Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Randomised, Double-blinded, Active-controlled 2-way Cross Over Trial to Assess the Effects of 6 Weeks Treatment of Once Daily Orally Inhaled Tiotropium + Olodaterol Fixed Dose Combination Delivered by RESPIMAT Inhaler Compared With Tiotropium Delivered by RESPIMAT Inhaler on Lung Hyperinflation, Exercise Capacity and Physical Activity in Japanese Patients With Chronic Obstructive Pulmonary Disease (COPD)
Brief Summary: This is a multi-centre, randomised, double-blinded, active-controlled, 2-way cross over trial to assess the effects of once daily administration of orally inhaled tiotropium + olodaterol FDC or tiotropium (both delivered by the RESPIMAT Inhaler) on pulmonary function (lung hyperinflation), exercise capacity (6-minute walk distance) and physical activities after 6 weeks of treatment in Japanese patients with Chronic Obstructive Pulmonary Disease.


Options:
A: Inclusion criteria:

1. Diagnosis of chronic obstructive pulmonary disease.
2. Relatively stable airway obstruction with post FEV1\< 80% predicted normal and post FEV1/FVC \<70%.
3. Male or female patients, 40 years of age or older.
4. Smoking history of more than 10 pack years.

Exclusion criteria:

1. Significant disease other than COPD
2. Clinically relevant abnormal lab values.
3. History of asthma.
4. Diagnosis of thyrotoxicosis
5. Diagnosis of paroxysmal tachycardia
6. History of myocardial infarction within 1 year of screening visit
7. Unstable or life-threatening cardiac arrhythmia.
8. Hospitalization for heart failure within the past year.
9. Known active tuberculosis.
10. Malignancy for which patient has undergone resection, radiation therapy or chemotherapy within last five years
11. History of life-threatening pulmonary obstruction.
12. History of cystic fibrosis.
13. Clinically evident bronchiectasis.
14. History of significant alcohol or drug abuse.
15. Thoracotomy with pulmonary resection
16. Oral ß-adrenergics.
17. Oral corticosteroid medication at unstable doses
18. Regular use of daytime oxygen therapy for more than one hour per day
19. Pulmonary rehabilitation program in the six weeks prior to the screening visit
20. Investigational drug within one month or six half lives (whichever is greater) prior to screening visit
21. Known hypersensitivity to ß-adrenergic drugs, anticholinergics, BAC, EDTA
22. Pregnant or nursing women.
23. Women of childbearing potential not using a highly effective method of birth control
24. Patients who are unable to comply with pulmonary medication restrictions
B: Inclusion criteria:

* 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.
* All patients must have a diagnosis of chronic obstructive pulmonary disease (COPD) and must meet the following spirometric criteria:

Patients must have relatively stable airway obstruction with a post-bronchodilator Forced expiratory volume in one second (FEV1) \< 80% of predicted normal and post-bronchodilator FEV1/forced vital capacity (FVC) \< 70% at Visit 1.

* Male or female patients, aged \>= 40 years.
* 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.
* Patients with score on the modified Medical Research Council (mMRC) \>= 1.
* Patients who walk \< 400 meters of 6MWT and have a score on the modified Borg \>= 4 at the end of 6 minute walk test (6MWT) at Visit 2.
* Patients must be able to perform technically acceptable pulmonary function tests (spirometry), to use the physical activity monitor and must be able to complete 6MWT during the study period as required in the protocol.
* Patients must be able to inhale medication in a competent manner from the RESPIMAT Inhaler and from a metered dose inhaler.

Exclusion criteria:

* Patients with a significant disease other than COPD; a significant disease is defined as a disease which, in the opinion of the investigator, may put the patient at risk because of participation in the study, influence the results of the study and cause concern regarding the patient's ability to participate in the study.
* Patients with clinically relevant abnormal baseline haematology, blood chemistry,urinalysis or creatinine \> x2 upper limit of normal (ULN) will be excluded regardless of clinical condition (a repeat laboratory evaluation can be conducted if deemed necessary by the investigator).
* Patients with a current documented diagnosis of asthma. For patients with allergic rhinitis or atopy, source documentation is required to verify that the patient does not have asthma.
* Further exclusion criteria apply
C: Inclusion Criteria:

* COPD patients aged ≥ 40 years with stable moderate-to-severe airflow obstruction (FEV1 \< 70% and FEV1/FVC ≤ 70% of predicted normal value) post-bronchodilator
* presenting with a long history of smoking (\> 20 pack-years) and chronic breathlessness (Baseline Dyspnoea Index total score \< 9)

Exclusion Criteria:

* significant cardiovascular disease, hospitalization for COPD exacerbation or presence of a respiratory tract infection within 1 month of screening
* current or childhood asthma
* a history of allergic rhinitis or other atopic disease
* inability to interrupt usual bronchodilator medication
* use of oral steroids within a month before screening
* need for long-term oxygen therapy, arterial oxygen saturation \< 85% at rest anemia, hypo- and hyperthyroidism, hyperadrenergic state
* uncontrolled insulin dependent diabetes mellitus, malignancy, or any disease or condition which limits exercise performance other than COPD
* change in inhaled corticosteroid or theophylline use within 1 month prior to screening
D: Key Inclusion Criteria:

* Male or female subjects at least 40 years of age and no older than 80 at Visit 1.
* 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.
* Average f the -60 and the -30 min pre-dose FEV1 assessments must be \< 80% predicted normal value calculated using National Health and Nutrition Examination Survey (NHANES) III reference equations.
* Subjects willing and, in the opinion of the investigator, able to adjust current COPD therapy as required by the protocol

Key Exclusion Criteria:

* Significant diseases other than COPD, i.e. 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 either the results of the study or the subject's ability to participate in the study
* Current diagnosis of asthma or alpha-1 antitrypsin deficiency
* Other active pulmonary disease such as active tuberculosis, lung cancer, bronchiectasis, sarcoidosis, idiopathic interstitial pulmonary fibrosis, primary pulmonary hypertension, or uncontrolled sleep apnea
* Hospitalized due to poorly controlled COPD within 3 months prior to screening or during the Screening Period
* 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
* Lower respiratory tract infections that required antibiotics within 6 weeks prior to screening or during the Screening Period
* Unstable ischemic heart disease, left ventricular failure, or documented myocardial infarction within 12 months of enrollment.
* Recent history of acute coronary syndrome, percutaneous coronary intervention, coronary artery bypass graft within the past three months
* Congestive heart failure (CHF) New York Heart Association (NYHA) Class III/IV)
* Clinically significant abnormal 12-lead ECG
* Abnormal liver function tests defined as aspartate transaminase (AST), alanine transaminase (ALT), or total bilirubin ≥ 1.5 times upper limit of normal at Visit 1 and on repeat testing
* Cancer not in complete remission for at least five years
* History of hypersensitivity to β2-agonists, glycopyrronium or other muscarinic anticholinergics, lactose/milk protein or any component of the MDI

Other protocol-defined inclusion/exclusion criteria may apply

Answer: B