Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Long-term, Randomized, Double-blind Extension Study of the Safety, Tolerability, and Efficacy of Aclidinium Bromide at Two Dose Levels When Administered to Patients With Moderate to Severe Chronic Obstructive Pulmonary Disease
Brief Summary: The purpose of this extension study is to evaluate the long-term safety, tolerability, and efficacy of inhaled aclidinium bromide at two dose levels in patients with moderate to severe chronic obstructive pulmonary disease (COPD). This study will be 54 weeks in duration; a 52-week double-blind treatment period and 2 week follow-up phone call, following a 12 week lead-in study. All patients will be randomized from the lead-in study at one of two doses of aclidinium.


Options:
A: Inclusion Criteria:

* A diagnosis of stable moderate to severe COPD as defined by the Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines, 2008; postbronchodilator FEV1/FVC \< 70%, and postbronchodilator FEV1 ≥ 30% and \< 80% predicted
* Current or former cigarette smokers

Exclusion Criteria:

* Patients who have been hospitalized for an acute COPD exacerbation within 3 months before the first visit
* Respiratory tract infection or COPD exacerbation in the 6 weeks before Visit 1
* Patient with any clinically significant respiratory conditions other than COPD, cardiovascular conditions or mental illness
* History or presence of asthma verified from medical records
* Chronic use of oxygen therapy greater than or equal to 15 hours per day
* Patient with uncontrolled infection due to HIV and/or active hepatitis
* Patients with a history of hypersensitivity reaction to inhaled anticholinergics
* Patients with clinically significant cardiovascular conditions, including myocardial infarction during the previous 6 months, newly diagnosed arrhythmia within the previous 3 months, unstable angina, unstable arrhythmia that had required changes in pharmacological therapy or other intervention.
B: Inclusion Criteria:

Subjects eligible for enrolment in this study must meet all of the following criteria:

* Male or female of at least 40 years of age at screening.

To be eligible for entry into the study, females of childbearing potential must commit to the consistent and correct use of an acceptable method of birth control starting on the day of visit 1, throughout the clinical trial, and for a period after the trial to account for elimination of the drug (minimum of six days), as defined by any one of the following:

* Abstinence Females of childbearing potential who are not sexually active must commit to complete abstinence from intercourse
* Oral contraceptive (either combined estrogen/progestin or progestin only)
* Injectable progestogen
* Implants of levonorgestrel or etonogestrel
* Percutaneous contraceptive patches
* Intrauterine device (IUD) or intrauterine system (IUS) with a documented failure rate of less than 1% per year,
* Male partner who is sterile (vasectomy with documentation of azoospermia) prior to the female subject's entry into the study and is the sole sexual partner for that female subject, or
* Double-barrier method; condom or occlusive cap (diaphragm or cervical /vault caps) plus spermicide.
* Current or former smokers with a \>10 pack-year cigarette smoking history \[number of pack years = (number of cigarettes per day / 20) X number of years smoked (e.g., 10 pack-years is equal to 20 cigarettes per day for 10 years, or 10 cigarettes per day for 20 years\]. Former smokers are defined as those who have quit smoking for at least 3 months prior to the screening visit.
* Any of the following populations:
* Patients hospitalized for a duration not exceeding 10 days due to an acute exacerbation of COPD, and who must be randomized within 10 days post-discharge.
* Patients with COPD who were treated and held for observation in the emergency department (i.e. emergency room, ER) for at least 24 hours due to an acute exacerbation of COPD, and who must be randomized within 10 days post-discharge.
* Patients who received oral corticosteroids or oral corticosteroids and antibiotics for treatment of an exacerbation of COPD during a physician's office visit and who must be randomized within 10 days of the visit, and who have been hospitalized within the previous six months due to an acute exacerbation of COPD.
* Clinical diagnosis of COPD (for at least 6 months). The following definition of COPD from the American Thoracic Society (ATS) will be used: COPD is a disease state characterized by the presence of airflow obstruction due to chronic bronchitis or emphysema; the airflow obstruction is generally progressive, may be accompanied by airway hyper-reactivity, and may be partially reversible \[American Thoracic Society, 1995\].
* Documented evidence (within a year prior to Visit 1) in the medical chart of spirometry confirming the diagnosis of COPD and/or spirometry performed prior to randomization (Visit 2) that confirms pre-bronchodilator FEV1/FVC ratio less than or equal to 0.70 and pre-bronchodilator FEV1 \<70% of predicted.
* Review and subject's completion of written informed consent: a subject-signed and dated written informed consent (form) must be obtained prior to any study procedure, and the subject must be willing to comply with all the requirements of the study protocol.
* Subject must be able to read, comprehend, and record information in English or Spanish.

Exclusion Criteria:

