Trial Outcomes & Findings for Safety and PK Study of BIBF 1120 in Japanese Patients With IPF (NCT NCT01136174)

NCT ID: NCT01136174

Last Updated: 2015-01-06

Results Overview

The number of patients with drug-related adverse events stratified according to pirfenidone use in each group

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 50 participants
• Primary outcome timeframe: after the first drug intake until 28 days from the last treatment administration, up to 60 days
• Results posted on: 2015-01-06

Participant Flow

Participant milestones

Measure	Placebo Placebo oral administration twice a day	BIBF 1120 50 mg BIBF 1120 50 mg oral administration twice a day	BIBF 1120 100 mg BIBF 1120 100 mg oral administration twice a day	BIBF 1120 150 mg BIBF 1120 150 mg oral administration twice a day
Overall Study STARTED	12	6	8	24
Overall Study COMPLETED	12	6	8	20
Overall Study NOT COMPLETED	0	0	0	4

Reasons for withdrawal

Measure	Placebo Placebo oral administration twice a day	BIBF 1120 50 mg BIBF 1120 50 mg oral administration twice a day	BIBF 1120 100 mg BIBF 1120 100 mg oral administration twice a day	BIBF 1120 150 mg BIBF 1120 150 mg oral administration twice a day
Overall Study Adverse Event	0	0	0	4

Baseline Characteristics

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

Baseline characteristics by cohort

Measure	Placebo n=12 Participants Placebo oral administration twice a day	BIBF 1120 50 mg n=6 Participants BIBF 1120 50 mg oral administration twice a day	BIBF 1120 100 mg n=8 Participants BIBF 1120 100 mg oral administration twice a day	BIBF 1120 150 mg n=24 Participants BIBF 1120 150 mg oral administration twice a day	Total n=50 Participants Total of all reporting groups
Age, Continuous	64.1 years STANDARD_DEVIATION 10.3 • n=5 Participants	66.7 years STANDARD_DEVIATION 2.9 • n=7 Participants	67.5 years STANDARD_DEVIATION 7.4 • n=5 Participants	64.7 years STANDARD_DEVIATION 8.5 • n=4 Participants	65.2 years STANDARD_DEVIATION 8.2 • n=21 Participants
Sex: Female, Male Female	1 Participants n=5 Participants	2 Participants n=7 Participants	4 Participants n=5 Participants	8 Participants n=4 Participants	15 Participants n=21 Participants
Sex: Female, Male Male	11 Participants n=5 Participants	4 Participants n=7 Participants	4 Participants n=5 Participants	16 Participants n=4 Participants	35 Participants n=21 Participants

PRIMARY outcome

Timeframe: after the first drug intake until 28 days from the last treatment administration, up to 60 days

Population: Treated set

The number of patients with drug-related adverse events stratified according to pirfenidone use in each group

Outcome measures

Measure	Placebo n=12 Participants Placebo oral administration twice a day	BIBF 1120 50 mg n=6 Participants BIBF 1120 50 mg oral administration twice a day	BIBF 1120 100 mg n=8 Participants BIBF 1120 100 mg oral administration twice a day	BIBF 1120 150 mg n=24 Participants BIBF 1120 150 mg oral administration twice a day
Drug-related Adverse Events Patients with Pirfenidone (N = 5, 4, 4, 13)	1 participants	0 participants	0 participants	7 participants
Drug-related Adverse Events Patients without Pirfenidone (N = 7, 2, 4, 11)	1 participants	0 participants	1 participants	3 participants

SECONDARY outcome

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)

Population: Treated set

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

Outcome measures

Measure	Placebo n=2 Participants Placebo oral administration twice a day	BIBF 1120 50 mg n=4 Participants BIBF 1120 50 mg oral administration twice a day	BIBF 1120 100 mg n=9 Participants BIBF 1120 100 mg oral administration twice a day	BIBF 1120 150 mg BIBF 1120 150 mg oral administration twice a day
AUCτ,ss After Multiple Doses of BIBF 1120 Without Pirfenidone	33.7 ng*h/mL Geometric Coefficient of Variation 165	115 ng*h/mL Geometric Coefficient of Variation 32.4	218 ng*h/mL Geometric Coefficient of Variation 58.3	—

SECONDARY outcome

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)

Population: Treated set- Only patients with valid final pharmacokinetic values were analysed

