Safety and PK Study of BIBF 1120 in Japanese Patients With IPF

Study Overview
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Brief Summary
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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.

Official Title
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A Double-blind, Randomised, Placebo-controlled (Within a Dose Group) Study to Evaluate Safety and Pharmacokinetics of Multiple Rising Doses of BIBF 1120 at 50 mg Bid (14 Days), 100 mg Bid (14 Days), and 150 mg Bid (28 Days) p.o., on Top of Standard Medical Care With Stratification According to Pirfenidone Use, in Japanese Patients With Idiopathic Pulmonary Fibrosis.

Conditions
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Idiopathic Pulmonary Fibrosis

Intervention / Treatment
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* Drug: Placebo
* Drug: BIBF 1120
* Drug: BIBF 1120
* Drug: BIBF 1120


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Diagnosis of idiopathic pulmonary fibrosis (IPF) according to American Thoracic Society (ATS) /European Respiratory Society (ERS) guideline Forced vital capacity (FVC) 50-90% Diffusing capacity for carbon monoxide (DLCO) 30-79% For patients on pirfenidone, have been on a steady dose for at least 3 months 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. Oral corticosteroid medication at unstable dose ketoconazole or atazanavir 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

Ages Eligible for Study
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Minimum Age: 40 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BIBF 1120 50 mg<br>Low dose for cohort 1 | Drug: BIBF 1120<br>* 50 mg, 100 mg, 150 mg BID will be used for Cohort 1, 2, and 3 respectively<br>|
| Experimental: BIBF 1120 100 mg<br>Middle dose for cohort 2 | Drug: BIBF 1120<br>* 50 mg, 100 mg, 150 mg BID will be used for Cohort 1, 2, and 3 respectively<br>|
| Experimental: BIBF 1120 150 mg<br>High dose for cohort 3 | Drug: BIBF 1120<br>* 50 mg, 100 mg, 150 mg BID will be used for Cohort 1, 2, and 3 respectively<br>|
| Placebo Comparator: Placebo<br>Placebo for cohort 1,2,3 | Drug: Placebo<br>* Placebo BID for cohort 1,2,3<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | 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 | 

Secondary Outcome Measures

| Outcome Measure | 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 | 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 |