Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Randomised, Double-blind, Placebo- and Active-controlled Parallel Group Study to Assess the Efficacy of 12 Weeks of Once Daily Treatment of Two Doses of Orally Inhaled Tiotropium + Olodaterol Fixed Dose Combination (Delivered by the Respimat Inhaler) in Patients With Moderate to Severe Chronic Obstructive Pulmonary Disease (COPD)
Brief Summary: The objective of this study is to assess the efficacy and safety of 12 weeks once daily treatment with orally inhaled tiotropium + olodaterol FDC (delivered by the Respimat inhaler) compared with tiotropium and placebo in patients with COPD.


Options:
A: Inclusion criteria:

1. All patients must sign an informed consent consistent with International Conference on Harmonization-Good Clinical Practice (ICH-GCP) guidelines prior to participation in the trial, 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 a relatively stable airway obstruction with a post-bronchodilator FEV1 = 30 % and \< 80% of predicted normal and a post-bronchodilator FEV1/FVC \<70% at Visit 1.
3. Male or female patients, 40 years of age or older.
4. Patients must be current or ex-smokers with a smoking history of more than 10 pack years
5. Patients must be able to: perform technically acceptable pulmonary function tests, and maintain records(paper diary).
6. Patients must be able to inhale medication in a competent manner from the Respimat Inhaler as well as the Handihaler.

Exclusion criteria:

1. Patients with a significant disease other than COPD; a significant disease is defined as a disease which, in the opinion of the investigator, may (i) put the patient at risk because of participation in the study, (ii) influence the results of the study, or (iii) cause concern regarding the patients ability to participate in the study.
2. Patients with clinically relevant abnormal baseline haematology, blood chemistry, or urinalysis; all patients with an AST \>x2 ULN, ALT \>x2 ULN, bilirubin \>x2 ULN or creatinine \>x2 ULN will be excluded regardless of clinical condition (a repeat laboratory evaluation will not be conducted in these patients).
3. Patients with a history of asthma. For patients with allergic rhinitis or atopy, source documentation is required to verify that the patient does not have asthma. If a patient has a total blood eosinophil count =600/mm3, source documentation is required to verify that the increased eosinophil count is related to a non-asthmatic condition.
4. A diagnosis of thyrotoxicosis (due to the known class side effect profile of ß2-agonists).
5. A diagnosis of paroxysmal tachycardia (\>100 beats per minute) (due to the known class side effect profile of ß2-agonists).
6. A history of myocardial infarction within 1 year of screening visit (Visit 1).
7. Unstable or life-threatening cardiac arrhythmia.
8. Hospitalization for heart failure within the past year.
9. Known active tuberculosis.
10. A malignancy for which patient has undergone resection, radiation therapy or chemotherapy within last five years (patients with treated basal cell carcinoma are allowed).
11. A history of life-threatening pulmonary obstruction.
12. A history of cystic fibrosis.
13. Clinically evident bronchiectasis.
14. A history of significant alcohol or drug abuse.
15. 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).
16. Patients being treated with oral or patch ß-adrenergics.
17. Patients being treated with 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.
18. Patients who regularly use daytime oxygen therapy for more than one hour per day and in the investigators opinion will be unable to abstain from the use of oxygen therapy during clinic visits.
19. 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.
20. Patients who have taken an investigational drug within one month or six half lives (whichever is greater) prior to screening visit (Visit 1).
21. Patients with known hypersensitivity to ß-adrenergic drugs, BAC, EDTA, or any other component of the Respimat® inhalation solution.
22. Patients with known hypersensitivity to anticholinergic drugs, lactose, or any other components of the HandiHaler®.
23. Pregnant or nursing women.
24. Women of childbearing potential not using a highly effective method of birth control\*. 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.

    \* as per ICH M3(R2) a highly effective method of birth control is defined as those which result in a low failure rate (i.e. less than 1% per year).
25. Patients who have previously been randomised in this study or are currently participating in another study.
26. Patients who are unable to comply with pulmonary medication restrictions prior to randomisation.
B: Inclusion Criteria:

* Patients with moderate to severe stable COPD (Stage II or Stage III) according to the current GOLD Guidelines (GOLD 2010).
* Patients with a post-bronchodilator Forced Expiratory Volume in 1 second (FEV1) ≥ 30% and \< 80% of the predicted normal, and a post-bronchodilator FEV1/ Forced Vital Capacity (FVC) \< 0.70 at screening
* Current or ex-smokers who have a smoking history of at least 10 pack years (e.g. 10 pack years = 1 pack/day x 10 yrs, or ½ pack/day x 20 yrs).
* Symptomatic patients, according to daily electronic diary data between Visit 2 (Day -14) and Visit 3 (Day 1), with a total score of 1 or more on at least 4 of the last 7 days prior to Visit 3.

Exclusion Criteria:

* Pregnant or nursing (lactating) women
* Patients who, in the judgment of the investigator, or the responsible Novartis personnel, have a clinically relevant laboratory abnormality or a clinically significant condition before Visit 1.
* Patients with narrow-angle glaucoma, symptomatic benign prostatic hyperplasia or bladder-neck obstruction or moderate to severe renal impairment or urinary retention. (BPH patients who are stable on treatment can be considered).
* Patients receiving medications in the classes listed in the protocol as prohibited.

Other protocol-defined inclusion/exclusion criteria apply and can be found in the study protocol
C: Inclusion Criteria:

* Type of subject: Outpatient
* Informed consent: Subjects must give their signed and dated written informed consent to participate.
* Gender: Male or female subjects.
* Age: greater then or equal to 40 years of age at Screening (Visit 1)
* COPD diagnosis: Subjects with a clinical history of COPD in accordance with the following definition by the American Thoracic Society (ATS) /European Respiratory Society(ERS).
* Subjects with a current or prior history ofgreater then or equal to 10 pack-years of cigarette smoking at Screening (Visit 1).
* Subjects with a measured post-albuterol/salbutamol FEV1 less then 70% of predicted at Screening (Visit 1).
* Subjects with a measured post-albuterol/salbutamol FEV1/FVC ratio of less then or equal to 0.70 at Screening (Visit 1).
* Exacerbation History: Subjects who have been hospitalised or have been treated with oral corticosteroids or antibiotics for their COPD within the last 3 years prior to Screening (V1).
* Baseline aPWV: subjects with a measured aPWV greater then 12.0 m/s at Screening (Visit 1).

Exclusion Criteria:

* Body Mass Index of less then or equal to 35
D: Inclusion criteria:

* Diagnosis chronic obstructive pulmonary disease
* Relatively stable airway obstruction with post FEV1 \>=30 and \< 80% predicted normal and post FEV1/ FVC \< 70%
* Male or female patients, 40 years of age or more
* Smoking history more than 10 pack years

Exclusion criteria:

* Significant diseases other than COPD
* History of asthma
* COPD exacerbation in previous 3 months
* Completion of pulmonary rehabilitation program within previous 6 weeks or current participation in pulmonary rehabilitation program.
* Pregnant or nursing women
* Patients unable to comply with pulmonary medication restrictions

Answer: D