Please select the eligibility criteria that correspond to the clinical trial below.
Title: An Exploratory, 12 Week, Randomised, Partially Double-blinded, Placebo-controlled Parallel Group Trial to Explore the Effects of Once Daily Treatments of Orally Inhaled Tiotropium + Olodaterol Fixed Dose Combination or Tiotropium (Both Delivered by Respimat® Inhaler), Supervised Exercise Training and Behavior Modification on Exercise Capacity and Physical Activity in Patients With Chronic Obstructive Pulmonary Disease (COPD)
Brief Summary: The primary objectives of the study are to explore the effect of treatment with orally inhaled tiotropium + olodaterol fixed dose combination with and without exercise training, and tiotropium comparing to placebo, on top of behavioural modification in improving exercise capacity in patients with COPD


Options:
A: Inclusion criteria:

* All patients must sign an informed consent consistent with International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) - Good Clinical Practice (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 and must meet the following spirometric criteria: Patients must have relatively stable airway obstruction with a post-bronchodilator forced expiratory volume in one second \>=30% and \<80% of predicted normal; Global Initiative for Chronic Obstructive Lung Disease grade II - III, and a post-bronchodilator Tiffeneau index \<70% at Visit 1.
* Male or female patients, aged \>=40 years and \<=75 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.

Exclusion criteria:

* Patients with a significant disease other than chronic obstructive pulmonary disease.
* Patients with clinically relevant abnormal baseline haematology, blood chemistry, or urinalysis.
* Patients with a history of asthma.
* A diagnosis of thyrotoxicosis.
* A diagnosis of paroxysmal tachycardia (\>100 beats per minute).
* A history of myocardial infarction within 1 year of screening visit.
* Unstable or life-threatening cardiac arrhythmia.
* Hospitalized for heart failure within the past year.
* Known active tuberculosis.
* A malignancy for which patient has undergone resection, radiation therapy or chemotherapy within last five years.
* A history of life-threatening pulmonary obstruction and patients with chronic respiratory failure.
* A history of cystic fibrosis.
* Clinically evident bronchiectasis.
* A history of significant alcohol or drug abuse.
* Any contraindications for exercise testing.
* Patients who have undergone thoracotomy with pulmonary resection.
* Patients being treated with any oral ß-adrenergics.
* 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.
* 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.
* Patients who have completed a pulmonary rehabilitation program in the six weeks prior to the screening visit or patients who are currently in a pulmonary rehabilitation program.
* Patients who have a limitation of exercise performance as a result of factors other than fatigue or exertional dyspnoea, such as arthritis in the leg, angina pectoris or claudication or morbid obesity.
* Patients who have taken an investigational drug within one month or six half lives (whichever is greater) prior to screening visit.
* Patients with known hypersensitivity to ß-adrenergics drugs, anticholinergic drugs, benzalkonium chloride, disodium edentat, or any other component of the Respimat® inhalation solution delivery system.
* Pregnant or nursing women.
* Women of childbearing potential not using highly effective methods of birth control.
* Patients who have previously been randomized in this study or are currently participating in another study.
B: 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
C: 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.
* Subjects with FEV1/FVC ratio of \<0.70 and FEV1 \<80% predicted normal and ≥750 mL if FEV1 \<30% of predicted normal value.
* 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 NYHA Class III/IV)
* Clinically significant abnormal 12-lead ECG
* Abnormal liver function tests defined as AST, 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
D: 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 A female is eligible to enter and participate in the study if she is of:
* Non-child bearing potential OR
* Child bearing potential, has a negative pregnancy test at screening, and agrees to one of the acceptable contraceptive methods defined in the protocol
* Age: ≥40 years of age at Screening (Visit 1)
* COPD diagnosis: Subjects with a clinical history of COPD in accordance with the definition by the American Thoracic Society/European Respiratory Society \[Celli, 2004\]
* Tobacco use: Subjects with a current or prior history of ≥10 pack-years of cigarette smoking at Screening (Visit 1).
* Severity of Disease: Subjects with a Screening (Visit 1) measured post-albuterol/salbutamol:
* FEV1/FVC ratio of ≤0.70 and
* FEV1 ≤70% of predicted normal values
* Dyspnea: Achieved a score of ≥2 on the Modified Medical Research Council Dyspnea Scale (mMRC) at Screening (Visit 1).

