Clinical trial NCT01136174: Safety and PK Study of BIBF 1120 in Japanese Patients With IPF
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.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Idiopathic Pulmonary Fibrosis
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2010-06-03
Enrollment: 50
Sex: ALL
Minimum age (years): 40
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL

Brief 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.


Eligibility 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

Primary outcomes:
measure: Drug-related Adverse Events
timeFrame: after the first drug intake until 28 days from the last treatment administration, up to 60 days
Secondary outcomes:
measure: AUCτ,ss After Multiple Doses of BIBF 1120 Without Pirfenidone
timeFrame: 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)
measure: Cmax,ss After Multiple Doses of BIBF 1120 Without Pirfenidone
timeFrame: 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)
measure: AUCτ,ss After Multiple Doses of BIBF 1120 With Pirfenidone
timeFrame: 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)
measure: Cmax,ss After Multiple Doses of BIBF 1120 With Pirfenidone
timeFrame: 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)
measure: AUC0-4,ss After Multiple Doses of Pirfenidone 600 mg Without BIBF 1120 (After Breakfast)
timeFrame: 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
measure: Cmax,ss After Multiple Doses of Pirfenidone 600 mg Without BIBF 1120 (After Breakfast)
timeFrame: 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
measure: AUC0-4,ss After Multiple Doses of Pirfenidone 600 mg With BIBF 1120 (After Breakfast)
timeFrame: 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
measure: Cmax,ss After Multiple Doses of Pirfenidone 600 mg With BIBF 1120 (After Breakfast)
timeFrame: 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
measure: AUC0-8,ss After Multiple Doses of Pirfenidone 600 mg Without BIBF 1120 (After Lunch)
timeFrame: 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
measure: Cmax,ss After Multiple Doses of Pirfenidone 600 mg Without BIBF 1120 (After Lunch)
timeFrame: 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
measure: AUC0-8,ss After Multiple Doses of Pirfenidone 600 mg With BIBF 1120 (After Lunch)
timeFrame: 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
measure: Cmax,ss After Multiple Doses of Pirfenidone 600 mg With BIBF 1120 (After Lunch)
timeFrame: 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
measure: Withdrawal Due to Adverse Event
timeFrame: after the first drug intake until 28 days from the last treatment administration, up to 60 days
measure: Clinical Relevant Abnormalities in Laboratory Parameters- No Pirfenidone Background
timeFrame: after the first drug intake until 28 days from the last treatment administration, up to 60 days
measure: Clinical Relevant Abnormalities in Laboratory Parameters- With Pirfenidone Background
timeFrame: after the first drug intake until 28 days from the last treatment administration, up to 60 days
measure: Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)
timeFrame: baseline and day 35
measure: Change From Baseline in Pulse Rate
timeFrame: baseline and day 35
measure: Lung Function Measurement: Diffusing Capacity for Carbon Monoxide (DLco)
timeFrame: baseline and day 35
measure: Lung Function Measurement: Diffusing Capacity for Carbon Monoxide Percent of Predicted (%DLco)
timeFrame: baseline and day 35
measure: Lung Function Measurement: Forced Expiratory Volume in 1 Second (FEV1)
timeFrame: baseline and day 35
measure: Lung Function Measurement: Forced Vital Capacity (FVC)
timeFrame: baseline and day 35
measure: Lung Function Measurement: Forced Vital Capacity Percent of Predicted (%FVC)
timeFrame: baseline and day 35
Other outcomes:
Locations:
city: Bunkyo-ku,Tokyo
country: Japan
facility: 1199.31.002 Boehringer Ingelheim Investigational Site
city: Hamamatsu, Shizuoka
country: Japan
facility: 1199.31.004 Boehringer Ingelheim Investigational Site
city: Himeji, Hyogo
country: Japan
facility: 1199.31.008 Boehringer Ingelheim Investigational Site
city: Nagoya, Aichi
country: Japan
facility: 1199.31.006 Boehringer Ingelheim Investigational Site
city: Sakai, Osaka
country: Japan
facility: 1199.31.007 Boehringer Ingelheim Investigational Site
city: Seto, Aichi
country: Japan
facility: 1199.31.005 Boehringer Ingelheim Investigational Site
city: Shimotsuke,Tochigi
country: Japan
facility: 1199.31.001 Boehringer Ingelheim Investigational Site
city: Yokohama, Kanagawa
country: Japan
facility: 1199.31.003 Boehringer Ingelheim Investigational Site
Study officials:
affiliation: Boehringer Ingelheim
name: Boehringer Ingelheim
role: STUDY_CHAIR
References:
citation: Ogura T, Taniguchi H, Azuma A, Inoue Y, Kondoh Y, Hasegawa Y, Bando M, Abe S, Mochizuki Y, Chida K, Kluglich 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. Epub 2014 Dec 10.