Safety, tolerability and PK of nintedanib in combination with pirfenidone in IPF

Phase 1

Conditions: Idiopathic Pulmonary Fibrosis
MedDRA version: 20.0Level: PTClassification code 10021240Term: Idiopathic pulmonary fibrosisSystem Organ Class: 10038738 - Respiratory, thoracic and mediastinal disorders
Therapeutic area: Diseases [C] - Respiratory Tract Diseases [C08]

Registration Number: EUCTR2015-000640-42-IT

Lead Sponsor: BOEHRINGER-INGELHEIM ITALIA S.P.A.

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 135

Inclusion Criteria

-Written informed consent consistent with ICH-GCP and local laws,
signed prior to any study procedures being performed (including any
required washout)
-Male or female patients aged greater than or equal to 40 years at visit 1
-Idiopathic Pulmonary Fibrosis (IPF) diagnosis, based upon the
ATS/ERS/JRS/ALAT 2011 guideline and confirmed by the investigator
based on chest high resolution computed tomography (HRCT) scan
performed within 12 months of visit 1
-FVC greater than or equal to 50% of predicted normal at visit 1
Are the trial subjects under 18? no
Number of subjects for this age range: 1
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 50
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 50

Exclusion Criteria

-ALT, AST > 1.5 fold upper limit of normal (ULN) at visit 1
-Total bilirubin > 1.5 fold ULN at visit 1
-Relevant airways obstruction (i.e. pre-bronchodilator FEV1/FVC <0.7)
at visit 1
-History of myocardial infarction within 6 months of visit 1 or unstable
angina within 1 month of visit 1
-Bleeding Risk: Known genetic predisposition to bleeding, Patients who
require fibrinolysis, full-dose therapeutic anticoagulation (e.g. vitamin K
antagonists, dabigatran, heparin, hirudin etc) or high dose antiplatelet
therapy, History of haemorrhagic central nervous system event within 12
months prior to visit 1, History of haemoptysis or haematuria, active
gastro-intestinal bleeding or ulcers and/or major injury or surgery
within 3 months prior to visit 1, International normalised ratio (INR) > 2
at visit 1, Prothrombin time and partial thromboplastin time (PTT) >
150% of
institutional ULN at visit 1
-Planned major surgery during the trial participation, including lung
transplantation,major abdominal or major intestinal surgery.
-History of thrombotic event (including stroke and transient ischemic
attack) within 12
months of visit 1
-Severe renal impairment (Creatinine clearance < 30 mL/min calculated by Cockcroft-Gault formula) or end-stage renal disease requiring dialisys.
-Treatment with NAC, prednisone >15 mg daily or >30 mg every 2 days
OR equivalent
dose of other oral corticosteroids and/or fluvoxamine within 2 weeks of
visit 2
-Treatment with azathioprine, cyclophosphamide, cyclosporine as well as
any other
investigational drug within 8 weeks of visit 2
-Previous treatment with pirfenidone
-Permanent discontinuation of nintedanib in the past due to AEs
considered drug-related
-Known hypersensitivity to nintedanib, pirfenidone, peanut or soya or to
any of the
excipients
-A disease or condition which in the opinion of the investigator may
interfere with testing procedures or put the patient at risk when
participating in this trial
-Alcohol or drug abuse which in the opinion of the treating physician
would interfere with treatment
-Women who are pregnant, nursing, or who plan to become pregnant
while in the trial.
-Women of childbearing potential not willing or able to use highly
effective methods of
birth control per ICH M3 (R2) that result in a low failure rate of less than
1% per year
when used consistently and correctly5 for 28 days prior to and 3 months
after nintedanib administration
-Patients not able to understand and follow study procedures including
completion of selfadministered questionnaires without help
-Patients who require dose reduction and/or temporary interruption
during the run-in period with nintedanib 150 mg bid

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: The main objective of the trial will be to assess safety and tolerability of<br>combined treatment with nintedanib and pirfenidone;Secondary Objective: A secondary objective is to assess the exposure, based on pharmacokinetic trough concentration values, to nintedanib either given alone or in combination with pirfenidone and to assess the assess the exposure of pirfenidone when combined with nintedanib;Primary end point(s): 1: The primary endpoint is the percentage of patients with on-treatment<br>gastrointestinal (GI) AEs (SOC GI disorders) from baseline to week 12;Timepoint(s) of evaluation of this end point: 12 weeks

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): 1: Pre-dose plasma concentrations at steady state (Cpre,ss) of<br>nintedanib at baseline, weeks<br>2 and 4<br>2: Pre-dose plasma concentrations at steady state (Cpre,ss) of<br>pirfenidone at weeks 2 and 4.;Timepoint(s) of evaluation of this end point: 1: baseline, week 2 and week 4<br>2: week 2 and week 4<br>

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