Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Randomized, Double-blind, Controlled, Parallel-group, 12-week Study to Compare the Efficacy and Safety of the Combination of Indacaterol 150 µg Once Daily With Open Label Tiotropium 18 µg Once Daily Versus Open Label Tiotropium 18 µg Once Daily in Patients With Moderate-to-severe Chronic Obstructive Pulmonary Disease
Brief Summary: This study assessed the efficacy and safety of indacaterol (150 µg once daily \[od\]) when combined with tiotropium (18 µg od) versus tiotropium (18 µg od) treatment alone in patients with chronic obstructive pulmonary disease (COPD)


Options:
A: Inclusion Criteria:

* Type of subject: Outpatient
* Informed Consent: A signed and dated written informed consent prior to study participation
* Age: Subjects 40 years of age or older at Visit 1
* Gender: Male or female subjects. A female is eligible to enter and participate in the study if she is of: Non-child bearing potential (i.e. physiologically incapable of becoming pregnant, including any female who is post-menopausal or surgically sterile); or Child bearing potential, has a negative pregnancy test at screening, and agrees to one of the acceptable contraceptive methods listed in the protocol used consistently and correctly
* Diagnosis: established clinical history of COPD in accordance with the definition by the American Thoracic Society/European Respiratory Society as follows: Chronic obstructive pulmonary disease is a preventable and treatable disease state characterized by airflow limitation that is not fully reversible. The airflow limitation is usually progressive and is associated with an abnormal inflammatory response of the lungs to noxious particles or gases, primarily caused by cigarette smoking. Although COPD affects the lungs, it also produces significant systemic consequences.
* Smoking history: Current or former cigarette smokers with a history of cigarette smoking of \>=10 pack-years \[number of pack years = (number of cigarettes per day/20) x number of years smoked (e.g., 20 cigarettes per day for 10 years, or 10 cigarettes per day for 20 years)\]. Previous smokers are defined as those who have stopped smoking for at least 6 months prior to Visit 1. Pipe and/or cigar smoking cannot be used to calculate pack year history.
* Severity of disease: A pre and post-salbutamol FEV1/FVC ratio of \<0.70 and a post-salbutamol FEV1 of \>=30% and \<=70% of predicted normal values calculated using NHANES III reference equations at Visit 1.
* Dyspnea: A score of \>=2 on the Modified Medical Research Council Dyspnea Scale (mMRC) at Visit 1.

Exclusion Criteria:

* Pregnancy: Women who are pregnant or lactating or are planning on becoming pregnant during the study
* Asthma: A current diagnosis of asthma
* Other Respiratory Disorders: Known alpha-1 antitrypsin deficiency, active lung infections (such as tuberculosis), and lung cancer are absolute exclusionary conditions. A subject, who, in the opinion of the investigator, has any other significant respiratory condition in addition to COPD should be excluded. Examples may include clinically significant bronchiectasis, pulmonary hypertension, sarcoidosis, or interstitial lung disease. Inactive tuberculosis in more than one lobe is exclusionary. Allergic rhinitis is not exclusionary.
* Other Diseases/Abnormalities: Subjects with historical or current evidence of clinically significant cardiovascular, neurological, psychiatric, renal, hepatic, immunological, endocrine (including uncontrolled diabetes or thyroid disease) or hematological abnormalities that are uncontrolled and/or a previous history of cancer in remission for \<5 years prior to Visit 1 (localized carcinoma of the skin that has been resected for cure is not exclusionary). Significant is defined as any disease that, in the opinion of the investigator, would put the safety of the subject at risk through participation, or which would affect the efficacy or safety analysis if the disease/condition exacerbated during the study.
* Contraindications: A history of allergy or hypersensitivity to any anticholinergic/muscarinic receptor antagonist, beta2-agonist, corticosteroid, lactose/milk protein or magnesium stearate or a medical condition such as narrow-angle glaucoma, prostatic hypertrophy or bladder neck obstruction that, in the opinion of the study physician contraindicates study participation or use of an inhaled anticholinergic.
* Hospitalization: Hospitalization for pneumonia within 12 weeks prior to Visit 1
* History of COPD Exacerbation: A documented history of at least one COPD exacerbation in the 12 months prior to Visit 1 that required either oral corticosteroids, antibiotics, and/or hospitalization. Prior use of antibiotics alone does not qualify as an exacerbation history unless the use was associated with treatment of worsening symptoms of COPD, such as increased dyspnea, sputum volume, or sputum purulence.
* Lung Resection: Subjects with lung volume reduction surgery within the 12 months prior to Screening (Visit 1)
* 12-Lead ECG: An abnormal and significant electrocardiogram (ECG) finding from the 12-lead ECG conducted at Visit 1. Investigators will be provided with ECG reviews conducted by a centralized independent cardiologist to assist in evaluation of subject eligibility.
* Medication Prior to Spirometry: Unable to withhold salbutamol for the 4 hour period required prior to spirometry testing at each study visit.
* Medications Prior to Screening: Use of the following medications according to the following defined time intervals prior to Visit 1: Depot corticosteroids - 12 weeks, Systemic, oral or parenteral corticosteroids - 6 weeks, Antibiotics (for lower respiratory tract infection) - 6 weeks, Cytochrome P450 3A4 strong inhibitors - 6 weeks, Herbal medications potentially containing oral or systemic steroids - 6 weeks, Inhaled corticosteroids (ICS) - 30 days, Long-acting beta2-agonist (LABA)/ICS combination products - 30 days, Phosphodiesterase 4 (PDE4) inhibitors (e.g., roflumilast) - 14 days, Inhaled long-acting anticholinergics - 7 days, Theophyllines - 48 hours, Oral leukotriene inhibitors (zafirlukast, montelukast, zileuton) - 48 hours, Oral beta2-agonists Long-acting-48 hours/Short-acting - 12 hours, Inhaled long acting beta2-agonists (LABA, e.g., salmeterol, formoterol, indacaterol) - 48 hours, Inhaled sodium cromoglycate or nedocromil sodium - 24 hours, Inhaled short acting beta2-agonists - 4 hours, Inhaled short-acting anticholinergics - 4 hours, Inhaled short-acting anticholinergic/short-acting beta2-agonist combination products - 4 hours, Any other investigational medication - 30 days or within 5 drug half-lives (whichever is longer)
* Oxygen: Use of long-term oxygen therapy (LTOT) described as oxygen therapy prescribed for greater than 12 hours a day. As-needed oxygen use (i.e., \<=12 hours per day) is not exclusionary.
* Nebulized Therapy: Regular use (prescribed for use every day, not for as-needed use) of short-acting bronchodilators (e.g., salbutamol) via nebulized therapy.
* Pulmonary Rehabilitation Program: Participation in the acute phase of a pulmonary rehabilitation program within 4 weeks prior to Visit 1. Subjects who are in the maintenance phase of a pulmonary rehabilitation program are not excluded.
* Drug or Alcohol Abuse: A known or suspected history of alcohol or drug abuse within 2 years prior to Visit 1.
* Affiliation with Investigator Site: A subject will not be eligible for this study if he/she is an immediate family member of the participating investigator, sub-investigator, study coordinator, or employee of the participating investigator
* Inability to read: A subject will not be eligible for the study if in the opinion of the investigator the subject cannot read.
B: Inclusion Criteria:

* Male and female adults aged ≥ 40 years, who have signed an Informed Consent Form prior to initiation of any study-related procedure
* Co-operative out patients with a diagnosis of chronic obstructive pulmonary disease (COPD) (moderate to severe as classified by the Global initiative for chronic obstructive lung disease (GOLD) Guidelines, 2006) and:

  1. Smoking history of at least 10 pack years (current or previous smokers)
  2. Post-bronchodilator forced expiratory volume in 1 second (FEV1) \< 80% and ≥30% of the predicted normal value.
  3. Post-bronchodilator FEV1/Forced vital capacity (FVC) \< 70%

Exclusion Criteria:

* Patients who have been hospitalized for a COPD exacerbation in the 6 weeks prior to Visit 1 or during the run-in period
* Patients requiring long-term oxygen therapy for chronic hypoxemia
* Patients who have had a respiratory tract infection within 6 weeks prior to Visit
* Patients with concomitant pulmonary disease
* Patients with a history of asthma
* Patients with diabetes Type I or uncontrolled diabetes Type II
* Any patient with lung cancer or a history of lung cancer
* Any patient with active cancer or a history of cancer with less than 5 years disease free survival time
* Patients with a history of long QT syndrome or whose QTc interval (Bazett's) measured at Visit 1 or randomization is prolonged
* Patients who have been vaccinated with live attenuated vaccines within 30 days prior to screening or during the run-in period.
* Patients unable to successfully use a dry powder inhaler device, MDI or perform spirometry measurements

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

1. The patient has signed an Informed Consent Form in accordance with GCP and local legislative requirements prior to participation in the trial, i.e., prior to pre-trial washout of any restricted medications.
2. The patient has a clinical diagnosis of chronic obstructive pulmonary disease (COPD).
3. The patient has relatively stable, moderate to severe airway obstruction.
4. The patient has a pre-bronchodilator forced expiratory volume in the first second (FEV1) less than or equal to 65% of predicted normal determined at Visit 1 using the following predicted equations (R94-1408):