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

Outcome measures

Measure	Placebo n=2 Participants Placebo oral administration twice a day	BIBF 1120 50 mg n=4 Participants BIBF 1120 50 mg oral administration twice a day	BIBF 1120 100 mg n=9 Participants BIBF 1120 100 mg oral administration twice a day	BIBF 1120 150 mg BIBF 1120 150 mg oral administration twice a day
Cmax,ss After Multiple Doses of BIBF 1120 Without Pirfenidone	9.09 ng/mL Geometric Coefficient of Variation 173	20.0 ng/mL Geometric Coefficient of Variation 64.5	39.7 ng/mL Geometric Coefficient of Variation 68.1	—

SECONDARY outcome

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)

Population: Treated set- Only patients with valid final pharmacokinetic values were analysed

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

Outcome measures

Measure	Placebo n=4 Participants Placebo oral administration twice a day	BIBF 1120 50 mg n=3 Participants BIBF 1120 50 mg oral administration twice a day	BIBF 1120 100 mg n=7 Participants BIBF 1120 100 mg oral administration twice a day	BIBF 1120 150 mg BIBF 1120 150 mg oral administration twice a day
AUCτ,ss After Multiple Doses of BIBF 1120 With Pirfenidone	67.9 ng*h/mL Geometric Coefficient of Variation 16.7	86.0 ng*h/mL Geometric Coefficient of Variation 62.7	149 ng*h/mL Geometric Coefficient of Variation 18.0	—

SECONDARY outcome

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)

Population: Treated set- Only patients with valid final pharmacokinetic values were analysed

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

Outcome measures

Measure	Placebo n=4 Participants Placebo oral administration twice a day	BIBF 1120 50 mg n=3 Participants BIBF 1120 50 mg oral administration twice a day	BIBF 1120 100 mg n=7 Participants BIBF 1120 100 mg oral administration twice a day	BIBF 1120 150 mg BIBF 1120 150 mg oral administration twice a day
Cmax,ss After Multiple Doses of BIBF 1120 With Pirfenidone	10.9 ng/mL Geometric Coefficient of Variation 50.3	13.8 ng/mL Geometric Coefficient of Variation 113	23.5 ng/mL Geometric Coefficient of Variation 27.2	—

SECONDARY outcome

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

Population: Treated set- Only patients with valid final pharmacokinetic values were analysed

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.

Outcome measures

Measure	Placebo n=4 Participants Placebo oral administration twice a day	BIBF 1120 50 mg n=4 Participants BIBF 1120 50 mg oral administration twice a day	BIBF 1120 100 mg n=3 Participants BIBF 1120 100 mg oral administration twice a day	BIBF 1120 150 mg n=9 Participants BIBF 1120 150 mg oral administration twice a day
AUC0-4,ss After Multiple Doses of Pirfenidone 600 mg Without BIBF 1120 (After Breakfast)	28900 ng*h/mL Geometric Coefficient of Variation 30.7	34400 ng*h/mL Geometric Coefficient of Variation 36.3	45800 ng*h/mL Geometric Coefficient of Variation 26.6	32500 ng*h/mL Geometric Coefficient of Variation 21.2

SECONDARY outcome

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

Population: Treated set-Only patients with valid final pharmacokinetic values were analysed

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)

Outcome measures

Measure	Placebo n=4 Participants Placebo oral administration twice a day	BIBF 1120 50 mg n=4 Participants BIBF 1120 50 mg oral administration twice a day	BIBF 1120 100 mg n=4 Participants BIBF 1120 100 mg oral administration twice a day	BIBF 1120 150 mg n=9 Participants BIBF 1120 150 mg oral administration twice a day
Cmax,ss After Multiple Doses of Pirfenidone 600 mg Without BIBF 1120 (After Breakfast)	11300 ng/mL Geometric Coefficient of Variation 22.1	11900 ng/mL Geometric Coefficient of Variation 28.9	14600 ng/mL Geometric Coefficient of Variation 41.5	11200 ng/mL Geometric Coefficient of Variation 26.6

SECONDARY outcome

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

Population: Treated set- Only patients with valid final pharmacokinetic values were analysed

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.

