E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Idiopathic Pulmonary Fibrosis |
|
E.1.1.1 | Medical condition in easily understood language |
Idiopathic pulmonary fibrosis
N/A |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Respiratory Tract Diseases [C08] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 19.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10021240 |
E.1.2 | Term | Idiopathic pulmonary fibrosis |
E.1.2 | System Organ Class | 10038738 - Respiratory, thoracic and mediastinal disorders |
|
E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The main objective of the trial will be to assess safety and tolerability of combined treatment with nintedanib and pirfenidone |
|
E.2.2 | Secondary objectives of the trial |
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 |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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 |
|
E.4 | Principal 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 formula6 at visit 1) or end-stage renal disease requiring 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 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
-Patients with underlying chronic liver disease (Child Pugh A, B or C hepatic impairment) |
|
E.5 End points |
E.5.1 | 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
|
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | 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.
|
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
1: baseline, week 2 and week 4
2: week 2 and week 4
|
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 21 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Canada |
France |
Germany |
Italy |
Netherlands |
United States |
|
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 2 |
E.8.9.1 | In the Member State concerned days | 21 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 2 |
E.8.9.2 | In all countries concerned by the trial days | 21 |