.34]ANCOVA
Secondary
Change From Baseline in TGV
Change from Baseline in Thoracic gas volume (TGV) at 52 weeks. Means were adjusted based on an ANCOVA with fixed terms for treatment, baseline, region.
Time frame: Baseline and 52 weeks
Population: LOCF-Randomised set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in TGV | -0.137 Liters | Standard Error 0.0657 |
| Nintedanib 50 qd | Change From Baseline in TGV | -0.075 Liters | Standard Error 0.0707 |
| Nintedanib 50 Bid | Change From Baseline in TGV | -0.035 Liters | Standard Error 0.0622 |
| Nintedanib 100 Bid | Change From Baseline in TGV | -0.016 Liters | Standard Error 0.0623 |
| Nintedanib 150 Bid | Change From Baseline in TGV | 0.200 Liters | Standard Error 0.0668 |
p-value: 0.479295% CI: [-0.111, 0.236]ANCOVA
p-value: 0.222195% CI: [-0.062, 0.268]ANCOVA
p-value: 0.15195% CI: [-0.044, 0.287]ANCOVA
p-value: 0.000195% CI: [0.165, 0.509]ANCOVA
Secondary
Change From Baseline in TLC
Change from Baseline in Total Lung Capacity (TLC) at 52 weeks. Means were adjusted based on an ANCOVA with fixed terms for treatment, baseline, region.
Time frame: Baseline and 52 weeks
Population: LOCF-Randomised set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in TLC | -0.240 Liters | Standard Error 0.0765 |
| Nintedanib 50 qd | Change From Baseline in TLC | -0.218 Liters | Standard Error 0.0809 |
| Nintedanib 50 Bid | Change From Baseline in TLC | -0.100 Liters | Standard Error 0.0725 |
| Nintedanib 100 Bid | Change From Baseline in TLC | -0.082 Liters | Standard Error 0.0723 |
| Nintedanib 150 Bid | Change From Baseline in TLC | 0.118 Liters | Standard Error 0.0774 |
p-value: 0.828895% CI: [-0.178, 0.222]ANCOVA
p-value: 0.150695% CI: [-0.051, 0.332]ANCOVA
p-value: 0.105995% CI: [-0.034, 0.351]ANCOVA
p-value: 0.000495% CI: [0.16, 0.556]ANCOVA
Secondary
Change From Baseline in VC
Change from baseline in Vital capacity (VC) at 52 weeks. Means were adjusted based on an ANCOVA with fixed terms for treatment, baseline, region.
Time frame: Baseline and 52 weeks
Population: LOCF-Randomised set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in VC | -0.191 Liters | Standard Error 0.0458 |
| Nintedanib 50 qd | Change From Baseline in VC | -0.095 Liters | Standard Error 0.0485 |
| Nintedanib 50 Bid | Change From Baseline in VC | -0.107 Liters | Standard Error 0.0433 |
| Nintedanib 100 Bid | Change From Baseline in VC | -0.082 Liters | Standard Error 0.0432 |
| Nintedanib 150 Bid | Change From Baseline in VC | 0.010 Liters | Standard Error 0.0462 |
p-value: 0.112995% CI: [-0.023, 0.217]ANCOVA
p-value: 0.149895% CI: [-0.031, 0.199]ANCOVA
p-value: 0.063295% CI: [-0.006, 0.224]ANCOVA
p-value: 0.000995% CI: [0.083, 0.32]ANCOVA
Secondary
Number of Participants With Change From Baseline in FVC by Categories
Change from baseline in percentage of Forced Vital Capacity (FVC) at 52 weeks in below mentioned categories: 1. Decrease \> 10% or 200mL 2. Change within \<= 10% or \<=200 mL 3. Increase \> 10% or 200mL
Time frame: Baseline and 52 weeks
Population: LOCF-Randomised set
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Number of Participants With Change From Baseline in FVC by Categories | Change within <= 10% or <=200mL | 41 participants |
| Placebo | Number of Participants With Change From Baseline in FVC by Categories | Decrease > 10% or 200mL | 37 participants |
| Placebo | Number of Participants With Change From Baseline in FVC by Categories | Increase > 10% or 200mL | 6 participants |
| Nintedanib 50 qd | Number of Participants With Change From Baseline in FVC by Categories | Increase > 10% or 200mL | 6 participants |
| Nintedanib 50 qd | Number of Participants With Change From Baseline in FVC by Categories | Decrease > 10% or 200mL | 35 participants |
