Effect of BIBW 2948 BS in COPD

Pulmonary Disease, Chronic Obstructive Clinical Trial

Official title:

A Randomized, Double-blind, Placebo-controlled, Parallel Group Study to Evaluate the Effects of a 4-week Treatment of 15 and 30 mg b.i.d BIBW2948 BS (Inhalation Powder, Hard Capsule for HandiHaler®) on Epithelial Mucin Stores and the Safety and Efficacy in COPD Patients With Symptoms Associated With Chronic Bronchitis

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00423137
• Other study ID #: 1219.5
• Secondary ID: 2006-001975-40
• Status: Completed
• Phase: Phase 2
• Start date: January 17, 2007
• Est. completion date: July 9, 2008

Study information

• Verified date: October 2021
• Source: Boehringer Ingelheim
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 48
• Est. completion date: July 9, 2008
• Est. primary completion date: July 9, 2008
• Accepts healthy volunteers: No
• Gender: All
• Age group: 40 Years to 70 Years

Eligibility

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

Related Conditions & MeSH terms

• Bronchitis
• Bronchitis, Chronic
• Pulmonary Disease, Chronic Obstructive

Intervention

Drug:
• BIBW 2948 BS
Capsule
• Placebo
Capsule

Locations

Country	Name	City	State
Germany	1219.5.06 Boehringer Ingelheim Investigational Site	Freiburg/Breisgau
Germany	1219.5.05 Boehringer Ingelheim Investigational Site	Hannover
United States	1219.5.03 Boehringer Ingelheim Investigational Site	Birmingham	Alabama
United States	1219.5.02 Boehringer Ingelheim Investigational Site	Denver	Colorado
United States	1219.5.04 Boehringer Ingelheim Investigational Site	Philadelphia	Pennsylvania
United States	1219.5.01 Boehringer Ingelheim Investigational Site	San Francisco	California

Sponsors (1)

Lead Sponsor	Collaborator
Boehringer Ingelheim

Countries where clinical trial is conducted

United States,  Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change From Baseline in Volume of Mucin Per Surface Area of Basal Lamina	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).	At baseline (visit 2) and at visit 5.
Secondary	Change From Baseline of Volume of Mucin Per Volume of Epithelium (Vv mu, ep) in Endobronchial Biopsies	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).	At baseline (visit 2) and at visit 5.
Secondary	Change From Baseline in Bronchoalveolar Lavage (BAL) Cell Differential (in %)	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).	At baseline (visit 2) and at visit 5.
Secondary	Change From Baseline in Bronchoalveolar Lavage (BAL) Cell Count	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.	At baseline (visit 2) and at visit 5.
Secondary	Change From Baseline in Log MUC2 Mucin Gene Expression (RNA) Obtained in Epithelial Brushings	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).	At baseline (visit 2) and at visit 5.
Secondary	Change From Baseline in Log Mucin Gene (MUC5AC) Expression Level Obtained in Epithelial Brushings	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).	At baseline (visit 2) and at visit 5.
Secondary	Change From Baseline in Log Mucin Gene (MUC5B) Expression Level Obtained in Epithelial Brushings	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).	At baseline (visit 2) and at visit 5.
Secondary	Change From Baseline in Log Mucin Gene (MUC8) Expression Level Obtained in Epithelial Brushings	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).	At baseline (visit 2) and at visit 5.
Secondary	Change From Baseline in Epidermal Growth Factor Receptor (EGRF) Internalization Assay in Epithelial Brushings - Cells With Bright Spots With Marker	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).	At baseline (visit 2) and at visit 5.
Secondary	Change From Baseline in Epidermal Growth Factor Receptor (EGRF) Internalization Assay in Epithelial Brushings - EGRF Spots at Nucleus	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).	At baseline (visit 2) and at visit 5.
Secondary	Change From Baseline in Epidermal Growth Factor Receptor (EGFR) Internalization Assay in Epithelial Brushings - EGRF Spots With Marker	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).	At baseline (visit 2) and at visit 5.
Secondary	Change From Baseline in Epidermal Growth Factor Receptor (EGFR) Internalization Assay in Epithelial Brushings - Total Area Bright Spots With Marker	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).	At baseline (visit 2) and at visit 5.
Secondary	Change From Baseline in Epidermal Growth Factor Receptor (EGFR) Internalization Assay in Epithelial Brushings - EGFR Spots	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).	At baseline (visit 2) and at visit 5.
Secondary	Change From Baseline in Epidermal Growth Factor Receptor (EGFR) Internalization Assay in Epithelial Brushings - EGFR Spots at Nucleus With Marker	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).	At baseline (visit 2) and at visit 5.
Secondary	Change From Baseline in Number of Goblet Cells Per Surface Area of Basel Lamina	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).	At baseline (visit 2) and at visit 5.
Secondary	Change From Baseline in Number of Goblet Cells Per Volume of Epithelium	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).	At baseline (visit 2) and visit 5.
Secondary	Change From Baseline in Goblet Cell Volume	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).	At baseline (visit 2) and visit 5.
Secondary	Change From Baseline of Interleukin-8 (IL-8) Levels in Bronchoalveolar Lavage	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).	At baseline (visit 2) and at visit 5.
Secondary	Change From Baseline in Myeloperoxidase (MPO) Levels in Bronchoalveolar Lavage	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).	At baseline (visit 2) and at visit 5.

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