Safety and Efficacy of BIBF 1120 at High Dose in Idiopathic Pulmonary Fibrosis Patients II

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Boehringer Ingelheim
ClinicalTrials.gov Identifier:
NCT01335477
First received: April 13, 2011
Last updated: January 15, 2014
Last verified: January 2014
  Purpose

Idiopathic Pulmonary Fibrosis (IPF) is a chronic disease of unknown cause that results in scarring of the lung and there is a high unmet medical need for effective treatment to halt lung function decline, delay or avoid exacerbation (flare-ups), and ultimately to reduce the death rate.

In a large Phase 2 trial (1199.30) (NCT00514683), investigating the effects of 52 weeks of treatment with BIBF 1120 in patients with IPF, a positive effect was seen on lung function of patients treated with high dose of BIBF 1120 compared to placebo.

Hence it is the purpose of this trial to investigate and confirm the efficacy and safety of BIBF 1120 at a high dose in treating patients with IPF, compared with placebo. The trial will be conducted as a prospective, randomised design with the aim to collect safety and efficacy data.

Respiratory function is globally accepted for assessment of treatment effects in IPF patients. The chosen endpoint (Forced Vital Capacity (FVC) decline) is easy to obtain and is part of the usual examinations done in IPF patients.


Condition Intervention Phase
Pulmonary Fibrosis
Drug: placebo
Drug: BIBF 1120
Phase 3

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 52 Weeks, Double Blind, Randomized, Placebo-controlled Trial Evaluating the Effect of Oral BIBF 1120, 150 mg Twice Daily, on Annual Forced Vital Capacity Decline, in Patients With Idiopathic Pulmonary Fibrosis (IPF)

Resource links provided by NLM:


Further study details as provided by Boehringer Ingelheim:

Primary Outcome Measures:
  • annual rate of decline in FVC (expressed in mL over 52 weeks). [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Absolute categorical change of FVC% up to 52 weeks: decrease by > 5, increase by > 5, and change within <= 5. [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]
  • Absolute categorical change of FVC% up to 52 weeks: decrease by > 10, increase by > 10, and change within <= 10. [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]
  • change from baseline in Shortness Of Breath Questionnaire (SOBQ) [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]
  • change from baseline in Cough And Sputum Assessment (CASAQ) score [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]
  • Proportion of Patient's Global Impression of Change (PGIC) responders [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]
  • change from baseline in EuroQol 5-Dimensional Quality of Life Questionnaire (EQ5D) total score [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]
  • Proportion of SGRQ responders [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]
  • change from baseline in SGRQ-I [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]
  • Change from baseline in SPO2 [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]
  • change from baseline in DLCO [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]
  • Change from baseline in Saint-George Respiratory Questionnaire (SGRQ) total score at 52 weeks (expressed in points). [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]
  • Respiratory mortality (adjudicated; all data collected based on randomized set, including vital status follow-up, censored at 52 weeks). [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]
  • Absolute and relative change from baseline of FVC and FVC %pred up to 52 weeks [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]
  • Overall survival (all data collected based on randomized set, including vital status follow-up, censored at 52 weeks). [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]
  • time to first acute IPF exacerbation [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]
  • risk ratio of an IPF exacerbation [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]
  • On-treatment survival (on-treatment based on fatal adverse event + 28 days). [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]
  • changes from baseline in SGRQ domains [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]
  • Time to death or lung transplant. [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]

Enrollment: 551
Study Start Date: May 2011
Study Completion Date: October 2013
Primary Completion Date: October 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: placebo
patient receives capsules identical to those containing active drug
Drug: placebo
placebo matching BIBF 1120 BID
Experimental: BIBF 1120
patient receives capsules containing BIBF 1120 twice a day
Drug: BIBF 1120
BIBF 1120 BID (twice daily)

  Eligibility

Ages Eligible for Study:   40 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion criteria:

  1. Age >= 40 years;
  2. IPF diagnosed, according to most recent American Thoracic Society (ATS), European Respiratory Society (ERS), Japanese Respiratory Society (JRS), Latin American Thoracic Association (ALAT) IPF guideline for diagnosis and management, within 5 years;
  3. Combination of High Resolution Computerized Tomography (HRCT) pattern, and if available surgical lung biopsy pattern, as assessed by central reviewers, are consistent with diagnosis of IPF
  4. Dlco (corrected for Hb): 30%-79% predicted of normal; 5.FVC>= 50% predicted of normal

Exclusion criteria:

  1. Aspartate Aminotransferase (AST), Alanine Aminotransferase (ALT) > 1.5 x Upper Limit of Normal (ULN)
  2. Bilirubin > 1.5 x ULN;
  3. Relevant airways obstruction (i.e. pre-bronchodilator FEV1/FVC < 0.7);
  4. Patient likely to have lung transplantation during study (being on transplantation list is acceptable for participation);
  5. Myocardial infarction within 6 months;
  6. Unstable angina within 1 month;
  7. Bleeding risk (genetic predisposition; fibrinolysis or full-dose therapeutic anticoagulation or high dose antiplatelet therapy; history of hemorrhagic CNS event within 12 months; haemoptysis or haematuria or active gastro-intestinal bleeding or ulcers or major injury or surgery within 3 months);
  8. Thrombotic risk (inherited predisposition; history of thrombotic event (including stroke and transient ischemic attacks) within 12 months;
  9. International normalised ratio (INR) > 2, prolongation of prothrombin time (PT) and partial thromboplastin time (PTT) by > 50% of institutional ULN);
  10. N-ACetyl Cystein, prednisone > 15mg/day or equivalent received within 2 weeks of visit 1;
  11. Pirfenidone, azathioprine, cyclophosphamide, cyclosporine A received within 8 weeks of visit 1;
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01335477

