Idiopathic Pulmonary Fibrosis
Conditions
Brief summary
To investigate safety of BIBF 1120 in Japanese patients with idiopathic pulmonary fibrosis (IPF), with and without pirfenidone background treatment. To assess pharmacokinetics of BIBF 1120 in Japanese patients, with and without pirfenidone background treatment. To assess pharmacokinetics of pirfenidone in Japanese patients, alone and in combination with BIBF 1120 treatment.
Interventions
DRUGPlacebo
Placebo BID for cohort 1,2,3
DRUGBIBF 1120
50 mg, 100 mg, 150 mg BID will be used for Cohort 1, 2, and 3 respectively
Sponsors
Boehringer Ingelheim
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Masking
DOUBLE
Eligibility
Sex/Gender
ALL
Age
40 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Diagnosis of idiopathic pulmonary fibrosis (IPF) according to American Thoracic Society (ATS) /European Respiratory Society (ERS) guideline 2. Forced vital capacity (FVC) 50-90% 3. Diffusing capacity for carbon monoxide (DLCO) 30-79% 4. For patients on pirfenidone, have been on a steady dose for at least 3 months
Exclusion criteria
1. Aspartate aminotransferase (AST), alanine aminotransferase (ALT) \> 1.5 x upper limit of normal range (ULN) at screening. 2. Bilirubin \> 1.5 x ULN at screening. 3. Relevant airways obstruction (i.e. pre-bronchodilator FEV1/FVC \<0.7) at screening. 4. Continuous oxygen supplementation. 5. Active infection at screening or randomisation. 6. Being treated with any of the following concomitant medications. * Oral corticosteroid medication at unstable dose * ketoconazole or atazanavir 7. Patients who are expected to go on to lung transplantation, have rapidly deteriorating disease, or have a life expectancy less than 3 months from screening
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Drug-related Adverse Events | after the first drug intake until 28 days from the last treatment administration, up to 60 days | The number of patients with drug-related adverse events stratified according to pirfenidone use in each group |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Cmax,ss After Multiple Doses of BIBF 1120 Without Pirfenidone | pre-dose, then 0.5 h, 1 h, 2 h, 3 h, 3.92 h, 6 h, 8 h, 12 h, 24 h, 48 h, 72 h after morning dose on days 14 to 17 (BIBF 1120 50 mg and 100 mg) or on days 28 to 31 (BIBF 1120 150 mg) | Maximum measured concentration of the analyte in plasma at steady state was identified from measurements obtained at multiple time points over a uniform dosing interval τ after multiple doses of BIBF 1120 without pirfenidone. Detailed outcome measure time frame: In 50 mg and 100 mg dose group: BIBF 1120: days 14 (-1, +3) to 17 at Visit 5: At pre-dose and 0.5 h, 1 h, 2 h, 3 h, 3.92 h, 6 h, 8 h, 12 h, 24 h, 48 h, 72 h after morning dose In 150 mg dose group: BIBF 1120: days 28 (-1, +3) to 31 at Visit 5: At pre-dose and 0.5 h, 1 h, 2 h, 3 h, 3.92 h, 6 h, 8 h, 12 h, 24 h, 48 h, 72 h after morning dose |
| AUCτ,ss After Multiple Doses of BIBF 1120 With Pirfenidone | pre-dose, then 0.5 h, 1 h, 2 h, 3 h, 3.92 h, 6 h, 8 h, 12 h, 24 h, 48 h, 72 h after morning dose on days 14 to 17 (BIBF 1120 50 mg and 100 mg) or on days 28 to 31 (BIBF 1120 150 mg) | AUCτ,ss was calculated as the area under the concentration-time curve of the concentration-time profile of the analyte in plasma at steady state over a uniform dosing interval τ after multiple doses of BIBF 1120 with pirfenidone in the time frame mentioned. Detailed outcome measure time frame: In 50 mg and 100 mg dose group: BIBF 1120: days 14 (-1, +3) to 17 at Visit 5: At pre-dose and 0.5 h, 1 h, 2 h, 3 h, 3.92 h, 6 h, 8 h, 12 h, 24 h, 48 h, 72 h after morning dose In 150 mg dose group: BIBF 1120: days 28 (-1, +3) to 31 at Visit 5: At pre-dose and 0.5 h, 1 h, 2 h, 3 h, 3.92 h, 6 h, 8 h, 12 h, 24 h, 48 h, 72 h after morning dose |
| Cmax,ss After Multiple Doses of BIBF 1120 With Pirfenidone | pre-dose, then 0.5 h, 1 h, 2 h, 3 h, 3.92 h, 6 h, 8 h, 12 h, 24 h, 48 h, 72 h after morning dose on days 14 to 17 (BIBF 1120 50 mg and 100 mg) or on days 28 to 31 (BIBF 1120 150 mg) | Maximum measured concentration of the analyte in plasma at steady state was identified from measurements obtained at multiple time points over a uniform dosing interval τ after multiple doses of BIBF 1120 with pirfenidone Detailed outcome measure time frame: In 50 mg and 100 mg dose group: BIBF 1120: days 14 (-1, +3) to 17 at Visit 5: At pre-dose and 0.5 h, 1 h, 2 h, 3 h, 3.92 h, 6 h, 8 h, 12 h, 24 h, 48 h, 72 h after morning dose In 150 mg dose group: BIBF 1120: days 28 (-1, +3) to 31 at Visit 5: At pre-dose and 0.5 h, 1 h, 2 h, 3 h, 3.92 h, 6 h, 8 h, 12 h, 24 h, 48 h, 72 h after morning dose |
| AUC0-4,ss After Multiple Doses of Pirfenidone 600 mg Without BIBF 1120 (After Breakfast) | Day -1 at Visit 1: At pre-dose and 0.5 h, 1 h, 2 h, 3 h after morning dose and pre-dose after lunch dose | AUC0-4,ss was calculated as the area under the curve of the concentration-time profile of the analyte in plasma at steady state over the time interval from 0 to 4 hours after multiple doses of Pirfenidone 600 mg without BIBF 1120 (after breakfast) in the time frame mentioned. |
