Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Long-Term, Randomized, Study of the Safety and Tolerability of a Fixed-Dose Combination of Aclidinium Bromide/Formoterol Fumarate Compared With Formoterol Fumarate in Patients With Moderate to Severe, Stable Chronic Obstructive Pulmonary Disease (COPD)
Brief Summary: The purpose of this study is to assess the long-term safety and tolerability of inhaled aclidinium bromide/formoterol in patients with moderate to severe, stable chronic obstructive pulmonary disease (COPD).


Options:
A: 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.
B: 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.
C: 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 a post-bronchodilator FEV1 \<80% of predicted normal and a post-bronchodilator FEV1/FVC \<70% at Visit 1.
3. Male or female patients, between 40 and 75 years of age (inclusive) on day of signing informed consent.
4. Patients must be current or ex-smokers with a smoking history of more than 10 pack years.

Exclusion criteria:

1. Patients with a significant disease other than COPD; a significant disease is defined as a disease which, in the opinion of the investigator, may (i) put the patient at risk because of participation in the study, (ii) influence the results of the study, or (iii) cause concern regarding the patient's ability to participate in the study
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. For patients with allergic rhinitis or atopy, source documentation is required to verify that the patient does not have asthma.

   Patients with any of the following conditions:
4. A diagnosis of thyrotoxicosis (due to the known class side effect profile of ß2-agonists)
5. A diagnosis of paroxysmal tachycardia (\>100 beats per minute) (due to the known class side effect profile of ß2-agonists)
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 (patients with treated basal cell carcinoma are allowed)
11. A history of life-threatening pulmonary obstruction
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 (patients with a history of thoracotomy for other reasons should be evaluated as per exclusion criterion No. 1)
17. Patients being treated with any oral ß-adrenergics
18. Patients being treated with oral corticosteroid medication at unstable doses
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 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, such as arthritis in the leg, angina pectoris or claudication or morbid obesity.
22. Patients who have taken an investigational drug within one month or six half lives (whichever is greater) prior to screening visit
23. Patients with known hypersensitivity to ß-adrenergics drugs, anticholinergic drugs, BAC, EDTA or any other component of the Respimat® inhalation solution delivery system
24. Pregnant or nursing women
25. Women of childbearing potential not using highly effective methods of birth control.
D: Inclusion Criteria:

* Current or former cigarette smokers with a cigarette smoking history of at least 10 pack-years
* A diagnosis of stable moderate to severe COPD and stable airway obstruction as defined by the Global Initiative for Chronic Obstructive Lung Disease guidelines and stable airway obstruction.

Exclusion Criteria:

* Patients who have been hospitalized for an acute COPD exacerbation within three months prior to Visit 1
* Any respiratory tract infection (including the upper respiratory tract) or COPD exacerbation in the six weeks before Visit 1.
* Patients with any clinically significant respiratory conditions other than COPD
* Clinical history that suggests that the patient has asthma as opposed to COPD
* Chronic use of oxygen therapy ≥ 15 hours/day
* Patients with clinically significant cardiovascular conditions
* Patients with uncontrolled infection that may place the patient at risk resulting from human immunodeficiency virus (HIV), active hepatitis and/or patients with diagnosed active tuberculosis
* Patients with a history of hypersensitivity reaction to inhaled anticholinergics,
* Patients with Stage II hypertension, defined as systolic pressure of 160 and above, and/or diastolic pressure of 100 and above
* Current diagnosis of cancer other than basal or squamous cell skin cancer

Answer: D