severe chronic obstructive pulmonary disease (COPD) MedDRA version: 17.1 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: 162401-32-3
Current Spons
Sponsors
Takeda Development Centre Europe Ltd.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Subjects meeting the following criteria will be considered for inclusion in the run-in period: 1) Written informed consent obtained according to local regulations before any trial-related activities. A trial-related activity is any procedure that would not have been performed during the routine management of the Subject. 2) History of COPD (according to GOLD 2009) for at least 12 months prior to baseline visit V0 associated with chronic productive cough for at least three months in each of the two years prior to baseline visit V0 (with other causes of productive cough ex-cluded) 3) Outpatients 40-80 years of age 4) Post-bronchodilator 50% =FEV1 =80% predicted 5) Post-bronchodilator FEV1/FVC ratio =70% 6) Current or former smokers with smoking history =20 pack years Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 130 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 20
Exclusion criteria
Exclusion criteria: 1) Clinical instability, defined as experiencing a COPD exacerbation six months prior to V0, as indicated by treatment with a systemically administered glucocorticosteroid and/or antibiotics and/or hospitalization 2) An upper/lower respiratory tract infection e.g. common cold, sinus symptoms, pneu-monia, which has not resolved four weeks prior to V0 3) Diagnosis of asthma and/or other relevant lung disease (e.g. history of primary or clinically significant bronchiectases, cystic fibrosis, bronchiolitis, lung resection, lung cancer, interstitial lung disease [e.g. fibrosis, silicosis, sarcoidosis], active tuberculo-sis) or previous episodes of pneumothorax 4) Known alpha-1-antitrypsin deficiency Criteria within ethical considerations in terms of general health: 5) Any Oxygen therapy at home 6) History of intubation for COPD or a respiratory failure of any cause in the past year 7) Hypoxemia defined as oxyhemoglobin concentration 180 mmHg) 14)History of increased intracranial pressure, superior vena cava obstruction, pulmonary hypertension, aneurysms and arteriovenous malformations within the lungs 15)Congestive heart failure severity grade IV according to New York Heart Association Functional Classification (NYHA) 16)Haemodynamically significant cardiac arrhythmias or heart valve deformations 17)History of angina pectoris (Class =II Canadian Cardiovascular Society Functional Classification of Angina Pectoris Scale) or a myocardial infarction within last 12 months, unless corrected with Percutaneous Transluminal Coronary Angioplasty (PTCA) or Coronary Artery Bypass Surgery (CABG) =3 months prior to V0 and as-ymptomatic since then 18) X-ray Computed Tomography (CT) or X-ray findings indicating an anomaly or pulmonary disease other than COPD (e.g. tuberculosis, clinically significant bronchiectases, tumours). 19) Immunological diseases or known infection with Human Immunodeficiency Virus (HIV) 20) Liver impairment Child-Pugh B/C and/or active viral hepatitis 21) Severe acute infectious diseases 22) Any diagnosis of a malignant disease (other than basal or squamous cell carcinoma) within five years before enrolment into the trial 23) Excessive alcohol intake or drug/substance abuse within the past year 24) Any history of allergies, suspected hypersensitivity and/or contraindication to local anaesthetics (e.g. xylocaine, lignocaine) and/or sedative agents (e.g. benzodiazepi-nes, propofol, opioids) that would not allow adequate anaesthesia and/or bronchoscopy sedation. Suspected hypersensitivity to the trial treatme
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To investigate the effect of Roflumilast 500 µg tablets once daily versus placebo on inflammation parameters in bronchial biopsy tissue specimen. ;Secondary Objective: To investigate inflammation parameters in sputum and blood serum. Safety status will be assessed by vital signs, physical examination (including electrocardiogram [ECG]), clinical laboratory tests, and monitoring of adverse events. ;Primary end point(s): The primary endpoint will be the number of inflammatory cells CD8+ in bronchial biopsy tissue specimen (sub-mucosa) ;Timepoint(s) of evaluation of this end point: Evaluated from randomization visit V2 (Week 0) to the end of the intervention period in Week 16 (V6). | — |
Secondary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: Evaluated from visit V1 (Week -2) or V2 (Week 0) (depending on parameter) to the end of the intervention period in Week 16 (V6) ;Secondary end point(s): Secondary endpoints will be the following parameters: Biopsy Material • Cell count in biopsied material (sub-mucosa) [cells/mm2]: 1) CD68+ 2) Neutrophils 3) CD4+ 4) CD45+ • Cell count in biopsied material (bronchial epithelium) [cells/mm2]: 1) CD8+ 2) CD68+ Induced Sputum • Total and differential cell counts in induced sputum (absolute [cells/mL] and percent-age [%]): 1) Neutrophils 2) Macrophages 3) Eosinophils 4) Lymphocytes • Concentration of inflammatory biomarkers in sputum: 1) Inflammatory mediators (Human InflammationMAP® v.1; Rules-Based Medicine, Inc. (RBM)) Blood Serum • Concentration of inflammatory biomarkers in blood serum: 1) Inflammatory mediators (Human InflammationMAP® v.1; Rules-Based Medicine, Inc. (RBM)) Pulmonary Function Changes in the Course of the Trial • Change from randomization (V2) over 16 weeks of treatment for: 1) Forced expiratory volume in the first 1 second (FEV1 [L]) 2) Forced vital capacity (FVC [L]) 3) FEV1/FVC [%] | — |
Countries
Denmark, Germany, Poland, Sweden, United Kingdom
Contacts
Public ContactClinical Trial Operations
Takeda Development Centre Europe Ltd.
Outcome results
None listed