| Cmax,ss After Multiple Doses of Pirfenidone 600 mg Without BIBF 1120 (After Breakfast) | Day -1 at Visit 1: At pre-dose and 0.5 h, 1 h, 2 h, 3 h after morning dose and pre-dose after lunch dose | Maximum measured concentration of the analyte in plasma at steady state was identified from measurements obtained at multiple time points after multiple doses of Pirfenidone 600 mg without BIBF 1120 (after breakfast) |
| AUC0-4,ss After Multiple Doses of Pirfenidone 600 mg With BIBF 1120 (After Breakfast) | Day 14 at Visit 5 (BIBF 1120 50mg and 100mg) and day 28 (visit 7) (BIBF 1120 150mg): At pre-dose and 0.5 h, 1 h, 2 h, 3 h after morning dose and pre-dose after lunch dose | AUC0-4,ss was calculated as the area under the concentration-time curve of the concentration-time profile of the analyte in plasma at steady state over the time interval from 0 to 4 hours after multiple doses of Pirfenidone 600 mg with BIBF 1120 (after breakfast) in the time frame mentioned. |
| Cmax,ss After Multiple Doses of Pirfenidone 600 mg With BIBF 1120 (After Breakfast) | Day 14 at Visit 5 (BIBF 1120 50mg and 100mg) and day 28 (visit 7) (BIBF 1120 150mg): At pre-dose and 0.5 h, 1 h, 2 h, 3 h after morning dose and pre-dose after lunch dose | Maximum measured concentration of the analyte in plasma at steady state was identified from measurements obtained at multiple time points after multiple doses of Pirfenidone 600 mg with BIBF 1120 (after breakfast) |
| AUC0-8,ss After Multiple Doses of Pirfenidone 600 mg Without BIBF 1120 (After Lunch) | Day -1 at Visit 1: at pre-dose and 0.5 h, 1 h, 2 h, 3 h, 4 h, 6 h, 8 h after lunch dose | AUC0-8,ss was calculated as the area under the concentration-time curve of the concentration-time profile of the analyte in plasma at steady state over the time interval from 0 to 8 hours after multiple doses of Pirfenidone 600 mg without BIBF 1120 (after lunch) in the time frame mentioned. |
| Cmax,ss After Multiple Doses of Pirfenidone 600 mg Without BIBF 1120 (After Lunch) | Day -1 at Visit 1: at pre-dose and 0.5 h, 1 h, 2 h, 3 h, 4 h, 6 h, 8 h after lunch dose | Maximum measured concentration of the analyte in plasma at steady state was identified from measurements obtained at multiple time points after multiple doses of Pirfenidone 600 mg Without BIBF 1120 (after lunch) |
| AUC0-8,ss After Multiple Doses of Pirfenidone 600 mg With BIBF 1120 (After Lunch) | Day 14 at Visit 5 (BIBF 1120 50mg and 100mg) and day 28 (visit 7) (BIBF 1120 150mg): at pre-dose and 0.5 h, 1 h, 2 h, 3 h, 4 h, 6 h, 8 h after lunch dose | AUC0-8,ss was calculated as the area under the concentration-time curve of the concentration-time profile of the analyte in plasma at steady state over the time interval from 0 to 8 hours after multiple doses of Pirfenidone 600 mg with BIBF 1120 (after lunch) in the time frame mentioned. |
| AUCτ,ss After Multiple Doses of BIBF 1120 Without Pirfenidone | pre-dose, then 0.5 h, 1 h, 2 h, 3 h, 3.92 h, 6 h, 8 h, 12 h, 24 h, 48 h, 72 h after morning dose on days 14 to 17 (BIBF 1120 50 mg and 100 mg) or on days 28 to 31 (BIBF 1120 150 mg) | AUCτ,ss was calculated as the area under the concentration-time curve of the concentration-time profile of the analyte in plasma at steady state over a uniform dosing interval τ after multiple doses of BIBF 1120 without pirfenidone in the time frame mentioned. Detailed outcome measure time frame: In 50 mg and 100 mg dose group: BIBF 1120: days 14 (-1, +3) to 17 at Visit 5: At pre-dose and 0.5 h, 1 h, 2 h, 3 h, 3.92 h, 6 h, 8 h, 12 h, 24 h, 48 h, 72 h after morning dose In 150 mg dose group: BIBF 1120: days 28 (-1, +3) to 31 at Visit 5: At pre-dose and 0.5 h, 1 h, 2 h, 3 h, 3.92 h, 6 h, 8 h, 12 h, 24 h, 48 h, 72 h after morning dose |
| Withdrawal Due to Adverse Event | after the first drug intake until 28 days from the last treatment administration, up to 60 days | Number of patients prematurely discontinued from trial medication due to adverse event. |
| Clinical Relevant Abnormalities in Laboratory Parameters- No Pirfenidone Background | after the first drug intake until 28 days from the last treatment administration, up to 60 days | Number of patients with Clinical Relevant Abnormalities in laboratory parameters reported as adverse events - No pirfenidone background |
| Clinical Relevant Abnormalities in Laboratory Parameters- With Pirfenidone Background | after the first drug intake until 28 days from the last treatment administration, up to 60 days | Number of patients with Clinical Relevant Abnormalities in laboratory parameters reported as adverse events - With pirfenidone background |
| Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | baseline and day 35 | Change from baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at day 35. Only the results for placebo and Nintedanib 150mg arm were reported for this endpoint as nintedanib 150mg is the target dose. |
