Safety And Efficacy of BIBF 1120 in Idiopathic Pulmonary Fibrosis

NCT ID: NCT00514683

Last Updated: 2015-01-06

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 432 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-08-31

Brief Summary

The general purpose of this trial is to investigate the efficacy and safety of 4 dose strategies of BIBF 1120 treatment for 12 months, compared to placebo in patients with idiopathic pulmonary fibrosis.

The primary objective of this study is to demonstrate whether at least one dose strategy is superior to placebo in patients with IPF, in modifying the rate of decline of Forced Vital Capacity (FVC).

As a secondary objective, additional parameters will be assessed in order to differentiate between dose strategies on the basis of safety and efficacy

Conditions

Pulmonary Fibrosis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

dose 1

low dose BIBF1120 once daily

Group Type: EXPERIMENTAL

low dose BIBF1120 once daily

Intervention Type: DRUG

low dose BIBF1120 once daily

dose 2

low dose BIBF 1120 twice daily

Group Type: EXPERIMENTAL

low dose BIBF 1120 twice daily

Intervention Type: DRUG

low dose BIBF 1120 twice daily

dose 3

intermediate dose BIBF 1120 twice daily

Group Type: EXPERIMENTAL

intermediate dose BIBF 1120 twice daily

Intervention Type: DRUG

intermediate dose BIBF 1120 twice daily

dose 4

high dose BIBF 1120 twice daily

Group Type: EXPERIMENTAL

high dose BIBF 1120 twice daily

Intervention Type: DRUG

high dose BIBF 1120 twice daily

placebo

placebo

Group Type: PLACEBO_COMPARATOR

placebo

Intervention Type: DRUG

placebo

Interventions

low dose BIBF1120 once daily

low dose BIBF1120 once daily

Intervention Type: DRUG

low dose BIBF 1120 twice daily

low dose BIBF 1120 twice daily

Intervention Type: DRUG

intermediate dose BIBF 1120 twice daily

intermediate dose BIBF 1120 twice daily

Intervention Type: DRUG

high dose BIBF 1120 twice daily

high dose BIBF 1120 twice daily

Intervention Type: DRUG

placebo

placebo

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Patient >40 years

2. Written informed consent signed prior to entry into the study

3. IPF diagnosed (according to ATS / ERS criteria) less than 5 years prior to screening visit.

4. HRCT within 12 months of randomisation and biopsy (the latter if needed to fulfil ATS/ERS criteria) centrally reviewed and consistent with diagnosis.

5. FVC>50 % of predicted value

Predicted normal values will be calculated according to ESCS (R94-1408):

Males :

FVC predicted (L) = 5.76 x height (meters)- 0.026 x age (years) -4.34

Females :

FVC predicted (L) = 4.43 x height (meters)- 0.026 x age (years) -2.89

6. Single breath DLCO (corrected for Hb) 30 - 79% inclusive of predicted .

Different sites may use different prediction formulas, based on the method used to measure DLco. In any case, the method used must be in compliance with the ATS/ERS guideline on DLCO measurements (R06-2002), and the prediction formula appropriate for that method. Raw data (gas mixture, equation used for prediction of normal, further adjustments made if so) must be traced.

Adjustment for haemoglobin (R06-2002):

Males :

DLCO predicted for Hb = DLCO predicted x (1.7Hb/[10.22+Hb])

Females :

DLCO predicted for Hb = DLCO predicted x (1.7Hb/[9.38+Hb]) where Hb is expressed in g/dL-1

7. PaO2 >= 55 mmHg (sea level to 1500 m) or 50 mmHg (above 1500 m) room air

Exclusion Criteria

1. AST, ALT > 1.5 x ULN ;

2. Bilirubin > 1.5 x ULN

3. Relevant airways obstruction

4. Continuous oxygen supplementation at randomisation (defined as > 15 hours supplemental oxygen per day).

5. Active infection at screening or randomisation.

6. Neutrophils < 1500 / mm3

7. International normalised ratio (INR) > 1.5 and/or Partial thromboplastin time (PTT) > 1.5 x ULN ;

8. Platelets < 100 000 /mL

9. Haemoglobin < 9.0 g/dL

10. In the opinion of the Investigator, patient is likely to have lung transplantation during study

11. Life expectancy for disease other than IPF < 2.5 years (Investigator assessment).

12. Other disease that may interfere with testing procedures or in judgement of Investigator may interfere with trial participation or may put the patient at risk when participating to this trial.

