Idiopathic Pulmonary Fibrosis
Conditions
Brief summary
The aim of this extension trial is to assess the long-term safety of BIBF 1120 treatment in patients with Idiopathic Pulmonary Fibrosis who have completed one year treatment and the follow up period in the double-blind phase III placebo controlled parent trials (1199.32 and 1199.34), who wish to continue treatment with BIBF 1120.
Interventions
DRUGNintedanib
Nintedanib twice a day
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. Signed Informed Consent consistent with International Conference on Harmonisation-Good Clinical Practices (ICH-GCP) and local laws prior to trial participation. 2. Patients from trials 1199.32 or 1199.34 who completed the 52 weeks treatment period and performed the follow-up visit.
Exclusion criteria
1. Aspartate aminotransferase (AST), Alanine aminotransferase (ALT) \> 1.5 fold Upper Limit of Normal (ULN) (Patients who completed the parent trial with transaminase values \> 1.5 fold ULN but \< 3 fold ULN are considered eligible) 2. Bilirubin \> 1.5 fold ULN 3. Bleeding risk 4. Planned major surgery within the next 3 months, including lung transplantation, major abdominal or major intestinal surgery. 5. New major thrombo-embolic events developed after completion of the parent trial. 6. Time period \> 12 weeks between Visit 9 of the parent trial and Visit 2 of this study. 7. Usage of any investigational drug after completion of the parent trial or planned usage of a specific investigational drug during the course of this trial. 8. A disease or condition which in the opinion of investigator may put the patient at risk because of participation in this trial or limit the patients' ability to participate in this trial. 9. Alcohol or drug abuse which in the opinion of the investigator would interfere with trial participation. 10. Pregnant women or women who are breast feeding or of child bearing potential not using two effective methods of birth control (one barrier and one highly effective non-barrier) for at least 1 month prior to Visit 2 and/or not committing to using it until 3 months after end of treatment.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Adverse Events (AEs) | From first drug administration until end of treatment period + 28 days, in total up to 56.3 months plus 28 days. | This is the measure for percentage of patients with adverse events (AEs) observed during the trial. The incidence of adverse events (% of patients) over the course of the trial, including the incidence of serious AEs, AEs leading to discontinuation, and fatal AEs are presented. |
Countries
Australia, Belgium, Canada, Chile, China, Czechia, Finland, France, Germany, Greece, India, Ireland, Israel, Italy, Japan, Mexico, Netherlands, Portugal, Russia, South Korea, Spain, Turkey (Türkiye), United Kingdom, United States
Participant flow
Recruitment details
This was a prospective, open-label extension trial in which patients with Idiopathic pulmonary fibrosis (IPF), who had completed 52 weeks of treatment and the follow-up period in the randomised, double-blind, placebo-controlled parent trials 1199.32(NCT01335464)/.34(NCT01335477) and who needed access to nintedanib outside of the discontinued parent trials 1199.35(NCT01170065)/.187(NCT01979952).
Pre-assignment details
All subjects were screened for eligibility prior to participation in the trial. Subjects attended a specialist site which ensured that they (the subjects) strictly met all inclusion and none of the exclusion criteria. Subjects were not to be allocated to a treatment group if any of the entry criteria were violated.
Participants by arm
| Arm | Count |
|---|---|
| Total (1199.32/.34) This group included patients originated from parent trials 1199.32/.34.
For patients participated in parent trials 1199.32/.34, they were to receive continuous dosing of soft gelatin capsules of nintedanib (orally) 150 milligrams (mg) twice daily (bid) in this study unless they had reduced the dose to 100 mg bid trial drug (nintedanib or placebo) in the parent trial; patients receiving 100 mg bid trial drug at the end of the parent trial could receive either nintedanib 100 mg bid or nintedanib 150 mg bid in this study. The daily nintedanib dose for such patients was decided at baseline visit based on discussion between the patient and the investigator. After unblinding of the parent trials, patients randomized to placebo in parent trials, who reduced the dose to 100 mg bid in the parent trial, could increase the dose to nintedanib 150 mg bid in this study. The dose could also be increased to 150 mg at a later time point if medically justified in this study.
In this study, patients were treated with nintedanib until they met one of the discontinuation criteria. Potential reasons for treatment discontinuation include impaired liver function, recurrence of diarrhoea, and progression of idiopathic pulmonary fibrosis. | 734 |
| Total | 734 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 231 |
| Overall Study | Death | 145 |
| Overall Study | Lost to Follow-up | 3 |
| Overall Study | Not treated | 1 |
| Overall Study | Other than specified | 96 |
| Overall Study | Protocol Violation | 4 |
| Overall Study | Withdrawal by Subject | 45 |
Baseline characteristics
| Characteristic | Total (1199.32/.34) |
|---|---|
| Age, Continuous | 67.2 Years STANDARD_DEVIATION 7.8 |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants |
| Race (NIH/OMB) Asian | 214 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 86 Participants |
| Race (NIH/OMB) White | 431 Participants |
| Sex: Female, Male Female | 147 Participants |
| Sex: Female, Male Male | 587 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk |
|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 182 / 734 | 78 / 304 | 104 / 430 | 0 / 7 | 0 / 2 | 0 / 8 | 0 / 17 | 182 / 751 |
| other Total, other adverse events | 671 / 734 | 281 / 304 | 390 / 430 | 3 / 7 | 1 / 2 | 2 / 8 | 6 / 17 | 677 / 751 |
| serious Total, serious adverse events | 509 / 734 | 208 / 304 | 301 / 430 | 0 / 7 | 0 / 2 | 1 / 8 | 1 / 17 | 510 / 751 |
Outcome results
Primary
Incidence of Adverse Events (AEs)
This is the measure for percentage of patients with adverse events (AEs) observed during the trial. The incidence of adverse events (% of patients) over the course of the trial, including the incidence of serious AEs, AEs leading to discontinuation, and fatal AEs are presented.
Time frame: From first drug administration until end of treatment period + 28 days, in total up to 56.3 months plus 28 days.
Population: Treated set (TS): The data set consisted of all patients who were dispensed trial medication and were documented to have taken at least one dose, and had participated in 1199.32/.34 parent trials.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Total (1199.32/.34) | Incidence of Adverse Events (AEs) | Any AEs | 98.5 Percentage of patients (%) |
| Total (1199.32/.34) | Incidence of Adverse Events (AEs) | AEs leading to discontinuation of trial drug | 42.6 Percentage of patients (%) |
| Total (1199.32/.34) | Incidence of Adverse Events (AEs) | Serious AEs | 68.9 Percentage of patients (%) |
| Total (1199.32/.34) | Incidence of Adverse Events (AEs) | Fatal AEs | 23.8 Percentage of patients (%) |