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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT02802345




Registration number
NCT02802345
Ethics application status
Date submitted
14/06/2016
Date registered
16/06/2016
Date last updated
11/01/2019

Titles & IDs
Public title
Efficacy and Safety of Nintedanib Co-administered With Sildenafil in Idiopathic Pulmonary Fibrosis Patients With Advanced Lung Function Impairment
Scientific title
INSTAGE: A 24-week, Double-blind, Randomized, Parallel-group Study Evaluating the Efficacy and Safety of Oral Nintedanib Co-administered With Oral Sildenafil, Compared to Treatment With Nintedanib Alone, in Patients With Idiopathic Pulmonary Fibrosis (IPF) and Advanced Lung Function Impairment
Secondary ID [1] 0 0
2015-002619-14
Secondary ID [2] 0 0
1199.36
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Idiopathic Pulmonary Fibrosis 0 0
Condition category
Condition code
Respiratory 0 0 0 0
Other respiratory disorders / diseases
Inflammatory and Immune System 0 0 0 0
Connective tissue diseases
Inflammatory and Immune System 0 0 0 0
Other inflammatory or immune system disorders

Intervention/exposure
Study type
Interventional(has expanded access)
Description of intervention(s) / exposure
Experimental: Nintedanib + placebo matching sildenafil -

Active comparator: Nintedanib + Sildenafil -

Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Change From Baseline in St George's Respiratory Questionnaire (SGRQ) Total Score at Week 12
Timepoint [1] 0 0
Baseline and week 12
Secondary outcome [1] 0 0
Change From Baseline in Dyspnoea Using the University of California San Diego Shortness of Breath Questionnaire (UCSD SOBQ) at Week 12
Timepoint [1] 0 0
Baseline and week 12
Secondary outcome [2] 0 0
Change From Baseline in SGRQ Total Score at Week 24
Timepoint [2] 0 0
Baseline and week 24
Secondary outcome [3] 0 0
Change From Baseline in Dyspnoea Using UCSD SOBQ at Week 24
Timepoint [3] 0 0
Baseline and week 24
Secondary outcome [4] 0 0
Percentage of Patients With On-treatment Serious Adverse Events (SAE) From Baseline to Week 24
Timepoint [4] 0 0
Baseline and week 24

Eligibility
Key inclusion criteria
Inclusion criteria:

* Written informed consent consistent with International Conference on Harmonization-Good Clinical Practice and local laws, signed prior to any study procedures being performed (including any required washout);
* Male or female patients aged >= 40 years at visit 1;
* A clinical diagnosis of IPF within the last 6 years before visit 1, based upon the American Thoracic Society/European Respiratory Society/Japanese Respiratory Society/Latin American thoracic Association 2011 guideline [P11-07084];
* 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;
* Carbon Monoxide Diffusion Capacity (corrected for Hb) less or equal to 35% predicted of normal at visit 1.
Minimum age
40 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Exclusion criteria:

