Safety And Efficacy of BIBF 1120 in Idiopathic Pulmonary Fibrosis

This study has been completed.
Sponsor:
Information provided by:
Boehringer Ingelheim
ClinicalTrials.gov Identifier:
NCT00514683
First received: August 9, 2007
Last updated: June 2, 2014
Last verified: June 2014
  Purpose

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


Condition Intervention Phase
Pulmonary Fibrosis
Drug: low dose BIBF1120 once daily
Drug: low dose BIBF 1120 twice daily
Drug: intermediate dose BIBF 1120 twice daily
Drug: high dose BIBF 1120 twice daily
Drug: placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double-Blind
Primary Purpose: Treatment
Official Title: A 12 Month, Double Blind, Randomized, Placebo-controlled Trial Evaluating the Effect of BIBF 1120 Administered at Oral Doses of 50 mg qd, 50 mg Bid, 100 mg Bid and 150 mg Bid on Forced Vital Capacity Decline During One Year, in Patients With Idiopathic Pulmonary Fibrosis, With Optional Active Treatment Extension Until Last Patient Out.

Resource links provided by NLM:


Further study details as provided by Boehringer Ingelheim:

Primary Outcome Measures:
  • The primary endpoint is the rate of decline in FVC (expressed in mL per year), evaluated from baseline until 12 month of treatment, compared to placebo. [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • FVC changes [ Time Frame: 6 and 12 months ] [ Designated as safety issue: No ]
  • Survival (all causes of death and lung-transplant free) [ Time Frame: 6 and 12 months ] [ Designated as safety issue: No ]
  • SpO2 (oxygen saturation) at rest [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  • DLCO changes [ Time Frame: 6 and 12 months ] [ Designated as safety issue: No ]
  • 6 minutes walking test changes [ Time Frame: 6 and 12 months ] [ Designated as safety issue: No ]
  • Patient reported outcomes [ Time Frame: 3, 6 and 12 months ] [ Designated as safety issue: No ]
  • Time to progression [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  • PaO2, PaCO2 and calculated P(A-a)O2 changes [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  • FEV1/FVC actual change [ Time Frame: 3, 6 and 12 months ] [ Designated as safety issue: No ]
  • Total lung capacity (TLC) change [ Time Frame: 6 and 12 months ] [ Designated as safety issue: No ]
  • Residual volume (RV) change [ Time Frame: 6 and 12 months ] [ Designated as safety issue: No ]
  • Total gas volume (TGV) change [ Time Frame: 6 and 12 months ] [ Designated as safety issue: No ]
  • Vital capacity (VC) change [ Time Frame: 6 and 12 months ] [ Designated as safety issue: No ]
  • Inspiratory capacity (IC) change [ Time Frame: 6 and 12 months ] [ Designated as safety issue: No ]
  • Incidence of IPF exacerbations [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  • Occurrences of IPF exacerbations per patient per year [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  • Time to first occurrence of IPF exacerbation [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  • Survival (death due to respiratory cause, and lung-transplant free) [ Time Frame: 6 and 12 months ] [ Designated as safety issue: No ]

Enrollment: 432
Study Start Date: August 2007
Primary Completion Date: June 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: dose 1
low dose BIBF1120 once daily
Drug: low dose BIBF1120 once daily
low dose BIBF1120 once daily
Experimental: dose 2
low dose BIBF 1120 twice daily
Drug: low dose BIBF 1120 twice daily
low dose BIBF 1120 twice daily
Experimental: dose 3
intermediate dose BIBF 1120 twice daily
Drug: intermediate dose BIBF 1120 twice daily
intermediate dose BIBF 1120 twice daily
Experimental: dose 4
high dose BIBF 1120 twice daily
Drug: high dose BIBF 1120 twice daily
high dose BIBF 1120 twice daily
Placebo Comparator: placebo
placebo
Drug: placebo
placebo

  Eligibility

Ages Eligible for Study:   40 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00514683

  Show 92 Study Locations
Sponsors and Collaborators
Boehringer Ingelheim
Investigators
Study Chair: Boehringer Ingelheim Boehringer Ingelheim
  More Information

No publications provided by Boehringer Ingelheim

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Boehringer Ingelheim, Study Chair, Boehringer Ingelheim
ClinicalTrials.gov Identifier: NCT00514683     History of Changes
Other Study ID Numbers: 1199.30
Study First Received: August 9, 2007
Last Updated: June 2, 2014
Health Authority: Argentina: A.N.M.A.T. (Administración Nacional de Medicamentos, Alimentos y Tecnologia Médica)
Australia: Dept of Health and Ageing Therapeutic Goods Admin
Belgium: Federal Agency for Medicines and Health Products, FAMHP
Brazil: ANVISA
Bulgaria: Bulgarian Drug Agency, BG-1504 Sofia
Canada: Therapeutic Products Directorate
Chile: Instituto de Salud Pública de Chile
China: Food and Drug Administration
Czech Republic: State Institute for Drug Control (SUKL), CZ-100 41 Prague 10
France: AGENCE FRANCAISE DE SECURITE SANITAIRE DES PRODUITS DE SANTE
Germany: Bundesinstitut für Arzneimittel und Medizinprodukte, Fachregistratur Z 14.02.06, Kurt-Georg-Kiesinger-Allee 3, 53175 Bonn
Great Britain: MHRA
Greece: National Organization for Medicines (EOF) National Ethics Committee
Hungary: National Institute of Pharmacy, H-1051 Budapest
Ireland: Irish Medicines Board
Italy: Comitato Etico Provinciale di Modena - MODENA
Korea, Republic of: Korea Food and Drug Administration (KFDA)
Mexico: Federal Commission for Protection Against Health Risks
Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
Portugal: National Pharmacy and Medicines Institute
Russia: Ministry of Healthcare and Social Development of Russian Federation, Moscow
South Africa: Medicines Control Council
Spain: Spanish Agency for Medicines and Health Products
Taiwan: Department of Health, Executive Yuan, Taiwan
Turkey: Ministry of Health Central Ethics Committee

Additional relevant MeSH terms:
Fibrosis
Pulmonary Fibrosis
Idiopathic Pulmonary Fibrosis
Pathologic Processes
Lung Diseases
Respiratory Tract Diseases
Idiopathic Interstitial Pneumonias
Lung Diseases, Interstitial
Nintedanib
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on August 28, 2014