| Nintedanib 50 qd | Number of Participants With Change From Baseline in FVC by Categories | Change within <= 10% or <=200mL | 44 participants |
| Nintedanib 50 Bid | Number of Participants With Change From Baseline in FVC by Categories | Decrease > 10% or 200mL | 41 participants |
| Nintedanib 50 Bid | Number of Participants With Change From Baseline in FVC by Categories | Increase > 10% or 200mL | 6 participants |
| Nintedanib 50 Bid | Number of Participants With Change From Baseline in FVC by Categories | Change within <= 10% or <=200mL | 39 participants |
| Nintedanib 100 Bid | Number of Participants With Change From Baseline in FVC by Categories | Decrease > 10% or 200mL | 30 participants |
| Nintedanib 100 Bid | Number of Participants With Change From Baseline in FVC by Categories | Change within <= 10% or <=200mL | 46 participants |
| Nintedanib 100 Bid | Number of Participants With Change From Baseline in FVC by Categories | Increase > 10% or 200mL | 9 participants |
| Nintedanib 150 Bid | Number of Participants With Change From Baseline in FVC by Categories | Change within <= 10% or <=200mL | 52 participants |
| Nintedanib 150 Bid | Number of Participants With Change From Baseline in FVC by Categories | Increase > 10% or 200mL | 12 participants |
| Nintedanib 150 Bid | Number of Participants With Change From Baseline in FVC by Categories | Decrease > 10% or 200mL | 20 participants |
p-value: 0.670495% CI: [0.631, 2.045]Regression, Logistic
p-value: 0.754395% CI: [0.506, 1.637]Regression, Logistic
p-value: 0.164995% CI: [0.363, 1.189]Regression, Logistic
p-value: 0.004195% CI: [0.227, 0.757]Regression, Logistic
Secondary
Number of Patients With at Least One IPF Exacerbation
Number of patients with at least one Idiopathic Pulmonary Fibrosis (IPF) exacerbation at 52 weeks
Time frame: 52 weeks
Population: OC-Randomised set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Number of Patients With at Least One IPF Exacerbation | 12 participants |
| Nintedanib 50 qd | Number of Patients With at Least One IPF Exacerbation | 10 participants |
| Nintedanib 50 Bid | Number of Patients With at Least One IPF Exacerbation | 10 participants |
| Nintedanib 100 Bid | Number of Patients With at Least One IPF Exacerbation | 6 participants |
| Nintedanib 150 Bid | Number of Patients With at Least One IPF Exacerbation | 2 participants |
p-value: 0.667195% CI: [0.36, 1.93]Negative binomial model
p-value: 0.592695% CI: [0.34, 1.84]Negative binomial model
p-value: 0.138195% CI: [0.18, 1.27]Negative binomial model
p-value: 0.01595% CI: [0.03, 0.7]Negative binomial model
Secondary
Occurrences of IPF Exacerbations Per Patient Per Year
Occurrences of Idiopathic Pulmonary Fibrosis (IPF) exacerbations per patient per year at 52 weeks
Time frame: 52 weeks
Population: OC-Randomised set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Occurrences of IPF Exacerbations Per Patient Per Year | 0.243 Exacerbations Per Year | Standard Deviation 0.8008 |
| Nintedanib 50 qd | Occurrences of IPF Exacerbations Per Patient Per Year | 0.243 Exacerbations Per Year | Standard Deviation 0.7884 |
| Nintedanib 50 Bid | Occurrences of IPF Exacerbations Per Patient Per Year | 0.242 Exacerbations Per Year | Standard Deviation 0.983 |
| Nintedanib 100 Bid | Occurrences of IPF Exacerbations Per Patient Per Year | 0.256 Exacerbations Per Year | Standard Deviation 1.7315 |
| Nintedanib 150 Bid | Occurrences of IPF Exacerbations Per Patient Per Year | 0.075 Exacerbations Per Year | Standard Deviation 0.5177 |
p-value: 0.828295% CI: [0.347, 2.336]Negative binomial model
p-value: 0.532695% CI: [0.278, 1.938]Negative Binomial model
p-value: 0.194495% CI: [0.167, 1.438]Negative Binomial model
p-value: 0.032495% CI: [0.056, 0.882]Negative Binomial model
Secondary
Pre-dose Plasma Concentration of Nintedanib in Plasma at Steady State on Day 365 (Cpre,ss,365) and Day 729 (Cpre,ss,729).
