severe chronic obstructive pulmonary disease (COPD) MedDRA version: 14.1 Level: LLT Classification code 10010952 Term: COPD System Organ Class: 100000004855
Conditions
Interventions
Trade Name: Daxas
Product Name: Roflumilast 500 µg film-coated tablet
Product Code: BY217
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: ROFLUMILAST
CAS Number: 162401323
Current Sponsor
Sponsors
Takeda Pharma A/S
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: According to Protocol Amendment 1, dated 02 May 2012. 1. Giving written informed consent 2. History of COPD (according to GOLD 2009) for at least 12 months prior to baseline Visit V0 associated with chronic productive cough for 3 months in each of the 2 years prior to baseline Visit V0 (with other causes of productive cough excluded) 3. Age = 40 years 4. Forced expiratory volume after one second (FEV1)/forced vital capacity (FVC) ratio (post-bronchodilator) =65 years) yes F.1.3.1 Number of subjects for this age range 1000
Exclusion criteria
Exclusion criteria: According to Protocol Amendment 1, dated 02 May 2012. Criteria affecting the read-out parameters of the trial: 1. Moderate or severe COPD exacerbation and/or COPD exacerbations treated with antibiotics ongoing at the baseline Visit V0 2. Lower respiratory tract infection not resolved 4 weeks prior to the baseline Visit V0 3. Diagnosis of asthma and/or other relevant lung disease (e.g. history of primary bronchiectases, cystic fibrosis, bronchiolitis, lung resection, lung cancer, interstitial lung disease [e.g. fibrosis, silicosis, sarcoidosis], or active tuberculosis) 4. Current participation in a pulmonary rehabilitation program or completion of a pulmonary rehabilitation program within 3 months preceding the baseline Visit V0. However, physical exercise maintenance following the completion of the initial pulmonary rehabilitation program and which is continuously performed within 3 months preceding baseline Visit V0 and during the complete trial is allowed 5. Known alpha-1-antitrypsin deficiency Criteria within ethical considerations in terms of general health: 6. Clinically relevant abnormal laboratory values suggesting an undiagnosed disease requiring further clinical evaluation (as assessed by the Investigator) 7. Severe psychiatric or neurological disorders 8. History of depression associated with suicidal ideation or behaviour 9. Congestive heart failure severity grade IV according to NYHA (New York Heart Association Functional Classification) 10. Haemodynamically significant cardiac arrhythmias or heart valve deformations 11. Computed tomography (CT) or chest x-ray findings indicating an acute pulmonary disease other than COPD (e.g. tuberculosis, severe bronchiectasis, tumours) 12. Severe immunological diseases (e.g. known HIV infection, multiple sclerosis, lupus erythematosus, progressive multifocal leukoencephalopathy) 13. Liver impairment Child-Pugh B or C and/or active viral hepatitis 14. Severe acute infectious diseases (e.g. tuberculosis, or acute hepatitis) 15. Any diagnosis of a malignant disease (except basal cell carcinoma) within 5 years before trial start 16. Alcohol or drug abuse within the past year 17. Suspected hypersensitivity to roflumilast or rescue medication or ingredients thereof, or any other contraindication for the use thereof 18. Female patients of childbearing potential, not using and not willing to continue using a medically reliable method of contraception for the entire trial duration, such as oral, injectable, or implantable contraceptives, or intrauterine contraceptive devices, unless they are surgically sterilized/hysterectomised or post-menopausal > 1 year or who are not using any other method of contraception considered sufficiently reliable by the Investigator in individual cases 19. Pregnancy, breast feeding, planned oocyte donation or oocyte implantation 20. Planned donation of germ cells, blood, organs or bone marrow during the course of the trial 21. Participation in another trial (use of investigational product) within 30 days preceding the baseline Visit V0 or re-entry of patients previously enrolled in this trial 22. Suspected inability or unwillingness to comply with trial procedures (e.g. language problems, psychological disorders, number and timing of visits at the site) 23. Suffering from any concomitant disease that might interfere with trial procedures or evaluations 24. Use of disallowed drugs (see below) 25. Employee at the investigational site, re
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To investigate the effect of roflumilast 500 µg tablets once daily versus placebo on exacerbation rate, pulmonary function and major adverse cardiovascular events (MACE) in COPD patients who are concomitantly treated with a fixed combination of long-acting ß2-agonists (LABA) and inhaled glucocorticosteroids (ICS).;Primary end point(s): Rate of moderate or severe COPD exacerbations per patient per year. Moderate exacerbations are defined as requiring oral or parenteral glucocorticosteroids, severe as requiring hospitalisation and/or leading to death;Timepoint(s) of evaluation of this end point: The 1-year treatment period is considered appropriate to investigate the primary endpoint, reduction of exacerbation rate, taking into account the seasonal variation of COPD exacerbations during the year;Secondary Objective: To obtain data on safety and tolerability of roflumilast in COPD patients concomitantly treated with a fixed combination of LABA and ICS. To further characterise the population pharmacokinetic profile of roflumilast and roflumilast N-oxide. To further characterise the pharmacokinetics/pharmacodynamics (PK/PD) relationship of roflumilast, roflumilast N-oxide and ‘total phosphodiesterase 4 inhibitory’ activity (tPDE4i) in terms of efficacy and relevant safety aspects. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Key secondary Endpoints 1. Change from randomisation (V2) over 52 weeks of treatment in postbronchodilator FEV1 [L] 2. Rate of severe COPD exacerbations per patient per year. Other secondary endpoints: 1. Spirometry - Lung Function 2. Diary endpoints: Use of rescue medication, COPD symptoms score. 3. Quality of Life (COPD Assessment Test (CAT) 4. Time to mortality and time to trial withdrawal 5. Major adverse cardiovascular events 6. Pharmacokinetic profiles and parameters 7. Safety;Timepoint(s) of evaluation of this end point: Over 52 weeks of treatment for end-points COPD exacerbations, Lung Function, COPD Symptoms , Use of rescue medication, Quality of Life (COPD Assessment Test), Major Adverse Cardiovascular Events. Other end-points are evaluated at timing of occurence. | — |
Countries
Australia, Austria, Belgium, Brazil, Canada, Denmark, France, Germany, Greece, Hungary, Israel, Italy, Korea, Democratic People's Republic of, Netherlands, Poland, Russian Federation, Slovakia, South Africa, Spain, Turkey, United Kingdom
Contacts
Public ContactClinical Trial Operations
Takeda Pharma A/S
Outcome results
None listed