Roll Over Study From 1199.30 BIBF 1120 in Idiopathic Pulmonary Fibrosis (IPF)

• ClinicalTrials.gov Identifier: NCT01170065
• Recruitment Status: Completed
• First Posted: July 27, 2010
• Results First Posted: June 6, 2019
• Last Update Posted: June 6, 2019
• Sponsor: Boehringer Ingelheim
• Information provided by (Responsible Party): Boehringer Ingelheim

• Study Type: Interventional
• Study Design: Allocation: Non-Randomized; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Pulmonary Fibrosis
• Intervention: Drug: BIBF 1120
• Enrollment: 198

Participant Flow

Recruitment Details	Treatment groups are displayed according to dose at randomisation in 1199.30 (NCT00514683).
Pre-assignment Details	Patients were not randomised to study medication in trial 1199.35 but were to receive open-label nintedanib, either at the dose received in period 2 of parent trial 1199.30 (NCT00514683) or they could increase their dose to nintedanib 150 mg twice daily (bid) after implementation of protocol amendment 1.

Arm/Group Title	Placebo	Nintedanib 50 mg- 100 mg	Nintedanib 150 mg
Arm/Group Description	Patients were treated with oral administration of placebo in period 1 of the parent trial and with soft gelatine capsules of Nintedanib 50 mg once daily (qd) in the second period of the 1199.30 (parent trial). In the 1199.35 trial they could remain on this last dose or increase to Nintedanib 150 mg twice daily (bid)	Patients were treated with oral administration of soft gelatine capsules of Nintedanib 50 mg qd, 50 mg bid or 100 mg bid in the parent trial. In the 1199.35 trial they could remain on their last dose in the parent trial or increase to Nintedanib 150 mg bid.	Patients were treated with oral administration of soft gelatine capsules of Nintedanib 150 mg bid and could step down to 100 mg bid. In the 1199.35 trial they could remain on their last dose in the parent trial.
Period Title: Overall Study
Started	37	126	35
Completed	9 [1]	34 [1]	9 [1]
Not Completed	28	92	26
Reason Not Completed
Adverse Event	17	50	10
Lost to Follow-up	1	4	1
Consent withdrawn, not due to AE	2	4	2
Reason other than specified	3	8	3
Ongoing after planned observation time	5	26	10
[1] Planned observation time is from first trial drug intake to follow-up visit

Baseline Characteristics

Arm/Group Title		Placebo	Nintedanib 50 mg- 100 mg	Nintedanib 150 mg	Total
Arm/Group Description		Patients were treated with oral administration of placebo in period 1 of the parent trial and with soft gelatine capsules of Nintedanib 50 mg once daily (qd) in the second period of the 1199.30 (parent trial). In the 1199.35 trial they could remain on this last dose or increase to Nintedanib 150 mg twice daily (bid)	Patients were treated with oral administration of soft gelatine capsules of Nintedanib 50 mg qd, 50 mg bid or 100 mg bid in the parent trial. In the 1199.35 trial they could remain on their last dose in the parent trial or increase to Nintedanib 150 mg bid.	Patients were treated with oral administration of soft gelatine capsules of Nintedanib 150 mg bid and could step down to 100 mg bid. In the 1199.35 trial they could remain on their last dose in the parent trial.	Total of all reporting groups
Overall Number of Baseline Participants		37	126	35	198
Baseline Analysis Population Description		Treated set (TS): The treated set which included all patients who received at least 1 dose of open-label study medication in trial 1199.35
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	37 participants	126 participants	35 participants	198 participants
		64.2 (7.3)	65.4 (8.6)	65.2 (7.2)	65.2 (8.1)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	37 participants	126 participants	35 participants	198 participants
	Female	14 37.8%	36 28.6%	7 20.0%	57 28.8%
	Male	23 62.2%	90 71.4%	28 80.0%	141 71.2%

Outcome Measures

1. Primary Outcome

Title	Annual Rate of Decline in Forced Vital Capacity (FVC)
Description	Forced vital capacity (FVC) is the total amount of air exhaled during the lung function test. For this endpoint reported means represent the adjusted rate.
Time Frame	From first drug administration in 1199.35 until database lock 15Oct2015, up to 61.8 Months

Outcome Measure Data

Analysis Population Description

The full analysis set (FAS): which included all patients in the treated set who provided baseline data (for the first trial visit) for at least 1 endpoint in trial 1199.35

Arm/Group Title	Placebo	Nintedanib 50 mg- 100 mg	Nintedanib 150 mg
Arm/Group Description:	Patients were treated with oral administration of placebo in period 1 of the parent trial and with soft gelatine capsules of Nintedanib 50 mg once daily (qd) in the second period of the 1199.30 (parent trial). In the 1199.35 trial they could remain on this last dose or increase to Nintedanib 150 mg twice daily (bid)	Patients were treated with oral administration of soft gelatine capsules of Nintedanib 50 mg qd, 50 mg bid or 100 mg bid in the parent trial. In the 1199.35 trial they could remain on their last dose in the parent trial or increase to Nintedanib 150 mg bid.	Patients were treated with oral administration of soft gelatine capsules of Nintedanib 150 mg bid and could step down to 100 mg bid. In the 1199.35 trial they could remain on their last dose in the parent trial.
Overall Number of Participants Analyzed	37	126	35
Mean (Standard Error); Unit of Measure: milliliters per year (mL/ yr)
	-129.0 (29.47)	-137.5 (14.60)	-132.9 (28.22)

