The main objective of the trial will be to assess safety and tolerability of combined treatmentwith nintedanib and pirfenidone.A secondary objective is to assess the exposure based on PK trough concentration values tonintedanib either given alone or…
ID
Source
Brief title
Condition
- Lower respiratory tract disorders (excl obstruction and infection)
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary endpoint is the percentage of patients with on-treatment
gastrointestinal (GI) AEs from baseline to week 12.
Secondary outcome
Pre-dose plasma concentrations at steady state of nintedanib
at baseline, weeks 2 and 4.
Pre-dose plasma concentrations at steady state of
pirfenidone at weeks 2 and 4.
Background summary
Idiopathic pulmonary fibrosis (IPF) is a rare disease of unknown aetiology that
is
characterized by progressive fibrosis of the interstitium of the lung, leading
to decreasing
lung volume and progressive pulmonary insufficiency.
Until recently, pirfenidone was the only approved drug for the indication of
IPF. Since October 2014 nintedanib has also been approved by the FDA as
treatment for IPF., based on the outcome of three previous trials, in which a
significant decrease in disease progression was observed.
The theory for this trial is, that the combination of the two drugs, with each
a different workingmechanism will show a synergetic effect. Therefore the
safety and tolerabilty of this combination will be investigated in a relative
small population of patients.
Study objective
The main objective of the trial will be to assess safety and tolerability of
combined treatment
with nintedanib and pirfenidone.
A secondary objective is to assess the exposure based on PK trough
concentration values to
nintedanib either given alone or in combination with pirfenidone and to assess
the exposure
of pirfenidone when combined with nintedanib
Study design
Open-label, randomized, parrallel group,multi centre trial
Intervention
12 weeks treatment (twice daily) with the combination of nintedanib and
pirfenidone. (both drugs are registered, but the combination is not)
Study burden and risks
spirometric test: every hospital visit except visit 2 and follow up
physical examination, including weight measuring, pulse and bloodpressure:
every hospital visit
laboratorium test : every hospital visit
pregnancy test (if applicable): every hospital visit
ECG: 3 times
questionaire: every hospial visit except visit1 and follow up visit
Comeniusstraat 6
Alkmaar 1817 MS
NL
Comeniusstraat 6
Alkmaar 1817 MS
NL
Listed location countries
Age
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
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),
Prothrombin time and partial thromboplastin time (PTT) > 150%
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 Cockroft-Gault formula at visit 1) or end stage renal disease requiering dialysis
-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 correctly 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
-patients with underlying chronic liver disease (Child Pugh A,B or C impairment)
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2015-000640-42-NL |
| CCMO | NL53288.100.15 |
| Other | nog niet bekend |