  Hide Study Locations
Locations
United States, Arizona
1199.34.10078 Boehringer Ingelheim Investigational Site
Scottsdale, Arizona, United States
United States, California
1199.34.10086 Boehringer Ingelheim Investigational Site
San Francisco, California, United States
1199.34.10093 Boehringer Ingelheim Investigational Site
Santa Barbara, California, United States
1199.34.10077 Boehringer Ingelheim Investigational Site
Stanford, California, United States
1199.34.10083 Boehringer Ingelheim Investigational Site
Torrance, California, United States
United States, Connecticut
1199.34.10080 Boehringer Ingelheim Investigational Site
Stamford, Connecticut, United States
United States, Florida
1199.34.10087 Boehringer Ingelheim Investigational Site
South Miami, Florida, United States
United States, Georgia
1199.34.10100 Boehringer Ingelheim Investigational Site
Austell, Georgia, United States
United States, Illinois
1199.34.10075 Boehringer Ingelheim Investigational Site
Chicago, Illinois, United States
United States, Kansas
1199.34.10069 Boehringer Ingelheim Investigational Site
Olathe, Kansas, United States
United States, Kentucky
1199.34.10090 Boehringer Ingelheim Investigational Site
Lexington, Kentucky, United States
United States, Minnesota
1199.34.10079 Boehringer Ingelheim Investigational Site
Rochester, Minnesota, United States
United States, Missouri
1199.34.10067 Boehringer Ingelheim Investigational Site
Chesterfield, Missouri, United States
United States, New Hampshire
1199.34.10066 Boehringer Ingelheim Investigational Site
Lebanon, New Hampshire, United States
United States, New York
1199.34.10085 Boehringer Ingelheim Investigational Site
Albany, New York, United States
1199.34.10092 Boehringer Ingelheim Investigational Site
Jamaica, New York, United States
United States, North Carolina
1199.34.10074 Boehringer Ingelheim Investigational Site
Durham, North Carolina, United States
United States, Ohio
1199.34.10088 Boehringer Ingelheim Investigational Site
Toledo, Ohio, United States
United States, Oregon
1199.34.10070 Boehringer Ingelheim Investigational Site
Portland, Oregon, United States
United States, Pennsylvania
1199.34.10064 Boehringer Ingelheim Investigational Site
Philadelphia, Pennsylvania, United States
1199.34.10089 Boehringer Ingelheim Investigational Site
Philadelphia, Pennsylvania, United States
United States, South Carolina
1199.34.10082 Boehringer Ingelheim Investigational Site
Charleston, South Carolina, United States
United States, Texas
1199.34.10095 Boehringer Ingelheim Investigational Site
Longview, Texas, United States
1199.34.10060 Boehringer Ingelheim Investigational Site
San Antonio, Texas, United States
United States, Utah
1199.34.10084 Boehringer Ingelheim Investigational Site
Salt Lake City, Utah, United States
United States, Vermont
1199.34.10101 Boehringer Ingelheim Investigational Site
Colchester, Vermont, United States
United States, Wisconsin
1199.34.10073 Boehringer Ingelheim Investigational Site
Madison, Wisconsin, United States
Canada, Alberta
1199.34.02001 Boehringer Ingelheim Investigational Site
Calgary, Alberta, Canada
Canada, Nova Scotia
1199.34.02003 Boehringer Ingelheim Investigational Site
Halifax, Nova Scotia, Canada
Canada, Ontario
1199.34.02002 Boehringer Ingelheim Investigational Site
Hamilton, Ontario, Canada
Chile
1199.34.56001 Boehringer Ingelheim Investigational Site
Santiago de Chile, Chile
China
1199.34.86056 Boehringer Ingelheim Investigational Site
Beijing, China
1199.34.86052 Boehringer Ingelheim Investigational Site
Shanghai, China
1199.34.86058 Boehringer Ingelheim Investigational Site
Shanghai, China
1199.34.86054 Boehringer Ingelheim Investigational Site
Shanghai, China
1199.34.86055 Boehringer Ingelheim Investigational Site
Shanghai, China
1199.34.86053 Boehringer Ingelheim Investigational Site
Shenyang, China
1199.34.86051 Boehringer Ingelheim Investigational Site
Shenyang, China
1199.34.86057 Boehringer Ingelheim Investigational Site
Yinchuan, China
Finland
1199.34.35801 Boehringer Ingelheim Investigational Site
Helsinki, Finland
France
1199.34.33004 Boehringer Ingelheim Investigational Site
Dijon Cedex, France
1199.34.33003 Boehringer Ingelheim Investigational Site
Lille Cedex, France
1199.34.33005 Boehringer Ingelheim Investigational Site
Lyon Cedex, France
1199.34.33007 Boehringer Ingelheim Investigational Site
Marseille, France
1199.34.33002 Boehringer Ingelheim Investigational Site
Montpellier cedex 5, France
1199.34.33006 Boehringer Ingelheim Investigational Site
Toulouse cedex 9, France
Germany
1199.34.49003 Boehringer Ingelheim Investigational Site
Bad Berka, Germany
1199.34.49002 Boehringer Ingelheim Investigational Site
Berlin, Germany
1199.34.49010 Boehringer Ingelheim Investigational Site
Berlin-Buch, Germany
1199.34.49005 Boehringer Ingelheim Investigational Site
Coswig, Germany
1199.34.49001 Boehringer Ingelheim Investigational Site
Essen, Germany
1199.34.49007 Boehringer Ingelheim Investigational Site
Greifswald, Germany
1199.34.49009 Boehringer Ingelheim Investigational Site
Immenhausen, Germany
1199.34.49011 Boehringer Ingelheim Investigational Site
Köln, Germany
1199.34.49006 Boehringer Ingelheim Investigational Site
München, Germany
1199.34.49004 Boehringer Ingelheim Investigational Site
Münster, Germany
Greece
1199.34.30005 Boehringer Ingelheim Investigational Site
Athens, Greece
1199.34.30001 Boehringer Ingelheim Investigational Site
Heraklion, Greece
1199.34.30004 Boehringer Ingelheim Investigational Site
Larisa, Greece
1199.34.30002 Boehringer Ingelheim Investigational Site
Maroussi, Athens, Greece
1199.34.30003 Boehringer Ingelheim Investigational Site
Nikaia, Greece
India
1199.34.91051 Boehringer Ingelheim Investigational Site
Ahmedabad, India
1199.34.91053 Boehringer Ingelheim Investigational Site
Banglore, India
1199.34.91056 Boehringer Ingelheim Investigational Site
Jaipur, India
1199.34.91054 Boehringer Ingelheim Investigational Site
Pune, India
1199.34.91055 Boehringer Ingelheim Investigational Site
Pune, India
Japan
1199.34.81059 Boehringer Ingelheim Investigational Site
Himeji, Hyogo, Japan
1199.34.81063 Boehringer Ingelheim Investigational Site
Kawasaki, Kanagawa, Japan
1199.34.81060 Boehringer Ingelheim Investigational Site
Kobe, Hyogo, Japan
1199.34.81051 Boehringer Ingelheim Investigational Site
Minato-ku, Tokyo, Japan
1199.34.81054 Boehringer Ingelheim Investigational Site
Nagoya, Aichi, Japan
1199.34.81055 Boehringer Ingelheim Investigational Site
Ogaki, Gifu, Japan
1199.34.81058 Boehringer Ingelheim Investigational Site
Osaka-Sayama, Osaka, Japan
1199.34.81057 Boehringer Ingelheim Investigational Site
Sakai, Osaka, Japan
1199.34.81053 Boehringer Ingelheim Investigational Site
Seto, Aichi, Japan
1199.34.81052 Boehringer Ingelheim Investigational Site
Shinjuku-ku, Tokyo, Japan
1199.34.81056 Boehringer Ingelheim Investigational Site
Tenri, Nara, Japan
1199.34.81062 Boehringer Ingelheim Investigational Site
Tokushima, Tokushima, Japan
1199.34.81061 Boehringer Ingelheim Investigational Site
Yonago, Tottori, Japan
Korea, Republic of
1199.34.82002 Boehringer Ingelheim Investigational Site
Bucheon, Korea, Republic of
1199.34.82004 Boehringer Ingelheim Investigational Site
Incheon, Korea, Republic of
1199.34.82003 Boehringer Ingelheim Investigational Site
Seoul, Korea, Republic of
1199.34.82007 Boehringer Ingelheim Investigational Site
Seoul, Korea, Republic of
1199.34.82006 Boehringer Ingelheim Investigational Site
Seoul, Korea, Republic of
1199.34.82001 Boehringer Ingelheim Investigational Site
Seoul, Korea, Republic of
Mexico
1199.34.52001 Boehringer Ingelheim Investigational Site
Mexico DF, Mexico
Netherlands
1199.34.31002 Boehringer Ingelheim Investigational Site
Amsterdam, Netherlands
1199.34.31001 Boehringer Ingelheim Investigational Site
Nieuwegein, Netherlands
1199.34.31003 Boehringer Ingelheim Investigational Site
Rotterdam, Netherlands
Portugal
1199.34.35107 Boehringer Ingelheim Investigational Site
Amadora, Portugal
1199.34.35105 Boehringer Ingelheim Investigational Site
Coimbra, Portugal
1199.34.35102 Boehringer Ingelheim Investigational Site
Lisboa, Portugal
1199.34.35103 Boehringer Ingelheim Investigational Site
Lisboa, Portugal
1199.34.35101 Boehringer Ingelheim Investigational Site
Porto, Portugal
1199.34.35106 Boehringer Ingelheim Investigational Site
Vila Nova de Gaia, Portugal
Russian Federation
1199.34.07001 Boehringer Ingelheim Investigational Site
Kazan, Russian Federation
1199.34.07003 Boehringer Ingelheim Investigational Site
St. Petersburg, Russian Federation
Spain
1199.34.34001 Boehringer Ingelheim Investigational Site
Barcelona, Spain
1199.34.34003 Boehringer Ingelheim Investigational Site
Barcelona, Spain
1199.34.34004 Boehringer Ingelheim Investigational Site
Barcelona, Spain
1199.34.34005 Boehringer Ingelheim Investigational Site
Hospitalet de Llobregat, Spain
1199.34.34009 Boehringer Ingelheim Investigational Site
Madrid, Spain
1199.34.34008 Boehringer Ingelheim Investigational Site
Sevilla, Spain
Turkey
1199.34.90003 Boehringer Ingelheim Investigational Site
Ankara, Turkey
1199.34.90005 Boehringer Ingelheim Investigational Site
Istanbul, Turkey
1199.34.90001 Boehringer Ingelheim Investigational Site
Istanbul, Turkey
1199.34.90004 Boehringer Ingelheim Investigational Site
Izmir, Turkey
1199.34.90002 Boehringer Ingelheim Investigational Site
Izmir, Turkey
Sponsors and Collaborators
Boehringer Ingelheim
Investigators
Study Chair: Boehringer Ingelheim Boehringer Ingelheim
  More Information

