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

• Register: EUCTR
• Last refreshed on: 12 March 2018
• Main ID: EUCTR2015-000640-42-IT
• Date of registration: 22/02/2018
• Prospective Registration: No
• Primary sponsor: BOEHRINGER-INGELHEIM ITALIA S.P.A.
• Public title: Safety, tolerability and PK of nintedanib in combination with pirfenidone in IPF
• Scientific title: A twelve week, open-label, randomised, parallel-group study evaluating safety, tolerability and pharmacokinetics (PK) of oral nintedanib in combination with oral pirfenidone, compared to treatment with nintedanib alone, in patients with idiopathic pulmonary fibrosis (IPF) - -
• Date of first enrolment: 22/12/2015
• Target sample size: 135
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2015-000640-42
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: yes; Single blind: no; Double blind: no; Parallel group: no; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: yes; Placebo: no; Other: no; Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): yes

Countries of recruitment

Canada, France, Germany, Italy, Netherlands, United States

Contacts

• Name: QRPE PSC CT Information Disclosure
• Affiliation: Boehringer Ingelheim

• Name: QRPE PSC CT Information Disclosure
• Affiliation: Boehringer Ingelheim

Key inclusion & exclusion criteria

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



Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Respiratory Tract Diseases [C08]

Idiopathic Pulmonary Fibrosis
MedDRA version: 20.0 Level: PT Classification code 10021240 Term: Idiopathic pulmonary fibrosis System Organ Class: 10038738 - Respiratory, thoracic and mediastinal disorders

Intervention(s)

Trade Name: Ofev
Pharmaceutical Form: Capsule, soft
INN or Proposed INN: nintedanib
CAS Number: 656247-17-5
Current Sponsor code: BIBF 1120
Other descriptive name: nintedanib
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 100-

Trade Name: Ofev
Pharmaceutical Form: Capsule, soft
INN or Proposed INN: Nintedanib
CAS Number: 656247-17-5
Current Sponsor code: BIBF 1120
Other descriptive name: NINTEDANIB
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 150-

Trade Name: Esbriet
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: PIRFENIDONE
CAS Number: 53179-13-8
Current Sponsor code: -
Other descriptive name: PIRFENIDONE
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 267-

Primary Outcome(s)

Primary end point(s): 1: The primary endpoint is the percentage of patients with on-treatment
gastrointestinal (GI) AEs (SOC GI disorders) from baseline to week 12

Timepoint(s) of evaluation of this end point: 12 weeks

Main Objective: The main objective of the trial will be to assess safety and tolerability of
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

Secondary Outcome(s)

Secondary end point(s): 1: Pre-dose plasma concentrations at steady state (Cpre,ss) of
nintedanib at baseline, weeks
2 and 4
2: Pre-dose plasma concentrations at steady state (Cpre,ss) of
pirfenidone at weeks 2 and 4.

Timepoint(s) of evaluation of this end point: 1: baseline, week 2 and week 4
2: week 2 and week 4

Secondary ID(s)

2015-000640-42-FR

1199.222

Source(s) of Monetary Support

Boehringer Ingelheim Italia Spa