Main
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Note: This record shows only 22 elements of the WHO Trial Registration Data Set. To view changes that have been made to the source record, or for additional information about this trial, click on the URL below to go to the source record in the primary register. |
Register:
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EUCTR |
Last refreshed on:
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5 June 2018 |
Main ID: |
EUCTR2015-002619-14-DE |
Date of registration:
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04/05/2016 |
Prospective Registration:
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Yes |
Primary sponsor: |
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Public title:
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Efficacy and safety of nintedanib when co-administered with sildenafil in IPF patients with advanced lung function impairment
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Scientific title:
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INSTAGE(TM): A 24-week, double-blind, randomized, parallel-group study evaluating the efficacy and safety of oral nintedanib coadministrated with oral sildenafil, compared to treatment with nintedanib alone, in patients with idiopathic pulmonary fibrosis (IPF) and advanced lung function impairment - INSTAGE(TM) |
Date of first enrolment:
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21/07/2016 |
Target sample size:
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300 |
Recruitment status: |
Not Recruiting |
URL:
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https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2015-002619-14 |
Study type:
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Interventional clinical trial of medicinal product |
Study design:
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Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 2
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Phase:
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Human pharmacology (Phase I): no
Therapeutic exploratory (Phase II): no
Therapeutic confirmatory - (Phase III): yes
Therapeutic use (Phase IV): no
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Countries of recruitment
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Australia
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Belgium
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Canada
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China
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France
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Germany
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India
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Italy
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Japan
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Korea, Republic of
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Mexico
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Spain
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United Kingdom
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United States
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Contacts
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Name:
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QRPE PSC CT Information Disclosure
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Address:
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Binger Straße 173
55216
Ingelheim am Rhein
Germany |
Telephone:
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00498002430127 |
Email:
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clintriage.rdg@boehringer-ingelheim.com |
Affiliation:
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Boehringer Ingelheim Pharma GmbH & Co. KG |
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Name:
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QRPE PSC CT Information Disclosure
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Address:
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Binger Straße 173
55216
Ingelheim am Rhein
Germany |
Telephone:
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00498002430127 |
Email:
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clintriage.rdg@boehringer-ingelheim.com |
Affiliation:
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Boehringer Ingelheim Pharma GmbH & Co. KG |
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Key inclusion & exclusion criteria
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Inclusion criteria: 1. Written informed consent consistent with ICH-GCP and local laws, signed prior to any study procedures being performed (including any required washout);
2. Male or female patients aged >=40 years at visit 1;
3. A clinical diagnosis of IPF within the last 6 years before visit 1, based upon the ATS/ERS/JRS/ALAT 2011 guideline;
4. Combination of high-resolution computed tomography (HRCT) pattern, and if available, surgical lung biopsy pattern consistent with a diagnosis of IPF as assessed by the investigator based on a HRCT scan performed within 18 months of visit 1;
5. DLCO (corrected for Hb) <= 35% predicted of normal at visit 1. Are the trial subjects under 18? no Number of subjects for this age range: 0 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 200
Exclusion criteria: 1. Previous enrolment in this trial;
2. ALT, AST > 1.5 fold upper limit of normal (ULN) at visit 1;
3. Total bilirubin > 1.5 fold ULN at visit 1;
4. Relevant airways obstruction (i.e. pre-bronchodilator FEV1/FVC <0.7 at visit 1);
5. History of myocardial infarction within 6 months of visit 1 or unstable angina within 1 month of visit 1;
6. Bleeding Risk: - Known genetic predisposition to bleeding; - Patients who require fibrinolysis, full-dose therapeutic anticoagulation (e.g. vitamin K antagonists, direct thrombin inhibitors, heparin, hirudin, etc.) or high dose antiplatelet therapy; - History of haemorrhagic central nervous system (CNS) 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 (PT) and activated partial thromboplastin time (aPTT) > 150% of institutional ULN at visit 1;
7. Planned major surgery during the trial participation, including lung transplantation, major abdominal or major intestinal surgery;
8. History of thrombotic event (including stroke and transient ischemic attack) within 12 months of visit 1;
9. Creatinine clearance < 30 mL/min calculated by Cockcroft-Gault formula at visit 1;
10. Presence of aortic stenosis (AS) per investigator judgement at visit 1;
11. Severe chronic heart failure: defined by left ventricular ejection fraction (EF) < 25% per investigator judgement at visit 1;
12. Presence of idiopathic hypertrophic subaortic stenosis (IHSS) per investigator judgement at visit 1; 13. Second-degree or third-degree atrioventricular (AV) block on electrocardiogram (ECG) per investigator judgement at visit 1;
14. Hypotension (systolic blood pressure [SBP] < 100 mm Hg or diastolic blood pressure [DBP] < 50 mm Hg) (symptomatic orthostatic hypotension) at visit 1;
15. Uncontrolled systemic hypertension (SBP > 180 mmHg or DBP > 100 mmHg) at visit 1;
16. Known penile deformities or conditions (e.g., sickle cell anemia, multiple myeloma, leukemia) that may predispose to priapism;