2. Secondary Outcome

Title	Overall Survival
Description	Overall survival is defined as the time from the first intake of nintedanib in trial 1199.35 to death. For presentation of overall survival results, Kaplan-Meier estimates and confidence intervals (using Greenwood variance formula) for the overall on-treatment survival is calculated within each treatment arm.
Time Frame	From first drug administration in 1199.35 until database lock 15Oct2015, up to 61.8 Months

Outcome Measure Data

Analysis Population Description

FAS

Arm/Group Title	Placebo	Nintedanib 50 mg- 100 mg	Nintedanib 150 mg
Arm/Group Description:	Patients were treated with oral administration of placebo in period 1 of the parent trial and with soft gelatine capsules of Nintedanib 50 mg once daily (qd) in the second period of the 1199.30 (parent trial). In the 1199.35 trial they could remain on this last dose or increase to Nintedanib 150 mg twice daily (bid)	Patients were treated with oral administration of soft gelatine capsules of Nintedanib 50 mg qd, 50 mg bid or 100 mg bid in the parent trial. In the 1199.35 trial they could remain on their last dose in the parent trial or increase to Nintedanib 150 mg bid.	Patients were treated with oral administration of soft gelatine capsules of Nintedanib 150 mg bid and could step down to 100 mg bid. In the 1199.35 trial they could remain on their last dose in the parent trial.
Overall Number of Participants Analyzed	37	126	35
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of participants
	37.4; (16.8 to 58.0)	46.8; (35.3 to 58.4)	66.2; (46.9 to 85.5)

3. Secondary Outcome

Title	Progression-Free Survival
Description	Progression-free survival was defined as the time from the first nintedanib intake in trial 1199.35 to disease progression. For presentation of progression-free survival results, Kaplan-Meier estimates and confidence intervals (using Greenwood variance formula) for the overall on-treatment progression-free survival is calculated within each treatment arm.
Time Frame	From first trial drug intake in 1199.35 to disease progression; up to 61.8 months

Outcome Measure Data

Analysis Population Description

FAS

Arm/Group Title	Placebo	Nintedanib 50 mg- 100 mg	Nintedanib 150 mg
Arm/Group Description:	Patients were treated with oral administration of placebo in period 1 of the parent trial and with soft gelatine capsules of Nintedanib 50 mg once daily (qd) in the second period of the 1199.30 (parent trial). In the 1199.35 trial they could remain on this last dose or increase to Nintedanib 150 mg twice daily (bid)	Patients were treated with oral administration of soft gelatine capsules of Nintedanib 50 mg qd, 50 mg bid or 100 mg bid in the parent trial. In the 1199.35 trial they could remain on their last dose in the parent trial or increase to Nintedanib 150 mg bid.	Patients were treated with oral administration of soft gelatine capsules of Nintedanib 150 mg bid and could step down to 100 mg bid. In the 1199.35 trial they could remain on their last dose in the parent trial.
Overall Number of Participants Analyzed	37	126	35
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of participants
	9.6; (0.0 to 22.0)	3.5; (0.0 to 7.4)	12.2; (0.0 to 24.9)

4. Secondary Outcome

Title	Annual Rate of Decline in Haemoglobin Corrected Diffusing Capacity of the Lung for Carbon Monoxide (DLCO) Decrease
Description	Haemoglobin corrected DLCO decrease was a secondary endpoint for the trial. It was considered important that all investigators used the same method of testing and recording data at each visit for each patient. Haemoglobin corrected DLCO was calculated for each patient using the following formulae: Males: Hb corrected DLCO = measured DLCO x (10.22 + Hb concentration) / (1.7 x Hb concentration) Females: Hb corrected DLCO = measured DLCO x (9.38 + Hb concentration) / (1.7 x Hb concentration). Annual rate of decline in haemoglobin corrected diffusing capacity of the lung for carbon monoxide (DLCO) decrease is presented.
Time Frame	From first drug administration in 1199.35 until database lock 15Oct2015, up to 61.8 Months

Outcome Measure Data

Analysis Population Description

FAS

Arm/Group Title	Placebo	Nintedanib 50 mg- 100 mg	Nintedanib 150 mg
Arm/Group Description:	Patients were treated with oral administration of placebo in period 1 of the parent trial and with soft gelatine capsules of Nintedanib 50 mg once daily (qd) in the second period of the 1199.30 (parent trial). In the 1199.35 trial they could remain on this last dose or increase to Nintedanib 150 mg twice daily (bid)	Patients were treated with oral administration of soft gelatine capsules of Nintedanib 50 mg qd, 50 mg bid or 100 mg bid in the parent trial. In the 1199.35 trial they could remain on their last dose in the parent trial or increase to Nintedanib 150 mg bid.	Patients were treated with oral administration of soft gelatine capsules of Nintedanib 150 mg bid and could step down to 100 mg bid. In the 1199.35 trial they could remain on their last dose in the parent trial.
Overall Number of Participants Analyzed	37	126	35
Mean (Standard Error); Unit of Measure: mmol/min/kPa/yr
	-0.4 (0.08)	-0.3 (0.04)	-0.2 (0.07)

5. Secondary Outcome

Title	Percentage of Patients With at Least One Acute Idiopathic Pulmonary Fibrosis (IPF) Exacerbation
Description	Percentage of patients with at least one acute idiopathic pulmonary fibrosis (IPF) exacerbation are presented. An exacerbation was defined as otherwise unexplained clinical features occurring within 1 month including all of the following: Progression of dyspnoea over several days to 4 weeks; New diffuse pulmonary infiltrates on chest X-ray and/or high-resolution computerised tomography (HRCT) Parenchymal abnormalities with no pneumothorax or pleural effusion (new ground-glass opacities) since the last visit; A decrease in arterial oxygen partial pressure (PaO2) of ≥10 mmHg or PaO2/fraction of inspired oxygen (FiO2) of <225 mmHg since the last visit; Exclusion of infection based on routine clinical practice and microbiological studies; Absence of other contributory causes such as congestive heart failure, pulmonary embolism, etc.
Time Frame	From first drug administration in 1199.35 until database lock 15Oct2015, up to 61.8 Months

