Safety And Efficacy of BIBF 1120 in Idiopathic Pulmonary Fibrosis

• Register: ClinicalTrials.gov
• Last refreshed on: 19 October 2017
• Main ID: NCT00514683
• Date of registration: 09/08/2007
• Prospective Registration: No
• Primary sponsor: Boehringer Ingelheim
• 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.
• Date of first enrolment: August 2007
• Target sample size: 432
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT00514683
• Study type: Interventional
• Phase: Phase 2

Countries of recruitment

Argentina, Australia, Belgium, Brazil, Bulgaria, Canada, Chile, China, Czech Republic, El Salvador, France, Germany, Greece, Hungary, Ireland, Italy, Korea, Republic of, Mexico, Netherlands, Portugal, Russian Federation, South Africa, Spain, Taiwan, Turkey, United Kingdom

Contacts

• Name: Boehringer Ingelheim
• Affiliation: Boehringer Ingelheim

Key inclusion & exclusion 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



Age minimum: 40 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Pulmonary Fibrosis

Intervention(s)

Drug: low dose BIBF 1120 twice daily

Drug: low dose BIBF1120 once daily

Drug: intermediate dose BIBF 1120 twice daily

Drug: high dose BIBF 1120 twice daily

Drug: placebo

Primary Outcome(s)

Rate of Decline in FVC [Time Frame: Baseline until 52 weeks]

Secondary Outcome(s)

Change From Baseline in RV [Time Frame: Baseline and 52 weeks]

Absolute Change From Baseline in FVC [Time Frame: Baseline and 52 weeks]

Absolute Change From Baseline in P(A-a) O2 by Categories [Time Frame: Baseline and 52 weeks]

Change From Baseline in St George's Respiratory Questionnaire (SGRQ) Domain Score Activities [Time Frame: Baseline and 52 weeks]

Absolute Change From Baseline in DLCO [Time Frame: Baseline and 52 weeks]

Absolute Change From Baseline in Dyspnoea Rating on Borg Scale Before Exercise (6-MWT) [Time Frame: Baseline and 52 weeks]

Absolute Change From Baseline in SpO2 at Rest by Categories [Time Frame: Baseline and 52 weeks]

Number of Patients With at Least One IPF Exacerbation [Time Frame: 52 weeks]

Occurrences of IPF Exacerbations Per Patient Per Year [Time Frame: 52 weeks]

Relative Change From Baseline in FVC%Pred [Time Frame: Baseline and 52 weeks]

Absolute Change From Baseline in FEV1/FVC [Time Frame: Baseline and 52 weeks]

Absolute Change From Baseline in P(A-a)O2 [Time Frame: Baseline and 52 weeks]

Survival (All Causes of Death and Lung-transplant Free) [Time Frame: 52 weeks]

Absolute Change From Baseline in MRC Dyspnea Scale by Categories [Time Frame: Baseline and 52 weeks]

Absolute Change From Baseline in PaO2 [Time Frame: Baseline and 52 weeks]

Change From Baseline in SGRQ Total Score [Time Frame: Baseline and 52 weeks]

Change From Baseline in TGV [Time Frame: Baseline and 52 weeks]

Absolute Change From Baseline in Distance Walk (6-MWT) [Time Frame: Baseline and 52 weeks]

Absolute Change From Baseline in DLCO by Categories [Time Frame: Baseline and 52 weeks]

Change From Baseline in IC [Time Frame: Baseline and 52 weeks]

Time to First Occurrence of IPF Exacerbation [Time Frame: 52 weeks]

Absolute Change From Baseline in PaCO2 [Time Frame: Baseline and 52 weeks]

Absolute Change From Baseline in SpO2 at Rest [Time Frame: Baseline and 52 weeks]

Change From Baseline in VC [Time Frame: Baseline and 52 weeks]

Number of Participants With Change From Baseline in FVC by Categories [Time Frame: Baseline and 52 weeks]

Absolute Change From Baseline in FVC%Pred [Time Frame: Baseline and 52 weeks]

Change From Baseline in Dyspnoea Rating on Borg Scale After Exercise (6-MWT) [Time Frame: Baseline and 52 weeks]

Absolute Change From Baseline in PaO2 by Categories [Time Frame: Baseline and 52 weeks]

Change From Baseline in SGRQ Domain Score Symptoms [Time Frame: Baseline and 52 weeks]

Pre-dose Plasma Concentration of Nintedanib in Plasma at Steady State on Day 365 (Cpre,ss,365) and Day 729 (Cpre,ss,729). [Time Frame: day 365 and day 729]

Change From Baseline in TLC [Time Frame: Baseline and 52 weeks]

Change From Baseline in SGRQ Domain Score Impacts [Time Frame: Baseline and 52 weeks]

St George's Respiratory Questionnaire (SGRQ) Responder [Time Frame: 52 weeks]

Relative Change From Baseline in FVC [Time Frame: Baseline and 52 weeks]

Survival (Death Due to Respiratory Cause, and Lung-transplant Free) [Time Frame: 52 weeks]

Time to Progression [Time Frame: 52 weeks]

Secondary ID(s)

1199.30

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Results

• Results available: Yes
• Date Posted: 06/01/2015
• URL: https://clinicaltrials.gov/ct2/show/results/NCT00514683