| Change From Baseline in Pulse Rate | baseline and day 35 | Change from baseline in pulse rate at day 35. Only the results for placebo and Nintedanib 150mg arm were reported for this endpoint as nintedanib 150mg is the target dose. |
| Lung Function Measurement: Diffusing Capacity for Carbon Monoxide (DLco) | baseline and day 35 | Change in diffusing capacity for carbon monoxide (DLco) from baseline to day 35. Only the results for placebo and Nintedanib 150mg arm were reported for this endpoint as nintedanib 150mg is the target dose. |
| Lung Function Measurement: Diffusing Capacity for Carbon Monoxide Percent of Predicted (%DLco) | baseline and day 35 | Change in Diffusing Capacity for Carbon Monoxide percent of predicted (%DLco) from baseline to day 35. Only the results for placebo and Nintedanib 150mg arm were reported for this endpoint as nintedanib 150mg is the target dose. |
| Lung Function Measurement: Forced Expiratory Volume in 1 Second (FEV1) | baseline and day 35 | Change in forced expiratory volume in 1 second (FEV1) from baseline to day 35. Only the results for placebo and Nintedanib 150mg arm were reported for this endpoint as nintedanib 150mg is the target dose. |
| Lung Function Measurement: Forced Vital Capacity (FVC) | baseline and day 35 | Change in forced vital capacity (FVC) from baseline to day 35. Only the results for placebo and Nintedanib 150mg arm were reported for this endpoint as nintedanib 150mg is the target dose. |
| Lung Function Measurement: Forced Vital Capacity Percent of Predicted (%FVC) | baseline and day 35 | Change in Forced Vital Capacity percent of predicted (%FVC) from baseline to day 35. Only the results for placebo and Nintedanib 150mg arm were reported for this endpoint as nintedanib 150mg is the target dose. |
| Cmax,ss After Multiple Doses of Pirfenidone 600 mg With BIBF 1120 (After Lunch) | Day 14 at Visit 5 (BIBF 1120 50mg and 100mg) and day 28 (visit 7) (BIBF 1120 150mg): at pre-dose and 0.5 h, 1 h, 2 h, 3 h, 4 h, 6 h, 8 h after lunch dose | Maximum measured concentration of the analyte in plasma at steady state was identified from measurements obtained at multiple time points after multiple doses of Pirfenidone 600 mg with BIBF 1120 (after lunch) |
Countries
Japan
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo Placebo oral administration twice a day | 12 |
| BIBF 1120 50 mg BIBF 1120 50 mg oral administration twice a day | 6 |
| BIBF 1120 100 mg BIBF 1120 100 mg oral administration twice a day | 8 |
| BIBF 1120 150 mg BIBF 1120 150 mg oral administration twice a day | 24 |
| Total | 50 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 0 | 0 | 4 |
Baseline characteristics
| Characteristic | Placebo | BIBF 1120 50 mg | BIBF 1120 100 mg | BIBF 1120 150 mg | Total |
|---|---|---|---|---|---|
| Age, Continuous | 64.1 years STANDARD_DEVIATION 10.3 | 66.7 years STANDARD_DEVIATION 2.9 | 67.5 years STANDARD_DEVIATION 7.4 | 64.7 years STANDARD_DEVIATION 8.5 | 65.2 years STANDARD_DEVIATION 8.2 |
| Sex: Female, Male Female | 1 Participants | 2 Participants | 4 Participants | 8 Participants | 15 Participants |
| Sex: Female, Male Male | 11 Participants | 4 Participants | 4 Participants | 16 Participants | 35 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 4 / 12 | 0 / 6 | 4 / 8 | 14 / 24 |
| serious Total, serious adverse events | 0 / 12 | 0 / 6 | 0 / 8 | 1 / 24 |
Outcome results
Primary
Drug-related Adverse Events
The number of patients with drug-related adverse events stratified according to pirfenidone use in each group
Time frame: after the first drug intake until 28 days from the last treatment administration, up to 60 days
Population: Treated set
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Drug-related Adverse Events | Patients without Pirfenidone (N = 7, 2, 4, 11) | 1 participants |
| Placebo | Drug-related Adverse Events | Patients with Pirfenidone (N = 5, 4, 4, 13) | 1 participants |
| BIBF 1120 50 mg | Drug-related Adverse Events | Patients with Pirfenidone (N = 5, 4, 4, 13) | 0 participants |
| BIBF 1120 50 mg | Drug-related Adverse Events | Patients without Pirfenidone (N = 7, 2, 4, 11) | 0 participants |
| BIBF 1120 100 mg | Drug-related Adverse Events | Patients with Pirfenidone (N = 5, 4, 4, 13) | 0 participants |
| BIBF 1120 100 mg | Drug-related Adverse Events | Patients without Pirfenidone (N = 7, 2, 4, 11) | 1 participants |
| BIBF 1120 150 mg | Drug-related Adverse Events | Patients without Pirfenidone (N = 7, 2, 4, 11) | 3 participants |
| BIBF 1120 150 mg | Drug-related Adverse Events | Patients with Pirfenidone (N = 5, 4, 4, 13) | 7 participants |
Secondary
AUC0-4,ss After Multiple Doses of Pirfenidone 600 mg With BIBF 1120 (After Breakfast)
AUC0-4,ss was calculated as the area under the concentration-time curve of the concentration-time profile of the analyte in plasma at steady state over the time interval from 0 to 4 hours after multiple doses of Pirfenidone 600 mg with BIBF 1120 (after breakfast) in the time frame mentioned.
