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

December 15, 2014 updated by: Boehringer Ingelheim

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.

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

50

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Japan
      • Bunkyo-ku,Tokyo, Japan
        • 1199.31.002 Boehringer Ingelheim Investigational Site
      • Hamamatsu, Shizuoka, Japan
        • 1199.31.004 Boehringer Ingelheim Investigational Site
      • Himeji, Hyogo, Japan
        • 1199.31.008 Boehringer Ingelheim Investigational Site
      • Nagoya, Aichi, Japan
        • 1199.31.006 Boehringer Ingelheim Investigational Site
      • Sakai, Osaka, Japan
        • 1199.31.007 Boehringer Ingelheim Investigational Site
      • Seto, Aichi, Japan
        • 1199.31.005 Boehringer Ingelheim Investigational Site
      • Shimotsuke,Tochigi, Japan
        • 1199.31.001 Boehringer Ingelheim Investigational Site
      • Yokohama, Kanagawa, Japan
        • 1199.31.003 Boehringer Ingelheim Investigational Site

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

40 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Drug-related Adverse Events
Time Frame: 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
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
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)

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
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)

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
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)

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
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)

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)
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
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)
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
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)
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
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)
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
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)
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
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)
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
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)
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
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)
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
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
Time Frame: 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.
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
Time Frame: 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
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
Time Frame: 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
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)
Time Frame: 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.
baseline and day 35
Change From Baseline in Pulse Rate
Time Frame: 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.
baseline and day 35
Lung Function Measurement: Diffusing Capacity for Carbon Monoxide (DLco)
Time Frame: 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.
baseline and day 35
Lung Function Measurement: Diffusing Capacity for Carbon Monoxide Percent of Predicted (%DLco)
Time Frame: 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.
baseline and day 35
Lung Function Measurement: Forced Expiratory Volume in 1 Second (FEV1)
Time Frame: 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.
baseline and day 35
Lung Function Measurement: Forced Vital Capacity (FVC)
Time Frame: 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.
baseline and day 35
Lung Function Measurement: Forced Vital Capacity Percent of Predicted (%FVC)
Time Frame: 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.
baseline and day 35

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Boehringer Ingelheim

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

May 1, 2010

Primary Completion (Actual)

March 1, 2011

Study Registration Dates

First Submitted

May 31, 2010

First Submitted That Met QC Criteria

June 2, 2010

First Posted (Estimate)

June 3, 2010

Study Record Updates

Last Update Posted (Estimate)

January 6, 2015

Last Update Submitted That Met QC Criteria

December 15, 2014

Last Verified

December 1, 2014

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 1199.31

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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