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

Idiopathic Pulmonary Fibrosis Clinical Trial

Official title:

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.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01136174
• Other study ID #: 1199.31
• Status: Completed
• Phase: Phase 2
• First received: May 31, 2010
• Last updated: December 15, 2014
• Start date: May 2010

Study information

• Verified date: December 2014
• Source: Boehringer Ingelheim
• Contact: n/a
• Is FDA regulated: No
• Health authority: Japan: Pharmaceuticals and Medical Devices Agency
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 50
• Est. primary completion date: March 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 40 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Double-Blind

Related Conditions & MeSH terms

• Fibrosis
• Idiopathic Interstitial Pneumonias
• Idiopathic Pulmonary Fibrosis
• Pulmonary Fibrosis

Intervention

Drug:
• Placebo
Placebo BID for cohort 1,2,3
• BIBF 1120
50 mg, 100 mg, 150 mg BID will be used for Cohort 1, 2, and 3 respectively
• BIBF 1120
50 mg, 100 mg, 150 mg BID will be used for Cohort 1, 2, and 3 respectively
• BIBF 1120
50 mg, 100 mg, 150 mg BID will be used for Cohort 1, 2, and 3 respectively

Locations

Country	Name	City	State
Japan	1199.31.002 Boehringer Ingelheim Investigational Site	Bunkyo-ku,Tokyo
Japan	1199.31.004 Boehringer Ingelheim Investigational Site	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

Sponsors (1)

Lead Sponsor	Collaborator
Boehringer Ingelheim

Country where clinical trial is conducted

Japan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	AUCt,ss After Multiple Doses of BIBF 1120 Without Pirfenidone	AUCt,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 t 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)	No
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 t 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)	No
Secondary	AUCt,ss After Multiple Doses of BIBF 1120 With Pirfenidone	AUCt,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 t 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)	No
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 t 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)	No
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.	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	No
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)	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	No
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.	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	No
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)	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	No
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.	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	No
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)	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	No
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.	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	No
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)	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	No
Secondary	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	No
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	after the first drug intake until 28 days from the last treatment administration, up to 60 days	No
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	after the first drug intake until 28 days from the last treatment administration, up to 60 days	No
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.	baseline and day 35	No
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.	baseline and day 35	No
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.	baseline and day 35	No
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.	baseline and day 35	No
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.	baseline and day 35	No
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.	baseline and day 35	No
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.	baseline and day 35	No

External Links

•   Related Info