Time frame: Day 14 at Visit 5 (BIBF 1120 50mg and 100mg) and day 28 (visit 7) (BIBF 1120 150mg): At pre-dose and 0.5 h, 1 h, 2 h, 3 h after morning dose and pre-dose after lunch dose
Population: Treated set- Only patients with valid final pharmacokinetic values were analysed
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | AUC0-4,ss After Multiple Doses of Pirfenidone 600 mg With BIBF 1120 (After Breakfast) | 28800 ng*h/mL | Geometric Coefficient of Variation 6.85 |
| BIBF 1120 50 mg | AUC0-4,ss After Multiple Doses of Pirfenidone 600 mg With BIBF 1120 (After Breakfast) | 34300 ng*h/mL | Geometric Coefficient of Variation 39.9 |
| BIBF 1120 100 mg | AUC0-4,ss After Multiple Doses of Pirfenidone 600 mg With BIBF 1120 (After Breakfast) | 35000 ng*h/mL | Geometric Coefficient of Variation 32.2 |
| BIBF 1120 150 mg | AUC0-4,ss After Multiple Doses of Pirfenidone 600 mg With BIBF 1120 (After Breakfast) | 35900 ng*h/mL | Geometric Coefficient of Variation 21.8 |
Secondary
AUC0-4,ss After Multiple Doses of Pirfenidone 600 mg Without BIBF 1120 (After Breakfast)
AUC0-4,ss was calculated as the area under the curve of the concentration-time profile of the analyte in plasma at steady state over the time interval from 0 to 4 hours after multiple doses of Pirfenidone 600 mg without BIBF 1120 (after breakfast) in the time frame mentioned.
Time frame: Day -1 at Visit 1: At pre-dose and 0.5 h, 1 h, 2 h, 3 h after morning dose and pre-dose after lunch dose
Population: Treated set- Only patients with valid final pharmacokinetic values were analysed
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | AUC0-4,ss After Multiple Doses of Pirfenidone 600 mg Without BIBF 1120 (After Breakfast) | 28900 ng*h/mL | Geometric Coefficient of Variation 30.7 |
| BIBF 1120 50 mg | AUC0-4,ss After Multiple Doses of Pirfenidone 600 mg Without BIBF 1120 (After Breakfast) | 34400 ng*h/mL | Geometric Coefficient of Variation 36.3 |
| BIBF 1120 100 mg | AUC0-4,ss After Multiple Doses of Pirfenidone 600 mg Without BIBF 1120 (After Breakfast) | 45800 ng*h/mL | Geometric Coefficient of Variation 26.6 |
| BIBF 1120 150 mg | AUC0-4,ss After Multiple Doses of Pirfenidone 600 mg Without BIBF 1120 (After Breakfast) | 32500 ng*h/mL | Geometric Coefficient of Variation 21.2 |
Secondary
AUC0-8,ss After Multiple Doses of Pirfenidone 600 mg With BIBF 1120 (After Lunch)
AUC0-8,ss was calculated as the area under the concentration-time curve of the concentration-time profile of the analyte in plasma at steady state over the time interval from 0 to 8 hours after multiple doses of Pirfenidone 600 mg with BIBF 1120 (after lunch) in the time frame mentioned.
Time frame: Day 14 at Visit 5 (BIBF 1120 50mg and 100mg) and day 28 (visit 7) (BIBF 1120 150mg): at pre-dose and 0.5 h, 1 h, 2 h, 3 h, 4 h, 6 h, 8 h after lunch dose
Population: Treated set- Only patients with valid final pharmacokinetic values were analysed
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | AUC0-8,ss After Multiple Doses of Pirfenidone 600 mg With BIBF 1120 (After Lunch) | 47000 ng*h/mL | Geometric Coefficient of Variation 13.6 |
| BIBF 1120 50 mg | AUC0-8,ss After Multiple Doses of Pirfenidone 600 mg With BIBF 1120 (After Lunch) | 71000 ng*h/mL | Geometric Coefficient of Variation 40.8 |
| BIBF 1120 100 mg | AUC0-8,ss After Multiple Doses of Pirfenidone 600 mg With BIBF 1120 (After Lunch) | 71500 ng*h/mL | Geometric Coefficient of Variation 19.1 |
| BIBF 1120 150 mg | AUC0-8,ss After Multiple Doses of Pirfenidone 600 mg With BIBF 1120 (After Lunch) | 63600 ng*h/mL | Geometric Coefficient of Variation 27.7 |
Secondary
AUC0-8,ss After Multiple Doses of Pirfenidone 600 mg Without BIBF 1120 (After Lunch)
AUC0-8,ss was calculated as the area under the concentration-time curve of the concentration-time profile of the analyte in plasma at steady state over the time interval from 0 to 8 hours after multiple doses of Pirfenidone 600 mg without BIBF 1120 (after lunch) in the time frame mentioned.