• Myocardial infarction during the previous 6 months
• Unstable angina during the previous month

13. Other investigational therapy received within 8 weeks prior to screening visit.

14. Pregnant women or women who are breast feeding or of child bearing potential not using a highly effective method of birth control for at least one month prior to enrolment.

15. Sexually active males not committing to using condoms during the course of the study (except if their partner is not of childbearing potential).

16. Known or suspected active alcohol or drug abuse.

17. Bleeding risk : Known inherited predisposition to bleeding, patients who require full-dose anticoagulation, Patients who require full-dose antiplatelet therapy, History of hemorrhagic CNS event within 12 months prior to screening , Any of the following within 3 months prior to screening : Gross / frank haemoptysis or haematuria, Active gastro-intestinal bleeding or ulcers, Major injury or surgery

18. Thrombotic risk

19. Surgical procedures planned to occur during trial period.

20. Coagulopathy

21. Uncontrolled systemic arterial hypertension

22. known hypersensitivity to lactose or any component of the study medication

• Minimum Eligible Age: 40 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Boehringer Ingelheim

INDUSTRY

Sponsor Role: lead

Responsible Party

Boehringer Ingelheim

Principal Investigators

Boehringer Ingelheim

Role: STUDY_CHAIR

Boehringer Ingelheim

Locations

1199.30.54002 Boehringer Ingelheim Investigational Site

Mendoza, , Argentina

1199.30.61005 Boehringer Ingelheim Investigational Site

South Brisbane, Queensland, Australia

1199.30.61003 Boehringer Ingelheim Investigational Site

Toorak Gardens, South Australia, Australia

1199.30.61004 Boehringer Ingelheim Investigational Site

Woodville, South Australia, Australia

1199.30.61001 Royal Perth Hospital

Perth, Western Australia, Australia

1199.30.32004 Boehringer Ingelheim Investigational Site

Brussels, , Belgium

1199.30.32001 Boehringer Ingelheim Investigational Site

Leuven, , Belgium

1199.30.32002 Boehringer Ingelheim Investigational Site

Yvoir, , Belgium

1199.30.55002 Boehringer Ingelheim Investigational Site

Porto Alegre, , Brazil

1199.30.55001 Boehringer Ingelheim Investigational Site

Vila Clementino, , Brazil

1199.30.06004 Boehringer Ingelheim Investigational Site

Sofia, , Bulgaria

1199.30.06005 Boehringer Ingelheim Investigational Site

Sofia, , Bulgaria

1199.30.01003 Division of Respirology

Halifax, Nova Scotia, Canada

1199.30.01002 St. Joseph's Healthcare

Hamilton, Ontario, Canada

1199.30.56001 Boehringer Ingelheim Investigational Site

Providencia, , Chile

1199.30.86001 Boehringer Ingelheim Investigational Site

Beijing, , China

1199.30.86002 Boehringer Ingelheim Investigational Site

Beijing, , China

1199.30.86005 Boehringer Ingelheim Investigational Site

Nanjing, , China

1199.30.86003 Boehringer Ingelheim Investigational Site

Shanghai, , China

1199.30.86004 Boehringer Ingelheim Investigational Site

Shenyang, , China

1199.30.42002 Boehringer Ingelheim Investigational Site

Prague, , Czechia

1199.30.42001 Boehringer Ingelheim Investigational Site

Ústí nad Labem, , Czechia

1199.30.3302A Boehringer Ingelheim Investigational Site

Bobigny, , France

1199.30.3306A Boehringer Ingelheim Investigational Site

Dijon, , France

1199.30.3303A Boehringer Ingelheim Investigational Site

Grenoble, , France

1199.30.3305A Boehringer Ingelheim Investigational Site

