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

Study Overview
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Brief Summary
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The aim of this trial is to offer continuation of BIBF 1120 treatment for patients with Idiopathic Pulmonary Fibrosis (IPF) who have completed a prior clinical trial with that drug. The primary objective will be to establish the long term tolerability and safety profile of BIBF 1120 in Idiopathic Pulmonary Fibrosis (IPF). As a secondary objective the effects of long term treatment with BIBF 1120 on survival as well as safety and efficacy parameters will be investigated in an open-label, not randomized, un-controlled design.

Official Title
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A Phase II Open Label, Roll Over Study of the Long Term Tolerability, Safety and Efficacy of Oral BIBF 1120 in Patients With Idiopathic Pulmonary Fibrosis

Conditions
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Pulmonary Fibrosis

Intervention / Treatment
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* Drug: BIBF 1120
* Drug: BIBF 1120
* Drug: BIBF 1120
* Drug: BIBF 1120


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Patient with a primary diagnosis of IPF (according to the 2000 American Thoracic Society/European Respiratory Society (ATS/ERS) criteria, who are willing to continue trial medication. Written informed consent signed prior to entry into the study, in accordance with International Conference on Harmonisation-Good Clinical Practice (ICH-GCP) and local law Completion of 1199.30 study and still under treatment (i.e. not discontinued in parent trial) Exclusion criteria: Any disease that may put the patient at risk when participating in this trial. Reconsider carefully all exclusion criteria of trial 1199.30. However, patients may qualify for participation even though exclusion criteria may have been met during the course of participation in 1199.30, if the investigator's benefit-risk assessment remains favourable. Participation in another experimental clinical trial (except 1199.30) in the last 8 weeks. Women who are breast feeding or of child bearing potential not using a highly effective method of birth control for at least one month prior to inclusion and at least 10 weeks after end of active therapy. Highly effective methods of birth control are defined as those which result in a low failure rate (i.e. less than 1 % per year) when used consistently and correctly, such as implants, injectables, combined oral contraceptives, some Intra Uterine Devices (IUDs), sexual abstinence or vasectomized partner. Female patients will be considered of childbearing potential unless surgically sterilized by hysterectomy or bilateral tubal ligation, or post-menopausal for at least two years. Sexually active males not committing to using condoms during the course of the study and at least 10 weeks after the end of active therapy (except if their partner is not of childbearing potential). Patients who require full-dose anticoagulation (e.g. vitamin K antagonists, heparin, hirudin etc). Patients who require full-dose antiplatelet (e.g. acetyl salicylic acid, clopidogrel etc) therapy. Known or suspected active alcohol or drug abuse. Patient not compliant in previous trial, with trial medication or trial visits.

Ages Eligible for Study
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Minimum Age: 40 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BIBF 1120 low qd<br>Low dose BIBF 1120 once daily | Drug: BIBF 1120<br>* Low dose BIBF 1120 once daily<br>|
| Experimental: BIBF 1120 low bid<br>Low dose BIBF 1120 twice daily | Drug: BIBF 1120<br>* Low dose BIBF 1120 twice daily<br>|
| Experimental: BIBF 1120 medium bid<br>Intermediate dose BIBF 1120 twice daily | Drug: BIBF 1120<br>* Intermediate dose BIBF 1120 twice daily<br>|
| Experimental: BIBF 1120 high bid<br>High dose BIBF 1120 twice daily | Drug: BIBF 1120<br>* High dose BIBF 1120 twice daily<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Annual Rate of Decline in Forced Vital Capacity (FVC) | 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. | From first drug administration in 1199.35 until database lock 15Oct2015, up to 61.8 Months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival | 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. | From first drug administration in 1199.35 until database lock 15Oct2015, up to 61.8 Months | 
| Progression-Free Survival | 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. | From first trial drug intake in 1199.35 to disease progression; up to 61.8 months | 
| Annual Rate of Decline in Haemoglobin Corrected Diffusing Capacity of the Lung for Carbon Monoxide (DLCO) Decrease | 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. | From first drug administration in 1199.35 until database lock 15Oct2015, up to 61.8 Months | 
| Percentage of Patients With at Least One Acute Idiopathic Pulmonary Fibrosis (IPF) Exacerbation | 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. | From first drug administration in 1199.35 until database lock 15Oct2015, up to 61.8 Months | 
| Incidence of Patients With at Least One Acute IPF Exacerbation Over Time | Incidence rate = (Patients with at least one acute IPF exacerbation / Total number of years at risk) x 100 | From first drug administration in 1199.35 until database lock 15Oct2015, up to 61.8 Months | 
| Time to First Acute IPF Exacerbation | 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. | From first drug administration in 1199.35 until database lock 15Oct2015, up to 61.8 Months | 
| 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 | 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 | From the first nintedanib intake in trial 1199.35 to the last nintedanib intake + 28 days; up to 61.8 months + 28 days |