Time frame: Day -1 at Visit 1: at pre-dose and 0.5 h, 1 h, 2 h, 3 h, 4 h, 6 h, 8 h after lunch dose
Population: Treated set- Only patients with valid final pharmacokinetic values were analysed
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | AUC0-8,ss After Multiple Doses of Pirfenidone 600 mg Without BIBF 1120 (After Lunch) | 56600 ng*h/mL | Geometric Coefficient of Variation 25.8 |
| BIBF 1120 50 mg | AUC0-8,ss After Multiple Doses of Pirfenidone 600 mg Without BIBF 1120 (After Lunch) | 72800 ng*h/mL | Geometric Coefficient of Variation 40.7 |
| BIBF 1120 100 mg | AUC0-8,ss After Multiple Doses of Pirfenidone 600 mg Without BIBF 1120 (After Lunch) | 84100 ng*h/mL | Geometric Coefficient of Variation 11.4 |
| BIBF 1120 150 mg | AUC0-8,ss After Multiple Doses of Pirfenidone 600 mg Without BIBF 1120 (After Lunch) | 60900 ng*h/mL | Geometric Coefficient of Variation 22.9 |
Secondary
AUCτ,ss After Multiple Doses of BIBF 1120 Without Pirfenidone
AUCτ,ss was calculated as the area under the concentration-time curve of the concentration-time profile of the analyte in plasma at steady state over a uniform dosing interval τ after multiple doses of BIBF 1120 without pirfenidone in the time frame mentioned. Detailed outcome measure time frame: In 50 mg and 100 mg dose group: BIBF 1120: days 14 (-1, +3) to 17 at Visit 5: At pre-dose and 0.5 h, 1 h, 2 h, 3 h, 3.92 h, 6 h, 8 h, 12 h, 24 h, 48 h, 72 h after morning dose In 150 mg dose group: BIBF 1120: days 28 (-1, +3) to 31 at Visit 5: At pre-dose and 0.5 h, 1 h, 2 h, 3 h, 3.92 h, 6 h, 8 h, 12 h, 24 h, 48 h, 72 h after morning dose
Time frame: pre-dose, then 0.5 h, 1 h, 2 h, 3 h, 3.92 h, 6 h, 8 h, 12 h, 24 h, 48 h, 72 h after morning dose on days 14 to 17 (BIBF 1120 50 mg and 100 mg) or on days 28 to 31 (BIBF 1120 150 mg)
Population: Treated set
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | AUCτ,ss After Multiple Doses of BIBF 1120 Without Pirfenidone | 33.7 ng*h/mL | Geometric Coefficient of Variation 165 |
| BIBF 1120 50 mg | AUCτ,ss After Multiple Doses of BIBF 1120 Without Pirfenidone | 115 ng*h/mL | Geometric Coefficient of Variation 32.4 |
| BIBF 1120 100 mg | AUCτ,ss After Multiple Doses of BIBF 1120 Without Pirfenidone | 218 ng*h/mL | Geometric Coefficient of Variation 58.3 |
Secondary
AUCτ,ss After Multiple Doses of BIBF 1120 With Pirfenidone
AUCτ,ss was calculated as the area under the concentration-time curve of the concentration-time profile of the analyte in plasma at steady state over a uniform dosing interval τ after multiple doses of BIBF 1120 with pirfenidone in the time frame mentioned. Detailed outcome measure time frame: In 50 mg and 100 mg dose group: BIBF 1120: days 14 (-1, +3) to 17 at Visit 5: At pre-dose and 0.5 h, 1 h, 2 h, 3 h, 3.92 h, 6 h, 8 h, 12 h, 24 h, 48 h, 72 h after morning dose In 150 mg dose group: BIBF 1120: days 28 (-1, +3) to 31 at Visit 5: At pre-dose and 0.5 h, 1 h, 2 h, 3 h, 3.92 h, 6 h, 8 h, 12 h, 24 h, 48 h, 72 h after morning dose
Time frame: pre-dose, then 0.5 h, 1 h, 2 h, 3 h, 3.92 h, 6 h, 8 h, 12 h, 24 h, 48 h, 72 h after morning dose on days 14 to 17 (BIBF 1120 50 mg and 100 mg) or on days 28 to 31 (BIBF 1120 150 mg)
Population: Treated set- Only patients with valid final pharmacokinetic values were analysed
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | AUCτ,ss After Multiple Doses of BIBF 1120 With Pirfenidone | 67.9 ng*h/mL | Geometric Coefficient of Variation 16.7 |
| BIBF 1120 50 mg | AUCτ,ss After Multiple Doses of BIBF 1120 With Pirfenidone | 86.0 ng*h/mL | Geometric Coefficient of Variation 62.7 |
| BIBF 1120 100 mg | AUCτ,ss After Multiple Doses of BIBF 1120 With Pirfenidone | 149 ng*h/mL | Geometric Coefficient of Variation 18 |
Secondary
Change From Baseline in Pulse Rate
Change from baseline in pulse rate at day 35. Only the results for placebo and Nintedanib 150mg arm were reported for this endpoint as nintedanib 150mg is the target dose.
Time frame: baseline and day 35
Population: Treated set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Pulse Rate | -2.5 bpm | Standard Deviation 15.4 |
| BIBF 1120 50 mg | Change From Baseline in Pulse Rate | 1.9 bpm | Standard Deviation 13.6 |
Secondary
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)
Change from baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at day 35. Only the results for placebo and Nintedanib 150mg arm were reported for this endpoint as nintedanib 150mg is the target dose.
Time frame: baseline and day 35
Population: Treated set
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP | 0.5 mmHg | Standard Deviation 13.3 |
| Placebo | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP | 1.3 mmHg | Standard Deviation 19.2 |
| BIBF 1120 50 mg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP | -0.8 mmHg | Standard Deviation 10.8 |
| BIBF 1120 50 mg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP | 2.5 mmHg | Standard Deviation 14.4 |
Secondary
Clinical Relevant Abnormalities in Laboratory Parameters- No Pirfenidone Background
Number of patients with Clinical Relevant Abnormalities in laboratory parameters reported as adverse events - No pirfenidone background
Time frame: after the first drug intake until 28 days from the last treatment administration, up to 60 days
Population: Treated set
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Clinical Relevant Abnormalities in Laboratory Parameters- No Pirfenidone Background | Alanine aminotransferase increased | 0 participants |
| Placebo | Clinical Relevant Abnormalities in Laboratory Parameters- No Pirfenidone Background | Aspartate aminotransferase increased | 0 participants |
| Placebo | Clinical Relevant Abnormalities in Laboratory Parameters- No Pirfenidone Background | Blood creatine phosphokinase increased | 0 participants |
