Comment Period Extended to 3/23/2015 for Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

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

This study has been completed.
Sponsor:
Information provided by:
Boehringer Ingelheim
ClinicalTrials.gov Identifier:
NCT01136174
First received: May 31, 2010
Last updated: December 15, 2014
Last verified: December 2014
  Purpose

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.


Condition Intervention Phase
Idiopathic Pulmonary Fibrosis
Drug: Placebo
Drug: BIBF 1120
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Double-Blind
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.

Resource links provided by NLM:


Further study details as provided by Boehringer Ingelheim:

Primary Outcome Measures:
  • Drug-related Adverse Events [ Time Frame: after the first drug intake until 28 days from the last treatment administration, up to 60 days ] [ Designated as safety issue: No ]
    The number of patients with drug-related adverse events stratified according to pirfenidone use in each group


Secondary Outcome Measures:
  • 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) ] [ Designated as safety issue: No ]

    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


  • 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) ] [ Designated as safety issue: No ]

    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 [ 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) ] [ Designated as safety issue: No ]

    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 [ 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) ] [ Designated as safety issue: No ]

    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) [ 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 ] [ Designated as safety issue: No ]
    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) [ 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 ] [ Designated as safety issue: No ]
    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) [ 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 ] [ Designated as safety issue: No ]
    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) [ 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 ] [ Designated as safety issue: No ]
    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) [ 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 ] [ Designated as safety issue: No ]
    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) [ 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 ] [ Designated as safety issue: No ]
    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) [ 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 ] [ Designated as safety issue: No ]
    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.

  • 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 ] [ Designated as safety issue: No ]
    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)

  • Withdrawal Due to Adverse Event [ Time Frame: after the first drug intake until 28 days from the last treatment administration, up to 60 days ] [ Designated as safety issue: No ]
    Number of patients prematurely discontinued from trial medication due to adverse event.

  • 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 ] [ Designated as safety issue: No ]
    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 [ Time Frame: after the first drug intake until 28 days from the last treatment administration, up to 60 days ] [ Designated as safety issue: No ]
    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) [ Time Frame: baseline and day 35 ] [ Designated as safety issue: No ]
    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 [ Time Frame: baseline and day 35 ] [ Designated as safety issue: No ]
    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) [ Time Frame: baseline and day 35 ] [ Designated as safety issue: No ]
    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) [ Time Frame: baseline and day 35 ] [ Designated as safety issue: No ]
    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) [ Time Frame: baseline and day 35 ] [ Designated as safety issue: No ]
    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) [ Time Frame: baseline and day 35 ] [ Designated as safety issue: No ]
    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) [ Time Frame: baseline and day 35 ] [ Designated as safety issue: No ]
    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.


Enrollment: 50
Study Start Date: May 2010
Primary Completion Date: March 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

  Eligibility

Ages Eligible for Study:   40 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01136174

Locations
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, Japan
Sponsors and Collaborators
Boehringer Ingelheim
Investigators
Study Chair: Boehringer Ingelheim Boehringer Ingelheim
  More Information

Additional Information:
No publications provided

Responsible Party: Boehringer Ingelheim, Study Chair, Boehringer Ingelheim
ClinicalTrials.gov Identifier: NCT01136174     History of Changes
Other Study ID Numbers: 1199.31
Study First Received: May 31, 2010
Results First Received: November 14, 2014
Last Updated: December 15, 2014
Health Authority: Japan: Pharmaceuticals and Medical Devices Agency

Additional relevant MeSH terms:
Idiopathic Pulmonary Fibrosis
Pulmonary Fibrosis
Idiopathic Interstitial Pneumonias
Lung Diseases
Lung Diseases, Interstitial
Respiratory Tract Diseases
Nintedanib
Antineoplastic Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on March 03, 2015