   1. Males Forced expiratory volume in the first second (FEV1) predicted \[Litres (L)\] = 4.30 x Height \[metres\] minus 0.029 x Age \[years\] minus 2.49
   2. Females Forced expiratory volume in the first second (FEV1) predicted \[Litres (L)\] = 3.95 x Height \[metres\] minus 0.025 x Age \[years\] minus 2.60 and a Thoracic Gas Volume (Functional residual volume) ((TGV)(FRC)) bigger than 120% predicted normal at visit 1 (or historical data not older than 6 month)
   3. Males Thoracic Gas Volume (Functional residual volume) ((TGV(FRC)) pred. \[Litres (L)\] = 2.34 x Height \[metres\] + 0.009 x Age \[years\] minus 1.09
   4. Females Thoracic Gas Volume (Functional residual volume) ((TGV(FRC)) pred. \[Litres (L)\] = 2.24 x Height \[metres\] + 0.001 x Age \[years\] minus 1.00
5. The patient is at least 40 years and less than or equal to 75 years old.
6. The patient has a cigarette smoking history of at least 10 pack-years. A pack-year is defined as the equivalent of smoking one pack of cigarettes per day for a year.
7. The patient is able to perform all specified procedures and able to maintain all necessary records during the study period as required in the protocol.
8. The patient is able to inhale the trial medication from the HandiHaler device.
9. The patient is able to inhale the trial medication from the Diskus/Accuhaler device.

Exclusion Criteria:

1. a significant disease other than chronic obstructive pulmonary disease (COPD). (review contraindications for exercise testing),
2. a recent history of myocardial infarction within one year.
3. a recent history of heart failure, pulmonary oedema, or patients with cardiac arrhythmia or any contraindication to exercise described in the CTProtocol within the last 3.
4. daytime supplemental oxygen.
5. a diagnosis of known active tuberculosis.
6. a history of cancer within the last 5 years.
7. a history of life-threatening pulmonary obstruction, or a history of cystic fibrosis or bronchiectasis.
8. thoracotomy with pulmonary resection.
9. an upper respiratory tract infection or an exacerbation of chronic obstructive pulmonary disease (COPD)
10. a known hypersensitivity to anticholinergic drug, ß-adrenergic or corticosteroids, lactose or any other component of the inhalation capsule delivery system.
11. a known symptomatic prostatic hypertrophy or bladder neck obstruction.
12. a known moderate or severe renal insufficiency.
13. a known narrow-angle glaucoma.
14. a known untreated hypokalemia.
15. a known untreated thyrotoxicosis.
16. a history of asthma, allergic rhinitis or atopy, or a total blood eosinophil count larger than 600/mm3.
17. treatment with cromolyn sodium or nedocromil sodium
18. treatment with antihistamines or antileukotrienes.
19. treatment with tiotropium for 1 month before Visit 1.
20. treatment with oral corticosteroid medication.
21. Pregnant or nursing women or women of childbearing potential not using a medically approved means of contraception
22. a history of or active alcohol or drug abuse.
23. an investigational drug within 1 month or 10 half lives
24. a limitation of exercise performance as a result of factors other than fatigue or exertional dyspnoea.
25. participation in a rehabilitation program for chronic obstructive pulmonary disease (COPD).
26. treatment with monoamine oxidase inhibitors inhibitors or tricyclic antidepressants.
27. participation in another study.
28. more than eight puffs of salbutamol/day during the run-in period
D: Inclusion Criteria:

* Diagnosis of chronic obstructive pulmonary disease (COPD) (moderate-to-severe as classified by the Global Initiative for Chronic Obstructive Lung Disease \[GOLD\] Guidelines, 2007) and:

  1. Smoking history of at least 10 pack-years
  2. Post-bronchodilator forced expiratory volume in 1 second (FEV1) ≤ 65% and ≥ 30% of the predicted normal value
  3. Post-bronchodilator FEV1/FVC (force vital capacity) \< 70%

Exclusion Criteria:

* Patients who have had a COPD exacerbation requiring systemic glucocorticosteroid treatment or antibiotics and/or hospitalization in the 6 weeks prior to screening or during the run-in period
* Patients who have had a respiratory tract infection within 6 weeks prior to screening or during the run-in period
* Patients with a body mass index less than 15 or more than 40 kg/m\^2
* Patients with concomitant pulmonary disease
* Patients with a history of asthma
* Patients with diabetes Type I or uncontrolled diabetes Type II
* Any patient with lung cancer or a history of lung cancer
* Patients with a history of certain cardiovascular comorbid conditions

Other protocol-defined inclusion/exclusion criteria applied to the study.

Answer: D