| Placebo | Clinical Relevant Abnormalities in Laboratory Parameters- No Pirfenidone Background | Gamma-glutamyltransferase increased | 0 participants |
| BIBF 1120 50 mg | Clinical Relevant Abnormalities in Laboratory Parameters- No Pirfenidone Background | Aspartate aminotransferase increased | 0 participants |
| BIBF 1120 50 mg | Clinical Relevant Abnormalities in Laboratory Parameters- No Pirfenidone Background | Blood creatine phosphokinase increased | 0 participants |
| BIBF 1120 50 mg | Clinical Relevant Abnormalities in Laboratory Parameters- No Pirfenidone Background | Gamma-glutamyltransferase increased | 0 participants |
| BIBF 1120 50 mg | Clinical Relevant Abnormalities in Laboratory Parameters- No Pirfenidone Background | Alanine aminotransferase increased | 0 participants |
| BIBF 1120 100 mg | Clinical Relevant Abnormalities in Laboratory Parameters- No Pirfenidone Background | Blood creatine phosphokinase increased | 0 participants |
| BIBF 1120 100 mg | Clinical Relevant Abnormalities in Laboratory Parameters- No Pirfenidone Background | Aspartate aminotransferase increased | 0 participants |
| BIBF 1120 100 mg | Clinical Relevant Abnormalities in Laboratory Parameters- No Pirfenidone Background | Gamma-glutamyltransferase increased | 0 participants |
| BIBF 1120 100 mg | Clinical Relevant Abnormalities in Laboratory Parameters- No Pirfenidone Background | Alanine aminotransferase increased | 0 participants |
| BIBF 1120 150 mg | Clinical Relevant Abnormalities in Laboratory Parameters- No Pirfenidone Background | Gamma-glutamyltransferase increased | 1 participants |
| BIBF 1120 150 mg | Clinical Relevant Abnormalities in Laboratory Parameters- No Pirfenidone Background | Aspartate aminotransferase increased | 2 participants |
| BIBF 1120 150 mg | Clinical Relevant Abnormalities in Laboratory Parameters- No Pirfenidone Background | Alanine aminotransferase increased | 2 participants |
| BIBF 1120 150 mg | Clinical Relevant Abnormalities in Laboratory Parameters- No Pirfenidone Background | Blood creatine phosphokinase increased | 1 participants |
Secondary
Clinical Relevant Abnormalities in Laboratory Parameters- With Pirfenidone Background
Number of patients with Clinical Relevant Abnormalities in laboratory parameters reported as adverse events - With pirfenidone background
Time frame: after the first drug intake until 28 days from the last treatment administration, up to 60 days
Population: Treated set
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Clinical Relevant Abnormalities in Laboratory Parameters- With Pirfenidone Background | Hypothyroidism | 0 participants |
| Placebo | Clinical Relevant Abnormalities in Laboratory Parameters- With Pirfenidone Background | Transaminases increased | 0 participants |
| BIBF 1120 50 mg | Clinical Relevant Abnormalities in Laboratory Parameters- With Pirfenidone Background | Transaminases increased | 0 participants |
| BIBF 1120 50 mg | Clinical Relevant Abnormalities in Laboratory Parameters- With Pirfenidone Background | Hypothyroidism | 0 participants |
| BIBF 1120 100 mg | Clinical Relevant Abnormalities in Laboratory Parameters- With Pirfenidone Background | Hypothyroidism | 0 participants |
| BIBF 1120 100 mg | Clinical Relevant Abnormalities in Laboratory Parameters- With Pirfenidone Background | Transaminases increased | 0 participants |
| BIBF 1120 150 mg | Clinical Relevant Abnormalities in Laboratory Parameters- With Pirfenidone Background | Hypothyroidism | 1 participants |
| BIBF 1120 150 mg | Clinical Relevant Abnormalities in Laboratory Parameters- With Pirfenidone Background | Transaminases increased | 1 participants |
Secondary
Cmax,ss After Multiple Doses of BIBF 1120 Without Pirfenidone
Maximum measured concentration of the analyte in plasma at steady state was identified from measurements obtained at multiple time points over a uniform dosing interval τ after multiple doses of BIBF 1120 without pirfenidone. Detailed outcome measure time frame: In 50 mg and 100 mg dose group: BIBF 1120: days 14 (-1, +3) to 17 at Visit 5: At pre-dose and 0.5 h, 1 h, 2 h, 3 h, 3.92 h, 6 h, 8 h, 12 h, 24 h, 48 h, 72 h after morning dose In 150 mg dose group: BIBF 1120: days 28 (-1, +3) to 31 at Visit 5: At pre-dose and 0.5 h, 1 h, 2 h, 3 h, 3.92 h, 6 h, 8 h, 12 h, 24 h, 48 h, 72 h after morning dose
Time frame: pre-dose, then 0.5 h, 1 h, 2 h, 3 h, 3.92 h, 6 h, 8 h, 12 h, 24 h, 48 h, 72 h after morning dose on days 14 to 17 (BIBF 1120 50 mg and 100 mg) or on days 28 to 31 (BIBF 1120 150 mg)
Population: Treated set- Only patients with valid final pharmacokinetic values were analysed
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Cmax,ss After Multiple Doses of BIBF 1120 Without Pirfenidone | 9.09 ng/mL | Geometric Coefficient of Variation 173 |
| BIBF 1120 50 mg | Cmax,ss After Multiple Doses of BIBF 1120 Without Pirfenidone | 20.0 ng/mL | Geometric Coefficient of Variation 64.5 |
| BIBF 1120 100 mg | Cmax,ss After Multiple Doses of BIBF 1120 Without Pirfenidone | 39.7 ng/mL | Geometric Coefficient of Variation 68.1 |
Secondary
Cmax,ss After Multiple Doses of BIBF 1120 With Pirfenidone
Maximum measured concentration of the analyte in plasma at steady state was identified from measurements obtained at multiple time points over a uniform dosing interval τ after multiple doses of BIBF 1120 with pirfenidone Detailed outcome measure time frame: In 50 mg and 100 mg dose group: BIBF 1120: days 14 (-1, +3) to 17 at Visit 5: At pre-dose and 0.5 h, 1 h, 2 h, 3 h, 3.92 h, 6 h, 8 h, 12 h, 24 h, 48 h, 72 h after morning dose In 150 mg dose group: BIBF 1120: days 28 (-1, +3) to 31 at Visit 5: At pre-dose and 0.5 h, 1 h, 2 h, 3 h, 3.92 h, 6 h, 8 h, 12 h, 24 h, 48 h, 72 h after morning dose
