Clinical trial NCT02242266 (phase 2, status: completed)
Conditions: pulmonary disease, chronic obstructive
ICD codes: J44.9, J44.1, J44.0
Drugs: tiotropium low dose, tiotropium medium dose, spiriva® handihaler® high dose, placebo via the blue handihaler®, placebo via the grey handihaler®
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Eligibility criteria:

        Inclusion Criteria:

          1. All patients must sign an informed consent consistent with International Conference on
             Harmonization Good Clinical Practice (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 chronic obstructive pulmonary disease and must
             meet the following spirometric criteria:

             Patients must have relatively stable* airway obstruction with a pre-dose FEV1 <= 60%
             of predicted normal and FEV1 <= 70% of FVC at Visits 1 and 2.

               -  * The randomization 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 randomized 6 weeks following
                  recovery from the infection or exacerbation

          3. At Visit 1, patients must demonstrate an improvement in FEV1 of >= 12% over the
             baseline FEV1 value 45 minutes after inhalation of 4 puffs of 20 µg ipratropium
             bromide (Atrovent® MDI)

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

          5. Patients must be current or ex-smokers with a smoking history of more than 10
             pack-years (Patients who had never smoked cigarettes had to be excluded)

          6. Patients must be able to perform technically acceptable pulmonary function tests
             during the study period as required in the protocol

          7. Patients must be able to inhale medication in a competent manner from the HandiHaler®
             2 and the HandiHaler® devices

        Exclusion Criteria:

          1. Patients with significant diseases other than COPD will be excluded. A significant
             disease is defined as a disease which in the opinion of the investigator may either
             put the patient at risk because of participation in the study or a disease which may
             influence the results of the study or the patient's ability to participate in the
             study

          2. Patients with a recent history (i.e., six months or less) of myocardial infarction

          3. Patients who have been hospitalized for heart failure (NYHA class III or IV) within
             the past year

          4. Patients with any unstable or life threatening cardiac arrhythmia or cardiac
             arrhythmia requiring intervention or a change in drug therapy within the past year

          5. Patients with malignancy for which the patient has undergone resection, radiation
             therapy or chemotherapy within the last five years. Patients with treated basal cell
             carcinoma are allowed

          6. Patients with a history of asthma, allergic rhinitis or atopy or who have a total
             blood eosinophil count ≥600/mm3. A repeat eosinophil count will not be conducted in
             these patients

          7. Patients with a history of life threatening pulmonary obstruction, or a history of
             cystic fibrosis or clinically evident bronchiectasis

          8. Patients with known active tuberculosis

          9. Patients with significant alcohol or drug abuse within the past two years

         10. Patients who have undergone thoracotomy with pulmonary resection. Patients with a
             history of thoracotomy for other reasons should be evaluated as per exclusion
             criterion No. 1

         11. Patients who have completed a pulmonary rehabilitation program in the six weeks prior
             to the Screening Visit (Visit 1) or patients who are currently in a pulmonary
             rehabilitation program that will not be maintained throughout the duration of the
             study

         12. Patients who regularly use daytime oxygen therapy for more than one hour per day and
             in the investigator's opinion will be unable to abstain from the use of oxygen therapy

         13. Patients who are being treated with antihistamines (H1 receptor antagonists),
             antileukotrienes or leukotriene receptor antagonists for asthma or excluded allergic
             conditions. See exclusion criterion No 6

         14. Patients who are being treated with cromolyn sodium or nedocromil sodium

         15. Patients using oral corticosteroid medication at unstable doses (i.e., less than six
             weeks on a stable dose) or at doses in excess of the equivalent of 10 mg of prednisone
             per day or 20 mg every other day

         16. Patients with known hypersensitivity to anticholinergic drugs, lactose or any other
             components of the inhalation capsule delivery system (Spiriva® HandiHaler®; tiotropium
             HandiHaler 2)

         17. Pregnant or nursing women or women of childbearing potential not using a medically
             approved means of contraception for the previous three months (i.e. oral
             contraceptives, intrauterine devices, diaphragm or subdermal implants, e.g.:
             Norplant®)

         18. Patients who have taken an investigational drug within one month or six half lives
             (whichever is greater) prior to Visit 1

         19. Patients who have been treated with oral beta-adrenergics within one month prior to
             Visit 1 or during the run-in period

         20. Patients who have been treated with theophylline preparations within one month prior
             to Visit 1 or during the run-in period

         21. Patients who have been treated with the long-acting anticholinergic tiotropium
             (Spiriva®) within one month prior to Visit 1 or during the run-in period

         22. Patients with any respiratory infections in the six weeks prior to the Screening Visit
             (Visit 1) or during the run-in period. In the case of a respiratory infection during
             the run-in period the latter may be extended up to six weeks

         23. Patients who are currently participating in another study23. The randomisation of
             patients with any respiratory infection or COPD exacerbation in the six weeks prior to
             the Screening Visit (Visit 1) or during the baseline period should be postponed.
             Patients may be randomised six weeks following recovery from the infection or
             exacerbation