Pulmonary Fibrosis
Conditions
Brief summary
Primary objective of this study is to investigate the long-term tolerability and safety profile of BIBF 1120 on top of pirfenidone treatment in patients with Idiopathic Pulmonary Fibrosis who have completed a prior clinical trial of BIBF 1120 (1199.31). Secondary objectives are to assess effects on some efficacy criteria during long term treatment with BIBF 1120 on top of pirfenidone.
Interventions
DRUGNintedanib
150 mg bid
DRUGPirfenidoneone
Existing treatment
Sponsors
Boehringer Ingelheim
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
40 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Written informed consent consistent with Good Clinical Practice (GCP) signed prior to entry into the study 2. Completion of 1199.31 study and still under treatment with pirfenidone at a stable dose
Exclusion criteria
1. Any disease that may interfere with testing procedures or in judgement of investigator may interfere with trial participation or may put the patient at risk when participating in this trial. Reconsider carefully all
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Overall Adverse Events | First drug administration until end of treatment, up to 5 years | Incidence (Number of patients) of Adverse events (AEs) over the course of treatment period including serious adverse events (SAEs), AEs leading to discontinuation of study medication, and fatal AEs. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Annual Rate of Decline in Forced Vital Capacity (FVC). | Baseline and every 8 weeks after drug administration until end of treatment, up to 5 years | The adjusted annual rate of decline in Forced Vital Capacity (FVC). The means presents actually the adjusted rate based on a random coefficient regression with fixed effects for gender, age, height and random effect of patient specific intercept and time. Within-patient errors are modelled by an Unstructured variance-covariance matrix. Inter-individual variability is modelled by a Variance-Components variance-covariance matrix. The result for Annual rate of decline (ROD) in FVC should be interpreted with caution and along with descriptive statistics, because inferences used for this analysis might not be valid as suggested by skewed distribution of the data. |
| Annual Rate of Decline in Haemoglobin (Hb) Corrected Diffusing Capacity of the Lung for Carbon Monoxide (DLCO) | Baseline & every 8 weeks after drug administration until end of treatment, up to 5 years | Adjusted annual rate of decline in Hb corrected DLCO. The means presents actually adjusted rate based on random coefficient regression with fixed effects for gender, age, height & random effect of patient specific intercept & time. Within-patient errors are modelled by Unstructured variance-covariance matrix.Inter-individual variability is modelled by a variance-Components variance-covariance matrix. mmHg: millimeters of mercury |
| Acute Exacerbations of IPF: Risk (Incidence Rate) of Acute Exacerbations of IPF. | First drug administration until end of treatment, up to 5 years | The risk (incidence rate calculated as number of patients with at least 1 exacerbation, divided by the total time at risk ×100) of acute exacerbation of IPF. |
| Percentage of Patient With First Occurrence of Acute Exacerbations of Idiopathic Pulmonary Fibrosis (IPF) Until Week 234. | Week 234 | The percentage of patient having first acute exacerbation of Idiopathic Pulmonary Fibrosis (IPF) based on investigator reported adverse events until week 234. |
Countries
Japan
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Nintedanib Patients were treated orally with 150 milligram (mg) Nintedanib (BIBF 1120) twice daily (b.i.d.) on top of pre-existing Pirfenidone treatment with the opportunity to reduce the dose to 100 mg bid to manage adverse events. | 20 |
| Total | 20 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 12 |
| Overall Study | Protocol Violation | 2 |
Baseline characteristics
| Characteristic | Nintedanib |
|---|---|
| Age, Continuous | 65.8 Years STANDARD_DEVIATION 9.5 |
| Gender Female | 6 Participants |
| Gender Male | 14 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 19 / 20 |
| serious Total, serious adverse events | 16 / 20 |
Outcome results
Primary
Incidence of Overall Adverse Events
Incidence (Number of patients) of Adverse events (AEs) over the course of treatment period including serious adverse events (SAEs), AEs leading to discontinuation of study medication, and fatal AEs.
Time frame: First drug administration until end of treatment, up to 5 years
Population: Treated set (TS)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Nintedanib | Incidence of Overall Adverse Events | AEs leading to discontinuation of trial drug | 12 participants |
| Nintedanib | Incidence of Overall Adverse Events | Fatal | 8 participants |
| Nintedanib | Incidence of Overall Adverse Events | Severe AEs | 11 participants |
Secondary
Acute Exacerbations of IPF: Risk (Incidence Rate) of Acute Exacerbations of IPF.
The risk (incidence rate calculated as number of patients with at least 1 exacerbation, divided by the total time at risk ×100) of acute exacerbation of IPF.
Time frame: First drug administration until end of treatment, up to 5 years
Population: TS
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Nintedanib | Acute Exacerbations of IPF: Risk (Incidence Rate) of Acute Exacerbations of IPF. | 19.2 patients per 100 patient-year |
Secondary
Annual Rate of Decline in Forced Vital Capacity (FVC).
The adjusted annual rate of decline in Forced Vital Capacity (FVC). The means presents actually the adjusted rate based on a random coefficient regression with fixed effects for gender, age, height and random effect of patient specific intercept and time. Within-patient errors are modelled by an Unstructured variance-covariance matrix. Inter-individual variability is modelled by a Variance-Components variance-covariance matrix. The result for Annual rate of decline (ROD) in FVC should be interpreted with caution and along with descriptive statistics, because inferences used for this analysis might not be valid as suggested by skewed distribution of the data.
Time frame: Baseline and every 8 weeks after drug administration until end of treatment, up to 5 years
Population: TS-OC Observed Case (OC): This method was used for the replacement of missing values.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Nintedanib | Annual Rate of Decline in Forced Vital Capacity (FVC). | -233.3 (mililitre (mL)/year) | Standard Error 72.59 |
Secondary
Annual Rate of Decline in Haemoglobin (Hb) Corrected Diffusing Capacity of the Lung for Carbon Monoxide (DLCO)
Adjusted annual rate of decline in Hb corrected DLCO. The means presents actually adjusted rate based on random coefficient regression with fixed effects for gender, age, height & random effect of patient specific intercept & time. Within-patient errors are modelled by Unstructured variance-covariance matrix.Inter-individual variability is modelled by a variance-Components variance-covariance matrix. mmHg: millimeters of mercury
Time frame: Baseline & every 8 weeks after drug administration until end of treatment, up to 5 years
Population: OC-TS
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Nintedanib | Annual Rate of Decline in Haemoglobin (Hb) Corrected Diffusing Capacity of the Lung for Carbon Monoxide (DLCO) | -1.3 mL/Minute(min)/mmHg per year | Standard Error 0.26 |
Secondary
Percentage of Patient With First Occurrence of Acute Exacerbations of Idiopathic Pulmonary Fibrosis (IPF) Until Week 234.
The percentage of patient having first acute exacerbation of Idiopathic Pulmonary Fibrosis (IPF) based on investigator reported adverse events until week 234.
Time frame: Week 234
Population: TS
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Nintedanib | Percentage of Patient With First Occurrence of Acute Exacerbations of Idiopathic Pulmonary Fibrosis (IPF) Until Week 234. | Failure (Week 234) | 40.0 percentage of participants |
| Nintedanib | Percentage of Patient With First Occurrence of Acute Exacerbations of Idiopathic Pulmonary Fibrosis (IPF) Until Week 234. | Censored (Week 234) | 60.0 percentage of participants |