Safety and Efficacy of 4-weeks Treatment of BIBW 2948 BS in Patients With Chronic Obstructive Bronchitis

A Phase II, Randomised, Double-blind, Placebo-controlled and Parallel Group Study to Evaluate the Safety and Efficacy of Four Weeks Treatment of 7.5 mg b.i.d, 15 mg q.d and 15 mg b.i.d. BIBW 2948 BS (Inhalation Powder, Hard Capsule for HandiHaler®) in Patients With COPD Associated With Chronic Bronchitis.

The primary objective of this study is to investigate the effect of 4-week treatment with 7.5 mg b.i.d, 15 mg q.d and 15 mg b.i.d. BIBW 2948 BS and placebo on cough and sputum as determined by the CASA-Q (Cough and Sputum Assessment Questionnaire

Inclusion Criteria:

1. Patients must sign an informed consent consistent with ICH-GCP guidelines prior to participation in the trial, which includes medication washout and restrictions.

2. Male or female patients 40 years of age or older.

3. Patients must have a diagnosis of COPD defined by a post-bronchodilator FEV1 < 80% of predicted and FEV1 < 70% of FVC (to be obtained 30 minutes after administration of salbutamol HFA). Predicted normal values will be calculated according to ECSC (R94-1408).

   For Height measured in inches

   Males:

   FEV1 predicted (L) = 4.30 x (height (inches)/39.37) - 0.029 x age (yrs) - 2.49

   Females:

   FEV1 predicted (L) = 3.95 x [height (inches)/39.37] - 0.025 x age (yrs) - 2.60

   or Height measured in meters

   Males:

   FEV1 predicted (L) = 4.30 x [height (meters)] - 0.029 x age (yrs) - 2.49

   Females:

   FEV1 predicted (L) = 3.95 x [height (meters)] - 0.025 x age (yrs) - 2.60

4. Patients must have a diagnosis of chronic bronchitis symptoms i.e., cough and sputum expectoration on most days for at least three months in each of two consecutive years.

5. Patients must be a current or ex-smoker with a smoking history of sup or egal to 10 pack years (Patients who have never smoked cigarettes must be excluded).

6. Patients must be able to perform all specified procedures and able to maintain all necessary records during the study period as required in the protocol.

7. Patients must be able to inhale medication in a competent manner from the HandiHaler® device for BIBW 2948 BS.

8. Patients must be able to read and understand the questionnaires in the languages provided (English in the U.S., French in France and German in Germany).

Exclusion Criteria:

1. Patients with significant diseases other than COPD will be excluded. A significant disease is defined as a disease or condition which, in the opinion of the investigator, may put the patients at risk because of participation in the study or may influence either the results of the study or the patient's ability to participate in the study.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.
2. Patients with an acute or chronic hepatitis or alpha one antitrypsin deficiency or other liver disease.
3. Patients with an aspartate aminotransferase (AST), alanine aminotransferase (ALT) 1.5 x the upper limit of the normal range will be excluded regardless of the clinical condition. A repeat laboratory evaluation will not be conducted in these patients.
4. Patients with history of asthma or allergic rhinitis.
5. Patients with history of post-nasal drip the last 3 months prior visit 1.
6. Patients with a clinical diagnosis of bronchiectasis.
7. Patients currently treated with expectorants and/or mucolytics drug.
8. Patients taking medications with known cough promoting side effects (e.g., angiotensin converting enzyme inhibitors or angiotensin II receptor blockers) that in the opinion of the investigator are causing symptoms of cough.
9. Patients with any respiratory tract infection or COPD exacerbation in the 30 days prior the visit 1 or during the 1-week period prior to visit 2 (visit 2 will not be postponed and the patient will be discontinued from the study).
10. Patients who have had any change in their respiratory medications within the last 6 weeks prior the visit 1.
11. Patients with a history of thoracotomy for other reasons should be evaluated as per Exclusion 1.
12. Patients with a history of gastroesophageal reflux disease that have changed medication (dose intensification or a change in therapy) to treat this disease within the 6 weeks prior the visit 1.
13. Patients with a history of cancer, other than treated basal cell carcinoma, within the last five years.
14. Women of childbearing potential or who have not been post-menopausal for a duration for at least 2 years and have not had a hysterectomy or tubal ligation procedure.
15. Participation in another trial with an investigational drug within 30 days or 6 half lives (whichever is greater) of the start of the study.
16. A known hypersensitivity to lactose or any other component of the inhalation capsule or any other components of the inhalation capsule delivery system.
17. Patients who are currently in a pulmonary rehabilitation program or who have completed a pulmonary rehabilitation program within four weeks prior the visit 1.
18. Patients with a significant history of significant alcohol or drug abuse.
19. Patients with previous participation in this study.