Outcome measures

Measure	Placebo n=4 Participants Placebo oral administration twice a day	BIBF 1120 50 mg n=4 Participants BIBF 1120 50 mg oral administration twice a day	BIBF 1120 100 mg n=3 Participants BIBF 1120 100 mg oral administration twice a day	BIBF 1120 150 mg n=7 Participants BIBF 1120 150 mg oral administration twice a day
AUC0-4,ss After Multiple Doses of Pirfenidone 600 mg With BIBF 1120 (After Breakfast)	28800 ng*h/mL Geometric Coefficient of Variation 6.85	34300 ng*h/mL Geometric Coefficient of Variation 39.9	35000 ng*h/mL Geometric Coefficient of Variation 32.2	35900 ng*h/mL Geometric Coefficient of Variation 21.8

SECONDARY outcome

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

Population: Treated set- Only patients with valid final pharmacokinetic values were analysed

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)

Outcome measures

Measure	Placebo n=4 Participants Placebo oral administration twice a day	BIBF 1120 50 mg n=4 Participants BIBF 1120 50 mg oral administration twice a day	BIBF 1120 100 mg n=3 Participants BIBF 1120 100 mg oral administration twice a day	BIBF 1120 150 mg n=8 Participants BIBF 1120 150 mg oral administration twice a day
Cmax,ss After Multiple Doses of Pirfenidone 600 mg With BIBF 1120 (After Breakfast)	12000 ng/mL Geometric Coefficient of Variation 23.1	12800 ng/mL Geometric Coefficient of Variation 44.3	15300 ng/mL Geometric Coefficient of Variation 51.1	12600 ng/mL Geometric Coefficient of Variation 27.2

SECONDARY outcome

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

Population: Treated set- Only patients with valid final pharmacokinetic values were analysed

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.

Outcome measures

Measure	Placebo n=4 Participants Placebo oral administration twice a day	BIBF 1120 50 mg n=4 Participants BIBF 1120 50 mg oral administration twice a day	BIBF 1120 100 mg n=3 Participants BIBF 1120 100 mg oral administration twice a day	BIBF 1120 150 mg n=8 Participants BIBF 1120 150 mg oral administration twice a day
AUC0-8,ss After Multiple Doses of Pirfenidone 600 mg Without BIBF 1120 (After Lunch)	56600 ng*h/mL Geometric Coefficient of Variation 25.8	72800 ng*h/mL Geometric Coefficient of Variation 40.7	84100 ng*h/mL Geometric Coefficient of Variation 11.4	60900 ng*h/mL Geometric Coefficient of Variation 22.9

SECONDARY outcome

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

Population: Treated set- Only patients with valid final pharmacokinetic values were analysed

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)

Outcome measures

Measure	Placebo n=4 Participants Placebo oral administration twice a day	BIBF 1120 50 mg n=4 Participants BIBF 1120 50 mg oral administration twice a day	BIBF 1120 100 mg n=4 Participants BIBF 1120 100 mg oral administration twice a day	BIBF 1120 150 mg n=9 Participants BIBF 1120 150 mg oral administration twice a day
Cmax,ss After Multiple Doses of Pirfenidone 600 mg Without BIBF 1120 (After Lunch)	13500 ng/mL Geometric Coefficient of Variation 19.9	14600 ng/mL Geometric Coefficient of Variation 20.9	15100 ng/mL Geometric Coefficient of Variation 19.5	12900 ng/mL Geometric Coefficient of Variation 30.2

SECONDARY outcome

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

Population: Treated set- Only patients with valid final pharmacokinetic values were analysed

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.

Outcome measures

Measure	Placebo n=4 Participants Placebo oral administration twice a day	BIBF 1120 50 mg n=4 Participants BIBF 1120 50 mg oral administration twice a day	BIBF 1120 100 mg n=3 Participants BIBF 1120 100 mg oral administration twice a day	BIBF 1120 150 mg n=6 Participants BIBF 1120 150 mg oral administration twice a day
AUC0-8,ss After Multiple Doses of Pirfenidone 600 mg With BIBF 1120 (After Lunch)	47000 ng*h/mL Geometric Coefficient of Variation 13.6	71000 ng*h/mL Geometric Coefficient of Variation 40.8	71500 ng*h/mL Geometric Coefficient of Variation 19.1	63600 ng*h/mL Geometric Coefficient of Variation 27.7

SECONDARY outcome

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

Population: Treated set- Only patients with valid final pharmacokinetic values were analysed

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)