Cpre,ss,729 represents the pre-dose plasma concentration of nintedanib in plasma at steady state on Day 729 and Cpre,ss,365 represents the pre-dose plasma concentration of nintedanib in plasma at steady state on Day 365. At day 365, values only for Nintedanib 50 qd group are presented as no values reported for other groups and at day 729, values are presented for all group except for Nintedanib 50 qd group as no values reported for it.
Time frame: day 365 and day 729
Population: Randomised set
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Pre-dose Plasma Concentration of Nintedanib in Plasma at Steady State on Day 365 (Cpre,ss,365) and Day 729 (Cpre,ss,729). | 1.07 ng/mL | Geometric Coefficient of Variation 41.6 |
| Nintedanib 50 qd | Pre-dose Plasma Concentration of Nintedanib in Plasma at Steady State on Day 365 (Cpre,ss,365) and Day 729 (Cpre,ss,729). | 2.12 ng/mL | Geometric Coefficient of Variation 91.1 |
| Nintedanib 50 Bid | Pre-dose Plasma Concentration of Nintedanib in Plasma at Steady State on Day 365 (Cpre,ss,365) and Day 729 (Cpre,ss,729). | 4.20 ng/mL | Geometric Coefficient of Variation 69 |
| Nintedanib 100 Bid | Pre-dose Plasma Concentration of Nintedanib in Plasma at Steady State on Day 365 (Cpre,ss,365) and Day 729 (Cpre,ss,729). | 6.66 ng/mL | Geometric Coefficient of Variation 94 |
Secondary
Relative Change From Baseline in FVC
Percent change from baseline in absolute Forced Vital Capacity (FVC) at 52 weeks. Means were adjusted based on an ANCOVA with fixed terms for treatment, baseline and region
Time frame: Baseline and 52 weeks
Population: LOCF-Randomised set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Relative Change From Baseline in FVC | -7.96 percentage change | Standard Error 1.314 |
| Nintedanib 50 qd | Relative Change From Baseline in FVC | -6.98 percentage change | Standard Error 1.327 |
| Nintedanib 50 Bid | Relative Change From Baseline in FVC | -7.16 percentage change | Standard Error 1.272 |
| Nintedanib 100 Bid | Relative Change From Baseline in FVC | -4.13 percentage change | Standard Error 1.285 |
| Nintedanib 150 Bid | Relative Change From Baseline in FVC | -2.52 percentage change | Standard Error 1.277 |
p-value: 0.560195% CI: [-2.34, 4.31]ANCOVA
p-value: 0.636695% CI: [-2.53, 4.13]ANCOVA
p-value: 0.024695% CI: [0.49, 7.18]ANCOVA
p-value: 0.001595% CI: [2.1, 8.78]ANCOVA
Secondary
Relative Change From Baseline in FVC%Pred
Percent change from baseline in percentage of predicted Forced Vital Capacity (FVC%pred) at 52 weeks. Means were adjusted based on an ANCOVA with fixed terms for treatment, baseline and region.