17. Retinitis pigmentosa;
18. History of vision loss;
19. History of nonarteritic ischemic optic neuropathy;
20. Veno-occlusive disease;
21. History of acute IPF exacerbation or respiratory infection within 8 weeks of visit 2.
22. Treatment with nitrates, n-acetylcysteine, pirfenidone, azathioprine, cyclophosphamide, cyclosporine, prednisone >15 mg daily or >30 mg every 2 days OR equivalent dose of other oral corticosteroids as well as any investigational drug within 4 weeks of visit 2;
23. Treatment with prostaglandins (e.g., epoprostenol, treprostinil), endothelin-1 antagonists (e.g., bosentan, sitaxsentan, ambrisentan), phosphodiesterase inhibitors (e.g., sildenafil, tadalafil, vardenafil) or a stimulator of guanylatcyclase (e.g., riociguat) within 4 weeks of visit 2;
24. Treatment with potent CYP3A4 inhibitors such as ketoconazole, itraconazole and ritonavir within 4 weeks of visit 2;
25. Supplementation with L-arginine and concurrent use of grapefruit juice or St John's wort within 4 weeks of visit 2;
26. Treatment with the reduced dose of nintedanib (100 mg bid) within 4 weeks of visit 2;
27. Permanent discontinuation of nintedanib in the past due to adverse events considered drug-related;
28. Known hypersensitivity or intolerance to nintedanib, sildenafil, galactose, peanut or soy
Age minimum:
Age maximum:
Gender:
Female: yes Male: yes
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Health Condition(s) or Problem(s) studied
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Therapeutic area: Diseases [C] - Respiratory Tract Diseases [C08]
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patients with idiopathic pulmonary fibrosis (IPF) and advanced lung function impairment MedDRA version: 19.0
Level: PT
Classification code 10021240
Term: Idiopathic pulmonary fibrosis
System Organ Class: 10038738 - Respiratory, thoracic and mediastinal disorders
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Intervention(s)
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Trade Name: Ofev Product Name: Ofev 100 mg capsule Product Code: nintedanib Pharmaceutical Form: Capsule, soft INN or Proposed INN: nintedanib CAS Number: 656247-17-5 Other descriptive name: NINTEDANIB Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 100-
Trade Name: Ofev Product Name: Ofev 150 mg capsule Product Code: nintedanib Pharmaceutical Form: Capsule, soft INN or Proposed INN: nintedanib CAS Number: 656247-17-5 Other descriptive name: NINTEDANIB Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 150-
Trade Name: Revatio Product Name: Revatio 20 mg Product Code: sildenafil Pharmaceutical Form: Capsule, hard INN or Proposed INN: SILDENAFIL CAS Number: 139755-83-2 Other descriptive name: sildenafil Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 20- Pharmaceutical form of the placebo: Capsule, hard Route of administration of the placebo: Oral use
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Primary Outcome(s)
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Main Objective: To assess efficacy and safety of concomitant treatment with nintedanib and sildenafil in IPF patients with advanced lung function impairment.
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Primary end point(s): 1: change from baseline in SGRQ total score at week 12
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Timepoint(s) of evaluation of this end point: 1: week 12
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Secondary Objective: To enlarge the existing nintedanib mono-therapy database with safety and tolerability data in this population.
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Secondary Outcome(s)
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Timepoint(s) of evaluation of this end point: 1: week 12
2: week 24
3: week 24
4: week 24
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Secondary end point(s): 1: change from baseline in UCSD SOBQ at week 12
2: change from baseline in SGRQ total score at week 24
3: change from baseline in UCSD SOBQ at week 24
4: % of patients with on-treatment SAE from baseline to week 24
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Source(s) of Monetary Support
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Boehringer Ingelheim Pharma GmbH & Co. KG
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Results
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Results available:
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Date Posted:
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Date Completed:
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URL:
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