Exclusion Criteria:

Subjects meeting any of the following criteria must not be enrolled in the study:

* Pregnancy: Women who are pregnant or lactating or are planning on becoming pregnant during the study.
* Asthma: Subjects with a current diagnosis of asthma
* α1-antitrypsin deficiency: Subjects with α1-antitrypsin deficiency as the underlying cause of COPD
* Other respiratory disorders: Subjects with active tuberculosis, lung cancer, bronchiectasis, sarcoidosis, lung fibrosis, pulmonary hypertension, interstitial lung diseases, or other active pulmonary diseases
* Lung resection: Subjects with lung volume reduction surgery within the 12 months prior to Screening (Visit 1)
* Chest X-ray (or CT scan): Subjects with a chest X-ray (or CT scan) that reveals evidence of clinically significant abnormalities not believed to be due to the presence of COPD.
* Hospitalization: Subjects who are hospitalized due to poorly controlled COPD within 12 weeks of Visit 1.
* Poorly controlled COPD: Subjects with poorly controlled COPD, defined as the occurrence of the following in the 6 weeks prior to Visit 1: Acute worsening of COPD that is managed by subject with corticosteroids or antibiotics or that requires treatment prescribed by a physician.
* Lower respiratory tract infection: Subjects with lower respiratory tract infection that required the use of antibiotics within 6 weeks prior to Visit 1.
* Other diseases/abnormalities: Subjects with historical or current evidence of clinically significant cardiovascular (i.e., pacemaker), neurological, psychiatric, renal, hepatic, immunological, endocrine (including uncontrolled diabetes or thyroid disease) or haematological abnormalities that are uncontrolled.
* Peptic Ulcer disease: Subjects with clinically significant peptic ulcer disease that is uncontrolled.
* Hypertension: Subjects with clinically significant hypertension that is uncontrolled.
* Cancer: Subjects with carcinoma that has not been in complete remission for at least 5 years. Carcinoma in situ of the cervix, squamous cell carcinoma and basal cell carcinoma of the skin would not be excluded if the subject has been considered cured within 5 years since diagnosis.
* Drug/food allergy: Subjects with a history of hypersensitivity to any of the study medication or components of the inhalation powder
* Drug/alcohol abuse: Subjects with a known or suspected history of alcohol or drug abuse within the last 2 years
* Medication prior to spirometry: Subjects who are medically unable to withhold their albuterol/salbutamol and/or their ipratropium 4 hours prior to spirometry testing at each study visit
* Additional medication: Use of certain medications such as bronchodilators and corticosteroids for the protocol-specified times prior to Visit 1 (the Investigator will discuss the specific medications)
* Oxygen therapy: Subjects receiving treatment with long-term oxygen therapy (LTOT) or nocturnal oxygen therapy required for greater than 12 hours a day. Oxygen prn use (i.e., ≤12 hours per day) is not exclusionary.
* Sleep apnea: Subjects with clinically significant sleep apnea who require use of continuous positive airway pressure (CPAP) device or non-invasive positive pressure ventilation (NIPPV) device.
* Pulmonary rehabilitation: Subjects who have participated in the acute phase of a Pulmonary Rehabilitation Program within 4 weeks prior to Screening (Visit 1) or who will enter the acute phase of a Pulmonary Rehabilitation Program during the study.
* Non-compliance: Subjects at risk of non-compliance, or unable to comply with the study procedures. Any infirmity, disability, or geographic location that would limit compliance for scheduled visits.
* Questionable validity of consent: Subjects with a history of psychiatric disease, intellectual deficiency, poor motivation or other conditions that will limit the validity of informed consent to participate in the study.
* Prior use of study medication/other investigational drugs
* Affiliation with investigator site: Study investigators, sub-investigators, study coordinators, employees of a participating investigator or immediate family members of the aforementioned are excluded from participating in this study.

Answer: A