Effect of BIBW 2948 BS in COPD

Phase 2

Completed

Conditions: Pulmonary Disease, Chronic Obstructive
Bronchitis, Chronic

Interventions: Drug: BIBW 2948 BS
Drug: Placebo

Registration Number: NCT00423137

Lead Sponsor: Boehringer Ingelheim

Brief Summary: Study of BIBW 2948 BS in Patients with COPD and Chronic Bronchitis

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 48

Inclusion Criteria

COPD smokers
ages between 40 and 70

Exclusion Criteria

Significant other diseases
abnormal hematology
abnormal liver function
psychiatric disorders
pulmonary obstruction
asthma, allergic rhinitis
dependance on oxygen
patients with history of myocardial infarction
patients with history of cancer
women of child bearing potential
antiplatelet or anticoagulation therapy

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
BIBW2948 - low dose	BIBW 2948 BS	Twice daily (b.i.d.)
BIBW2948 - high dose	BIBW 2948 BS	Twice daily (b.i.d.)
Placebo - high dose	Placebo	Twice daily (b.i.d.)
Placebo - low dose	Placebo	Twice daily (b.i.d.)

Primary Outcome Measures

Name	Time	Method
Change From Baseline in Volume of Mucin Per Surface Area of Basal Lamina	At baseline (visit 2) and at visit 5.	Change from baseline in volume of mucin per surface area of basal lamina. Volume of mucin per surface area of basal lamina (vs mu,bala) was determined by stereologic quantification of Periodic Acid Schiff's (AB/PAS) reagent staining in endobronchial biopsies at visit 2 (baseline) and at the end of the 4-week period of randomized treatment (visit 5).