Outcome Measure Data

Analysis Population Description

FAS

Arm/Group Title	Placebo	Nintedanib 50 mg- 100 mg	Nintedanib 150 mg
Arm/Group Description:	Patients were treated with oral administration of placebo in period 1 of the parent trial and with soft gelatine capsules of Nintedanib 50 mg once daily (qd) in the second period of the 1199.30 (parent trial). In the 1199.35 trial they could remain on this last dose or increase to Nintedanib 150 mg twice daily (bid)	Patients were treated with oral administration of soft gelatine capsules of Nintedanib 50 mg qd, 50 mg bid or 100 mg bid in the parent trial. In the 1199.35 trial they could remain on their last dose in the parent trial or increase to Nintedanib 150 mg bid.	Patients were treated with oral administration of soft gelatine capsules of Nintedanib 150 mg bid and could step down to 100 mg bid. In the 1199.35 trial they could remain on their last dose in the parent trial.
Overall Number of Participants Analyzed	37	126	35
Measure Type: Number; Unit of Measure: Percentage of participants
	13.5	19.8	20.0

6. Secondary Outcome

Title	Incidence of Patients With at Least One Acute IPF Exacerbation Over Time
Description	Incidence rate = (Patients with at least one acute IPF exacerbation / Total number of years at risk) x 100
Time Frame	From first drug administration in 1199.35 until database lock 15Oct2015, up to 61.8 Months

Outcome Measure Data

Analysis Population Description

FAS

Arm/Group Title	Placebo	Nintedanib 50 mg- 100 mg	Nintedanib 150 mg
Arm/Group Description:	Patients were treated with oral administration of placebo in period 1 of the parent trial and with soft gelatine capsules of Nintedanib 50 mg once daily (qd) in the second period of the 1199.30 (parent trial). In the 1199.35 trial they could remain on this last dose or increase to Nintedanib 150 mg twice daily (bid)	Patients were treated with oral administration of soft gelatine capsules of Nintedanib 50 mg qd, 50 mg bid or 100 mg bid in the parent trial. In the 1199.35 trial they could remain on their last dose in the parent trial or increase to Nintedanib 150 mg bid.	Patients were treated with oral administration of soft gelatine capsules of Nintedanib 150 mg bid and could step down to 100 mg bid. In the 1199.35 trial they could remain on their last dose in the parent trial.
Overall Number of Participants Analyzed	37	126	35
Measure Type: Number; Unit of Measure: Exacerbations Per Year
	6.1	7.6	7.8

7. Secondary Outcome

Title	Time to First Acute IPF Exacerbation
Description	Due to rare events, the median of time to event is not calculable, thus Kaplan-Meier estimates (providing the percentage of patients without acute IPF exacerbation for a certain amount of time after treatment) and confidence intervals (using Greenwood variance formula) are reported and presented within each treatment arm as secondary endpoint.
Time Frame	From first drug administration in 1199.35 until database lock 15Oct2015, up to 61.8 Months

Outcome Measure Data

Analysis Population Description

FAS

Arm/Group Title	Placebo	Nintedanib 50 mg- 100 mg	Nintedanib 150 mg
Arm/Group Description:	Patients were treated with oral administration of placebo in period 1 of the parent trial and with soft gelatine capsules of Nintedanib 50 mg once daily (qd) in the second period of the 1199.30 (parent trial). In the 1199.35 trial they could remain on this last dose or increase to Nintedanib 150 mg twice daily (bid)	Patients were treated with oral administration of soft gelatine capsules of Nintedanib 50 mg qd, 50 mg bid or 100 mg bid in the parent trial. In the 1199.35 trial they could remain on their last dose in the parent trial or increase to Nintedanib 150 mg bid.	Patients were treated with oral administration of soft gelatine capsules of Nintedanib 150 mg bid and could step down to 100 mg bid. In the 1199.35 trial they could remain on their last dose in the parent trial.
Overall Number of Participants Analyzed	37	126	35
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of participants
	67.7; (39.4 to 95.9)	68.6; (56.8 to 80.4)	73.5; (55.9 to 91.1)

8. Secondary Outcome

Title	Percentage of Patients With at Least One Adverse Events (AEs), With Investigator Defined Drug-Related AEs, AEs Leading to Discontinuation of Trial Drug, Serious AEs
Description	Percentage of patients with at least one Adverse events (AEs), with investigator defined drug-related AEs, AEs leading to discontinuation of trial drug, serious AEs are presented
Time Frame	From the first nintedanib intake in trial 1199.35 to the last nintedanib intake + 28 days; up to 61.8 months + 28 days

