Efficacy and Safety Comparison of Tiotropium Daily + Salmeterol Daily or Twice Daily Versus Tiotropium Daily in Patients With COPD

A Randomised, Double-blind Clinical Efficacy and Safety Comparison of Tiotropium/Salmeterol 7.5/25 Inhalation Powder in the Morning Via Tiotropium/Salmeterol HandiHaler, Tiotropium 18 Mcg Inhalation Powder in the Morning Via Spiriva HandiHaler, Salmeterol 50 Mcg MDPI in the Morning and Evening and the Free Combination Tiotropium 18 Mcg Inhalation Powder in the Morning Via Spiriva HandiHaler Plus Salmeterol 50 Mcg MDPI in the Morning and Evening Following Chronic Administration (6-week Treatment Periods) in Patients With COPD

The primary objective of this trial is to establish superiority of the once-daily Tiotropium plus Salmeterol Inhalation Powder in daytime lung function response and non-inferiority in night-time lung function response over the comparator treatments inhaled in their established dose regimens when administered for 6-week periods to patients with chronic obstructive pulmonary disease (COPD). The main secondary objective is to evaluate the safety of the Tiotropium plus Salmeterol Inhalation Powder versus the comparator treatments.

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 washout and restrictions.

2. All patients must have a diagnosis of COPD and must meet the following criteria:

   relatively stable* airway obstruction with a post-bronchodilator FEV1 < 80% of predicted normal and post-bronchodilator FEV1 < 70% of post-bronchodilator FVC at Visit 1 (according to GOLD criteria).

   * The randomisation of patients with any respiratory infection or COPD exacerbation in the 6 weeks prior to the Screening Visit (Visit 1) or during the baseline period should be postponed. Patients may be randomised 6 weeks following recovery from the infection or exacerbation. Predicted normal values will be calculated according to ECSC.

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

4. Patients must be current or ex-smokers with a smoking history of 10 pack-years.

5. Patients must be able to perform technically acceptable pulmonary function tests

6. Patients must be able to inhale medication in a competent manner.

7. Patients must be able to perform all necessary recordings in the diary.

Exclusion Criteria:

1. Significant diseases other than COPD
2. Patients with clinically significant abnormal baseline haematology, blood chemistry or urinalysis, if the abnormality defines a significant disease as defined in exclusion criterion No. 1.
3. Patients with a recent history of myocardial infarction.
4. Patients with any unstable or life-threatening cardiac arrhythmia requiring intervention or change in drug therapy during the past year.
5. Hospitalisation for cardiac failure during the past year.
6. Malignancy within the last five years excluded basal cell carcinoma.
7. Patients with a history of asthma or who have a total blood eosinophil count 600/mm3.
8. Patients with a history of life threatening pulmonary obstruction, or a history of cystic fibrosis or clinically evident bronchiectasis.
9. Known active tuberculosis.
10. Patients with a history of alcohol or drug abuse.
11. Thoracotomy with pulmonary resection.
12. Rehabilitation program within the last six weeks
13. Patients who regularly use daytime oxygen therapy
14. Patients who have taken an investigational drug within 30 days
15. Use of not allowed medications
16. Known hypersensitivity to used drugs or other components of the study medication.
17. Pregnant or nursing women
18. Women of childbearing potential not using a highly effective method of birth control. Highly effective methods of birth control are defined as those which result in a low failure rate (i.e. less than 1% per year) when used consistently and correctly such as implants, injectables, combined oral contraceptives, some IUDs, sexual abstinence or vasectomised partner. Female patients will be considered to be of childbearing potential unless surgically sterilised by hysterectomy or bilateral tubal ligation, or post-menopausal for at least two years.
19. Patients who are currently participating in another study.