Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Multicener, Randomised, Double-blind, Placebo-controlled Study, to Assess the Long Term Safety of 52 Weeks Treatment With QVA149 (110 ug Indacaterol/50ug Glycopyrrolate) in Patients With Moderate to Severe Chronic Obstructive Pulmonary Disease (COPD)
Brief Summary: The study is designed to provide long-term safety data for QVA149 in patients with moderate to severe chronic obstructive pulmonary disease (COPD).


Options:
A: Inclusion Criteria:

* Moderate to severe COPD based on prebronchodilator FEV1/forced vital capacity (FVC) ratio of \<=70%.
* At Screening \& Baseline, postbronchodilator FEV1 must be \>= 60% predicted normal \& \>=25% predicted normal.
* COPD symptoms for \>=24 months.
* \>=2 COPD exacerbations requiring course of oral corticosteroid \&/or antibiotics within 2-12 months before screening.
* Ex- or current smoker with smoking history \>=10 pack years.
* Only albuterol/salbutamol for relief for at least 2 weeks prior to randomization.
* Withdraw from parenteral \& oral steroids, anticholinergics, \& antibiotics 4 weeks prior to Screening.
* No harm in changing current COPD therapy, willing to discontinue his/her anticholinergics, inhaled corticosteroids (ICS) or ICS/long-acting beta agonists (LABA) at Screening, \& transferred to albuterol/salbutamol for relief for 2 weeks prior to Randomization.
* Lab tests conducted at Screening must be acceptable to investigator. Electrocardiogram (ECG) performed at Screening or within 30 days prior to Screening must be acceptable to investigator. Chest X-ray or computerized tomography (CT) scan is acceptable within 12 months prior to Screening must be acceptable to investigator.
* Female of childbearing potential must use birth control. Includes: hormonal contraceptives, intra-uterine device (IUD), condom in combination with spermicide, monogamous relationship with male partner who had vasectomy. Started birth control at least 3 months prior to Screening (exception condom), \& must agree to continue. Female who is not currently sexually active must agree/consent to using a method should she become sexually active. Women who have been surgically sterilized or are at least 1 year postmenopausal are not considered to be of childbearing potential. Female must have negative serum pregnancy test at Screening.

Exclusion Criteria:

* Evidence (upon visual inspection) of oropharyngeal candidiasis at Baseline with or without treatment. If there is evidence at Screening, may be treated as appropriate \& visit can be scheduled upon resolution. If there is evidence at Baseline, may be treated as appropriate \& visit can be rescheduled upon resolution.
* History of renal, hepatic, cardiovascular, metabolic, neurologic, hematologic, ophthalmological, respiratory, gastrointestinal, cerebrovascular, or other which could interfere with study or require treatment which might interfere with study. Examples include (but are not limited to) hypertension treated with beta-blockers), active hepatitis, coronary artery disease, arrhythmia, significant QTc prolongation (ie QTcF or QTcB \[Fridericia or Bazett corrections, respectively \>500 milliseconds (msecs)\]) stroke, severe rheumatoid arthritis, chronic open-angle glaucoma or posterior subcapsular cataracts, acquired immune deficiency syndrome (AIDS), or conditions that may interfere with respiratory function such as asthma, bronchiectasis, cystic fibrosis. Others which are well-controlled \& stable (eg hypertension not requiring beta-blockers) will not prohibit participation if appropriate to investigator.
* Allergy/sensitivity to glucocorticosteroids, beta-2 agonists, study drug/excipients.
* Female who is breast-feeding, pregnant, or intends to become pregnant.
* Illicit drug user.
* Human immunodeficiency virus (HIV) positive (testing not conducted).
* Unable to correctly use oral MDI.
* Taking any restricted medications prior to Screening without meeting washout.
* Cannot adhere to permitted concomitant \& prohibited medications.
* May not participate in this same study at another investigational site. Cannot participate in different investigational study at any site, during same time.
* Not be randomized into study more than once.
* No person directly associated with administration of study may participate.
* Previously participated in MF/F trial.
* Increase in absolute volume of \>=400 milliliters (mL) at Screening or prior to Baseline within 30 minutes after administration of 4 inhalations of albuterol/salbutamol (total dose of 360 to 400 mcg), or nebulized 2.5 mg albuterol/salbutamol.
* Asthma.
* Lobectomy, pneumonectomy or lung volume reduction surgery.
* Lung cancer.
* Requires long-term administration of oxygen (\>15 hours/day).
* Alpha-1-antitrypsin deficiency.
* A history and/or presence of intraocular pressure in either eye \>=22 millimeters of mercury (mm Hg), glaucoma, and/or posterior subcapsular cataracts. A subject who has undergone incisional or intraocular surgery in which the natural lens is still present in the eye. A subject with a history of penetrating trauma to both eyes. A subject with one or more of the following Lens Opacities Classification System (LOCS) III grades at screening:

  * nuclear opalescence (NO): \>=3.0,
  * nuclear color (NC): \>=3.0,
  * cortical cataract (C): \>=2.0,
  * posterior subcapsular (P): \>=0.5.
B: 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
C: Inclusion Criteria:

* Male or female adults aged ≥40 yrs
* Smoking history of at least 10 pack years
* Diagnosis of COPD (moderate-to-severe as classified by the Global Initiative for Chronic Obstructive Lung Disease (GOLD) Guidelines, 2008)
* Post-bronchodilator FEV1 \< 80% and ≥ 30% of the predicted normal value and post-bronchodilator FEV1/FVC (forced vital capacity) \<70%

Exclusion Criteria:

* 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
* Patients with a history of certain cardiovascular co-morbid conditions
* Patients with a known history and diagnosis of alpha-1 antitrypsin deficiency
* Patients in the active phase of a supervised pulmonary rehabilitation program
* Patients contraindicated for inhaled anticholinergic agents and β2 agonists
* Other protocol-defined inclusion/exclusion criteria may apply
D: 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

Answer: C