Outcome Measure Data

Analysis Population Description

TS

Arm/Group Title	Placebo	Nintedanib 50 mg- 100 mg	Nintedanib 150 mg
Arm/Group Description:	Patients were treated with oral administration of placebo in period 1 of the parent trial and with soft gelatine capsules of Nintedanib 50 mg once daily (qd) in the second period of the 1199.30 (parent trial). In the 1199.35 trial they could remain on this last dose or increase to Nintedanib 150 mg twice daily (bid)	Patients were treated with oral administration of soft gelatine capsules of Nintedanib 50 mg qd, 50 mg bid or 100 mg bid in the parent trial. In the 1199.35 trial they could remain on their last dose in the parent trial or increase to Nintedanib 150 mg bid.	Patients were treated with oral administration of soft gelatine capsules of Nintedanib 150 mg bid and could step down to 100 mg bid. In the 1199.35 trial they could remain on their last dose in the parent trial.
Overall Number of Participants Analyzed	37	126	35
Measure Type: Number; Unit of Measure: Percentage of participants
AEs	100.0	99.2	97.1
Investigator defined drug-related AEs	70.3	65.9	54.3
AEs leading to discontinuation of trial drug	48.6	41.3	34.3
Serious AE	67.6	74.6	62.9

Adverse Events

Time Frame	From the first nintedanib intake in trial 1199.35 to the last nintedanib intake + 28 days; up to 61.8 months + 28 days
Adverse Event Reporting Description	[Not Specified]
Arm/Group Title	Placebo	Nintedanib 50 mg- 100 mg	Nintedanib 150 mg
Arm/Group Description	Patients were treated with oral administration of placebo in period 1 of the parent trial and with soft gelatine capsules of Nintedanib 50 mg once daily (qd) in the second period of the 1199.30 (parent trial). In the 1199.35 trial they could remain on this last dose or increase to Nintedanib 150 mg twice daily (bid)	Patients were treated with oral administration of soft gelatine capsules of Nintedanib 50 mg qd, 50 mg bid or 100 mg bid in the parent trial. In the 1199.35 trial they could remain on their last dose in the parent trial or increase to Nintedanib 150 mg bid.	Patients were treated with oral administration of soft gelatine capsules of Nintedanib 150 mg bid and could step down to 100 mg bid. In the 1199.35 trial they could remain on their last dose in the parent trial.
All-Cause Mortality
	Placebo	Nintedanib 50 mg- 100 mg	Nintedanib 150 mg
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	--/--	--/--	--/--
Serious Adverse Events
	Placebo	Nintedanib 50 mg- 100 mg	Nintedanib 150 mg
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	25/37 (67.57%)	94/126 (74.60%)	22/35 (62.86%)
Cardiac disorders
Acute coronary syndrome † 1	0/37 (0.00%)	1/126 (0.79%)	1/35 (2.86%)
Acute myocardial infarction † 1	0/37 (0.00%)	3/126 (2.38%)	0/35 (0.00%)
Angina unstable † 1	0/37 (0.00%)	3/126 (2.38%)	0/35 (0.00%)
Arrhythmia † 1	1/37 (2.70%)	0/126 (0.00%)	0/35 (0.00%)
Atrial fibrillation † 1	1/37 (2.70%)	2/126 (1.59%)	0/35 (0.00%)
Bradycardia † 1	0/37 (0.00%)	0/126 (0.00%)	1/35 (2.86%)
Bundle branch block † 1	0/37 (0.00%)	1/126 (0.79%)	0/35 (0.00%)
Cardiac arrest † 1	2/37 (5.41%)	1/126 (0.79%)	0/35 (0.00%)
Cardiac disorder † 1	0/37 (0.00%)	0/126 (0.00%)	2/35 (5.71%)
Cardiac failure † 1	0/37 (0.00%)	5/126 (3.97%)	1/35 (2.86%)
Cardiac failure acute † 1	0/37 (0.00%)	1/126 (0.79%)	0/35 (0.00%)
Cardio-respiratory arrest † 1	0/37 (0.00%)	0/126 (0.00%)	1/35 (2.86%)
Cardiopulmonary failure † 1	0/37 (0.00%)	1/126 (0.79%)	0/35 (0.00%)
Coronary artery disease † 1	1/37 (2.70%)	1/126 (0.79%)	0/35 (0.00%)
Coronary artery stenosis † 1	0/37 (0.00%)	1/126 (0.79%)	0/35 (0.00%)
Myocardial infarction † 1	0/37 (0.00%)	1/126 (0.79%)	0/35 (0.00%)
Myocardial ischaemia † 1	0/37 (0.00%)	2/126 (1.59%)	1/35 (2.86%)
Right ventricular failure † 1	0/37 (0.00%)	2/126 (1.59%)	0/35 (0.00%)
Ventricular tachycardia † 1	0/37 (0.00%)	1/126 (0.79%)	0/35 (0.00%)
Gastrointestinal disorders
Anal haemorrhage † 1	1/37 (2.70%)	0/126 (0.00%)	0/35 (0.00%)
Diarrhoea † 1	3/37 (8.11%)	2/126 (1.59%)	1/35 (2.86%)
Diverticulum intestinal † 1	1/37 (2.70%)	0/126 (0.00%)	0/35 (0.00%)
Dysphagia † 1	0/37 (0.00%)	1/126 (0.79%)	0/35 (0.00%)