Lille, , France

1199.30.3305B Boehringer Ingelheim Investigational Site

Lille, , France

1199.30.3305C Boehringer Ingelheim Investigational Site

Lille, , France

1199.30.3304C Boehringer Ingelheim Investigational Site

Montpellier, , France

1199.30.3307A Boehringer Ingelheim Investigational Site

Nice, , France

1199.30.3301A Boehringer Ingelheim Investigational Site

Paris, , France

1199.30.49008 Boehringer Ingelheim Investigational Site

Bad Berka, , Germany

1199.30.49007 Boehringer Ingelheim Investigational Site

Berlin, , Germany

1199.30.49006 Boehringer Ingelheim Investigational Site

Donaustauf, , Germany

1199.30.49001 Boehringer Ingelheim Investigational Site

Essen, , Germany

1199.30.49002 Boehringer Ingelheim Investigational Site

Freiburg/Breisgau, , Germany

1199.30.49003 Boehringer Ingelheim Investigational Site

Großhansdorf, , Germany

1199.30.49009 Boehringer Ingelheim Investigational Site

Leipzig, , Germany

1199.30.49004 Boehringer Ingelheim Investigational Site

Mainz, , Germany

1199.30.49005 Boehringer Ingelheim Investigational Site

München, , Germany

1199.30.30004 Boehringer Ingelheim Investigational Site

Alexandroupoli, , Greece

1199.30.30001 Boehringer Ingelheim Investigational Site

Heraklion, , Greece

1199.30.30002 Boehringer Ingelheim Investigational Site

Larissa, , Greece

1199.30.36002 Boehringer Ingelheim Investigational Site

Budapest, , Hungary

1199.30.36003 Boehringer Ingelheim Investigational Site

Budapest, , Hungary

1199.30.36004 Boehringer Ingelheim Investigational Site

Deszk, , Hungary

1199.30.36001 Boehringer Ingelheim Investigational Site

Pécs, , Hungary

1199.30.36005 Boehringer Ingelheim Investigational Site

Székesfehérvár, , Hungary

1199.30.35301 Mater Misericordiae Hospital

Dublin, , Ireland

1199.30.39008 Boehringer Ingelheim Investigational Site

Ascoli Piceno, , Italy

1199.30.39013 Boehringer Ingelheim Investigational Site

Busto Arsizio (va), , Italy

1199.30.39007 Boehringer Ingelheim Investigational Site

Milan, , Italy

1199.30.39001 Boehringer Ingelheim Investigational Site

Modena, , Italy

1199.30.39012 Boehringer Ingelheim Investigational Site

Napoli, , Italy

1199.30.39009 Boehringer Ingelheim Investigational Site

Pavia, , Italy

1199.30.39011 Boehringer Ingelheim Investigational Site

Roma, , Italy

1199.30.39010 Boehringer Ingelheim Investigational Site

Siena, , Italy

1199.30.39003 Boehringer Ingelheim Investigational Site

Terni, , Italy

1199.30.39004 Boehringer Ingelheim Investigational Site

Trieste, , Italy

1199.30.52001 Boehringer Ingelheim Investigational Site

Distrito Federal, , Mexico

1199.30.31002 Boehringer Ingelheim Investigational Site

Nieuwegein, , Netherlands

1199.30.35105 Boehringer Ingelheim Investigational Site

Coimbra, , Portugal

1199.30.35106 Boehringer Ingelheim Investigational Site

Coimbra, , Portugal

1199.30.35107 Boehringer Ingelheim Investigational Site

Lisbon, , Portugal

1199.30.35108 Boehringer Ingelheim Investigational Site

Lisbon, , Portugal

1199.30.35109 Boehringer Ingelheim Investigational Site

Lisbon, , Portugal

1199.30.35101 Boehringer Ingelheim Investigational Site

Porto, , Portugal

1199.30.07001 Boehringer Ingelheim Investigational Site

Moscow, , Russia

1199.30.07002 Boehringer Ingelheim Investigational Site

Moscow, , Russia

1199.30.07003 Boehringer Ingelheim Investigational Site

Saint Petersburg, , Russia

1199.30.27001 Boehringer Ingelheim Investigational Site

Bellville, , South Africa