Time frame: Baseline and 52 weeks
Population: LOCF-Randomised set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Relative Change From Baseline in FVC%Pred | -7.28 percentage of change | Standard Error 1.321 |
| Nintedanib 50 qd | Relative Change From Baseline in FVC%Pred | -6.37 percentage of change | Standard Error 1.334 |
| Nintedanib 50 Bid | Relative Change From Baseline in FVC%Pred | -6.42 percentage of change | Standard Error 1.277 |
| Nintedanib 100 Bid | Relative Change From Baseline in FVC%Pred | -3.47 percentage of change | Standard Error 1.302 |
| Nintedanib 150 Bid | Relative Change From Baseline in FVC%Pred | -1.81 percentage of change | Standard Error 1.283 |
p-value: 0.59295% CI: [-2.43, 4.26]ANCOVA
p-value: 0.615595% CI: [-2.49, 4.2]ANCOVA
p-value: 0.027195% CI: [0.43, 7.18]ANCOVA
p-value: 0.001595% CI: [2.11, 8.83]ANCOVA
Secondary
St George's Respiratory Questionnaire (SGRQ) Responder
St George's Respiratory Questionnaire (SGRQ) responder (\<= -4 points change) (%) at 52 weeks-worst case
Time frame: 52 weeks
Population: Worst case - Randomised set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | St George's Respiratory Questionnaire (SGRQ) Responder | 16.1 percentage of participants |
| Nintedanib 50 qd | St George's Respiratory Questionnaire (SGRQ) Responder | 23.0 percentage of participants |
| Nintedanib 50 Bid | St George's Respiratory Questionnaire (SGRQ) Responder | 26.7 percentage of participants |
| Nintedanib 100 Bid | St George's Respiratory Questionnaire (SGRQ) Responder | 32.6 percentage of participants |
| Nintedanib 150 Bid | St George's Respiratory Questionnaire (SGRQ) Responder | 29.1 percentage of participants |
p-value: 0.034195% CI: [1.05, 4.61]Cochran-Mantel-Haenszel
p-value: 0.269895% CI: [0.72, 3.31]Cochran-Mantel-Haenszel
p-value: 0.089195% CI: [0.9, 4.01]Cochran-Mantel-Haenszel
p-value: 0.006995% CI: [1.29, 5.66]Cochran-Mantel-Haenszel
Secondary
Survival (All Causes of Death and Lung-transplant Free)
Survival (all causes of death and lung-transplant free) at 52 weeks, based on overall mortality and on-treatment survival. Failure means participants with event and Censored means participants with no event.
Time frame: 52 weeks
Population: OC-Randomised set
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Survival (All Causes of Death and Lung-transplant Free) | Failure | 9 participants |
| Placebo | Survival (All Causes of Death and Lung-transplant Free) | Censored | 78 participants |
| Nintedanib 50 qd | Survival (All Causes of Death and Lung-transplant Free) | Failure | 11 participants |
| Nintedanib 50 qd | Survival (All Causes of Death and Lung-transplant Free) | Censored | 76 participants |
| Nintedanib 50 Bid | Survival (All Causes of Death and Lung-transplant Free) | Failure | 3 participants |
| Nintedanib 50 Bid | Survival (All Causes of Death and Lung-transplant Free) | Censored | 83 participants |
| Nintedanib 100 Bid | Survival (All Causes of Death and Lung-transplant Free) | Censored | 82 participants |
| Nintedanib 100 Bid | Survival (All Causes of Death and Lung-transplant Free) | Failure | 4 participants |
| Nintedanib 150 Bid | Survival (All Causes of Death and Lung-transplant Free) | Failure | 7 participants |
| Nintedanib 150 Bid | Survival (All Causes of Death and Lung-transplant Free) | Censored | 79 participants |
p-value: 0.588295% CI: [0.526, 3.102]Regression, Cox
p-value: 0.065395% CI: [0.078, 1.081]Regression, Cox
p-value: 0.084795% CI: [0.106, 1.154]Regression, Cox
p-value: 0.538395% CI: [0.271, 1.977]Regression, Cox
Secondary
Survival (Death Due to Respiratory Cause, and Lung-transplant Free)
Survival (death due to respiratory cause, and lung-transplant free) at 52 weeks. Failure means participants with event and Censored means participants with no event.