Outcome measures

Measure	Placebo n=4 Participants Placebo oral administration twice a day	BIBF 1120 50 mg n=4 Participants BIBF 1120 50 mg oral administration twice a day	BIBF 1120 100 mg n=3 Participants BIBF 1120 100 mg oral administration twice a day	BIBF 1120 150 mg n=8 Participants BIBF 1120 150 mg oral administration twice a day
Cmax,ss After Multiple Doses of Pirfenidone 600 mg With BIBF 1120 (After Lunch)	10700 ng/mL Geometric Coefficient of Variation 18.8	12000 ng/mL Geometric Coefficient of Variation 37.3	12100 ng/mL Geometric Coefficient of Variation 10.7	12500 ng/mL Geometric Coefficient of Variation 23.0

SECONDARY outcome

Timeframe: after the first drug intake until 28 days from the last treatment administration, up to 60 days

Population: Treated set

Number of patients prematurely discontinued from trial medication due to adverse event.

Outcome measures

Measure	Placebo n=12 Participants Placebo oral administration twice a day	BIBF 1120 50 mg n=6 Participants BIBF 1120 50 mg oral administration twice a day	BIBF 1120 100 mg n=8 Participants BIBF 1120 100 mg oral administration twice a day	BIBF 1120 150 mg n=24 Participants BIBF 1120 150 mg oral administration twice a day
Withdrawal Due to Adverse Event With Pirfenidone (N= 5, 4, 4, 13)	0 participants	0 participants	0 participants	2 participants
Withdrawal Due to Adverse Event Without Pirfenidone (N = 7, 2, 4, 11)	0 participants	0 participants	0 participants	2 participants

SECONDARY outcome

Timeframe: after the first drug intake until 28 days from the last treatment administration, up to 60 days

Population: Treated set

Number of patients with Clinical Relevant Abnormalities in laboratory parameters reported as adverse events - No pirfenidone background

Outcome measures

Measure	Placebo n=7 Participants Placebo oral administration twice a day	BIBF 1120 50 mg n=2 Participants BIBF 1120 50 mg oral administration twice a day	BIBF 1120 100 mg n=4 Participants BIBF 1120 100 mg oral administration twice a day	BIBF 1120 150 mg n=11 Participants BIBF 1120 150 mg oral administration twice a day
Clinical Relevant Abnormalities in Laboratory Parameters- No Pirfenidone Background Alanine aminotransferase increased	0 participants	0 participants	0 participants	2 participants
Clinical Relevant Abnormalities in Laboratory Parameters- No Pirfenidone Background Aspartate aminotransferase increased	0 participants	0 participants	0 participants	2 participants
Clinical Relevant Abnormalities in Laboratory Parameters- No Pirfenidone Background Blood creatine phosphokinase increased	0 participants	0 participants	0 participants	1 participants
Clinical Relevant Abnormalities in Laboratory Parameters- No Pirfenidone Background Gamma-glutamyltransferase increased	0 participants	0 participants	0 participants	1 participants

SECONDARY outcome

Timeframe: after the first drug intake until 28 days from the last treatment administration, up to 60 days

Population: Treated set

Number of patients with Clinical Relevant Abnormalities in laboratory parameters reported as adverse events - With pirfenidone background

Outcome measures

Measure	Placebo n=5 Participants Placebo oral administration twice a day	BIBF 1120 50 mg n=4 Participants BIBF 1120 50 mg oral administration twice a day	BIBF 1120 100 mg n=4 Participants BIBF 1120 100 mg oral administration twice a day	BIBF 1120 150 mg n=13 Participants BIBF 1120 150 mg oral administration twice a day
Clinical Relevant Abnormalities in Laboratory Parameters- With Pirfenidone Background Hypothyroidism	0 participants	0 participants	0 participants	1 participants
Clinical Relevant Abnormalities in Laboratory Parameters- With Pirfenidone Background Transaminases increased	0 participants	0 participants	0 participants	1 participants

SECONDARY outcome

Timeframe: baseline and day 35

Population: Treated set

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.

Outcome measures

Measure	Placebo n=8 Participants Placebo oral administration twice a day	BIBF 1120 50 mg n=24 Participants BIBF 1120 50 mg oral administration twice a day	BIBF 1120 100 mg BIBF 1120 100 mg oral administration twice a day	BIBF 1120 150 mg BIBF 1120 150 mg oral administration twice a day
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) DBP	0.5 mmHg Standard Deviation 13.3	-0.8 mmHg Standard Deviation 10.8	—	—
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) SBP	1.3 mmHg Standard Deviation 19.2	2.5 mmHg Standard Deviation 14.4	—	—

SECONDARY outcome

Timeframe: baseline and day 35

Population: Treated set

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.

