Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Randomized, Blinded, Double Dummy, Multi-center, Placebo Controlled, 3 Period, Crossover Study to Assess the Effect of QVA149 (110/50 µg o.d.) on Exercise Endurance in Patients With Moderate to Severe Chronic Obstructive Pulmonary Disease (COPD), Using Tiotropium as an Active Control.
Brief Summary: This study assessed the effect of once-daily indacaterol and glycopyrronium bromide (QVA149) on exercise endurance in patients with moderate to severe Chronic Obstructive Pulmonary Disease (COPD).


Options:
A: Inclusion Criteria:

* Diagnosis of moderate to severe stable Chronic Obstructive Pulmonary Disease (COPD) stage II or stage III according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) Guidelines (2009)
* Qualifying spirometry, Forced Expiratory Volume in one second (FEV1) and post-bronchodilator FEV1/FVC (Forced Vital capacity)
* Smoking history ≥ 10 pack years

Exclusion Criteria:

* Pregnant women or nursing mothers or women of child-bearing potential not using adequate contraception
* Cardiac abnormality
* History of asthma
* Contraindications to cardiopulmonary exercise testing
* Participation in active phase of pulmonary rehabilitation program
* History of cancer within the past 5 years

Other protocol-defined inclusion/exclusion criteria may apply
B: Inclusion Criteria:

* Smoking history of at least 10 pack years
* Diagnosis of Chronic Obstructive Pulmonary Disease (COPD) (moderate-to-severe as classified by the Global Initiative for Chronic Obstructive Lung Disease \[GOLD\] Guidelines, 2009)
* Post-bronchodilator Forced Expiratory Volume in 1 second (FEV1) \>40% and \< 80% of the predicted normal value and post-bronchodilator FEV1/Forced Vital Capacity (FVC) \<70%

Exclusion Criteria:

* Patients who have had a COPD exacerbation that required treatment with antibiotics, systemic steroids (oral or intravenous) or hospitalization in the last year.
* Patients requiring long term oxygen therapy on a daily basis for chronic hypoxemia.
* Patients who have had a respiratory tract infection within 4 weeks prior to Visit 1.
* Patients with concomitant pulmonary disease
* Patients with a history of asthma
* Any patient with lung cancer or a history of lung cancer (within last 5 years)
* Patients with a history of certain cardiovascular co-morbid conditions
C: Inclusion Criteria:

* At least 40 years of age and no older than 80 at Screening
* Women of non-child bearing potential or negative serum pregnancy test at Screening, and agrees to acceptable contraceptive methods used consistently and correctly Screening until 14 days after final visit
* Subjects with an established clinical history of COPD as defined by the American Thoracic Society (ATS)/European Respiratory Society (ERS)
* Current or former smokers with a history of at least 10 pack-years of cigarette smoking
* Pre- and post-bronchodilator FEV1/FVC ratio of \<0.70
* Post-bronchodilator FEV1 must be \<80% predicted normal value, calculated using NHANES III reference equations, and the measured FEV1 must also be ≥750 mL if FEV1 \<30% of predicted normal value

Exclusion Criteria:

* Significant diseases other than COPD, i.e., disease or condition which, in the opinion of the Investigator, may put the subject at risk because of participation in the study or may influence either the results of the study or the subject's ability to participate in the study
* Women who are pregnant or lactating
* Subjects, who in the opinion of the Investigator, have a current diagnosis of asthma
* Subjects who have been hospitalized due to poorly controlled COPD within 3 months prior to Screening or during the Screening Period
* Subjects who have poorly controlled COPD, defined as acute worsening of COPD that requires treatment with oral corticosteroids or antibiotics within 6 weeks prior to Screening or during the Screening Period
* Subjects who have clinically significant uncontrolled hypertension.
* Subjects who have cancer that has not been in complete remission for at least five years
* Subjects with abnormal liver function tests defined as AST, ALT, or total bilirubin ≥1.5 times upper limit of normal at Screening and on repeat testing
* Subjects with a diagnosis of angle closure glaucoma will be excluded, regardless of whether or not they have been treated. Subjects with a diagnosis of open angle glaucoma who have intraocular pressure controlled with medication(s) are eligible
* Subjects with symptomatic prostatic hypertrophy that is clinically significant in the opinion of the Investigator. Subjects with a trans-urethral resection of prostate (TURP) or full resection of the prostate within 6 months prior to Screening are excluded from the study
* Subjects with bladder neck obstruction or urinary retention that is clinically significant in the opinion of the Investigator
D: Inclusion criteria:

1. All patients must sign an informed consent consistent with 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 relatively stable airway obstruction with, at visit 1:

   a post-bronchodilator 30% \<= FEV1 \<80% of predicted normal (ECSC) and a post-bronchodilator FEV1/FVC \<70% at Visit 1
3. Male or female patients, between 40 and 75 years (inclusive) of age on day of signing informed consent.
4. Patients must be current or ex-smokers with a smoking history of more than 10 pack years Patients who have never smoked cigarettes must be excluded.
5. Patients must be able to perform technically acceptable pulmonary function tests (spirometry), must be able to complete multiple symptom-limited cycle ergometry tests (and for a subset also shuttle walk tests), as required in the protocol.
6. Patients must be able to inhale medication in a competent manner from the RESPIMAT inhaler and from a metered dose inhaler (MDI).

Exclusion criteria:

1. Patients with a significant disease other than COPD
2. Patients with clinically relevant abnormal baseline haematology, blood chemistry, or urinalysis; all patients with an SGOT \> x2 ULN, SGPT \> x2 ULN, bilirubin \> x2 ULN or creatinine \> x2 ULN will be excluded regardless of clinical condition
3. Patients with a history of asthma
4. A diagnosis of thyrotoxicosis
5. A diagnosis of paroxysmal tachycardia (\>100 beats per minute)
6. A history of myocardial infarction within 1 year of screening visit (Visit 1)
7. Unstable or life-threatening cardiac arrhythmia
8. Hospitalized 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
11. A history of life-threatening pulmonary obstruction and patients with chronic respiratory failure
12. A history of cystic fibrosis
13. Clinically evident bronchiectasis
14. A history of significant alcohol or drug abuse
15. Any contraindications for exercise testing
16. Patients who have undergone thoracotomy with pulmonary resection
17. Patients being treated with any oral ß-adrenergics
18. 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
19. 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 during clinic visits
20. 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
21. Patients who have a limitation of exercise performance as a result of factors other than fatigue or exertional dyspnoea or morbid obesity
22. Patients with an endurance time \>=25 minutes during the training (Visit 2) or baseline (Visit 3) constant work rate cycle ergometry
23. Patients who have taken an investigational drug within one month or six half lives (whichever is greater) prior to screening visit (Visit 1)
24. Patients with known hypersensitivity to ß-adrenergic drugs, anticholinergic drugs, BAC, EDTA or any other component of the RESPIMAT inhalation solution delivery system
25. Pregnant or nursing women
26. 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
27. Patients who have previously been randomized in this study or are currently participating in another study
28. Patients who are unable to comply with pulmonary medication restrictions prior to randomization

    At sites performing the shuttle walk tests, patients with the following criteria will be excluded from the shuttle walk tests:
29. Patients who complete level 12 at the incremental shuttle walk test at visit 1a.
30. Patients with an endurance time \>=15 minutes during the training (Visit 2a) or baseline (visit 3a) endurance shuttle walk test.

Answer: A