* Previous enrolment in this trial;
* Alanine Transaminase, Aspartate Transaminase > 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 Forced Expiratory Volume in 1 second/Forced Vital Capacity <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, 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;
* 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;
* Creatinine clearance < 30 mL/min calculated by Cockcroft-Gault formula at visit 1;
* Presence of aortic stenosis (AS) per investigator judgement at visit 1;
* Severe chronic heart failure: defined by left ventricular ejection fraction (EF) < 25% per investigator judgement at visit 1;
* Presence of idiopathic hypertrophic subaortic stenosis (IHSS) per investigator judgement at visit 1;
* Second-degree or third-degree atrioventricular (AV) block on electrocardiogram (ECG) per investigator judgement at visit 1;
* Hypotension (systolic blood pressure [SBP] < 100 mm Hg or diastolic blood pressure [DBP] < 50 mm Hg) (symptomatic orthostatic hypotension) at visit 1;
* Uncontrolled systemic hypertension (SBP > 180 mmHg; or DBP > 100 mmHg) at visit 1;
* Known penile deformities or conditions (e.g., sickle cell anemia, multiple myeloma, leukemia) that may predispose to priapism;
* Retinitis pigmentosa;
* History of vision loss;
* History of nonarteritic ischemic optic neuropathy;
* Veno-occlusive disease;
* History of acute IPF exacerbation or respiratory infection within 8 weeks of visit 2.
* 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;
* 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;
* Treatment with potent cytochrome CYP3A4 inhibitors such as ketoconazole, itraconazole and ritonavir within 4 weeks of visit 2;
* Supplementation with L-arginine and concurrent use of grapefruit juice or St John's wort within 4 weeks of visit 2;
* 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;
* Known hypersensitivity or intolerance to nintedanib, sildenafil, galactose, peanut or soya or any other components of the study medication;
* 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;
* Further exclusion criteria apply.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
30/06/2016
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
13/04/2018
Sample size
Target
Accrual to date
Final
274
Recruitment in Australia
Recruitment state(s)
NSW,SA,VIC
Recruitment hospital [1] 0 0
Royal Prince Alfred Hospital - Camperdown, Sydney
Recruitment hospital [2] 0 0
Royal Adelaide Hospital - Adelaide
Recruitment hospital [3] 0 0
The Alfred Hospital - Melbourne
Recruitment postcode(s) [1] 0 0
2050 - Camperdown, Sydney
Recruitment postcode(s) [2] 0 0
5000 - Adelaide
Recruitment postcode(s) [3] 0 0
3004 - Melbourne
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
Connecticut
Country [3] 0 0
United States of America
State/province [3] 0 0
Florida
Country [4] 0 0
United States of America
State/province [4] 0 0
Illinois
Country [5] 0 0
United States of America
State/province [5] 0 0
Kansas
Country [6] 0 0
United States of America
State/province [6] 0 0
Michigan
Country [7] 0 0
United States of America
State/province [7] 0 0
Minnesota
Country [8] 0 0
United States of America
State/province [8] 0 0
Missouri
Country [9] 0 0
United States of America
State/province [9] 0 0
New York
Country [10] 0 0
United States of America
State/province [10] 0 0
North Carolina
Country [11] 0 0
United States of America
State/province [11] 0 0
Ohio
Country [12] 0 0
United States of America
State/province [12] 0 0
Oregon
Country [13] 0 0
United States of America
State/province [13] 0 0
South Carolina
Country [14] 0 0
United States of America
State/province [14] 0 0
Texas
Country [15] 0 0
United States of America
State/province [15] 0 0
Virginia
Country [16] 0 0
Belgium
State/province [16] 0 0
Antwerpen
Country [17] 0 0
Belgium
State/province [17] 0 0
Bruxelles
Country [18] 0 0
Belgium
State/province [18] 0 0
Leuven
Country [19] 0 0
