A randomised, double-blind, parallel group study to assess the efficacy and safety of 52 weeks of once daily treatment of orally inhaled tiotropium + olodaterol fixed dose combination (2.5 µg / 5 µg; 5 µg / 5 µg) (delivered by the RESPIMAT) compared with the individual components (2.5 µg and 5 µg tiotropium, 5 µg olodaterol) (delivered by the RESPIMAT) in patients with Chronic Obstructive Pulmonary Disease (COPD) [TOnadoTM 1]

The COPD treatment guidelines advise treatment with bronchodilators with
different mechanisms of action. Short acting anticholinergics and
beta2-agonists in fixed dose combinations have shown to be effective and safe
and are user-friendly to patients. Once daily fixed dose combinations of
long-acting anticholinergics and beta2-agonists are not yet available.
Tiotropium bromide is a registered once daily long-acting anticholinergic for
the treatment of COPD and will be combined with a once daily long-acting
beta2-agonist, olodaterol, in this study. Olodaterol is being developed for
the treatment of COPD. Is is expected that the combination of these two once
daily bronchodilators with different mechanisms of action will provide an
optimal long term bronchodilation and is user-friendly.

The objective of this study is to assess the efficacy and safety of 52 weeks
once daily treatment with orally inhaled tiotropium plus olodaterol fixed dose
combination compared with the individual components tiotropium and olodaterol
(delivered by the Respimat® Inhaler) in patients with Chronic Obstructive
Pulmonary Disease (COPD).

This is a 52-week multi-centre, multinational, randomised, double-blind,
parallel-group study.

Once daily inhalation of study medication with the Respimat® Inhaler
(1:1:1:1:1) randomisation to one of the following groups:
- tiotropium plus olodaterol (FDC) 2,5 mcg / 5 mcg) inhalation solution
- titropium plus olodaterol (FDC 5 mcg / 5 mcg) inhalation solution
- olodaterol (5 mcg) inhalation solution
- tiotropium 2,5 mcg inhalation solution
- tiotropium 5 mcg inhalation solution

Twice daily peak flow measurements through the Asthma Monitor 3 (AM3) deivce
and documentation of use of rescue medicaiton and study medication.
Restrictions prior to the lung function assessments (See protocol page 38/39).

At visits 2, 5, 7 and 10 (week 0, 12, 24 and 52) 3-hr (post-inhalation of study
medication) lung function assessments are performed. These visits will take
about 5 hours. The patients will receive a compensation for these visits.
During their participation, patients are asked to perform twice daily peak flow
assessments with their AM3 monitor and to register the use of
rescue medication and study medication.

All patients will receive active medication. Inhalation steroids (except
combination preparations with LABAs and SABAs) are both prior and during the
study allowed provided that the dosage is stable during 6 weeks prior to the
start of the study.
During the screening period patients will receive Ventolin as rescue
medication. Besides this, patients who have to wash out tiotropium prior to
randomisation are allowed to use atrovent. See for complete overview protocol
page 35-37.