Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Randomized, Active-controlled, Double-blind, Double-dummy, Parallel Group Design, Multi-center Trial to Compare the Efficacy and Safety of 2.5 µg and 5 µg Tiotropium Inhalation Solution Delivered by the Respimat Inhaler With Tiotropium Inhalation Capsules 18 µg Delivered by the HandiHaler (TIOSPIR)
Brief Summary: Direct comparison studies of the tiotropium HandiHaler® 18 µg and Respimat® 5 µg formulations have been limited to 4-week crossover studies. Therefore, prospective data from a trial of adequate size and duration is required to establish that compared to tiotropium HandiHaler®, tiotropium Respimat® will have (a) similar effects on safety and (b) similar or superior effects on exacerbations.


Options:
A: Main Inclusion criteria: 1.Diagnosis of chronic obstructive pulmonary disease. 2.Patient is male or female, age \<=than 40 years. 3. Patient has a smoking history of \<=10 pack-year.4.Patient is able to be trained in the proper use of HandiHaler 5.Patient is able to be trained to perform technically satisfactory spirometry and must be able to maintain records during the study period as required by the protocol. 6.Patient must be willing and able to sign informed consent prior to participation in the study i.e. prior to washout of their usual pulmonary medications.

Main exclusion criteria 1.History of asthma, allergic rhinitis or atopy. 2. A lower respiratory tract infection or any COPD exacerbation in the past 4 weeks prior to Visit 1 or during the two week Screening Period 3.History of life threatening bronchial obstruction, cystic fibrosis or bronchiectasis 4. Oral corticosteroid medication if initiated or modified within the last 6 weeks prior to Visit 1 or if daily dose \> 10 mg prednisone or 20 mg or more every other day (or equivalent). 5.Patients who have started or stopped an exercise rehabilitation program within 4 weeks of visit 6.Patients who regularly use daytime oxygen therapy for more than one hour per day and who, in the investigator's opinion, will be unable to abstain from the use of oxygen therapy during testing. 7. Patients who have undergone thoracotomy with pulmonary resection or lobectomy (lung volume reduction surgery). 8.Tuberculosis with indication for treatment. 9. Recent history (i.e. 6 months or less) of myocardial infarction.10. Patients with known moderate or severe renal insufficiency.11. Patients with symptomatic prostatic hypertrophy or bladder neck obstruction. 12.Patients with known narrow-angle glaucoma.13.History of unstable arrhythmia with a life threatening event or change of therapy during the past year.14. History of cancer, other than treated basal cell carcinoma, within the last 5 years 15.Intolerance to anticholinergic containing products, and/or to lactose or any other components of the inhalation capsule delivery system.16.Patients who are being treated with beta-blockers including eye drops.17.Patients who are being treated with antihistamines (H1 receptor antagonists), for asthma or excluded allergic conditions (See Exclusion Criteria No.2).18.Patients who are being treated with monoamine oxidase inhibitors or tricyclic antidepressants.19. Patients who are being treated with oral beta-adrenergics.20. Patients who have taken cromolyn sodium or nedocromil sodium within 1 month of Visit 1.21.Patients who have taken antileukotrienes or leukotriene receptor antagonists within 1 month of Visit 1. 22.Concomitant or recent (within the last month or 6 half lives, whichever is greater) use of investigational drugs prior to the screening visit (Visit 1). 23. Significant alcohol or drug abuse within the past 12 months. 24. Pregnant or nursing women or women of childbearing potential not using a medically approved means of contraception.24. Previous participation in this study (i.e. randomized).26. Patients who have taken commercially available Spiriva. 27.History of any clinically significant disease, defined as a disease which in the opinion of the investigator may 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.
B: 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. Male or female patients 40 years of age or older.
3. Patients must be current or ex-smokers with a smoking history of ≥10 pack-years. (Patients who have never smoked cigarettes must be excluded)
4. All patients must have a diagnosis of COPD (P06-12085), and must meet the following criteria: Relatively stable airway obstruction with a post-bronchodilator FEV1 ≤ 70% of predicted normal and post-bronchodilator FEV1 / FVC ≤70%.

   Pulmonary function tests (PFTs) were conducted after the inhalation of 400 μg salbutamol / albuterol (preferred), however testing with either 200 μg salbutamol/albuterol or a combination of salbutamol / albuterol with ipratropium bromide (2 to 4 actuations) was acceptable. Other short-acting beta agonists, such as terbutaline, may have been used for the testing. The medication used for the testing was documented. Further, historical data from measurements within the past 6 months either at the site or at a referral site may have been used (see Section 6.2.1 of the CTP, located in Appendix 16.1.1). Subjects were not to have been randomized to the study without the availability of spirometry data at the actual study site.