Secondary Outcome Measures

Name	Time	Method
Change From Baseline of Interleukin-8 (IL-8) Levels in Bronchoalveolar Lavage	At baseline (visit 2) and at visit 5.	Change from baseline of Interleukin-8 (IL-8) levels in bronchoalveolar lavage. IL-8 levels, were measured by enzyme linked immunosorbent assay in bronchoalveolar lavage samples at visit 2 (baseline) and at the end of the 4-week period of treatment (visit 5).
Change From Baseline in Bronchoalveolar Lavage (BAL) Cell Count	At baseline (visit 2) and at visit 5.	Change from baseline in bronchoalveolar lavage (BAL) cell count. Total cell counts were performed on bronchoalveolar lavage (BAL) samples obtained during visit 2 (baseline) and at the end of the 4-week period of randomised treatment.
Change From Baseline in Log Mucin Gene (MUC5AC) Expression Level Obtained in Epithelial Brushings	At baseline (visit 2) and at visit 5.	Change from baseline in log mucin gene (MUC5AC) expression level obtained in epithelial brushings. Gene expression levels of the gel-forming mucins (MUC5AC) were quantified using two-step real time polymerase chain reaction (PCR) from RNA extracted from the cells obtained from the epithelial brushings during the endobronchial biopsy at visit 2 (baseline) and at the end of the 4-week period of randomised treatment (visit 5).
Change From Baseline of Volume of Mucin Per Volume of Epithelium (Vv mu, ep) in Endobronchial Biopsies	At baseline (visit 2) and at visit 5.	Change from baseline of volume of mucin per volume of epithelium (Vv mu, ep) in endobronchial biopsies. The volume of mucin per volume of epithelium (Vv mu, ep), as measured by stereological quantification of AB/PAS staining in endobronchial biopsies was performed at baseline (visit 2) and at the end of the 4-week period of randomised treatment (visit 5).
Change From Baseline in Epidermal Growth Factor Receptor (EGFR) Internalization Assay in Epithelial Brushings - EGRF Spots With Marker	At baseline (visit 2) and at visit 5.	Change in number of EGRF spots with marker per cell. The degree of EGFR internalization (and hence activation) was measured using antibody or ligand labeling techniques in epithelial brushing samples obtained during the endobronchial biopsy at visit 2 (baseline) and at the end of the 4-week period of randomised treatment (visit 5). Measurements visit 2 are used to standardize measurements at visit 5, and the standardized visit 5 value is calculated in percent (%) control as (visit5/visit2\*100).
Change From Baseline in Bronchoalveolar Lavage (BAL) Cell Differential (in %)	At baseline (visit 2) and at visit 5.	Change from baseline in bronchoalveolar lavage (BAL) cell differential (in %). Differential cell counts were performed on bronchoalveolar lavage samples obtained during visit 2 (baseline) and at the end of the 4-week period of randomised treatment (visit 5).
Change From Baseline in Log Mucin Gene (MUC8) Expression Level Obtained in Epithelial Brushings	At baseline (visit 2) and at visit 5.	Change from baseline in log mucin gene (MUC8) expression level obtained in epithelial brushings. Gene expression levels of the gel-forming mucins (MUC8) were quantified using two-step real time polymerase chain reaction (PCR) from RNA extracted from the cells obtained from the epithelial brushings during the endobronchial biopsy at visit 2 (baseline) and at the end of the 4-week period of randomised treatment (visit 5).
Change From Baseline in Epidermal Growth Factor Receptor (EGFR) Internalization Assay in Epithelial Brushings - Total Area Bright Spots With Marker	At baseline (visit 2) and at visit 5.	Change in total area bright spots with marker. The degree of EGFR internalization (and hence activation) was measured using antibody or ligand labeling techniques in epithelial brushing samples obtained during the endobronchial biopsy at visit 2 (baseline) and at the end of the 4-week period of randomised treatment (visit 5). Measurements visit 2 are used to standardize measurements at visit 5, and the standardized visit 5 value is calculated in percent (%) control as (visit5/visit2\*100).
Change From Baseline in Number of Goblet Cells Per Surface Area of Basel Lamina	At baseline (visit 2) and at visit 5.	Change from baseline in number of goblet cells per surface area of basel lamina, using endobronchial biopsies, taken at visit 2 (baseline) and at the end of the 4-week period of randomised treatment (visit 5).
Change From Baseline in Myeloperoxidase (MPO) Levels in Bronchoalveolar Lavage	At baseline (visit 2) and at visit 5.	Change from baseline in Myeloperoxidase (MPO) levels in bronchoalveolar lavage. Myeloperoxidase (MPO) activity levels were measured by enzyme linked immunosorbent or radioimmunoassay assay in bronchoalveolar lavage samples at visit 2 (baseline) and at the end of the 4-week period of randomised treatment (visit 5).
Change From Baseline in Log MUC2 Mucin Gene Expression (RNA) Obtained in Epithelial Brushings	At baseline (visit 2) and at visit 5.	Change from baseline in log MUC2 Mucin gene expression (RNA) obtained in epithelial brushings. Gene expression levels of the gel-forming mucins (MUC2) were quantified using two-step real time polymerase chain reaction (PCR) from RNA extracted from the cells obtained from the epithelial brushings during the endobronchial biopsy at visit 2 (baseline) and at the end of the 4-week period of randomised treatment (visit 5).
Change From Baseline in Epidermal Growth Factor Receptor (EGRF) Internalization Assay in Epithelial Brushings - EGRF Spots at Nucleus	At baseline (visit 2) and at visit 5.	Change in number of EGRF spots at nucleus. The degree of EGFR internalization (and hence activation) was measured using antibody or ligand labeling techniques in epithelial brushing samples obtained during the endobronchial biopsy at visit 2 (baseline) and at the end of the 4-week period of randomised treatment (visit 5). Measurements visit 2 are used to standardize measurements at visit 5, and the standardized visit 5 value is calculated in percent (%) control as (visit5/visit2\*100).
Change From Baseline in Epidermal Growth Factor Receptor (EGFR) Internalization Assay in Epithelial Brushings - EGFR Spots	At baseline (visit 2) and at visit 5.	Change in number of EGFR spots per cell. The degree of EGFR internalization (and hence activation) was measured using antibody or ligand labeling techniques in epithelial brushing samples obtained during the endobronchial biopsy at visit 2 (baseline) and at the end of the 4-week period of randomised treatment (visit 5). Measurements visit 2 are used to standardize measurements at visit 5, and the standardized visit 5 value is calculated in % control as (visit5/visit2\*100).
Change From Baseline in Goblet Cell Volume	At baseline (visit 2) and visit 5.	Change from baseline in goblet cell volume, using endobronchial biopsies, taken at visit 2 (baseline) and at the end of the 4-week period of randomised treatment (visit 5).
Change From Baseline in Log Mucin Gene (MUC5B) Expression Level Obtained in Epithelial Brushings	At baseline (visit 2) and at visit 5.	Change from baseline in log mucin gene (MUC5B) expression level obtained in epithelial brushings. Gene expression levels of the gel-forming mucins (MUC5B) were quantified using two-step real time polymerase chain reaction (PCR) from RNA extracted from the cells obtained from the epithelial brushings during the endobronchial biopsy at visit 2 (baseline) and at the end of the 4-week period of randomised treatment (visit 5).
Change From Baseline in Epidermal Growth Factor Receptor (EGRF) Internalization Assay in Epithelial Brushings - Cells With Bright Spots With Marker	At baseline (visit 2) and at visit 5.	Change in percentage of cells with bright spots with marker. The degree of EGFR internalization (and hence activation) was measured using antibody or ligand labeling techniques in epithelial brushing samples obtained during the endobronchial biopsy at visit 2 (baseline) and at the end of the 4-week period of randomised treatment (visit 5). Measurements visit 2 are used to standardize measurements at visit 5, and the standardized visit 5 value is calculated in percent (%) control as (visit5/visit2\*100).
Change From Baseline in Epidermal Growth Factor Receptor (EGFR) Internalization Assay in Epithelial Brushings - EGFR Spots at Nucleus With Marker	At baseline (visit 2) and at visit 5.	Change in number of EGFR spots at nucleus per cell with marker. The degree of EGFR internalization (and hence activation) was measured using antibody or ligand labeling techniques in epithelial brushing samples obtained during the endobronchial biopsy at visit 2 (baseline) and at the end of the 4-week period of randomised treatment (visit 5). Measurements visit 2 are used to standardize measurements at visit 5, and the standardized visit 5 value is calculated in % control as (visit5/visit2\*100).
Change From Baseline in Number of Goblet Cells Per Volume of Epithelium	At baseline (visit 2) and visit 5.	Change from baseline in number of goblet cells per volume of epithelium, using endobronchial biopsies, taken at visit 2 (baseline) and at the end of the 4-week period of randomised treatment (visit 5).

Trial Locations

Locations (6): 1219.5.01 Boehringer Ingelheim Investigational Site
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San Francisco, California, United States
1219.5.06 Boehringer Ingelheim Investigational Site
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Freiburg/Breisgau, Germany
1219.5.04 Boehringer Ingelheim Investigational Site
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Philadelphia, Pennsylvania, United States
1219.5.03 Boehringer Ingelheim Investigational Site
🇺🇸
Birmingham, Alabama, United States
1219.5.02 Boehringer Ingelheim Investigational Site
🇺🇸
Denver, Colorado, United States
1219.5.05 Boehringer Ingelheim Investigational Site
🇩🇪
Hannover, Germany