* Subjects meeting any of the following criteria must not be enrolled in the study:
* Diagnosis of pneumonia, congestive heart failure (CHF), or other complicating co-morbid condition while hospitalized within the last 6 months for an exacerbation of COPD.
* Historical or current evidence of clinically significant uncontrolled disease including, but not limited to, those listed below. Significant is defined as any disease that, in the opinion of the investigator, would put the safety of the subjects at risk through study participation, or which would affect the safety analysis or other analyses if the disease/condition exacerbated during the study.
* A previous lung resection surgery (e.g. lobectomy, pneumonectomy, etc) within the year preceding Visit 1 (Screening)
* Asthma as primary diagnosis
* Lung cancer
* Cystic fibrosis, pulmonary fibrosis, active tuberculosis, or sarcoidosis
* Clinically significant cardiac arrhythmias
* Uncontrolled hypertension
* Unstable angina
* Current malignancy or a previous history of cancer in remission for \< 5yrs (localized basal cell or squamous cell carcinoma of the skin that has been resected is not excluded)
* Uncontrolled diabetes mellitus
* Uncontrolled hyperthyroidism or hypothyroidism
* Immunologic compromise
* Cushing's or Addison's disease
* An abnormal 12-lead electrocardiogram (ECG) at Visit 1 (Screening) deemed to be clinically significant by the investigator.
* A chest X-ray or computed tomography (CT) scan performed in the 6 months preceding Visit 1 that revealed evidence of clinically significant abnormalities not believed to be due to the presence of COPD. If the subject does not have a record of a chest X-ray, one must be obtained and reviewed prior to randomization.
* Female patients with a positive urine pregnancy test at Visit 1.
* Any infirmity, physical disability, or geographic location that would limit compliance for scheduled visits.
* Any adverse reaction, immediate or delayed, hypersensitivity to any Beta-agonist, sympathomimetic drug, or corticosteroid including any components of the study drug formulations.
* Limited ability to provide a valid informed consent due to psychiatric disease, intellectual deficiency, poor motivation, current substance abuse (including illicit drugs and alcohol), or neurological disorders that might interfere with completion of study procedures or hearing problems that may impede effective communication.
* Study site staff (i.e. participating investigator, sub-investigator, study coordinator, employee of the participating investigator) or family members of site staffs.
C: Inclusion Criteria:

* Completion of a lead-in study (NCT00891462)

Exclusion Criteria:

* Use or anticipated use of any medication prohibited in this study
* Evidence of abnormal clinical laboratory values, vital signs, or electrocardiographic (ECG) results or the presence of abnormities in physical examination findings
* The presence of anti-cholinergic effects (eg, dry mouth, urinary retention, narrow angle glaucoma)
* QTcB of \>500 msec on both the pre-dose and post-dose ECG
* Women who are pregnant, intend to become pregnant, or are breast-feeding
* A life expectancy of less than 1 year
* Noncompliance with IP dosing and/or attending clinic visits during the lead-in study
* Significant interruption of double-blind therapy during the transition from the lead-in study into the extension study.
D: Inclusion Criteria:

1. All patients must sign an informed consent prior to participation in the trial, which includes medication washout and restrictions.
2. All patients must have a diagnosis of chronic obstructive pulmonary disease according to the GOLD criteria and must meet the following spirometric criteria:

   a post-bronchodilator FEV1 \< 80% of predicted normal, a post-bronchodilator FEV1/FVC \< 70% at Visit 1, and a morning FEV1 \<= 65% predicted at Visit 2.
3. Male or female patients 40 years of age or older.
4. Patients must be current or ex-smokers with a smoking history of more than 10 pack-years.
5. Patients must be able to perform technically acceptable pulmonary function tests.
6. Patients must be able to inhale medication in a competent manner from the HandiHaler® device, the Blue Inhaler device, and from a metered dose inhaler (MDI).

Exclusion Criteria:

1. Patients with significant diseases other than COPD.
2. Patients with a recent history (i.e., six months or less) of myocardial infarction.
3. Patients who have been hospitalized for heart failure (NYHA class III or IV) within the past year.
4. Any unstable or life threatening cardiac arrhythmia or cardiac arrhythmia requiring intervention or a change in drug therapy within the past year.
5. Patients with a history of cancer within the last five years.
6. Patients with known narrow-angle glaucoma.
7. Patients with a history of asthma, allergic rhinitis or atopy or who have a total blood eosinophil count \>= 600/mm3.
8. Patients with a history of life threatening pulmonary obstruction, or a history of cystic fibrosis or clinically evident bronchiectasis.
9. Patients with known active tuberculosis.
10. Patients with significant alcohol or drug abuse within the past two years.
11. Patients who have undergone thoracotomy with pulmonary resection.
12. Patients who have completed a pulmonary rehabilitation program in the six weeks prior to the Screening Visit (Visit 1) or patients who are currently in a pulmonary rehabilitation program that will not be maintained throughout the study.
13. 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.
14. Patients who are being treated with antihistamines (H1 receptor antagonists) for asthma or excluded allergic conditions.
15. Patients who have taken an investigational drug within one month or six half lives prior to Visit 1.
16. Patients who have been treated with oral beta-adrenergics within one month prior to Visit 1.
17. Patients who have been treated with antileukotrienes or leukotriene receptor antagonists for any disease within one month prior to Visit 1.
18. Patients who have been treated with oral steroids within six weeks prior to Visit 1.
19. Patients who have been treated with monoamine oxidase inhibitors or tricyclic antidepressants within one month prior to Visit 1.
20. Patients who have been treated with cromolyn sodium or nedocromil sodium within one month prior to Visit 1.
21. Patients who have been treated with inhaled steroids within two months prior to Visit 1, including combinations of inhaled steroids and long-acting beta-adrenergics.
22. Patients with known hypersensitivity to anticholinergic drugs, beta adrenergics, lactose or any other components of the inhalation capsule delivery system or any other components of the aerosol delivery systems.
23. Pregnant or nursing women or women of childbearing potential not using a medically approved means of contraception for the previous three months.
24. Patients with any respiratory infections in the six weeks prior to the Screening Visit (Visit 1) or during the run-in period.
25. Patients who are currently participating in another study.
26. Patients requiring more than eight puffs of salbutamol on three or more consecutive days during the run-in period.

Answer: C