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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| BIBF 1120 50 mg | Experimental | Low dose for cohort 1 |
|
| BIBF 1120 100 mg | Experimental | Middle dose for cohort 2 |
|
| BIBF 1120 150 mg | Experimental | High dose for cohort 3 |
|
| Placebo | Placebo Comparator | Placebo for cohort 1,2,3 |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Placebo | Drug | Placebo BID for cohort 1,2,3 |
| |
| BIBF 1120 |
| Measure | Description | Time Frame |
|---|---|---|
| Drug-related Adverse Events | The number of patients with drug-related adverse events stratified according to pirfenidone use in each group | after the first drug intake until 28 days from the last treatment administration, up to 60 days |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
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Inclusion criteria:
Exclusion criteria:
Aspartate aminotransferase (AST), alanine aminotransferase (ALT) > 1.5 x upper limit of normal range (ULN) at screening.
Bilirubin > 1.5 x ULN at screening.
Relevant airways obstruction (i.e. pre-bronchodilator FEV1/FVC <0.7) at screening.
Continuous oxygen supplementation.
Active infection at screening or randomisation.
Being treated with any of the following concomitant medications.
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
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| Name | Affiliation | Role |
|---|---|---|
| Boehringer Ingelheim | Boehringer Ingelheim | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| 1199.31.002 Boehringer Ingelheim Investigational Site | Bunkyo-ku,Tokyo | Japan | ||||
| 1199.31.004 Boehringer Ingelheim Investigational Site |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 25504994 | Derived | Ogura T, Taniguchi H, Azuma A, Inoue Y, Kondoh Y, Hasegawa Y, Bando M, Abe S, Mochizuki Y, Chida K, Kluglich M, Fujimoto T, Okazaki K, Tadayasu Y, Sakamoto W, Sugiyama Y. Safety and pharmacokinetics of nintedanib and pirfenidone in idiopathic pulmonary fibrosis. Eur Respir J. 2015 May;45(5):1382-92. doi: 10.1183/09031936.00198013. Epub 2014 Dec 10. |
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| ID | Title | Description |
|---|---|---|
| FG000 | Placebo | Placebo oral administration twice a day |
| FG001 | BIBF 1120 50 mg | BIBF 1120 50 mg oral administration twice a day |
| FG002 | BIBF 1120 100 mg | BIBF 1120 100 mg oral administration twice a day |
| FG003 | BIBF 1120 150 mg | BIBF 1120 150 mg oral administration twice a day |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
Treated set: all patients who received study medication and were documented to have taken at least one dose of investigational treatment
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| ID | Title | Description |
|---|---|---|
| BG000 | Placebo | Placebo oral administration twice a day |
| BG001 | BIBF 1120 50 mg | BIBF 1120 50 mg oral administration twice a day |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Drug-related Adverse Events | The number of patients with drug-related adverse events stratified according to pirfenidone use in each group | Treated set | Posted | Number | participants | after the first drug intake until 28 days from the last treatment administration, up to 60 days |
|
after the first drug intake until 28 days from the last treatment administration, up to 60 days
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Placebo | Placebo oral administration twice a day for cohort 1, 2, 3 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Hepatic neoplasm malignant | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MEDDRA 13.1 | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Abdominal discomfort | Gastrointestinal disorders | MEDDRA 13.1 | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Boehringer Ingelheim Call Center | Boehringer Ingelheim Pharmaceuticals | 1-800-243-0127 | clintriage.rdg@boehringer-ingelheim.com |
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| ID | Term |
|---|---|
| D054990 | Idiopathic Pulmonary Fibrosis |
| ID | Term |
|---|---|
| D011658 | Pulmonary Fibrosis |
| D017563 | Lung Diseases, Interstitial |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
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| ID | Term |
|---|---|
| C530716 | nintedanib |
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| Drug |
50 mg, 100 mg, 150 mg BID will be used for Cohort 1, 2, and 3 respectively |
|
| BIBF 1120 | Drug | 50 mg, 100 mg, 150 mg BID will be used for Cohort 1, 2, and 3 respectively |
|
| BIBF 1120 | Drug | 50 mg, 100 mg, 150 mg BID will be used for Cohort 1, 2, and 3 respectively |
|
| 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) |
| 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 | 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 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 | 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) |
| 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 | 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) |
| 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. | 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 |
| 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) | 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 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. | 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 |
| 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) | 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 |
| AUC0-8,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. | 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 |