Outcome measures

Measure	Placebo n=8 Participants Placebo oral administration twice a day	BIBF 1120 50 mg n=24 Participants BIBF 1120 50 mg oral administration twice a day	BIBF 1120 100 mg BIBF 1120 100 mg oral administration twice a day	BIBF 1120 150 mg BIBF 1120 150 mg oral administration twice a day
Change From Baseline in Pulse Rate	-2.5 bpm Standard Deviation 15.4	1.9 bpm Standard Deviation 13.6	—	—

SECONDARY outcome

Timeframe: baseline and day 35

Population: Treated set

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.

Outcome measures

Measure	Placebo n=8 Participants Placebo oral administration twice a day	BIBF 1120 50 mg n=24 Participants BIBF 1120 50 mg oral administration twice a day	BIBF 1120 100 mg BIBF 1120 100 mg oral administration twice a day	BIBF 1120 150 mg BIBF 1120 150 mg oral administration twice a day
Lung Function Measurement: Diffusing Capacity for Carbon Monoxide (DLco)	-1.131 mL/min/mmHg Standard Deviation 1.397	-0.707 mL/min/mmHg Standard Deviation 2.005	—	—

SECONDARY outcome

Timeframe: baseline and day 35

Population: Treated set- Only patients with valid measurements were analysed.

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.

Outcome measures

Measure	Placebo n=8 Participants Placebo oral administration twice a day	BIBF 1120 50 mg n=23 Participants BIBF 1120 50 mg oral administration twice a day	BIBF 1120 100 mg BIBF 1120 100 mg oral administration twice a day	BIBF 1120 150 mg BIBF 1120 150 mg oral administration twice a day
Lung Function Measurement: Diffusing Capacity for Carbon Monoxide Percent of Predicted (%DLco)	-4.660 % predicted Standard Deviation 8.020	-1.193 % predicted Standard Deviation 5.948	—	—

SECONDARY outcome

Timeframe: baseline and day 35

Population: Treated set

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.

Outcome measures

Measure	Placebo n=8 Participants Placebo oral administration twice a day	BIBF 1120 50 mg n=24 Participants BIBF 1120 50 mg oral administration twice a day	BIBF 1120 100 mg BIBF 1120 100 mg oral administration twice a day	BIBF 1120 150 mg BIBF 1120 150 mg oral administration twice a day
Lung Function Measurement: Forced Expiratory Volume in 1 Second (FEV1)	-0.021 Liter Standard Deviation 0.107	0.036 Liter Standard Deviation 0.078	—	—

SECONDARY outcome

Timeframe: baseline and day 35

Population: Treated set

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.

Outcome measures

Measure	Placebo n=8 Participants Placebo oral administration twice a day	BIBF 1120 50 mg n=24 Participants BIBF 1120 50 mg oral administration twice a day	BIBF 1120 100 mg BIBF 1120 100 mg oral administration twice a day	BIBF 1120 150 mg BIBF 1120 150 mg oral administration twice a day
Lung Function Measurement: Forced Vital Capacity (FVC)	-0.081 Liter Standard Deviation 0.175	0.050 Liter Standard Deviation 0.086	—	—

SECONDARY outcome

Timeframe: baseline and day 35

Population: Treated set

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.

Outcome measures

Measure	Placebo n=8 Participants Placebo oral administration twice a day	BIBF 1120 50 mg n=24 Participants BIBF 1120 50 mg oral administration twice a day	BIBF 1120 100 mg BIBF 1120 100 mg oral administration twice a day	BIBF 1120 150 mg BIBF 1120 150 mg oral administration twice a day
Lung Function Measurement: Forced Vital Capacity Percent of Predicted (%FVC)	-2.311 % predicted Standard Deviation 5.193	1.432 % predicted Standard Deviation 2.671	—	—

