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Study of Nintedanib and Sildenafil in advanced IPF patients.

Phase 3
Conditions
Health Condition 1: null- Idiopathic Pulmonary Fibrosis
Registration Number
CTRI/2017/01/007727
Lead Sponsor
Boehringer Ingelheim
Brief Summary

Not available

Detailed Description

Not available

Recruitment & Eligibility

Status
ot Yet Recruiting
Sex
Not specified
Target Recruitment
250
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 more than or equal to 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 less than or equal to 35 percent predicted of normal at visit 1

Exclusion Criteria

1 Previous enrolment in this trial

2 ALT AST more than 1.5 fold upper limit of normalat visit 1

3 Total bilirubin more than 1.5 fold ULN at visit 1

4 Relevant airways obstruction pre-bronchodialator FEV1/FVC less than 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 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 gastrointestinal bleeding or

ulcers and or major injury or surgery within 3 months prior to visit 1

International normalised ratio more than 2 at visit 1

Prothrombin time and activated partial thromboplastin time more than

150 percent 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 within 12

months of visit 1

9 Creatinine clearance less than 30 mL per min calculated by CockcroftGault formula

10 Presence of aortic stenosis per investigator judgement at visit 1

11 Severe chronic heart failure defined by left ventricular ejection fraction < 25 percent

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; 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 for pulmonary hypertension 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 Johnâ??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 nint

Study & Design

Study Type
Interventional
Study Design
Not specified
Primary Outcome Measures
NameTimeMethod
Change from baseline in SGRQ total scoreTimepoint: 12 Week
Secondary Outcome Measures
NameTimeMethod
Change from baseline in dyspnea using UCSD SOBQ <br/ ><br>Change from baseline in SGRQ total score <br/ ><br>Change from baseline in dyspnea using UCSD SOBQ <br/ ><br>Percentage of patients with on-treatment SAEs from baselineTimepoint: 24 Week
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