| 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) | 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 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. | 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 |
| 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) | 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 |
| Withdrawal Due to Adverse Event | Number of patients prematurely discontinued from trial medication due to adverse event. | after the first drug intake until 28 days from the last treatment administration, up to 60 days |
| 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 | after the first drug intake until 28 days from the last treatment administration, up to 60 days |
| 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 | after the first drug intake until 28 days from the last treatment administration, up to 60 days |
| 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. | baseline and day 35 |
| 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. | baseline and day 35 |
| 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. | baseline and day 35 |
| 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. | baseline and day 35 |
| 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. | baseline and day 35 |
| 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. | baseline and day 35 |
| 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. | baseline and day 35 |
| Hamamatsu, Shizuoka |
| Japan |
| 1199.31.008 Boehringer Ingelheim Investigational Site | Himeji, Hyogo | Japan |
| 1199.31.006 Boehringer Ingelheim Investigational Site | Nagoya, Aichi | Japan |
| 1199.31.007 Boehringer Ingelheim Investigational Site | Sakai, Osaka | Japan |
| 1199.31.005 Boehringer Ingelheim Investigational Site | Seto, Aichi | Japan |
| 1199.31.001 Boehringer Ingelheim Investigational Site | Shimotsuke,Tochigi | Japan |
| 1199.31.003 Boehringer Ingelheim Investigational Site | Yokohama, Kanagawa | Japan |
| BG002 | BIBF 1120 100 mg | BIBF 1120 100 mg oral administration twice a day |
| BG003 | BIBF 1120 150 mg | BIBF 1120 150 mg oral administration twice a day |
| BG004 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
BIBF 1120 100 mg oral administration twice a day |
| OG003 | BIBF 1120 150 mg | BIBF 1120 150 mg oral administration twice a day |
|
|
| 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 | Treated set | Posted | Geometric Mean | Geometric Coefficient of Variation | ng*h/mL | 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) |
|
|
|
| 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 | Treated set- Only patients with valid final pharmacokinetic values were analysed | Posted | Geometric Mean | Geometric Coefficient of Variation | ng/mL | 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) |
|
|
|
| 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 | Treated set- Only patients with valid final pharmacokinetic values were analysed | Posted | Geometric Mean | Geometric Coefficient of Variation | ng*h/mL | 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) |
|
|
|
| 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 | Treated set- Only patients with valid final pharmacokinetic values were analysed | Posted | Geometric Mean | Geometric Coefficient of Variation | ng/mL | 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) |
|
|
|
| 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. | Treated set- Only patients with valid final pharmacokinetic values were analysed | Posted | Geometric Mean | Geometric Coefficient of Variation | ng*h/mL | 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 |
|
|
|
| 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) | Treated set-Only patients with valid final pharmacokinetic values were analysed | Posted | Geometric Mean | Geometric Coefficient of Variation | ng/mL | 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 |
|
|
|
| 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. | Treated set- Only patients with valid final pharmacokinetic values were analysed | Posted | Geometric Mean | Geometric Coefficient of Variation | ng*h/mL | 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 |
|
|
|
| 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) | Treated set- Only patients with valid final pharmacokinetic values were analysed | Posted | Geometric Mean | Geometric Coefficient of Variation | ng/mL | 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 |
|
|
|
| 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. | Treated set- Only patients with valid final pharmacokinetic values were analysed | Posted | Geometric Mean | Geometric Coefficient of Variation | ng*h/mL | 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 |
|
|
|
| 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) | Treated set- Only patients with valid final pharmacokinetic values were analysed | Posted | Geometric Mean | Geometric Coefficient of Variation | ng/mL | 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 |
|
|
|
| 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. | Treated set- Only patients with valid final pharmacokinetic values were analysed | Posted | Geometric Mean | Geometric Coefficient of Variation | ng*h/mL | 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 |
|
|
|
| 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) | Treated set- Only patients with valid final pharmacokinetic values were analysed | Posted | Geometric Mean | Geometric Coefficient of Variation | ng/mL | 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 |
|
|
|