Time frame: pre-dose, then 0.5 h, 1 h, 2 h, 3 h, 3.92 h, 6 h, 8 h, 12 h, 24 h, 48 h, 72 h after morning dose on days 14 to 17 (BIBF 1120 50 mg and 100 mg) or on days 28 to 31 (BIBF 1120 150 mg)
Population: Treated set- Only patients with valid final pharmacokinetic values were analysed
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Cmax,ss After Multiple Doses of BIBF 1120 With Pirfenidone | 10.9 ng/mL | Geometric Coefficient of Variation 50.3 |
| BIBF 1120 50 mg | Cmax,ss After Multiple Doses of BIBF 1120 With Pirfenidone | 13.8 ng/mL | Geometric Coefficient of Variation 113 |
| BIBF 1120 100 mg | Cmax,ss After Multiple Doses of BIBF 1120 With Pirfenidone | 23.5 ng/mL | Geometric Coefficient of Variation 27.2 |
Secondary
Cmax,ss After Multiple Doses of Pirfenidone 600 mg With BIBF 1120 (After Breakfast)
Maximum measured concentration of the analyte in plasma at steady state was identified from measurements obtained at multiple time points after multiple doses of Pirfenidone 600 mg with BIBF 1120 (after breakfast)
Time frame: Day 14 at Visit 5 (BIBF 1120 50mg and 100mg) and day 28 (visit 7) (BIBF 1120 150mg): At pre-dose and 0.5 h, 1 h, 2 h, 3 h after morning dose and pre-dose after lunch dose
Population: Treated set- Only patients with valid final pharmacokinetic values were analysed
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Cmax,ss After Multiple Doses of Pirfenidone 600 mg With BIBF 1120 (After Breakfast) | 12000 ng/mL | Geometric Coefficient of Variation 23.1 |
| BIBF 1120 50 mg | Cmax,ss After Multiple Doses of Pirfenidone 600 mg With BIBF 1120 (After Breakfast) | 12800 ng/mL | Geometric Coefficient of Variation 44.3 |
| BIBF 1120 100 mg | Cmax,ss After Multiple Doses of Pirfenidone 600 mg With BIBF 1120 (After Breakfast) | 15300 ng/mL | Geometric Coefficient of Variation 51.1 |
| BIBF 1120 150 mg | Cmax,ss After Multiple Doses of Pirfenidone 600 mg With BIBF 1120 (After Breakfast) | 12600 ng/mL | Geometric Coefficient of Variation 27.2 |
Secondary
Cmax,ss After Multiple Doses of Pirfenidone 600 mg With BIBF 1120 (After Lunch)
Maximum measured concentration of the analyte in plasma at steady state was identified from measurements obtained at multiple time points after multiple doses of Pirfenidone 600 mg with BIBF 1120 (after lunch)
Time frame: Day 14 at Visit 5 (BIBF 1120 50mg and 100mg) and day 28 (visit 7) (BIBF 1120 150mg): at pre-dose and 0.5 h, 1 h, 2 h, 3 h, 4 h, 6 h, 8 h after lunch dose
Population: Treated set- Only patients with valid final pharmacokinetic values were analysed
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Cmax,ss After Multiple Doses of Pirfenidone 600 mg With BIBF 1120 (After Lunch) | 10700 ng/mL | Geometric Coefficient of Variation 18.8 |
| BIBF 1120 50 mg | Cmax,ss After Multiple Doses of Pirfenidone 600 mg With BIBF 1120 (After Lunch) | 12000 ng/mL | Geometric Coefficient of Variation 37.3 |
| BIBF 1120 100 mg | Cmax,ss After Multiple Doses of Pirfenidone 600 mg With BIBF 1120 (After Lunch) | 12100 ng/mL | Geometric Coefficient of Variation 10.7 |
| BIBF 1120 150 mg | Cmax,ss After Multiple Doses of Pirfenidone 600 mg With BIBF 1120 (After Lunch) | 12500 ng/mL | Geometric Coefficient of Variation 23 |
Secondary
Cmax,ss After Multiple Doses of Pirfenidone 600 mg Without BIBF 1120 (After Breakfast)
Maximum measured concentration of the analyte in plasma at steady state was identified from measurements obtained at multiple time points after multiple doses of Pirfenidone 600 mg without BIBF 1120 (after breakfast)
Time frame: Day -1 at Visit 1: At pre-dose and 0.5 h, 1 h, 2 h, 3 h after morning dose and pre-dose after lunch dose
Population: Treated set-Only patients with valid final pharmacokinetic values were analysed
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Cmax,ss After Multiple Doses of Pirfenidone 600 mg Without BIBF 1120 (After Breakfast) | 11300 ng/mL | Geometric Coefficient of Variation 22.1 |
| BIBF 1120 50 mg | Cmax,ss After Multiple Doses of Pirfenidone 600 mg Without BIBF 1120 (After Breakfast) | 11900 ng/mL | Geometric Coefficient of Variation 28.9 |
| BIBF 1120 100 mg | Cmax,ss After Multiple Doses of Pirfenidone 600 mg Without BIBF 1120 (After Breakfast) | 14600 ng/mL | Geometric Coefficient of Variation 41.5 |
| BIBF 1120 150 mg | Cmax,ss After Multiple Doses of Pirfenidone 600 mg Without BIBF 1120 (After Breakfast) | 11200 ng/mL | Geometric Coefficient of Variation 26.6 |
Secondary
Cmax,ss After Multiple Doses of Pirfenidone 600 mg Without BIBF 1120 (After Lunch)
Maximum measured concentration of the analyte in plasma at steady state was identified from measurements obtained at multiple time points after multiple doses of Pirfenidone 600 mg Without BIBF 1120 (after lunch)
Time frame: Day -1 at Visit 1: at pre-dose and 0.5 h, 1 h, 2 h, 3 h, 4 h, 6 h, 8 h after lunch dose
Population: Treated set- Only patients with valid final pharmacokinetic values were analysed
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Cmax,ss After Multiple Doses of Pirfenidone 600 mg Without BIBF 1120 (After Lunch) | 13500 ng/mL | Geometric Coefficient of Variation 19.9 |
| BIBF 1120 50 mg | Cmax,ss After Multiple Doses of Pirfenidone 600 mg Without BIBF 1120 (After Lunch) | 14600 ng/mL | Geometric Coefficient of Variation 20.9 |
| BIBF 1120 100 mg | Cmax,ss After Multiple Doses of Pirfenidone 600 mg Without BIBF 1120 (After Lunch) | 15100 ng/mL | Geometric Coefficient of Variation 19.5 |
| BIBF 1120 150 mg | Cmax,ss After Multiple Doses of Pirfenidone 600 mg Without BIBF 1120 (After Lunch) | 12900 ng/mL | Geometric Coefficient of Variation 30.2 |
Secondary
Lung Function Measurement: Diffusing Capacity for Carbon Monoxide (DLco)
Change in diffusing capacity for carbon monoxide (DLco) from baseline to day 35. Only the results for placebo and Nintedanib 150mg arm were reported for this endpoint as nintedanib 150mg is the target dose.