Canada
State/province [19] 0 0
Alberta
Country [20] 0 0
Canada
State/province [20] 0 0
British Columbia
Country [21] 0 0
Canada
State/province [21] 0 0
Nova Scotia
Country [22] 0 0
Canada
State/province [22] 0 0
Ontario
Country [23] 0 0
France
State/province [23] 0 0
Bron cedex
Country [24] 0 0
France
State/province [24] 0 0
Lille
Country [25] 0 0
France
State/province [25] 0 0
Marseille
Country [26] 0 0
France
State/province [26] 0 0
Montpellier
Country [27] 0 0
France
State/province [27] 0 0
Nice
Country [28] 0 0
France
State/province [28] 0 0
Paris
Country [29] 0 0
France
State/province [29] 0 0
Rennes
Country [30] 0 0
Germany
State/province [30] 0 0
Coswig
Country [31] 0 0
Germany
State/province [31] 0 0
Essen
Country [32] 0 0
Germany
State/province [32] 0 0
Freiburg im Breisgau
Country [33] 0 0
Germany
State/province [33] 0 0
Gießen
Country [34] 0 0
Germany
State/province [34] 0 0
Greifswald
Country [35] 0 0
Germany
State/province [35] 0 0
Hannover
Country [36] 0 0
Germany
State/province [36] 0 0
Immenhausen
Country [37] 0 0
Germany
State/province [37] 0 0
Solingen
Country [38] 0 0
India
State/province [38] 0 0
Ahmedabad
Country [39] 0 0
India
State/province [39] 0 0
Coimbatore
Country [40] 0 0
India
State/province [40] 0 0
Kolkata
Country [41] 0 0
India
State/province [41] 0 0
Pune
Country [42] 0 0
Italy
State/province [42] 0 0
Chieti Scalo
Country [43] 0 0
Italy
State/province [43] 0 0
Foggia
Country [44] 0 0
Italy
State/province [44] 0 0
FORLì
Country [45] 0 0
Italy
State/province [45] 0 0
Milano
Country [46] 0 0
Italy
State/province [46] 0 0
Modena
Country [47] 0 0
Italy
State/province [47] 0 0
Padova
Country [48] 0 0
Italy
State/province [48] 0 0
Roma
Country [49] 0 0
Italy
State/province [49] 0 0
Siena
Country [50] 0 0
Italy
State/province [50] 0 0
Torrette Di Ancona (Ancona)
Country [51] 0 0
Japan
State/province [51] 0 0
Aichi, Seto
Country [52] 0 0
Japan
State/province [52] 0 0
Fukuoka, Kurume
Country [53] 0 0
Japan
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Gifu, Ogaki
Country [54] 0 0
Japan
State/province [54] 0 0
Hyogo, Himeji
Country [55] 0 0
Japan
State/province [55] 0 0
Ibaraki, Naka-gun
Country [56] 0 0
Japan
State/province [56] 0 0
Kanagawa, Yokohama
Country [57] 0 0
Japan
State/province [57] 0 0
Osaka, Sakai
Country [58] 0 0
Japan
State/province [58] 0 0
Tokyo, Bunkyo-ku
Country [59] 0 0
Japan
State/province [59] 0 0
Tokyo, Ota-ku
Country [60] 0 0
Korea, Republic of
State/province [60] 0 0
Seoul
Country [61] 0 0
Mexico
State/province [61] 0 0
Guadalajara
Country [62] 0 0
Mexico
State/province [62] 0 0
Mexico
Country [63] 0 0
Mexico
State/province [63] 0 0
Monterrey
Country [64] 0 0
Mexico
State/province [64] 0 0
México
Country [65] 0 0
Spain
State/province [65] 0 0
Barcelona
Country [66] 0 0
Spain
State/province [66] 0 0
Girona
Country [67] 0 0
Spain
State/province [67] 0 0
Madrid
Country [68] 0 0
Spain
State/province [68] 0 0
Pozuelo de Alarcón
Country [69] 0 0
Spain
State/province [69] 0 0
Valencia
Country [70] 0 0
United Kingdom
State/province [70] 0 0
Bristol
Country [71] 0 0
United Kingdom
State/province [71] 0 0
Cambridge
Country [72] 0 0
United Kingdom
State/province [72] 0 0
Dundee, Scotland
Country [73] 0 0
United Kingdom
State/province [73] 0 0
Glasgow
Country [74] 0 0
United Kingdom
State/province [74] 0 0
Sheffield
Country [75] 0 0
United Kingdom
State/province [75] 0 0
Tyne And Wear

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Boehringer Ingelheim
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Boehringer Ingelheim
Address 0 0
Boehringer Ingelheim
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

No information has been provided regarding IPD availability


What supporting documents are/will be available?




Results publications and other study-related documents

No documents have been uploaded by study researchers.

Results are available at https://clinicaltrials.gov/study/NCT02802345