Trial Outcomes & Findings for Roll Over Study From 1199.30 BIBF 1120 in Idiopathic Pulmonary Fibrosis (IPF) (NCT NCT01170065)

Last Updated: 2019-06-06

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

198 participants

Primary outcome timeframe

From first drug administration in 1199.35 until database lock 15Oct2015, up to 61.8 Months

Results posted on

2019-06-06

Participant Flow

Treatment groups are displayed according to dose at randomisation in 1199.30 (NCT00514683).

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.

Participant milestones

Participant milestones
Measure	Placebo 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)	Nintedanib 50 mg- 100 mg 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.	Nintedanib 150 mg 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 Study STARTED	37	126	35
Overall Study COMPLETED	9	34	9
Overall Study NOT COMPLETED	28	92	26

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo 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)	Nintedanib 50 mg- 100 mg 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.	Nintedanib 150 mg 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 Study Adverse Event	17	50	10
Overall Study Lost to Follow-up	1	4	1
Overall Study Consent withdrawn, not due to AE	2	4	2
Overall Study Reason other than specified	3	8	3
Overall Study Ongoing after planned observation time	5	26	10

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=37 Participants 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)	Nintedanib 50 mg- 100 mg n=126 Participants 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.	Nintedanib 150 mg n=35 Participants 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 n=198 Participants Total of all reporting groups
Age, Continuous	64.2 years STANDARD_DEVIATION 7.3 • n=5 Participants	65.4 years STANDARD_DEVIATION 8.6 • n=7 Participants	65.2 years STANDARD_DEVIATION 7.2 • n=5 Participants	65.2 years STANDARD_DEVIATION 8.1 • n=4 Participants
Sex: Female, Male Female	14 Participants n=5 Participants	36 Participants n=7 Participants	7 Participants n=5 Participants	57 Participants n=4 Participants
Sex: Female, Male Male	23 Participants n=5 Participants	90 Participants n=7 Participants	28 Participants n=5 Participants	141 Participants n=4 Participants

PRIMARY outcome

Timeframe: From first drug administration in 1199.35 until database lock 15Oct2015, up to 61.8 Months

Population: 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

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.

Outcome measures

Outcome measures
Measure	Placebo n=37 Participants 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)	Nintedanib 50 mg- 100 mg n=126 Participants 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.	Nintedanib 150 mg n=35 Participants 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.
Annual Rate of Decline in Forced Vital Capacity (FVC)	-129.0 milliliters per year (mL/ yr) Standard Error 29.47	-137.5 milliliters per year (mL/ yr) Standard Error 14.60	-132.9 milliliters per year (mL/ yr) Standard Error 28.22

SECONDARY outcome

Timeframe: From first drug administration in 1199.35 until database lock 15Oct2015, up to 61.8 Months

Population: FAS

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.

Outcome measures

Outcome measures
Measure	Placebo n=37 Participants 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)	Nintedanib 50 mg- 100 mg n=126 Participants 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.	Nintedanib 150 mg n=35 Participants 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 Survival	37.4 percentage of participants 95% Confidence Interval 29.47 • Interval 16.8 to 58.0	46.8 percentage of participants 95% Confidence Interval 14.60 • Interval 35.3 to 58.4	66.2 percentage of participants 95% Confidence Interval 28.22 • Interval 46.9 to 85.5

SECONDARY outcome

Timeframe: From first trial drug intake in 1199.35 to disease progression; up to 61.8 months

Population: FAS

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.

Outcome measures

Outcome measures
Measure	Placebo n=37 Participants 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)	Nintedanib 50 mg- 100 mg n=126 Participants 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.	Nintedanib 150 mg n=35 Participants 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.
Progression-Free Survival	9.6 percentage of participants 95% Confidence Interval 29.47 • Interval 0.0 to 22.0	3.5 percentage of participants 95% Confidence Interval 14.60 • Interval 0.0 to 7.4	12.2 percentage of participants 95% Confidence Interval 28.22 • Interval 0.0 to 24.9

SECONDARY outcome

Timeframe: From first drug administration in 1199.35 until database lock 15Oct2015, up to 61.8 Months

Population: FAS

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.