Time frame: baseline and day 35
Population: Treated set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Lung Function Measurement: Diffusing Capacity for Carbon Monoxide (DLco) | -1.131 mL/min/mmHg | Standard Deviation 1.397 |
| BIBF 1120 50 mg | Lung Function Measurement: Diffusing Capacity for Carbon Monoxide (DLco) | -0.707 mL/min/mmHg | Standard Deviation 2.005 |
Secondary
Lung Function Measurement: Diffusing Capacity for Carbon Monoxide Percent of Predicted (%DLco)
Change in Diffusing Capacity for Carbon Monoxide percent of predicted (%DLco) from baseline to day 35. Only the results for placebo and Nintedanib 150mg arm were reported for this endpoint as nintedanib 150mg is the target dose.
Time frame: baseline and day 35
Population: Treated set- Only patients with valid measurements were analysed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Lung Function Measurement: Diffusing Capacity for Carbon Monoxide Percent of Predicted (%DLco) | -4.660 % predicted | Standard Deviation 8.02 |
| BIBF 1120 50 mg | Lung Function Measurement: Diffusing Capacity for Carbon Monoxide Percent of Predicted (%DLco) | -1.193 % predicted | Standard Deviation 5.948 |
Secondary
Lung Function Measurement: Forced Expiratory Volume in 1 Second (FEV1)
Change in forced expiratory volume in 1 second (FEV1) from baseline to day 35. Only the results for placebo and Nintedanib 150mg arm were reported for this endpoint as nintedanib 150mg is the target dose.
Time frame: baseline and day 35
Population: Treated set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Lung Function Measurement: Forced Expiratory Volume in 1 Second (FEV1) | -0.021 Liter | Standard Deviation 0.107 |
| BIBF 1120 50 mg | Lung Function Measurement: Forced Expiratory Volume in 1 Second (FEV1) | 0.036 Liter | Standard Deviation 0.078 |
Secondary
Lung Function Measurement: Forced Vital Capacity (FVC)
Change in forced vital capacity (FVC) from baseline to day 35. Only the results for placebo and Nintedanib 150mg arm were reported for this endpoint as nintedanib 150mg is the target dose.
Time frame: baseline and day 35
Population: Treated set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Lung Function Measurement: Forced Vital Capacity (FVC) | -0.081 Liter | Standard Deviation 0.175 |
| BIBF 1120 50 mg | Lung Function Measurement: Forced Vital Capacity (FVC) | 0.050 Liter | Standard Deviation 0.086 |
Secondary
Lung Function Measurement: Forced Vital Capacity Percent of Predicted (%FVC)
Change in Forced Vital Capacity percent of predicted (%FVC) from baseline to day 35. Only the results for placebo and Nintedanib 150mg arm were reported for this endpoint as nintedanib 150mg is the target dose.
Time frame: baseline and day 35
Population: Treated set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Lung Function Measurement: Forced Vital Capacity Percent of Predicted (%FVC) | -2.311 % predicted | Standard Deviation 5.193 |
| BIBF 1120 50 mg | Lung Function Measurement: Forced Vital Capacity Percent of Predicted (%FVC) | 1.432 % predicted | Standard Deviation 2.671 |
Secondary
Withdrawal Due to Adverse Event
Number of patients prematurely discontinued from trial medication due to adverse event.
Time frame: after the first drug intake until 28 days from the last treatment administration, up to 60 days
Population: Treated set
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Withdrawal Due to Adverse Event | With Pirfenidone (N= 5, 4, 4, 13) | 0 participants |
| Placebo | Withdrawal Due to Adverse Event | Without Pirfenidone (N = 7, 2, 4, 11) | 0 participants |
| BIBF 1120 50 mg | Withdrawal Due to Adverse Event | Without Pirfenidone (N = 7, 2, 4, 11) | 0 participants |
| BIBF 1120 50 mg | Withdrawal Due to Adverse Event | With Pirfenidone (N= 5, 4, 4, 13) | 0 participants |
| BIBF 1120 100 mg | Withdrawal Due to Adverse Event | With Pirfenidone (N= 5, 4, 4, 13) | 0 participants |
| BIBF 1120 100 mg | Withdrawal Due to Adverse Event | Without Pirfenidone (N = 7, 2, 4, 11) | 0 participants |
| BIBF 1120 150 mg | Withdrawal Due to Adverse Event | With Pirfenidone (N= 5, 4, 4, 13) | 2 participants |
| BIBF 1120 150 mg | Withdrawal Due to Adverse Event | Without Pirfenidone (N = 7, 2, 4, 11) | 2 participants |