The trial investigates the anti-inflammatory effects of 500 µg roflumilast tablets once daily in patients with chronic obstructive pulmonary disease (COPD)
- Conditions
- severe chronic obstructive pulmonary disease (COPD)MedDRA version: 17.1Level: LLTClassification code 10010952Term: COPDSystem Organ Class: 100000004855Therapeutic area: Diseases [C] - Respiratory Tract Diseases [C08]
- Registration Number
- EUCTR2011-000582-13-SE
- Lead Sponsor
- Takeda Development Centre Europe Ltd.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 150
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 30% =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
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) Duration of oxygen therapy =12 h/day
6) History of intubation for COPD or a respiratory failure of any cause in the past year
7) Hypoxemia defined as oxyhemoglobin concentration <88% when breathing room air measured by pulse oximetry
8) Formal contraindications to sputum collection or impossibility to obtain a sample of sputum valid for analysis
9) Clinically relevant abnormal laboratory values suggesting an undiagnosed disease requiring further clinical evaluation (as assessed by the Investigator)
10) Suspicion or diagnosis of a bleeding disorders irrespective of its pathophysiological mechanism: Thrombocytopenia (platelets <50000/mL) and platelet dysfunction (e.g. uraemia), thrombotic or coagulation disorders and bleeding due to abnormal blood vessels (e.g. purpura simplex)
11) Severe psychiatric or neurological disorders
12)History of depression associated with suicidal ideation or behaviour
13) Hemodynamic instability (e.g. bradycardia with resting heart rate <60 beats per min, tachycardia with resting heart rate =120 beats per min and/or a systolic blood pres-sure <100 or >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 a pulmonary disease other than COPD (e.g. tuberculosis, clinically significant bronchiectases, tumours). CT or X-ray results within 12 months prior to visit V0 are required.
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 broncho
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method 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.<br><br>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 Outcome Measures
Name Time Method