   Eligibility for PFT sub-study: For subjects participating in the spirometry sub-study, historical data may not have been used for inclusion. These subjects must have qualified in the clinic at Visit 1 after performing a baseline measurement. These subjects performed a pre-dose PFT which was followed by the administration of 400 μg salbutamol / albuterol only (no other short-acting beta agonist was allowed), followed by a post-dose PFT for qualification.
5. Able to inhale from the HandiHaler® and the Respimat® devices.

Exclusion criteria:

1. Significant diseases other than COPD. A significant disease is defined as a disease or condition which, in the opinion of the investigator, may put the patient at risk because of participation in the study or may influence the patients ability to participate in the study.
2. Patients with a recent history (i.e., six months or less) of myocardial infarction.
3. Patients with any unstable or life-threatening cardiac arrhythmia requiring intervention or change in drug therapy during the last year.
4. Hospitalisation for cardiac failure (New York Heart Association (NYHA) Class III or IV) during the past year.
5. Known active tuberculosis.
6. Patients with a history of asthma, cystic fibrosis, clinically evident bronchiectasis, interstitial lung disease, or pulmonary thromboembolic disease.
7. History of thoracotomy with pulmonary resection. Subjects with a history of thoracotomy for other reasons were to have been evaluated per exclusion criterion 1.
8. Subject was planning to undergo lung transplant or lung volume reduction surgery (LVRS).
9. Malignancy for which the subject had undergone resection, radiation, chemotherapy or biological treatments within the last 5 years. Subjects with treated basal cell carcinoma were allowed.
10. Known respiratory infection or exacerbation of COPD in the 4 weeks prior to randomization.
11. Known hypersensitivity to anticholinergic drugs, lactose, benzalkonium chloride (BAC), ethylenediaminetetraacetic acid (EDTA), or any other components of the HandiHaler® or Respimat® inhalation solution delivery system.
12. Known moderate to severe renal impairment (as judged by the investigator).
13. Known narrow angle glaucoma.
14. Known significant symptomatic prostatic hyperplasia or bladder-neck obstruction. Subjects whose symptoms were controlled on treatment may have been included.
15. Use of systemic corticosteroid medication at unstable doses (i.e., less than 6 weeks on stable dose) or at doses in excess of the equivalent of 10 mg prednisolone per day.
16. Pregnant or nursing women or women of childbearing potential not using a medically approved means of contraception for at least 3 months prior to and for the duration of the trial.
17. Significant alcohol or drug abuse within the past 12 months.
18. Subjects requiring the use of supplemental oxygen therapy for \> 12 hours per day.
19. Subjects who had completed a pulmonary rehabilitation program in the 6 weeks prior to the screening visit or subjects who were currently in a pulmonary rehabilitation program that was not maintained throughout the duration of the study.
20. Subjects who had taken an investigational drug within 30 days prior to the Screening Visit.
21. Previous participation (receipt of randomized treatment) in this study.
22. Subjects who were currently participating in an interventional study.
C: Inclusion criteria:

* COPD patients with \> 10 pack years.
* Written informed consent.
* Able to complete a diary card.
* At least one of the following symptoms: chronic cough, chronic sputum production, frequent exacerbations, or dyspnoea at exertion.
* Postbronchodilator FEV1 below 90% confidence interval of predicted and postbronchodilator FEV1/FVC below 90% confidence interval of predicted.

Exclusion criteria:

* No oral corticosteroids 3 months prior to the study or maintenance treatment with corticostroids 6 months prior to the study.
* No history of asthma, lung diseases other than COPD, other diseases likely to interfere with the study.
D: Inclusion Criteria:

* A diagnosis of stable moderate to severe COPD as defined by the Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines, 2009; postbronchodilator FEV1/FVC \< 70%, and postbronchodilator FEV1 ≥ 30% and \< 80% predicted
* Current or former cigarette smokers

Exclusion Criteria:

* Patients who have been hospitalized for an acute COPD exacerbation within 3 months before the first visit
* Respiratory tract infection or COPD exacerbation in the 6 weeks before Visit 1
* Patient with any clinically significant respiratory conditions other than COPD, cardiovascular conditions or mental illness
* History or presence of asthma verified from medical records
* Chronic use of oxygen therapy greater than or equal to 15 hours per day
* Patient with uncontrolled infection due to HIV and/or active hepatitis
* Patients with a history of hypersensitivity reaction to inhaled anticholinergics
* Patients with clinically significant cardiovascular conditions, including myocardial infarction during the previous 6 months, newly diagnosed arrhythmia within the previous 3 months, unstable angina, unstable arrhythmia that had required changes in pharmacological therapy or other intervention.

Answer: B