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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

May 31, 2010
December 15, 2014
May 2010
March 2011   (final data collection date for primary outcome measure)
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
  • Incidence and intensity of adverse events [ Time Frame: 2 weeks for cohort 1& 2 and 4 weeks for cohort 3 ] [ Designated as safety issue: No ]
  • Withdrawal due to adverse events [ Time Frame: 2 weeks for cohort 1& 2 and 4 weeks for cohort 3 ] [ Designated as safety issue: No ]
Complete list of historical versions of study NCT01136174 on ClinicalTrials.gov Archive Site
  • 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.
  • Laboratory tests (Hematology, Biochemistry, Urine, Stool). Data will be analysed both quantitatively as well as qualitatively. [ Time Frame: 2 weeks for cohort 1& 2 and 4 weeks for cohort 3 ] [ Designated as safety issue: No ]
  • Lung function measurement: Spirometry: Forced vital capacity (FVC), Foced expiratory volume in 1second (FEV), Diffusing capacity for carbon monoxide(DLco). [ Time Frame: 2 weeks for cohort 1& 2 and 4 weeks for cohort 3 ] [ Designated as safety issue: No ]
  • Vital signs (systolic and diastolic blood pressure and pulse rate). Data will be assessed with regard to possible changes compared to findings before start of treatment. [ Time Frame: 2 weeks for cohort 1& 2 and 4 weeks for cohort 3 ] [ Designated as safety issue: No ]
Not Provided
Not Provided
 
Safety and PK Study of BIBF 1120 in Japanese Patients With IPF
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.

Not Provided
Interventional
Phase 2
Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Double-Blind
Idiopathic Pulmonary Fibrosis
  • Drug: Placebo
    Placebo BID for cohort 1,2,3
  • Drug: BIBF 1120
    50 mg, 100 mg, 150 mg BID will be used for Cohort 1, 2, and 3 respectively
  • Experimental: BIBF 1120 50 mg
    Low dose for cohort 1
    Intervention: Drug: BIBF 1120
  • Experimental: BIBF 1120 100 mg
    Middle dose for cohort 2
    Intervention: Drug: BIBF 1120
  • Experimental: BIBF 1120 150 mg
    High dose for cohort 3
    Intervention: Drug: BIBF 1120
  • Placebo Comparator: Placebo
    Placebo for cohort 1,2,3
    Intervention: Drug: Placebo
Ogura T, Taniguchi H, Azuma A, Inoue Y, Kondoh Y, Hasegawa Y, Bando M, Abe S, Mochizuki Y, Chida K, Klüglich 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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
50
Not Provided
March 2011   (final data collection date for primary outcome measure)

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
Both
40 Years and older   (Adult, Senior)
No
Contact information is only displayed when the study is recruiting subjects
Japan
 
NCT01136174
1199.31
Not Provided
Not Provided
Not Provided
Boehringer Ingelheim, Study Chair, Boehringer Ingelheim
Boehringer Ingelheim
Not Provided
Study Chair: Boehringer Ingelheim Boehringer Ingelheim
Boehringer Ingelheim
December 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP