Effect of BIBW 2948 BS in COPD

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

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

Study Overview

• Status: Completed
• Conditions: Pulmonary Disease, Chronic Obstructive; Bronchitis, Chronic
• Intervention / Treatment: Drug: Placebo; Drug: BIBW 2948 BS

• Study Type: Interventional
• Enrollment (Actual): 48
• Phase: Phase 2

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo - low dose; Twice daily (b.i.d.)	Drug: Placebo; Capsule
Placebo Comparator: Placebo - high dose; Twice daily (b.i.d.)	Drug: Placebo; Capsule
Experimental: BIBW2948 - low dose; Twice daily (b.i.d.)	Drug: BIBW 2948 BS; Capsule
Experimental: BIBW2948 - high dose; Twice daily (b.i.d.)	Drug: BIBW 2948 BS; Capsule

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.

Collaborators and Investigators

• Sponsor: Boehringer Ingelheim

Publications and helpful links

General Publications

• Woodruff PG, Wolff M, Hohlfeld JM, Krug N, Dransfield MT, Sutherland ER, Criner GJ, Kim V, Prasse A, Nivens MC, Tetzlaff K, Heilker R, Fahy JV. Safety and efficacy of an inhaled epidermal growth factor receptor inhibitor (BIBW 2948 BS) in chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2010 Mar 1;181(5):438-45. doi: 10.1164/rccm.200909-1415OC. Epub 2009 Dec 10.

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start (Actual): January 17, 2007
• Primary Completion (Actual): July 9, 2008
• Study Completion (Actual): July 9, 2008

Study Registration Dates

• First Submitted: January 17, 2007
• First Submitted That Met QC Criteria: January 17, 2007
• First Posted (Estimate): January 18, 2007

Study Record Updates

• Last Update Posted (Actual): November 19, 2021
• Last Update Submitted That Met QC Criteria: October 21, 2021
• Last Verified: October 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Lung Diseases; Bronchial Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive; Bronchitis; Bronchitis, Chronic
• Other Study ID Numbers: 1219.5; 2006-001975-40