Safety and PK Study of BIBF 1120 in Japanese Patients With IPF: Follow up Study From 1199.31(NCT01136174)

Study Overview
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Brief Summary
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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.

Official Title
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A Phase II Open Label, Follow up Study to Investigate the Long Term Tolerability and Safety of Oral BIBF 1120 on Top of Pirfenidone in Japanese Patients With Idiopathic Pulmonary Fibrosis

Conditions
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Pulmonary Fibrosis

Intervention / Treatment
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* Drug: Nintedanib
* Drug: Pirfenidoneone


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Written informed consent consistent with Good Clinical Practice (GCP) signed prior to entry into the study Completion of 1199.31 study and still under treatment with pirfenidone at a stable dose Exclusion criteria: 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 exclusion criteria of trial 1199.31. However, patients may qualify for participation even though they meet the exclusion criteria (for 1199.31), if the investigators benefit-risk assessment remains favorable. Any other investigational therapy received within 8 weeks before visit 1. For female: Pregnant women or women who are breast feeding or of child bearing potential not using a highly effective method of birth control for both at least 4 weeks prior to enrolment and 10 weeks after last study drug intake. For male: Sexually active males not committing to using condoms both during the course of the study and ten weeks after last study drug intake (except if their partner is not of childbearing potential). Known or suspected active alcohol or drug abuse. Patients who require full-dose therapeutic anticoagulation (e.g. vitamin K antagonists, heparin), except low dose heparin and/or heparin flash as needed for maintenance of an indwelling intravenous device. As an example, prophylactic use of heparin, e.g. enoxaparin 2000 International unit (I.U.) subcutaneously (s.c.) per day, should be allowed. Patients who require full-dose antiplatelet (e.g. acetyl salicylic acid, clopidogrel) therapy. As an example, chronic low-dose acetyl salicylic acid, below or equal to 100 mg per day, should be allowed. 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: All patients<br> | Drug: Nintedanib<br>* 150 mg bid<br>Drug: Pirfenidoneone<br>* Existing treatment<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | First drug administration until end of treatment, up to 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Baseline and every 8 weeks after drug administration until end of treatment, up to 5 years | 
| 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 | Baseline & every 8 weeks after drug administration until end of treatment, up to 5 years | 
| 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. | First drug administration until end of treatment, up to 5 years | 
| 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. | Week 234 |