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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT00514683




Registration number
NCT00514683
Ethics application status
Date submitted
9/08/2007
Date registered
10/08/2007
Date last updated
6/01/2015

Titles & IDs
Public title
Safety And Efficacy of BIBF 1120 in Idiopathic Pulmonary Fibrosis
Scientific 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.
Secondary ID [1] 0 0
1199.30
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Pulmonary Fibrosis 0 0
Condition category
Condition code
Respiratory 0 0 0 0
Other respiratory disorders / diseases
Inflammatory and Immune System 0 0 0 0
Connective tissue diseases
Inflammatory and Immune System 0 0 0 0
Other inflammatory or immune system disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - low dose BIBF1120 once daily
Treatment: Drugs - low dose BIBF 1120 twice daily
Treatment: Drugs - intermediate dose BIBF 1120 twice daily
Treatment: Drugs - high dose BIBF 1120 twice daily
Treatment: Drugs - placebo

Experimental: dose 1 - low dose BIBF1120 once daily

Experimental: dose 2 - low dose BIBF 1120 twice daily

Experimental: dose 3 - intermediate dose BIBF 1120 twice daily

Experimental: dose 4 - high dose BIBF 1120 twice daily

Placebo comparator: placebo - placebo


Treatment: Drugs: low dose BIBF1120 once daily
low dose BIBF1120 once daily

Treatment: Drugs: low dose BIBF 1120 twice daily
low dose BIBF 1120 twice daily

Treatment: Drugs: intermediate dose BIBF 1120 twice daily
intermediate dose BIBF 1120 twice daily

Treatment: Drugs: high dose BIBF 1120 twice daily
high dose BIBF 1120 twice daily

Treatment: Drugs: placebo
placebo
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Rate of Decline in FVC
Timepoint [1] 0 0
Baseline until 52 weeks
Secondary outcome [1] 0 0
Absolute Change From Baseline in FVC%Pred
Timepoint [1] 0 0
Baseline and 52 weeks
Secondary outcome [2] 0 0
Absolute Change From Baseline in FVC
Timepoint [2] 0 0
Baseline and 52 weeks
Secondary outcome [3] 0 0
Relative Change From Baseline in FVC%Pred
Timepoint [3] 0 0
Baseline and 52 weeks
Secondary outcome [4] 0 0
Relative Change From Baseline in FVC
Timepoint [4] 0 0
Baseline and 52 weeks
Secondary outcome [5] 0 0
Number of Participants With Change From Baseline in FVC by Categories
Timepoint [5] 0 0
Baseline and 52 weeks
Secondary outcome [6] 0 0
Survival (All Causes of Death and Lung-transplant Free)
Timepoint [6] 0 0
52 weeks
Secondary outcome [7] 0 0
Absolute Change From Baseline in SpO2 at Rest
Timepoint [7] 0 0
Baseline and 52 weeks
Secondary outcome [8] 0 0
Absolute Change From Baseline in SpO2 at Rest by Categories
Timepoint [8] 0 0
Baseline and 52 weeks
Secondary outcome [9] 0 0
Absolute Change From Baseline in PaO2
Timepoint [9] 0 0
Baseline and 52 weeks
Secondary outcome [10] 0 0
Absolute Change From Baseline in P(A-a)O2
Timepoint [10] 0 0
Baseline and 52 weeks
Secondary outcome [11] 0 0
Absolute Change From Baseline in PaCO2