Adverse Events

Placebo

Serious events: 0 serious events

Other events: 4 other events

Deaths: 0 deaths

BIBF 1120 50 mg

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

BIBF 1120 100 mg

Serious events: 0 serious events

Other events: 4 other events

Deaths: 0 deaths

BIBF 1120 150 mg

Serious events: 1 serious events

Other events: 14 other events

Deaths: 0 deaths

Serious adverse events

Measure	Placebo n=12 participants at risk Placebo oral administration twice a day for cohort 1, 2, 3	BIBF 1120 50 mg n=6 participants at risk BIBF 1120 50 mg oral administration twice a day for cohort 1	BIBF 1120 100 mg n=8 participants at risk BIBF 1120 100 mg oral administration twice a day for cohort 2	BIBF 1120 150 mg n=24 participants at risk BIBF 1120 150 mg oral administration twice a day for cohort 3
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Hepatic neoplasm malignant	0.00% 0/12 • after the first drug intake until 28 days from the last treatment administration, up to 60 days	0.00% 0/6 • after the first drug intake until 28 days from the last treatment administration, up to 60 days	0.00% 0/8 • after the first drug intake until 28 days from the last treatment administration, up to 60 days	4.2% 1/24 • after the first drug intake until 28 days from the last treatment administration, up to 60 days