Gastric ulcer † 1	0/37 (0.00%)	1/126 (0.79%)	0/35 (0.00%)
Gastrointestinal disorder † 1	0/37 (0.00%)	1/126 (0.79%)	0/35 (0.00%)
Haemorrhoids † 1	2/37 (5.41%)	1/126 (0.79%)	0/35 (0.00%)
Inguinal hernia † 1	0/37 (0.00%)	1/126 (0.79%)	1/35 (2.86%)
Intestinal obstruction † 1	0/37 (0.00%)	1/126 (0.79%)	0/35 (0.00%)
Intestinal perforation † 1	0/37 (0.00%)	0/126 (0.00%)	1/35 (2.86%)
Lower gastrointestinal haemorrhage † 1	0/37 (0.00%)	1/126 (0.79%)	0/35 (0.00%)
Nausea † 1	1/37 (2.70%)	0/126 (0.00%)	0/35 (0.00%)
Oesophageal ulcer † 1	0/37 (0.00%)	1/126 (0.79%)	0/35 (0.00%)
Umbilical hernia † 1	0/37 (0.00%)	2/126 (1.59%)	0/35 (0.00%)
Volvulus † 1	0/37 (0.00%)	1/126 (0.79%)	0/35 (0.00%)
Vomiting † 1	1/37 (2.70%)	0/126 (0.00%)	0/35 (0.00%)
General disorders
Chest pain † 1	1/37 (2.70%)	2/126 (1.59%)	1/35 (2.86%)
Death † 1	1/37 (2.70%)	1/126 (0.79%)	0/35 (0.00%)
Disease progression † 1	0/37 (0.00%)	2/126 (1.59%)	0/35 (0.00%)
General physical health deterioration † 1	0/37 (0.00%)	1/126 (0.79%)	0/35 (0.00%)
Impaired healing † 1	0/37 (0.00%)	0/126 (0.00%)	1/35 (2.86%)
Multi-organ failure † 1	0/37 (0.00%)	1/126 (0.79%)	0/35 (0.00%)
Pyrexia † 1	1/37 (2.70%)	1/126 (0.79%)	0/35 (0.00%)
Sudden death † 1	0/37 (0.00%)	2/126 (1.59%)	0/35 (0.00%)
Infections and infestations
Bacterial infection † 1	0/37 (0.00%)	0/126 (0.00%)	1/35 (2.86%)
Bronchitis † 1	1/37 (2.70%)	3/126 (2.38%)	1/35 (2.86%)
Bronchopneumonia † 1	0/37 (0.00%)	0/126 (0.00%)	1/35 (2.86%)
Chlamydial infection † 1	0/37 (0.00%)	1/126 (0.79%)	0/35 (0.00%)
Escherichia urinary tract infection † 1	0/37 (0.00%)	1/126 (0.79%)	0/35 (0.00%)
Fungal infection † 1	0/37 (0.00%)	0/126 (0.00%)	1/35 (2.86%)
Gastroenteritis † 1	0/37 (0.00%)	1/126 (0.79%)	0/35 (0.00%)
Gastroenteritis clostridial † 1	1/37 (2.70%)	0/126 (0.00%)	0/35 (0.00%)
Herpes zoster † 1	0/37 (0.00%)	0/126 (0.00%)	1/35 (2.86%)
Influenza † 1	0/37 (0.00%)	1/126 (0.79%)	0/35 (0.00%)
Lower respiratory tract infection † 1	0/37 (0.00%)	4/126 (3.17%)	1/35 (2.86%)
Lower respiratory tract infection bacterial † 1	0/37 (0.00%)	1/126 (0.79%)	1/35 (2.86%)
Lung infection † 1	1/37 (2.70%)	5/126 (3.97%)	3/35 (8.57%)
Pneumonia † 1	3/37 (8.11%)	6/126 (4.76%)	2/35 (5.71%)
Pneumonia escherichia † 1	0/37 (0.00%)	1/126 (0.79%)	0/35 (0.00%)
Respiratory tract infection † 1	1/37 (2.70%)	4/126 (3.17%)	1/35 (2.86%)
Sepsis † 1	0/37 (0.00%)	1/126 (0.79%)	0/35 (0.00%)
Septic shock † 1	0/37 (0.00%)	1/126 (0.79%)	0/35 (0.00%)
Urinary tract infection † 1	1/37 (2.70%)	0/126 (0.00%)	0/35 (0.00%)
Urosepsis † 1	1/37 (2.70%)	0/126 (0.00%)	0/35 (0.00%)
Injury, poisoning and procedural complications
Cervical vertebral fracture † 1	1/37 (2.70%)	0/126 (0.00%)	0/35 (0.00%)
Contusion † 1	0/37 (0.00%)	1/126 (0.79%)	0/35 (0.00%)
Fall † 1	3/37 (8.11%)	2/126 (1.59%)	1/35 (2.86%)
Gastrointestinal stoma complication † 1	0/37 (0.00%)	1/126 (0.79%)	0/35 (0.00%)
Hip fracture † 1	0/37 (0.00%)	0/126 (0.00%)	1/35 (2.86%)
Meniscus injury † 1	0/37 (0.00%)	1/126 (0.79%)	0/35 (0.00%)
Overdose † 1	0/37 (0.00%)	1/126 (0.79%)	0/35 (0.00%)
Rib fracture † 1	0/37 (0.00%)	0/126 (0.00%)	1/35 (2.86%)
Toxicity to various agents † 1	0/37 (0.00%)	1/126 (0.79%)	0/35 (0.00%)
Investigations
Pancreatic enzymes increased † 1	0/37 (0.00%)	1/126 (0.79%)	0/35 (0.00%)
Troponin I † 1	0/37 (0.00%)	1/126 (0.79%)	0/35 (0.00%)
Weight decreased † 1	1/37 (2.70%)	2/126 (1.59%)	0/35 (0.00%)
Metabolism and nutrition disorders
Decreased appetite † 1	0/37 (0.00%)	1/126 (0.79%)	0/35 (0.00%)
Diabetes mellitus † 1	0/37 (0.00%)	1/126 (0.79%)	0/35 (0.00%)
Hypoglycaemia † 1	1/37 (2.70%)	0/126 (0.00%)	0/35 (0.00%)
Hyponatraemia † 1	0/37 (0.00%)	0/126 (0.00%)	1/35 (2.86%)
Musculoskeletal and connective tissue disorders
Arthropathy † 1	0/37 (0.00%)	1/126 (0.79%)	0/35 (0.00%)
Back pain † 1	0/37 (0.00%)	1/126 (0.79%)	0/35 (0.00%)
Exostosis † 1	0/37 (0.00%)	1/126 (0.79%)	0/35 (0.00%)
Foot deformity † 1	0/37 (0.00%)	1/126 (0.79%)	0/35 (0.00%)
Groin pain † 1	0/37 (0.00%)	1/126 (0.79%)	0/35 (0.00%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Adenocarcinoma of colon † 1	0/37 (0.00%)	1/126 (0.79%)	0/35 (0.00%)
Basal cell carcinoma † 1	0/37 (0.00%)	2/126 (1.59%)	0/35 (0.00%)
