Chronic Obstructive Pulmonary Disease (COPD) patients with symptoms associated with chronic bronchitis MedDRA version: 8.1 Level: LLT Classification code 10010952 Term: COPD
Conditions
Interventions
Product Name: BIBW2948 BS inhalation powder, hard capsule
Product Code: BIBW2948 BS
Pharmaceutical Form: Inhalation powder, hard capsule
Current Sponsor code: BIBW2948BS
Concentration unit: mg milligr
Sponsors
Boehringer Ingelheim Pharma GmbH & Co. KG
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. All patients must sign an informed consent consistent with ICH-GCP guidelines and local legislations prior to any study-related procedures, which includes medication restrictions. 2. All patients must have a diagnosis of COPD. 3. Patients must have post-bronchodilator forced expiratory volume in 1 second/forced vital capacity FEV1/FVC =65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Patients with significant diseases other than COPD or chronic bronchitis are excluded. A significant disease is defined as a disease which in the opinion of the investigator may either put the subject at risk because of participation in the study or a disease which may influence the results of the study or the subject’s ability to participate in the study. 2. Patients with clinically relevant abnormal baseline haematology, blood chemistry, or urinalysis if the abnormality defines a significant disease as defined in exclusion criteria No. 1. 3. All patients with a serum glutamate oxaloactetate transferase (SGOT) >80 IU/L, SGPT >80 IU/L, bilirubin >2.0 mg/dL or creatinine >2.0 mg/dL will be excluded regardless of the clinical condition. Repeat laboratory evaluation will not be conducted in these patients. 4. Patients with a history of thoracotomy with pulmonary resection. 5. Patients with known active tuberculosis. 6. Patients with current significant psychiatric disorders. 7. Patients with a history of life-threatening pulmonary obstruction, or a history of cystic fibrosis or clinically evident bronchiectasis. 8. Patients with history of asthma or allergic rhinitis. 9. Patients with a history of sinusitis within the last 3 months. 10. Patients with a significant history of alcohol or drug abuse or current significant use of these substances based on the investigators judgement. 11. Use of oral corticosteroids in the 4 weeks prior to screening or during the baseline or treatment periods will be excluded. The use of inhaled corticosteroids (ICS) will be permitted provided there are no changes to the therapeutic plan in the prior 6 weeks (or at any time during the study).. 12. Patients who are being treated with cromolyn sodium or nedocromil sodium. 13. Patients with a dependence of supplementary oxygen for activities of daily living. 14. Patients who have experienced an exacerbation of COPD or chronic bronchitis (purulent sputum, significant worsening of the symptoms, etc.) in the six weeks prior to the Screening Visit (Visit 1) or between Visits 1 and 3 will be excluded. 15. Patients who have taken an investigational drug within 1 month or 6 half lives of the active ingredient (what ever is greater) prior to screening visit (Visit 1). 16. Patients with a recent history (i.e., one year or less) of myocardial infarction. 17. Patients with a recent history (i.e., three years or less) of heart failure or patients with any cardiac arrhythmia requiring drug therapy. 18. Patients with a history of cancer, other than treated basal cell carcinoma, within the last five years. 19. Patients who have had changes in their pulmonary therapeutic plan within the last four weeks prior to the Screening Visit (Visit 1). 20. Previous participation in this study, or current participation in other clinical study. 21. Women are of child-bearing potential or who have not been post menopausal for a duration of less than 2 years and have not a hysterectomy or tubal ligation procedure. 22. Patients using anticoagulation or antiplatelet therapy (within 6 half lives time prior to bronchoscopy procedure) or those that have a predisposition to uncontrolled bleeding events. 23. Donation of greater than 100 mL of blood within the past 2 weeks prior to screening. 24. Patients with known hypersensitivity to lactose or any other components of the inhalation capsule delivery system.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary end point(s): The primary efficacy variable for the study will be the volume of mucin per surface area of basal lamina (Vs mu,bala). Vs mu,bala will be determined by stereologic quantification of AB/PAS staining in endobronchial biopsies at Visit 2 (baseline) and at the end of the 4-week period of randomised treatment (Visit 5).;Main Objective: The general aim of this study is to evaluate the effects of a 4-week treatment of BIBW 2948 BS on epithelial mucin stores in patients with COPD associated with symptoms of chronic bronchitis. Additionally the safety and tolerability of a 15 mg b.i.d. dose of BIBW 2948 BS via the HandiHaler® device will be evaluated. The primary efficacy variable for the study will be the volume of mucin per surface area of basal lamina (Vs mu,bala). Vs mu,bala will be determined by stereologic quantification of per-iodic acid Schiff's reagent AB/PAS staining in endobronchial biopsies at Visit 2 (baseline) and at the end of the 4-week period of randomised treatment (Visit 5).;Secondary Objective: Secondary endpoints: 1)Volume of mucin per volume of epithelium (Vv mu, ep) in endobronchial biopsies 2)Total and Differential Cell Counts in bronchoalveolar lavage (BAL) 3)Mucin gene, and epidermal growth factor receptor (EGFR) gene expression (RNA) in epithelial brushings 4)EGFR and phosphorylated EGFR expression (Protein) in epithelial brushings 5)Goblet cell size and number in endobronchial biopsies 6)Interleukin-8 (IL-8) levels in bronchoalveolar lavage 7)Myeloperoxidase (MPO) levels in bronchoalveolar lavage. 8)Pharmacokinetics after single and multiple doses | — |
Countries
Germany, Ireland
Outcome results
None listed