| Secondary | Withdrawal Due to Adverse Event | Number of patients prematurely discontinued from trial medication due to adverse event. | Treated set | Posted | Number | participants | after the first drug intake until 28 days from the last treatment administration, up to 60 days |
|
|
|
| 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 | Treated set | Posted | Number | participants | after the first drug intake until 28 days from the last treatment administration, up to 60 days |
|
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| 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 | Treated set | Posted | Number | participants | after the first drug intake until 28 days from the last treatment administration, up to 60 days |
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| 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. | Treated set | Posted | Mean | Standard Deviation | mmHg | baseline and day 35 |
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| 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. | Treated set | Posted | Mean | Standard Deviation | bpm | baseline and day 35 |
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| 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. | Treated set | Posted | Mean | Standard Deviation | mL/min/mmHg | baseline and day 35 |
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| 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. | Treated set- Only patients with valid measurements were analysed. | Posted | Mean | Standard Deviation | % predicted | baseline and day 35 |
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| 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. | Treated set | Posted | Mean | Standard Deviation | Liter | baseline and day 35 |
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| 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. | Treated set | Posted | Mean | Standard Deviation | Liter | baseline and day 35 |
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| 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. | Treated set | Posted | Mean | Standard Deviation | % predicted | baseline and day 35 |
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| 0 |
| 12 |
| 4 |
| 12 |
| EG001 | BIBF 1120 50 mg | BIBF 1120 50 mg oral administration twice a day for cohort 1 | 0 | 6 | 0 | 6 |
| EG002 | BIBF 1120 100 mg | BIBF 1120 100 mg oral administration twice a day for cohort 2 | 0 | 8 | 4 | 8 |
| EG003 | BIBF 1120 150 mg | BIBF 1120 150 mg oral administration twice a day for cohort 3 | 1 | 24 | 14 | 24 |
| Abdominal pain upper | Gastrointestinal disorders | MEDDRA 13.1 | Systematic Assessment |
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| Diarrhoea | Gastrointestinal disorders | MEDDRA 13.1 | Systematic Assessment |
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| Gastritis erosive | Gastrointestinal disorders | MEDDRA 13.1 | Systematic Assessment |
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| Nausea | Gastrointestinal disorders | MEDDRA 13.1 | Systematic Assessment |
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| Periproctitis | Gastrointestinal disorders | MEDDRA 13.1 | Systematic Assessment |
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| Stomatitis | Gastrointestinal disorders | MEDDRA 13.1 | Systematic Assessment |
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| Vomiting | Gastrointestinal disorders | MEDDRA 13.1 | Systematic Assessment |
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| Bronchitis | Infections and infestations | MEDDRA 13.1 | Systematic Assessment |
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| Gastroenteritis | Infections and infestations | MEDDRA 13.1 | Systematic Assessment |
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| Nasopharyngitis | Infections and infestations | MEDDRA 13.1 | Systematic Assessment |
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| Alanine aminotransferase increased | Investigations | MEDDRA 13.1 | Systematic Assessment |
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| Aspartate aminotransferase increased | Investigations | MEDDRA 13.1 | Systematic Assessment |
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| Dysgeusia | Nervous system disorders | MEDDRA 13.1 | Systematic Assessment |
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| Dysphonia | Respiratory, thoracic and mediastinal disorders | MEDDRA 13.1 | Systematic Assessment |
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| Erythema | Skin and subcutaneous tissue disorders | MEDDRA 13.1 | Systematic Assessment |
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| Photosensitivity reaction | Skin and subcutaneous tissue disorders | MEDDRA 13.1 | Systematic Assessment |
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Boehringer Ingelheim (BI) acknowledges that investigators have the right to publish the study results. Investigators shall provide BI with a copy of any publication or presentation for review prior to any submission. Such review will be done with regard to proprietary information, information related to patentable inventions, medical, scientific, and statistical accuracy within 60 days. BI may request a delay of the publication in order to protect BI's intellectual property rights.
| Without Pirfenidone (N = 7, 2, 4, 11) |
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| Aspartate aminotransferase increased |
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| Blood creatine phosphokinase increased |
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| Gamma-glutamyltransferase increased |
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| Transaminases increased |
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