Colon cancer † 1	0/37 (0.00%)	1/126 (0.79%)	0/35 (0.00%)
Lung neoplasm malignant † 1	2/37 (5.41%)	2/126 (1.59%)	0/35 (0.00%)
Malignant neoplasm progression † 1	0/37 (0.00%)	1/126 (0.79%)	0/35 (0.00%)
Metastases to liver † 1	1/37 (2.70%)	2/126 (1.59%)	0/35 (0.00%)
Metastases to lung † 1	0/37 (0.00%)	1/126 (0.79%)	0/35 (0.00%)
Metastases to spine † 1	0/37 (0.00%)	1/126 (0.79%)	0/35 (0.00%)
Non-small cell lung cancer † 1	0/37 (0.00%)	1/126 (0.79%)	0/35 (0.00%)
Pancreatic carcinoma † 1	0/37 (0.00%)	1/126 (0.79%)	0/35 (0.00%)
Renal neoplasm † 1	0/37 (0.00%)	0/126 (0.00%)	1/35 (2.86%)
Squamous cell carcinoma † 1	0/37 (0.00%)	3/126 (2.38%)	0/35 (0.00%)
Squamous cell carcinoma of skin † 1	0/37 (0.00%)	1/126 (0.79%)	0/35 (0.00%)
Thyroid cancer † 1	0/37 (0.00%)	1/126 (0.79%)	0/35 (0.00%)
Nervous system disorders
Cerebral infarction † 1	0/37 (0.00%)	0/126 (0.00%)	1/35 (2.86%)
Cerebrovascular accident † 1	0/37 (0.00%)	1/126 (0.79%)	1/35 (2.86%)
Coma † 1	0/37 (0.00%)	1/126 (0.79%)	0/35 (0.00%)
Dizziness † 1	0/37 (0.00%)	1/126 (0.79%)	0/35 (0.00%)
Epilepsy † 1	0/37 (0.00%)	0/126 (0.00%)	1/35 (2.86%)
Hemiplegia † 1	0/37 (0.00%)	0/126 (0.00%)	1/35 (2.86%)
Ischaemic stroke † 1	0/37 (0.00%)	1/126 (0.79%)	0/35 (0.00%)
Loss of consciousness † 1	1/37 (2.70%)	0/126 (0.00%)	0/35 (0.00%)
Syncope † 1	0/37 (0.00%)	3/126 (2.38%)	0/35 (0.00%)
Transient ischaemic attack † 1	0/37 (0.00%)	0/126 (0.00%)	1/35 (2.86%)
Tremor † 1	1/37 (2.70%)	0/126 (0.00%)	0/35 (0.00%)
Psychiatric disorders
Depression † 1	0/37 (0.00%)	1/126 (0.79%)	0/35 (0.00%)
Suicide attempt † 1	0/37 (0.00%)	1/126 (0.79%)	0/35 (0.00%)
Renal and urinary disorders
Acute kidney injury † 1	0/37 (0.00%)	1/126 (0.79%)	0/35 (0.00%)
Haematuria † 1	1/37 (2.70%)	0/126 (0.00%)	0/35 (0.00%)
Nephrolithiasis † 1	0/37 (0.00%)	2/126 (1.59%)	0/35 (0.00%)
Urinary bladder polyp † 1	0/37 (0.00%)	1/126 (0.79%)	0/35 (0.00%)
Urinary tract obstruction † 1	0/37 (0.00%)	0/126 (0.00%)	1/35 (2.86%)
Respiratory, thoracic and mediastinal disorders
Acute pulmonary oedema † 1	0/37 (0.00%)	1/126 (0.79%)	0/35 (0.00%)
Acute respiratory failure † 1	1/37 (2.70%)	2/126 (1.59%)	0/35 (0.00%)
Bronchial hyperreactivity † 1	0/37 (0.00%)	1/126 (0.79%)	0/35 (0.00%)
Bronchiectasis † 1	0/37 (0.00%)	1/126 (0.79%)	0/35 (0.00%)
Bronchostenosis † 1	0/37 (0.00%)	1/126 (0.79%)	0/35 (0.00%)
Bullous lung disease † 1	0/37 (0.00%)	1/126 (0.79%)	0/35 (0.00%)
Dyspnoea † 1	2/37 (5.41%)	11/126 (8.73%)	0/35 (0.00%)
Hypoventilation † 1	0/37 (0.00%)	1/126 (0.79%)	0/35 (0.00%)
Hypoxia † 1	0/37 (0.00%)	1/126 (0.79%)	0/35 (0.00%)
Idiopathic pulmonary fibrosis † 1	11/37 (29.73%)	41/126 (32.54%)	10/35 (28.57%)
Lung consolidation † 1	0/37 (0.00%)	1/126 (0.79%)	0/35 (0.00%)
Lung disorder † 1	0/37 (0.00%)	1/126 (0.79%)	1/35 (2.86%)
Pneumomediastinum † 1	0/37 (0.00%)	0/126 (0.00%)	1/35 (2.86%)
Pneumothorax spontaneous † 1	0/37 (0.00%)	1/126 (0.79%)	0/35 (0.00%)
Pulmonary arterial hypertension † 1	0/37 (0.00%)	0/126 (0.00%)	1/35 (2.86%)
Pulmonary congestion † 1	0/37 (0.00%)	1/126 (0.79%)	0/35 (0.00%)
Pulmonary embolism † 1	1/37 (2.70%)	6/126 (4.76%)	1/35 (2.86%)
Pulmonary fibrosis † 1	1/37 (2.70%)	0/126 (0.00%)	0/35 (0.00%)
Pulmonary hypertension † 1	0/37 (0.00%)	5/126 (3.97%)	1/35 (2.86%)
Respiratory disorder † 1	1/37 (2.70%)	0/126 (0.00%)	0/35 (0.00%)
Respiratory failure † 1	1/37 (2.70%)	7/126 (5.56%)	1/35 (2.86%)
Skin and subcutaneous tissue disorders
Erythema multiforme † 1	0/37 (0.00%)	1/126 (0.79%)	0/35 (0.00%)
Granuloma skin † 1	0/37 (0.00%)	1/126 (0.79%)	0/35 (0.00%)
Vascular disorders
Aortic aneurysm † 1	0/37 (0.00%)	0/126 (0.00%)	1/35 (2.86%)
Deep vein thrombosis † 1	0/37 (0.00%)	1/126 (0.79%)	0/35 (0.00%)
Hypertension † 1	0/37 (0.00%)	1/126 (0.79%)	1/35 (2.86%)
Hypotension † 1	0/37 (0.00%)	1/126 (0.79%)	0/35 (0.00%)
Orthostatic hypotension † 1	1/37 (2.70%)	0/126 (0.00%)	0/35 (0.00%)
Peripheral artery aneurysm † 1	0/37 (0.00%)	1/126 (0.79%)	0/35 (0.00%)
† Indicates events were collected by systematic assessment; 1 Term from vocabulary, MedDRA 18.0
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Placebo	Nintedanib 50 mg- 100 mg	Nintedanib 150 mg
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	34/37 (91.89%)	111/126 (88.10%)	32/35 (91.43%)
