Efficacy and safety of nintedanib when co-administered with sildenafil in IPF patients with advanced lung function impairment

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)

Status

Active, not recruiting

Phases

Phase 3

Study type

Interventional

Source

EU CTR

Registry ID

EUCTR2015-002619-14-DE

Enrollment

300

Registered

2016-05-04

Start date

2016-07-21

Completion date

Unknown

Last updated

2018-06-05

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

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

Interventions

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: NINTEDANI

Eligibility

Sex/Gender

All

Inclusion criteria

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) =65 years) yes F.1.3.1 Number of subjects for this age range 200

Exclusion criteria

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 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 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

Design outcomes

Primary

Measure	Time frame
Main Objective: To assess efficacy and safety of concomitant treatment with nintedanib and sildenafil in IPF patients with advanced lung function impairment.;Secondary Objective: To enlarge the existing nintedanib mono-therapy database with safety and tolerability data in this population.;Primary end point(s): 1: change from baseline in SGRQ total score at week 12 ;Timepoint(s) of evaluation of this end point: 1: week 12	—

Measure

Time frame

Main Objective: To assess efficacy and safety of concomitant treatment with nintedanib and sildenafil in IPF patients with advanced lung function impairment.;Secondary Objective: To enlarge the existing nintedanib mono-therapy database with safety and tolerability data in this population.;Primary end point(s): 1: change from baseline in SGRQ total score at week 12 ;Timepoint(s) of evaluation of this end point: 1: week 12

—

Secondary

Measure	Time frame
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 ;Timepoint(s) of evaluation of this end point: 1: week 12 2: week 24 3: week 24 4: week 24	—

Countries

Australia, Belgium, Canada, China, France, Germany, India, Italy, Japan, Korea, Republic of, Mexico, Spain, United Kingdom, United States

Contacts

Public ContactQRPE PSC CT Information Disclosure

Boehringer Ingelheim Pharma GmbH & Co. KG

clintriage.rdg@boehringer-ingelheim.com00498002430127

Outcome results

None listed

Source: EU CTR (via WHO ICTRP) · Data processed: Feb 4, 2026