No publications provided

Responsible Party: Boehringer Ingelheim
ClinicalTrials.gov Identifier: NCT01335477     History of Changes
Other Study ID Numbers: 1199.34, 2010-024252-29
Study First Received: April 13, 2011
Last Updated: January 15, 2014
Health Authority: Canada: Health Canada
Chile: Instituto de Salud Publica de Chile
China: Food and Drug Administration
Finland: Finnish Medicines Agency
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Germany: Federal Institute for Drugs and Medical Devices
Greece: Ethics Committee
India: Drugs Controller General of India
Japan: Ministry of Health, Labor and Welfare
Mexico: Ministry of Health
Netherlands: Central Committee Research Involving Human Subjects
Portugal: National Pharmacy and Medicines Institute
Russia: Pharmacological Committee, Ministry of Health
South Korea: Ministry of Food and Drug Safety (MFDS)
Spain: Spanish Agency of Medicines
Turkey: Ministry of Health
United States: Food and Drug Administration

Additional relevant MeSH terms:
Fibrosis
Pulmonary Fibrosis
Idiopathic Pulmonary Fibrosis
Pathologic Processes
Lung Diseases
Respiratory Tract Diseases
Idiopathic Interstitial Pneumonias
Lung Diseases, Interstitial

ClinicalTrials.gov processed this record on April 16, 2014