Timepoint [11] 0 0
Baseline and 52 weeks
Secondary outcome [12] 0 0
Absolute Change From Baseline in PaO2 by Categories
Timepoint [12] 0 0
Baseline and 52 weeks
Secondary outcome [13] 0 0
Absolute Change From Baseline in P(A-a) O2 by Categories
Timepoint [13] 0 0
Baseline and 52 weeks
Secondary outcome [14] 0 0
Absolute Change From Baseline in DLCO
Timepoint [14] 0 0
Baseline and 52 weeks
Secondary outcome [15] 0 0
Absolute Change From Baseline in DLCO by Categories
Timepoint [15] 0 0
Baseline and 52 weeks
Secondary outcome [16] 0 0
Absolute Change From Baseline in Distance Walk (6-MWT)
Timepoint [16] 0 0
Baseline and 52 weeks
Secondary outcome [17] 0 0
Absolute Change From Baseline in Dyspnoea Rating on Borg Scale Before Exercise (6-MWT)
Timepoint [17] 0 0
Baseline and 52 weeks
Secondary outcome [18] 0 0
Change From Baseline in Dyspnoea Rating on Borg Scale After Exercise (6-MWT)
Timepoint [18] 0 0
Baseline and 52 weeks
Secondary outcome [19] 0 0
Absolute Change From Baseline in MRC Dyspnea Scale by Categories
Timepoint [19] 0 0
Baseline and 52 weeks
Secondary outcome [20] 0 0
Absolute Change From Baseline in FEV1/FVC
Timepoint [20] 0 0
Baseline and 52 weeks
Secondary outcome [21] 0 0
Change From Baseline in SGRQ Total Score
Timepoint [21] 0 0
Baseline and 52 weeks
Secondary outcome [22] 0 0
Change From Baseline in SGRQ Domain Score Symptoms
Timepoint [22] 0 0
Baseline and 52 weeks
Secondary outcome [23] 0 0
Change From Baseline in SGRQ Domain Score Impacts
Timepoint [23] 0 0
Baseline and 52 weeks
Secondary outcome [24] 0 0
Change From Baseline in St George's Respiratory Questionnaire (SGRQ) Domain Score Activities
Timepoint [24] 0 0
Baseline and 52 weeks
Secondary outcome [25] 0 0
St George's Respiratory Questionnaire (SGRQ) Responder
Timepoint [25] 0 0
52 weeks
Secondary outcome [26] 0 0
Change From Baseline in TLC
Timepoint [26] 0 0
Baseline and 52 weeks
Secondary outcome [27] 0 0
Change From Baseline in RV
Timepoint [27] 0 0
Baseline and 52 weeks
Secondary outcome [28] 0 0
Change From Baseline in TGV
Timepoint [28] 0 0
Baseline and 52 weeks
Secondary outcome [29] 0 0
Change From Baseline in VC
Timepoint [29] 0 0
Baseline and 52 weeks
Secondary outcome [30] 0 0
Change From Baseline in IC
Timepoint [30] 0 0
Baseline and 52 weeks
Secondary outcome [31] 0 0
Number of Patients With at Least One IPF Exacerbation
Timepoint [31] 0 0
52 weeks
Secondary outcome [32] 0 0
Occurrences of IPF Exacerbations Per Patient Per Year
Timepoint [32] 0 0
52 weeks
Secondary outcome [33] 0 0
Time to First Occurrence of IPF Exacerbation
Timepoint [33] 0 0
52 weeks
Secondary outcome [34] 0 0
Survival (Death Due to Respiratory Cause, and Lung-transplant Free)
Timepoint [34] 0 0
52 weeks
Secondary outcome [35] 0 0
Time to Progression
Timepoint [35] 0 0
52 weeks
Secondary outcome [36] 0 0
Pre-dose Plasma Concentration of Nintedanib in Plasma at Steady State on Day 365 (Cpre,ss,365) and Day 729 (Cpre,ss,729).
Timepoint [36] 0 0
day 365 and day 729