Blood and lymphatic system disorders
Anaemia † 1	2/37 (5.41%)	1/126 (0.79%)	2/35 (5.71%)
Cardiac disorders
Atrial fibrillation † 1	0/37 (0.00%)	1/126 (0.79%)	2/35 (5.71%)
Ear and labyrinth disorders
Vertigo † 1	2/37 (5.41%)	1/126 (0.79%)	0/35 (0.00%)
Eye disorders
Cataract † 1	2/37 (5.41%)	9/126 (7.14%)	3/35 (8.57%)
Glaucoma † 1	0/37 (0.00%)	1/126 (0.79%)	2/35 (5.71%)
Gastrointestinal disorders
Abdominal pain † 1	2/37 (5.41%)	9/126 (7.14%)	4/35 (11.43%)
Abdominal pain upper † 1	2/37 (5.41%)	4/126 (3.17%)	0/35 (0.00%)
Constipation † 1	2/37 (5.41%)	11/126 (8.73%)	1/35 (2.86%)
Diarrhoea † 1	19/37 (51.35%)	68/126 (53.97%)	22/35 (62.86%)
Frequent bowel movements † 1	1/37 (2.70%)	0/126 (0.00%)	2/35 (5.71%)
Gastrooesophageal reflux disease † 1	3/37 (8.11%)	4/126 (3.17%)	2/35 (5.71%)
Nausea † 1	9/37 (24.32%)	22/126 (17.46%)	2/35 (5.71%)
Vomiting † 1	7/37 (18.92%)	17/126 (13.49%)	3/35 (8.57%)
General disorders
Chest pain † 1	2/37 (5.41%)	10/126 (7.94%)	1/35 (2.86%)
Condition aggravated † 1	2/37 (5.41%)	0/126 (0.00%)	1/35 (2.86%)
Fatigue † 1	2/37 (5.41%)	9/126 (7.14%)	4/35 (11.43%)
Influenza like illness † 1	0/37 (0.00%)	0/126 (0.00%)	2/35 (5.71%)
Hepatobiliary disorders
Hepatic function abnormal † 1	1/37 (2.70%)	2/126 (1.59%)	2/35 (5.71%)
Infections and infestations
Bronchitis † 1	12/37 (32.43%)	27/126 (21.43%)	6/35 (17.14%)
Cystitis † 1	2/37 (5.41%)	2/126 (1.59%)	1/35 (2.86%)
Gastroenteritis † 1	0/37 (0.00%)	8/126 (6.35%)	4/35 (11.43%)
Influenza † 1	1/37 (2.70%)	9/126 (7.14%)	6/35 (17.14%)
Lower respiratory tract infection † 1	4/37 (10.81%)	12/126 (9.52%)	1/35 (2.86%)
Nasopharyngitis † 1	8/37 (21.62%)	24/126 (19.05%)	6/35 (17.14%)
Pneumonia † 1	2/37 (5.41%)	3/126 (2.38%)	1/35 (2.86%)
Respiratory tract infection † 1	3/37 (8.11%)	8/126 (6.35%)	3/35 (8.57%)
Sinusitis † 1	0/37 (0.00%)	9/126 (7.14%)	0/35 (0.00%)
Tinea pedis † 1	0/37 (0.00%)	0/126 (0.00%)	2/35 (5.71%)
Tooth abscess † 1	2/37 (5.41%)	2/126 (1.59%)	0/35 (0.00%)
Tracheobronchitis † 1	2/37 (5.41%)	2/126 (1.59%)	2/35 (5.71%)
Upper respiratory tract infection † 1	1/37 (2.70%)	10/126 (7.94%)	1/35 (2.86%)
Urinary tract infection † 1	2/37 (5.41%)	11/126 (8.73%)	1/35 (2.86%)
Investigations
Gamma-glutamyltransferase increased † 1	2/37 (5.41%)	6/126 (4.76%)	0/35 (0.00%)
Hepatic enzyme increased † 1	2/37 (5.41%)	3/126 (2.38%)	0/35 (0.00%)
Weight decreased † 1	10/37 (27.03%)	29/126 (23.02%)	7/35 (20.00%)
Metabolism and nutrition disorders
Decreased appetite † 1	6/37 (16.22%)	17/126 (13.49%)	2/35 (5.71%)
Hypokalaemia † 1	1/37 (2.70%)	3/126 (2.38%)	2/35 (5.71%)
Hyponatraemia † 1	0/37 (0.00%)	0/126 (0.00%)	2/35 (5.71%)
Musculoskeletal and connective tissue disorders
Arthralgia † 1	2/37 (5.41%)	4/126 (3.17%)	1/35 (2.86%)
Back pain † 1	2/37 (5.41%)	10/126 (7.94%)	1/35 (2.86%)
Muscle spasms † 1	2/37 (5.41%)	2/126 (1.59%)	1/35 (2.86%)
Osteoporosis † 1	0/37 (0.00%)	1/126 (0.79%)	2/35 (5.71%)
Nervous system disorders
Dizziness † 1	4/37 (10.81%)	11/126 (8.73%)	2/35 (5.71%)
Paraesthesia † 1	0/37 (0.00%)	1/126 (0.79%)	2/35 (5.71%)
Sciatica † 1	0/37 (0.00%)	1/126 (0.79%)	3/35 (8.57%)
Psychiatric disorders
Anxiety † 1	0/37 (0.00%)	4/126 (3.17%)	3/35 (8.57%)
Depression † 1	2/37 (5.41%)	4/126 (3.17%)	1/35 (2.86%)
Insomnia † 1	0/37 (0.00%)	2/126 (1.59%)	2/35 (5.71%)
Renal and urinary disorders
Haematuria † 1	0/37 (0.00%)	3/126 (2.38%)	2/35 (5.71%)
Proteinuria † 1	1/37 (2.70%)	2/126 (1.59%)	2/35 (5.71%)
Urinary retention † 1	0/37 (0.00%)	0/126 (0.00%)	2/35 (5.71%)
Respiratory, thoracic and mediastinal disorders
Cough † 1	3/37 (8.11%)	27/126 (21.43%)	4/35 (11.43%)
Dyspnoea † 1	5/37 (13.51%)	19/126 (15.08%)	3/35 (8.57%)
Epistaxis † 1	2/37 (5.41%)	8/126 (6.35%)	1/35 (2.86%)
Idiopathic pulmonary fibrosis † 1	0/37 (0.00%)	22/126 (17.46%)	3/35 (8.57%)
Skin and subcutaneous tissue disorders
Pruritus † 1	1/37 (2.70%)	7/126 (5.56%)	2/35 (5.71%)
Rash † 1	2/37 (5.41%)	3/126 (2.38%)	0/35 (0.00%)
Vascular disorders
Hypertension † 1	0/37 (0.00%)	7/126 (5.56%)	3/35 (8.57%)
Hypotension † 1	0/37 (0.00%)	3/126 (2.38%)	2/35 (5.71%)
† Indicates events were collected by systematic assessment; 1 Term from vocabulary, MedDRA 18.0