Time frame: 52 weeks
Population: OC-Randomised set
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Survival (Death Due to Respiratory Cause, and Lung-transplant Free) | Failure | 9.2 percentage of participants |
| Placebo | Survival (Death Due to Respiratory Cause, and Lung-transplant Free) | Censored | 90.8 percentage of participants |
| Nintedanib 50 qd | Survival (Death Due to Respiratory Cause, and Lung-transplant Free) | Failure | 10.3 percentage of participants |
| Nintedanib 50 qd | Survival (Death Due to Respiratory Cause, and Lung-transplant Free) | Censored | 89.7 percentage of participants |
| Nintedanib 50 Bid | Survival (Death Due to Respiratory Cause, and Lung-transplant Free) | Failure | 3.5 percentage of participants |
| Nintedanib 50 Bid | Survival (Death Due to Respiratory Cause, and Lung-transplant Free) | Censored | 96.5 percentage of participants |
| Nintedanib 100 Bid | Survival (Death Due to Respiratory Cause, and Lung-transplant Free) | Censored | 97.7 percentage of participants |
| Nintedanib 100 Bid | Survival (Death Due to Respiratory Cause, and Lung-transplant Free) | Failure | 2.3 percentage of participants |
| Nintedanib 150 Bid | Survival (Death Due to Respiratory Cause, and Lung-transplant Free) | Failure | 2.3 percentage of participants |
| Nintedanib 150 Bid | Survival (Death Due to Respiratory Cause, and Lung-transplant Free) | Censored | 97.7 percentage of participants |
p-value: 0.744995% CI: [0.448, 3.072]Regression, Cox
p-value: 0.092595% CI: [0.083, 1.209]Regression, Cox
p-value: 0.037995% CI: [0.04, 0.911]Regression, Cox
p-value: 0.0695% CI: [0.048, 1.065]Regression, Cox
Secondary
Time to First Occurrence of IPF Exacerbation
This endpoint is called time to first occurrence of IPF exacerbation however it was actually analysed as the proportion of patients having occurrence of Idiopathic Pulmonary Fibrosis (IPF) exacerbation at 52 weeks. Failure means participants with event and Censored means participants with no event.
Time frame: 52 weeks
Population: OC-Randomised set
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Time to First Occurrence of IPF Exacerbation | Failure | 13.8 percentage of participants |
| Placebo | Time to First Occurrence of IPF Exacerbation | Censored | 86.2 percentage of participants |
| Nintedanib 50 qd | Time to First Occurrence of IPF Exacerbation | Failure | 11.5 percentage of participants |
| Nintedanib 50 qd | Time to First Occurrence of IPF Exacerbation | Censored | 88.5 percentage of participants |
| Nintedanib 50 Bid | Time to First Occurrence of IPF Exacerbation | Failure | 11.6 percentage of participants |
| Nintedanib 50 Bid | Time to First Occurrence of IPF Exacerbation | Censored | 88.4 percentage of participants |
| Nintedanib 100 Bid | Time to First Occurrence of IPF Exacerbation | Censored | 93.0 percentage of participants |
| Nintedanib 100 Bid | Time to First Occurrence of IPF Exacerbation | Failure | 7.0 percentage of participants |
| Nintedanib 150 Bid | Time to First Occurrence of IPF Exacerbation | Failure | 2.3 percentage of participants |
| Nintedanib 150 Bid | Time to First Occurrence of IPF Exacerbation | Censored | 97.7 percentage of participants |
p-value: 0.520695% CI: [0.326, 1.765]Regression, Cox
p-value: 0.686295% CI: [0.362, 1.952]Regression, Cox
p-value: 0.189195% CI: [0.193, 1.384]Regression, Cox
p-value: 0.016195% CI: [0.035, 0.711]Regression, Cox
Secondary
Time to Progression
Time to progression. Progression was defined as at least one of the following: 5mmHg increase in the alveolo-arterial pressure difference in oxygen (P(A-a)O2), 10% decrease in FVC (FVC(baseline)-FVC(progression) \>= 10%) or Death. Failure means participants with event and Censored means participants with no event.
Time frame: 52 weeks
Population: OC - Randomised set
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Time to Progression | 363 Days |
| Nintedanib 50 qd | Time to Progression | 365 Days |
| Nintedanib 50 Bid | Time to Progression | 365 Days |
| Nintedanib 100 Bid | Time to Progression | 365 Days |
| Nintedanib 150 Bid | Time to Progression | 365 Days |
p-value: 0.788395% CI: [0.713, 1.563]Regression, Cox
p-value: 0.829395% CI: [0.646, 1.419]Regression, Cox
p-value: 0.30395% CI: [0.534, 1.216]Regression, Cox
p-value: 0.650595% CI: [0.605, 1.369]Regression, Cox