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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/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
Treatment: Drugs - Nintedanib
Treatment: Drugs - Placebo
Treatment: Drugs - Sildenafil

Experimental: Nintedanib + placebo matching sildenafil -

Active Comparator: Nintedanib + Sildenafil -


Treatment: Drugs: Nintedanib


Treatment: Drugs: Placebo


Treatment: Drugs: Sildenafil


Intervention code [1] 0 0
Treatment: Drugs
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 - The SGRQ is a 50-item questionnaire developed to measure health status (quality of life). Scores are calculated for three domains: Symptoms, Activity and Impacts (Psycho-social) as well as a total score. A minimum change in score of 4 units was established as clinically relevant after patient and clinician testing. Scores range from 0 to 100, with higher scores indicating more limitations. The mean and standard error presented are actually adjusted mean for change from baseline and its standard error.
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 - The UCSD SOBQ is a 24-item questionnaire developed to measure breathlessness on a scale between zero and five where 0 is not at all breathless and 5 is maximally breathless or too breathless to do the activity. The mean and standard error presented for descriptive statistics are actually adjusted mean for change from baseline and its standard error.
Timepoint [1] 0 0
Baseline and week 12
Secondary outcome [2] 0 0
Change From Baseline in SGRQ Total Score at Week 24 - The SGRQ is a 50-item questionnaire developed to measure health status (quality of life). Scores are calculated for three domains: Symptoms, Activity and Impacts (Psycho-social) as well as a total score. A minimum change in score of 4 units was established as clinically relevant after patient and clinician testing. The mean and standard error presented for descriptive statistics are actually adjusted mean for change from baseline and its standard error.
Timepoint [2] 0 0
Baseline and week 24
Secondary outcome [3] 0 0
Change From Baseline in Dyspnoea Using UCSD SOBQ at Week 24 - The UCSD SOBQ is a 24-item questionnaire developed to to measure breathlessness on a scale between zero and five where 0 is not at all breathless and 5 is maximally breathless or too breathless to do the activity. The mean and standard error presented for descriptive statistics are actually adjusted mean for change from baseline and its standard error.
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 - Percentage of patients with on-treatment serious adverse events (SAE) from baseline to Week 24 is presented.
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
Gender
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
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
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
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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
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Chieti Scalo
Country [43] 0 0
Italy
State/province [43] 0 0
Foggia
Country [44] 0 0
Italy
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FORLì
Country [45] 0 0
Italy
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Milano
Country [46] 0 0
Italy
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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
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Fukuoka, Kurume
Country [53] 0 0
Japan
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Gifu, Ogaki
Country [54] 0 0
Japan
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Hyogo, Himeji
Country [55] 0 0
Japan
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Ibaraki, Naka-gun
Country [56] 0 0
Japan
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Kanagawa, Yokohama
Country [57] 0 0
Japan
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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
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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
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Dundee, Scotland
Country [73] 0 0
United Kingdom
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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
To assess efficacy and safety of concomitant treatment with nintedanib and sildenafil in
Idiopathic Pulmonary Fibrosis (IPF) patients with advanced lung function impairment.
Trial website
https://clinicaltrials.gov/show/NCT02802345
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

Summary results
Other publications