Safety And Efficacy of BIBF 1120 in Idiopathic Pulmonary Fibrosis

Boehringer Ingelheim

Status and phase: Completed; Phase 2

Conditions: Pulmonary Fibrosis

Treatments: Drug: low dose BIBF 1120 twice daily; Drug: placebo; Drug: intermediate dose BIBF 1120 twice daily; Drug: high dose BIBF 1120 twice daily; Drug: low dose BIBF1120 once daily

Study type: Interventional

Funder types: Industry

Identifiers

NCT00514683

1199.30

Details and patient eligibility

About

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

Enrollment: 432 patients

Sex: All

Ages: 40+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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432 participants in 5 patient groups, including a placebo group

dose 1

Experimental group

Description:

low dose BIBF1120 once daily

Treatment:

Drug: low dose BIBF1120 once daily

dose 2

Experimental group

Description:

low dose BIBF 1120 twice daily

Treatment:

Drug: low dose BIBF 1120 twice daily

dose 3

Experimental group

Description:

intermediate dose BIBF 1120 twice daily

Treatment:

Drug: intermediate dose BIBF 1120 twice daily

dose 4

Experimental group

Description:

high dose BIBF 1120 twice daily

Treatment:

Drug: high dose BIBF 1120 twice daily

placebo

Placebo Comparator group

Description:

placebo

Treatment:

Drug: placebo