Other adverse events

Measure	Placebo n=12 participants at risk Placebo oral administration twice a day for cohort 1, 2, 3	BIBF 1120 50 mg n=6 participants at risk BIBF 1120 50 mg oral administration twice a day for cohort 1	BIBF 1120 100 mg n=8 participants at risk BIBF 1120 100 mg oral administration twice a day for cohort 2	BIBF 1120 150 mg n=24 participants at risk BIBF 1120 150 mg oral administration twice a day for cohort 3
Gastrointestinal disorders Abdominal discomfort	8.3% 1/12 • after the first drug intake until 28 days from the last treatment administration, up to 60 days	0.00% 0/6 • after the first drug intake until 28 days from the last treatment administration, up to 60 days	0.00% 0/8 • after the first drug intake until 28 days from the last treatment administration, up to 60 days	4.2% 1/24 • after the first drug intake until 28 days from the last treatment administration, up to 60 days
Gastrointestinal disorders Abdominal pain upper	8.3% 1/12 • after the first drug intake until 28 days from the last treatment administration, up to 60 days	0.00% 0/6 • after the first drug intake until 28 days from the last treatment administration, up to 60 days	0.00% 0/8 • after the first drug intake until 28 days from the last treatment administration, up to 60 days	0.00% 0/24 • after the first drug intake until 28 days from the last treatment administration, up to 60 days
Gastrointestinal disorders Diarrhoea	0.00% 0/12 • after the first drug intake until 28 days from the last treatment administration, up to 60 days	0.00% 0/6 • after the first drug intake until 28 days from the last treatment administration, up to 60 days	0.00% 0/8 • after the first drug intake until 28 days from the last treatment administration, up to 60 days	16.7% 4/24 • after the first drug intake until 28 days from the last treatment administration, up to 60 days
Gastrointestinal disorders Gastritis erosive	8.3% 1/12 • after the first drug intake until 28 days from the last treatment administration, up to 60 days	0.00% 0/6 • after the first drug intake until 28 days from the last treatment administration, up to 60 days	0.00% 0/8 • after the first drug intake until 28 days from the last treatment administration, up to 60 days	0.00% 0/24 • after the first drug intake until 28 days from the last treatment administration, up to 60 days
Gastrointestinal disorders Nausea	0.00% 0/12 • after the first drug intake until 28 days from the last treatment administration, up to 60 days	0.00% 0/6 • after the first drug intake until 28 days from the last treatment administration, up to 60 days	0.00% 0/8 • after the first drug intake until 28 days from the last treatment administration, up to 60 days	20.8% 5/24 • after the first drug intake until 28 days from the last treatment administration, up to 60 days
Gastrointestinal disorders Periproctitis	8.3% 1/12 • after the first drug intake until 28 days from the last treatment administration, up to 60 days	0.00% 0/6 • after the first drug intake until 28 days from the last treatment administration, up to 60 days	0.00% 0/8 • after the first drug intake until 28 days from the last treatment administration, up to 60 days	0.00% 0/24 • after the first drug intake until 28 days from the last treatment administration, up to 60 days
Gastrointestinal disorders Stomatitis	0.00% 0/12 • after the first drug intake until 28 days from the last treatment administration, up to 60 days	0.00% 0/6 • after the first drug intake until 28 days from the last treatment administration, up to 60 days	12.5% 1/8 • after the first drug intake until 28 days from the last treatment administration, up to 60 days	4.2% 1/24 • after the first drug intake until 28 days from the last treatment administration, up to 60 days
Gastrointestinal disorders Vomiting	0.00% 0/12 • after the first drug intake until 28 days from the last treatment administration, up to 60 days	0.00% 0/6 • after the first drug intake until 28 days from the last treatment administration, up to 60 days	0.00% 0/8 • after the first drug intake until 28 days from the last treatment administration, up to 60 days	20.8% 5/24 • after the first drug intake until 28 days from the last treatment administration, up to 60 days
Infections and infestations Bronchitis	8.3% 1/12 • after the first drug intake until 28 days from the last treatment administration, up to 60 days	0.00% 0/6 • after the first drug intake until 28 days from the last treatment administration, up to 60 days	0.00% 0/8 • after the first drug intake until 28 days from the last treatment administration, up to 60 days	0.00% 0/24 • after the first drug intake until 28 days from the last treatment administration, up to 60 days
Infections and infestations Gastroenteritis	8.3% 1/12 • after the first drug intake until 28 days from the last treatment administration, up to 60 days	0.00% 0/6 • after the first drug intake until 28 days from the last treatment administration, up to 60 days	0.00% 0/8 • after the first drug intake until 28 days from the last treatment administration, up to 60 days	0.00% 0/24 • after the first drug intake until 28 days from the last treatment administration, up to 60 days
Infections and infestations Nasopharyngitis	0.00% 0/12 • after the first drug intake until 28 days from the last treatment administration, up to 60 days	0.00% 0/6 • after the first drug intake until 28 days from the last treatment administration, up to 60 days	12.5% 1/8 • after the first drug intake until 28 days from the last treatment administration, up to 60 days	8.3% 2/24 • after the first drug intake until 28 days from the last treatment administration, up to 60 days
Investigations Alanine aminotransferase increased	0.00% 0/12 • after the first drug intake until 28 days from the last treatment administration, up to 60 days	0.00% 0/6 • after the first drug intake until 28 days from the last treatment administration, up to 60 days	0.00% 0/8 • after the first drug intake until 28 days from the last treatment administration, up to 60 days	8.3% 2/24 • after the first drug intake until 28 days from the last treatment administration, up to 60 days
Investigations Aspartate aminotransferase increased	0.00% 0/12 • after the first drug intake until 28 days from the last treatment administration, up to 60 days	0.00% 0/6 • after the first drug intake until 28 days from the last treatment administration, up to 60 days	0.00% 0/8 • after the first drug intake until 28 days from the last treatment administration, up to 60 days	8.3% 2/24 • after the first drug intake until 28 days from the last treatment administration, up to 60 days
Nervous system disorders Dysgeusia	8.3% 1/12 • after the first drug intake until 28 days from the last treatment administration, up to 60 days	0.00% 0/6 • after the first drug intake until 28 days from the last treatment administration, up to 60 days	0.00% 0/8 • after the first drug intake until 28 days from the last treatment administration, up to 60 days	0.00% 0/24 • after the first drug intake until 28 days from the last treatment administration, up to 60 days
Respiratory, thoracic and mediastinal disorders Dysphonia	0.00% 0/12 • after the first drug intake until 28 days from the last treatment administration, up to 60 days	0.00% 0/6 • after the first drug intake until 28 days from the last treatment administration, up to 60 days	12.5% 1/8 • after the first drug intake until 28 days from the last treatment administration, up to 60 days	0.00% 0/24 • after the first drug intake until 28 days from the last treatment administration, up to 60 days
Skin and subcutaneous tissue disorders Erythema	0.00% 0/12 • after the first drug intake until 28 days from the last treatment administration, up to 60 days	0.00% 0/6 • after the first drug intake until 28 days from the last treatment administration, up to 60 days	12.5% 1/8 • after the first drug intake until 28 days from the last treatment administration, up to 60 days	0.00% 0/24 • after the first drug intake until 28 days from the last treatment administration, up to 60 days
Skin and subcutaneous tissue disorders Photosensitivity reaction	8.3% 1/12 • after the first drug intake until 28 days from the last treatment administration, up to 60 days	0.00% 0/6 • after the first drug intake until 28 days from the last treatment administration, up to 60 days	0.00% 0/8 • after the first drug intake until 28 days from the last treatment administration, up to 60 days	0.00% 0/24 • after the first drug intake until 28 days from the last treatment administration, up to 60 days

Additional Information

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