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

Boehringer Ingelheim (BI) acknowledges that investigators have the right to publish the study results. Investigators shall provide BI with a copy of any publication or presentation for review prior to any submission. Such review will be done with regard to proprietary information, information related to patentable inventions, medical, scientific, and statistical accuracy within 60 days. BI may request a delay of the publication in order to protect BI's intellectual property rights.

Results Point of Contact

• Name/Title: Boehringer Ingelheim Call Center
• Organization: Boehringer Ingelheim
• Phone: 1-800-243-0127
• EMail: clintriage.rdg@boehringer-ingelheim.com

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Richeldi L, Kreuter M, Selman M, Crestani B, Kirsten AM, Wuyts WA, Xu Z, Bernois K, Stowasser S, Quaresma M, Costabel U. Long-term treatment of patients with idiopathic pulmonary fibrosis with nintedanib: results from the TOMORROW trial and its open-label extension. Thorax. 2018 Jun;73(6):581-583. doi: 10.1136/thoraxjnl-2016-209701. Epub 2017 Oct 9.

• Responsible Party: Boehringer Ingelheim
• ClinicalTrials.gov Identifier: NCT01170065
• Other Study ID Numbers: 1199.35; 2009-013788-21 ( EudraCT Number )
• First Submitted: July 6, 2010
• First Posted: July 27, 2010
• Results First Submitted: September 25, 2017
• Results First Posted: June 6, 2019
• Last Update Posted: June 6, 2019