1199.30.27003 Boehringer Ingelheim Investigational Site

Cape Town, , South Africa

1199.30.27002 Boehringer Ingelheim Investigational Site

Tygerberg, , South Africa

1199.30.82002 Boehringer Ingelheim Investigational Site

Gyunggido, , South Korea

1199.30.82004 Boehringer Ingelheim Investigational Site

Incheon, , South Korea

1199.30.82001 Boehringer Ingelheim Investigational Site

Seoul, , South Korea

1199.30.82003 Boehringer Ingelheim Investigational Site

Seoul, , South Korea

1199.30.82005 Boehringer Ingelheim Investigational Site

Seoul, , South Korea

1199.30.34001 Boehringer Ingelheim Investigational Site

Barcelona, , Spain

1199.30.34002 Boehringer Ingelheim Investigational Site

Valencia, , Spain

1199.30.88605 Boehringer Ingelheim Investigational Site

Taichung, , Taiwan

1199.30.88601 National Taiwan University

Taipei, , Taiwan

1199.30.88603 Tri-service General Hospital

Taipei, , Taiwan

1199.30.88606 Boehringer Ingelheim Investigational Site

Taipei, , Taiwan

1199.30.88604 Chang Gung Memorial Hosp-Linkou

Taoyuan District, , Taiwan

1199.30.90001 Boehringer Ingelheim Investigational Site

Ankara, , Turkey (Türkiye)

1199.30.90002 Boehringer Ingelheim Investigational Site

Istanbul, , Turkey (Türkiye)

1199.30.44006 Boehringer Ingelheim Investigational Site

Aberdeen, , United Kingdom

1199.30.44003 Boehringer Ingelheim Investigational Site

Birmingham, , United Kingdom

1199.30.44005 Boehringer Ingelheim Investigational Site

Birmingham, , United Kingdom

1199.30.44007 Boehringer Ingelheim Investigational Site

Manchester, , United Kingdom

1199.30.44001 Boehringer Ingelheim Investigational Site

Westbury on Trym, , United Kingdom

Countries

Argentina; Australia; Belgium; Brazil; Bulgaria; Canada; Chile; China; Czechia; France; Germany; Greece; Hungary; Ireland; Italy; Mexico; Netherlands; Portugal; Russia; South Africa; South Korea; Spain; Taiwan; Turkey (Türkiye); United Kingdom

References

Glaspole I, Bonella F, Bargagli E, Glassberg MK, Caro F, Stansen W, Quaresma M, Orsatti L, Bendstrup E. Efficacy and safety of nintedanib in patients with idiopathic pulmonary fibrosis who are elderly or have comorbidities. Respir Res. 2021 Apr 26;22(1):125. doi: 10.1186/s12931-021-01695-y.

Reference Type: DERIVED

PMID: 33902584 (View on PubMed)

Richeldi L, Kreuter M, Selman M, Crestani B, Kirsten AM, Wuyts WA, Xu Z, Bernois K, Stowasser S, Quaresma M, Costabel U. Long-term treatment of patients with idiopathic pulmonary fibrosis with nintedanib: results from the TOMORROW trial and its open-label extension. Thorax. 2018 Jun;73(6):581-583. doi: 10.1136/thoraxjnl-2016-209701. Epub 2017 Oct 9.

Reference Type: DERIVED

PMID: 28993537 (View on PubMed)

Paterniti MO, Bi Y, Rekic D, Wang Y, Karimi-Shah BA, Chowdhury BA. Acute Exacerbation and Decline in Forced Vital Capacity Are Associated with Increased Mortality in Idiopathic Pulmonary Fibrosis. Ann Am Thorac Soc. 2017 Sep;14(9):1395-1402. doi: 10.1513/AnnalsATS.201606-458OC.

Reference Type: DERIVED

PMID: 28388260 (View on PubMed)

Richeldi L, Costabel U, Selman M, Kim DS, Hansell DM, Nicholson AG, Brown KK, Flaherty KR, Noble PW, Raghu G, Brun M, Gupta A, Juhel N, Kluglich M, du Bois RM. Efficacy of a tyrosine kinase inhibitor in idiopathic pulmonary fibrosis. N Engl J Med. 2011 Sep 22;365(12):1079-87. doi: 10.1056/NEJMoa1103690.

Reference Type: DERIVED

PMID: 21992121 (View on PubMed)

Other Identifiers

1199.30

Identifier Type: -

Identifier Source: org_study_id