Eligibility
Key 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
Minimum age
40 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/08/2007
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
432
Recruitment in Australia
Recruitment state(s)
QLD,SA,WA
Recruitment hospital [1] 0 0
1199.30.61005 Boehringer Ingelheim Investigational Site - South Brisbane
Recruitment hospital [2] 0 0
1199.30.61003 Boehringer Ingelheim Investigational Site - Toorak Gardens
Recruitment hospital [3] 0 0
1199.30.61004 Boehringer Ingelheim Investigational Site - Woodville
Recruitment hospital [4] 0 0
1199.30.61001 Royal Perth Hospital - Perth
Recruitment postcode(s) [1] 0 0
- South Brisbane
Recruitment postcode(s) [2] 0 0
- Toorak Gardens
Recruitment postcode(s) [3] 0 0
- Woodville
Recruitment postcode(s) [4] 0 0
- Perth
Recruitment outside Australia
Country [1] 0 0
Argentina
State/province [1] 0 0
Mendoza
Country [2] 0 0
Belgium
State/province [2] 0 0
Bruxelles
Country [3] 0 0
Belgium
State/province [3] 0 0
Leuven
Country [4] 0 0
Belgium
State/province [4] 0 0
Yvoir
Country [5] 0 0
Brazil
State/province [5] 0 0
Porto Alegre
Country [6] 0 0
Brazil
State/province [6] 0 0
Vila Clementino
Country [7] 0 0
Bulgaria
State/province [7] 0 0
Sofia
Country [8] 0 0
Canada
State/province [8] 0 0
Nova Scotia
Country [9] 0 0
Canada
State/province [9] 0 0
Ontario
Country [10] 0 0
Chile
State/province [10] 0 0
Providencia
Country [11] 0 0
China
State/province [11] 0 0
Beijing
Country [12] 0 0
China
State/province [12] 0 0
Nanjing
Country [13] 0 0
China
State/province [13] 0 0
Shanghai
Country [14] 0 0
China
State/province [14] 0 0
Shenyang
Country [15] 0 0
Czech Republic
State/province [15] 0 0
Prague 8
Country [16] 0 0
Czech Republic
State/province [16] 0 0
Usti nad Labem
Country [17] 0 0
France
State/province [17] 0 0
Bobigny
Country [18] 0 0
France
State/province [18] 0 0
Dijon
Country [19] 0 0
France
State/province [19] 0 0
Grenoble
Country [20] 0 0
France
State/province [20] 0 0
Lille Cedex
Country [21] 0 0
France
State/province [21] 0 0
Montpellier
Country [22] 0 0
France
State/province [22] 0 0
Nice Cedex 1
Country [23] 0 0
France
State/province [23] 0 0
Paris Cedex 18
Country [24] 0 0
Germany
State/province [24] 0 0
Bad Berka
Country [25] 0 0
Germany
State/province [25] 0 0
Berlin
Country [26] 0 0
Germany
State/province [26] 0 0
Donaustauf
Country [27] 0 0
Germany
State/province [27] 0 0
Essen
Country [28] 0 0
Germany
State/province [28] 0 0
Freiburg/Breisgau
Country [29] 0 0
Germany
State/province [29] 0 0
Großhansdorf
Country [30] 0 0
Germany
State/province [30] 0 0
Leipzig
Country [31] 0 0
Germany
State/province [31] 0 0
Mainz
Country [32] 0 0
Germany
State/province [32] 0 0
München
Country [33] 0 0
Greece
State/province [33] 0 0
Alexandroupolis
Country [34] 0 0
Greece
State/province [34] 0 0
Heraklion
Country [35] 0 0
Greece
State/province [35] 0 0
Larisa
Country [36] 0 0
Hungary
State/province [36] 0 0
Budapest
Country [37] 0 0
Hungary
State/province [37] 0 0
Deszk
Country [38] 0 0
Hungary
State/province [38] 0 0
Pecs
Country [39] 0 0
Hungary
State/province [39] 0 0
Szekesfehervar
Country [40] 0 0
Ireland
State/province [40] 0 0
Dublin 7
Country [41] 0 0
Italy
State/province [41] 0 0
Ascoli Piceno
Country [42] 0 0
Italy
State/province [42] 0 0
Busto Arsizio (va)
Country [43] 0 0
Italy
State/province [43] 0 0
Milano
Country [44] 0 0
Italy
State/province [44] 0 0
Modena
Country [45] 0 0
Italy
State/province [45] 0 0
Napoli
Country [46] 0 0
Italy
State/province [46] 0 0
Pavia
Country [47] 0 0
Italy
State/province [47] 0 0
Roma
Country [48] 0 0
Italy
State/province [48] 0 0
Siena
Country [49] 0 0
Italy
State/province [49] 0 0
Terni
Country [50] 0 0
Italy
State/province [50] 0 0
Trieste
Country [51] 0 0
Korea, Republic of
State/province [51] 0 0
Gyunggido
Country [52] 0 0
Korea, Republic of
State/province [52] 0 0
Incheon
Country [53] 0 0
Korea, Republic of
State/province [53] 0 0
Seoul
Country [54] 0 0
Mexico
State/province [54] 0 0
Distrito Federal
Country [55] 0 0
Netherlands
State/province [55] 0 0
Nieuwegein
Country [56] 0 0
Portugal
State/province [56] 0 0
Coimbra
Country [57] 0 0
Portugal
State/province [57] 0 0
Lisboa
Country [58] 0 0
Portugal
State/province [58] 0 0
Porto
Country [59] 0 0
Russian Federation
State/province [59] 0 0
Moscow
Country [60] 0 0
Russian Federation
State/province [60] 0 0
St. Petersburg
Country [61] 0 0
South Africa
State/province [61] 0 0
Bellville
Country [62] 0 0
South Africa
State/province [62] 0 0
Cape Town
Country [63] 0 0
South Africa
State/province [63] 0 0
Tygerberg
Country [64] 0 0
Spain
State/province [64] 0 0
Barcelona
Country [65] 0 0
Spain
State/province [65] 0 0
Valencia
Country [66] 0 0
Taiwan
State/province [66] 0 0
Taichung
Country [67] 0 0
Taiwan
State/province [67] 0 0
Taipei
Country [68] 0 0
Taiwan
State/province [68] 0 0
Taoyuan
Country [69] 0 0
Turkey
State/province [69] 0 0
Ankara
Country [70] 0 0
Turkey
State/province [70] 0 0
Istanbul
Country [71] 0 0
United Kingdom
State/province [71] 0 0
Aberdeen
Country [72] 0 0
United Kingdom
State/province [72] 0 0
Birmingham
Country [73] 0 0
United Kingdom
State/province [73] 0 0
Manchester
Country [74] 0 0
United Kingdom
State/province [74] 0 0
Westbury on Trym

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Boehringer Ingelheim
Address
Country

Ethics approval
Ethics application status

Summary
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
Trial website
https://clinicaltrials.gov/study/NCT00514683
Trial related presentations / publications
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.
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.
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.
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.
Public notes

Contacts
Principal investigator
Name 0 0
Boehringer Ingelheim
Address 0 0
Boehringer Ingelheim
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT00514683