Outcome measures

Outcome measures
Measure	Placebo n=37 Participants 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)	Nintedanib 50 mg- 100 mg n=126 Participants 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.	Nintedanib 150 mg n=35 Participants 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.
Annual Rate of Decline in Haemoglobin Corrected Diffusing Capacity of the Lung for Carbon Monoxide (DLCO) Decrease	-0.4 mmol/min/kPa/yr Standard Error 0.08	-0.3 mmol/min/kPa/yr Standard Error 0.04	-0.2 mmol/min/kPa/yr Standard Error 0.07

SECONDARY outcome

Timeframe: From first drug administration in 1199.35 until database lock 15Oct2015, up to 61.8 Months

Population: FAS

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.

Outcome measures

Outcome measures
Measure	Placebo n=37 Participants 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)	Nintedanib 50 mg- 100 mg n=126 Participants 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.	Nintedanib 150 mg n=35 Participants 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.
Percentage of Patients With at Least One Acute Idiopathic Pulmonary Fibrosis (IPF) Exacerbation	13.5 Percentage of participants 0.08	19.8 Percentage of participants 0.04	20.0 Percentage of participants 0.07

SECONDARY outcome

Timeframe: From first drug administration in 1199.35 until database lock 15Oct2015, up to 61.8 Months

Population: FAS

Incidence rate = (Patients with at least one acute IPF exacerbation / Total number of years at risk) x 100

Outcome measures

Outcome measures
Measure	Placebo n=37 Participants 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)	Nintedanib 50 mg- 100 mg n=126 Participants 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.	Nintedanib 150 mg n=35 Participants 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.
Incidence of Patients With at Least One Acute IPF Exacerbation Over Time	6.1 Exacerbations Per Year 0.08	7.6 Exacerbations Per Year 0.04	7.8 Exacerbations Per Year 0.07

SECONDARY outcome

Timeframe: From first drug administration in 1199.35 until database lock 15Oct2015, up to 61.8 Months

Population: FAS

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.

Outcome measures

Outcome measures
Measure	Placebo n=37 Participants 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)	Nintedanib 50 mg- 100 mg n=126 Participants 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.	Nintedanib 150 mg n=35 Participants 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.
Time to First Acute IPF Exacerbation	67.7 percentage of participants 95% Confidence Interval 29.47 • Interval 39.4 to 95.9	68.6 percentage of participants 95% Confidence Interval 14.60 • Interval 56.8 to 80.4	73.5 percentage of participants 95% Confidence Interval 28.22 • Interval 55.9 to 91.1

SECONDARY outcome

Timeframe: From the first nintedanib intake in trial 1199.35 to the last nintedanib intake + 28 days; up to 61.8 months + 28 days

Population: TS

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

Outcome measures

Outcome measures
Measure	Placebo n=37 Participants 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)	Nintedanib 50 mg- 100 mg n=126 Participants 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.	Nintedanib 150 mg n=35 Participants 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.
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 AEs	100.0 Percentage of participants 0.08	99.2 Percentage of participants 0.04	97.1 Percentage of participants 0.07
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 Investigator defined drug-related AEs	70.3 Percentage of participants	65.9 Percentage of participants	54.3 Percentage of participants
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 AEs leading to discontinuation of trial drug	48.6 Percentage of participants	41.3 Percentage of participants	34.3 Percentage of participants
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 Serious AE	67.6 Percentage of participants	74.6 Percentage of participants	62.9 Percentage of participants

Adverse Events

Placebo

Serious events: 25 serious events

Other events: 34 other events

Deaths: 0 deaths

Nintedanib 50 mg- 100 mg

Serious events: 94 serious events

Other events: 111 other events

Deaths: 0 deaths

Nintedanib 150 mg

Serious events: 22 serious events

Other events: 32 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Boehringer Ingelheim Call Center

Boehringer Ingelheim

Phone: 1-800-243-0127

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee 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.
Publication restrictions are in place

Restriction type: OTHER